Major References:

http://en.wikipedia.org/wiki/Wiki Comprehensive Pharmacy Review Reference Guide for Foreign Pharmacy Licensing Exam Questions and A by Manan H. Shroff, R. Ph, Krisman Therapeutic choices Pre-test Pharmacology 10th edition Appleton and Lange's Review of Pharmacy Manon Shroff Calculations

Most of the contents (esp drug's information) come from wiki and CPR. other mentioned books are all helpful for my study. Thanks a lot for those

This is just for studying and preparing the exam, not for other uses. The please check the original book or make your own judgement. Bring all the best wishes for your way to be a good pharmacist

Please go to the different sheets below the screen..

in the last exam of January 2011, we were asked a lot of questions about Bioethics,pharmacoepidemiology/biostatistics,Manag Where exactly , in all in one, we can find the above topics,especially Bioethics ?and do you k Thanks again and again

Atropine: origin tells action or vice versa Atropine causes your pupils to dilate, and it came from nightshade [belladona] In the night or in shade, your pupils dilate so you can see --- Mydriasis

Atropine use: tachycardia or bradycardia "A goes with B": Atropine used clinically to treat Bradycardia

Reserpine action Reserpine depletes the Reserves of catecholamines [and serotonin]

Botulism toxin: action, related bungarotoxin Action: "Botulism Bottles up the Ach so it can't be the released"

Related bungarotoxin: "Botulism is related to Beta Bungarotoxin (beta-, not alpha-bungarotoxin--alpha has Ipratropium action Atropine is buried in the middle: iprAtropium, so it behaves like Atropine Succinylcholine: action, use Succinylcholine gets Stuck to Ach receptor, then Sucks ions(Na+) in through open pore You Suck stuff in through a mouth-tube, and drug is used for intubation Cholinergics (eg: organophosphates) effects If you get cholinergics, you will be "LESS DUMB": Lacrimation Excitation of nicotinic synapses Salivation Sweating Diarrhea Urination Micturition Bronchoconstriction Anticholinergic Overdose Not really a mnemonic: Blind as a bat Dry as a bone Red as a beet Mad as a hatter Hot as a hare and: mydriasis, absent BS, urinary retention Depression: 5 drugs causing it PROMS: depression Propranolol Reserpine Oral contraceptives

Methyl dopa Steroids Benzodiazepines: actions "Ben SCAMs Pam into seduction not by brain but by muscle": Sedation anti-Convulsant anti-Anxiety Muscle relaxant Not by brain: No antipsychotic activity. Short TOM in benzodiazepines: Short acting: Trizaolam, Oxazepam, Midazolam

Comp Long-Pheno; Medium- AB; Short - PS; Ultra-short- MTT Long-acting: Phenobarbital Intermediate: Amobarbital; Butabarbital short: Pentobarbital; Secobarbital ultra-short: Methohexital; Thiamylal; Thiopental

Dia-fluma Flumazenil is a specific antagonist for Diazepam Methyldopa side effects METHYLDOPA: Mental retardation Electrolyte imbalance Tolerance Headache/ Hepatotoxicity psYcological upset Lactation in female Dry mouth Oedema = edema Parkinsonism Anaemia (haemolytic)

Sodium valproate side effects VALPROATE: Vomiting Alopecia [7AlEu5pi:siE] Liver toxicity Pancreatitis/ Pancytopenia Retention of fats (weight gain) Oedema (peripheral oedema) Appetite increase Tremor

Enzyme inducer (liver) Lead poisoning ABCDEFG: Anemia Basophilic stripping Colicky pain Diarrhea Encephalopathy Foot drop Gum (lead line) Lithium side effects LITTH: Leukocytosis Insipidus [diabetes insipidus, tied to polyuria] Tremor/ Teratogenesis Hypothyroidism

SSRI side effects SSRI: Serotonin syndrome Stimulate CNS Reproductive disfunctions in male Insomnia Narcotic antagonists The Narcotic Antagonists are NAloxone and NAltrexone. Important clinically to treat narcotic overdose.

Inhalation anesthetics SHINE Sevoflurane Halothane Isoflurane Nitrous oxide Enflurane If want the defunct Methoxyflurane too, make it MoonSHINE.

Opioid effects of (morphine, codeine, thebaine derivatives (hydrocodone, acetyldihydrocodeine, oxymorph BAD AMERICANS: Bradycardia & hypotension Anorexia Diminished pupilary size Analgesics / Ameliorate cough reflex Miosis Euphoria

Respiratory depression Increased smooth muscle activity (biliary tract constriction) Constipation Ameliorate cough reflex Nausea and vomiting Sedations Morphine effects MORPHINE: Miosis Orthostatic hypotension Respiratory depression Pain supression Histamine release/ Hormonal alterations Increased ICT Nausea Euphoria Sedation

Anticholinergic toxidrome: "Hot as a Hare, Dry as a Bone, Red as a Beet, Mad as a Hatter, Blind as a Ba

The symptoms include blurred vision, choreoathetosis, coma, decreased bowel sounds, delirium, dry skin memory loss, mydriasis (dilated pupils), myoclonus, psychosis, seizures, and urinary retention. Complic hyperthermia, and tachycardia. Substances that may cause this toxidrome include antihistamines, atropine, benztropine, datura, tricycl scopolamine.

Delirium-causing drugs ACUTE CHANGE IN MoodS, will make you Delirium Antibiotics (Biaxin, Penicillin, Ciprofloxacin) Cardiac drugs (Digoxin, Lidocaine) Urinary incontinence drugs (Anticholinergics) Theophylline Ethanol Corticosteroids H2 blockers Antiparkinsonian drugs Narcotics (especially Mepridine) Geriatric psychiatric drugs ENT drugs Insomnia drugs NSAIDs (eg Indomethacin, Naproxin) Muscle relaxants Seizure medicines

ENT drugs: related to ear, nose and throat

4-Aminopyradine (4-AP) use "4-AP is For AP": For AP (action potential) propagation in Multiple Sclerosis.

Direct sympathomimetic catecholamines DINED: Direct sym cate: Do iSo, or NoEp Do Dopamine Isoproterenol Norepinephrine Epinephrine Dobutamine Anesthesia: 4 stages "Anesthesiologists Enjoy S & M": Analgesia Excitement Surgical anesthesia Medullary paralysis

Benzodiazepene antidote "Benz off flu": Benzodiazepine effects off with Flumazenil.

Narcotic side effects "SCRAM if you donot want be drowzy": Synergistic CNS depression with other drugs Constipation Respiratory depression Addiction Miosis Benzodiazepene: drugs which decrease its metabolism "I'm Overly Calm" even get rid of my Benz Isoniazid Oral contraceptive pills Cimetidine These drugs increase calming effect of BZDs by retarding metabolism.

Myasthenia gravis: edrophonium vs. pyridostigmine eDrophonium is for Diagnosis. pyRIDostigmine is to get RID of symptoms. Lithium: side effects

LITHIUm: (low therapeutic index, ataxia,convulsion, confusion, tremor, dry mouth, polydipsia, polyuria( treat with ami Leukocytes Increased (leukocytosis). Tremors. Hypothyroidism.

Increased Urine (ADH antagonist).

Monoamine oxidase inhibitors: members "PIT of despair": Phenelzine Isocarboxazid Tranylcypromine A pit of despair, since MAOs treat depression.

Propylthiouracil (PTU) used in hyperthyroidism, including Graves disease----a risk of causing agran PTU ---- hyPer Thyroidism --- Graves disease --- aGranulocytosis

Cardiovascular system beta2-adrenergic agonists "I D-R-E-A-M-T of practicing medicine as easy as ABC." "I D-R-E-A-M-T" (where Dream rhymes with -ine, -drine) I-Isoproterenol D-Dobutamine R-Ritodrine E-Epinephrine A-Albuterol M-Metaproterenol T-Terbutaline beta2 agonist therapy is indicated in A-B-C A-Asthma B-Bronchospasm in Bronchiolitis C-CHF, COPD

Propranolol and related '-olol' drugs: usage "olol" is just two backwards lower case b's Backward b's stand for "beta blocker" Beta blockers include acebutolol, betaxolol, bisoprolol, oxprenolol, propranolol

Warfarin: action, monitoring

WePT: Warfarin works on the extrinsic pathway and is monitored by PT.

Beta-blockers side effects "BBC Loses Viewers In Rochedale": Bradycardia Bronchoconstriction Claudication Lipids Vivid dreams & nightmares -ve Inotropic action Reduced sensitivity to hypoglycaemia

Captopril (an ACE inhibitor) side effects CAPTOPRIL: Cough Angioedema/ Agranulocystosis Proteinuria Taste changes Orthostatic hypotension Pregnancy contraindication/ Pancreatitis Renal failure (and renal artery stenosis contraindication)/ Rash Increased potassium Leukopenia/ Liver toxicity

Beta-blocker main contraindications / cautions ABCDE: Asthma Block (heart block) COPD Diabetes mellitus Electrolyte disorders (hyperkalemia) Ca++ channel blockers: uses CA++ MASH: Cerebral vasospasm/ CHF Angina Migranes Atrial flutter/fibrillation Supraventricular tachycardia Hypertension Alternatively: "CHASM": Cererbral vasospasm / CHF Hypertension Angina Suprventricular tachyarrhythmia Migranes

Situations can cause Hypercalcemia: CHIMPANZEES makes people hypercalcemia

Caused by Calcium ingestion (milk-alkali syndrome), Hyperparathyroid, Hyperthyroid, Iatrogenic (thiazides), Multiple myeloma, Pagets disease, Addisons disease, Neoplasms, Zollinger-Ellison syndrome Excess vitamin D, Excess vitamin A, Sarcoidosis.

Antihypertensives AA-ABCD AA-Angiotensin II Antagonists A-ACE inhibitors B-Beta blockers C-Calcium channel blockers D-Diuretics AB: most effective in hypertensive patients who are young and white

A and B grades are reserved for the young and white, but C and D grades are given to the elderly and blac CD: most effective in hypertensive patients who are elderly and African-American

Hypertensive Emergencies Lucy and Desi Arnaz of the I Love Lucy fame were an intense, Hypertense couple, but now... "Lucy and Desi's Ghosts Reside in the Night Sky." Lucy - Labetol Desi - Diazoxide Ghosts - Ganglionic blocking agent: Trimethaphan, hexamethonium, mecamylamine Reside - Reserpine Night - Nitroglycerin, nifedipine Sky - Sodium Nitroprusside

CHF treatment "Captains Calling For Girls' Debut": In order from 1st to 5th: Furosemide, diuretics Captopril Calcium channel blokers cardiac Glycosides dobutamine

Drugs that may exacerbate CHF "AAABC" A-Antiarrhythmic drugs A-Aspirin (NSAIDs) A-Alcohol B-Beta blockers C-Calcium channel blockers

Warfarin metabolism SLOW: Has a slow onset of action. A quicK Vitamin K antagonist, though it is SLOW in Small lipid-soluble molecule Liver: site of action Oral route of administration. Warfarin

Amiodarone: action, side effects 6 P's: Prolongs action potential duration Photosensitivity Pigmentation of skin Peripheral neuropathy Pulmonary alveolitis and fibrosis Peripheral conversion of T4 to T3 is inhibited -> hypothyroidism

Patent ductus arteriosus: PDA treatment "Come In and Close the door": INdomethacin is used to Close PDA.

Pulmonary system

Therapy for Asthma A-S-Th-M-A A-Albuterol S-Steroids (corticosteroids) Th-Theophylline M-Muscarinic antagonists: ipratropium A-Aminophylline Agents for exercise-induced bronchospasm (EIB) : Short-acting inhaled 2-agonistsalbuterol. bitolterol, pirbuterol; Long-acting agents (salmeterol, formoterol) Mast cell stabilizing agents (cromolyn, nedocromil) .

Gastrointestinal system

Endotracheal tube deliverable drugs NAVEL: Narcan Atropine

Valium Epinephrine Lidocaine

Hepatic necrosis: drugs causing focal to massive necrosis "Very Angry Hepatocytes": Valproic acid Acetaminophen Halothane

Misoprostol "You need this in BED": gastric mucous Barrier PGE1 Diarrhea

Amphotericin B ---used for A-B-C-D-E-F A-Aspergillosis B-Blastomycosis C-Coccidiodes immitis D-Disseminated histoplasmosis E-swEEt Candida sp. F-F**ed up brain, e.g., AIDS patients with cryptococcal meningitis

_____________________________________________________________________________________ 5-flucytosine -used for 3C Candidiasis - localized infections Chromomycosis Combination therapy with amphotericin B: Cryptococcal meningitis

*F*luconazole - 3C + 1F CS*F* penetration is good. Candidiasis Cryptococcal meningitis: prophylaxis in AIDS patients

Opioid effects, intoxication, antagonists See the Hopi [Opioids] Indians on Horseback [Heroin] B-U-R-N B-A-D A-M-E-R-I-C-A-N-S. B-Biliary smooth muscle constriction and spasm of sphincter of Oddi UR - Urinary Retention N-Naloxone, Naltrexone, Nalmefene are opioid antagonists. B-Bradycardia and hypotension A-Antitussive effect (cough reflex suppression) D-Deep tendon reflexes are Depressed. A-Analgesic effect M-Miosis E-Euphoria R-Respiratory depression I-Intracranial pressure is increased. (This effect is minimal with normal or low pCO2.) C-Constipation A-Acute opiate intoxication morbidity and mortality due to A-Anaphylaxis, ARDS, Acute respiratory Acidosis, and Aspiration pneumonitis. N-Nausea and vomiting S-Sedation

Acute opiate intoxication is characterized by abnormal mental status, decreased respiration, and miotic p Hopi [Opioids] means a Calm, Peaceful people" [reduced HR, BP, temperature, respirations]. They use their eagle Eyes to hunt down a Pin [Pinpoint pupils indicate overdose: use antagonists]. ARDS: Adult respiratory distress syndrome (noncardiogenic pulmonary edema) Cholinergic Overdose cholinergic too much ,you will get some "SLUDGE" S - Salivation L - Lacrimation U - Urination D - Diarrhea G - Gastric upset E - Emesis or, alternatively: "Dumbbels" D - Diarrhea U - Urination M - Miosis/muscle weakness B - Bronchorrea

B - Bradycardia E - Emesis L - Lacrimation S - Salivation/ sweating

Antineoplastic agents & Adverse effects

Drugs affecting prolactin: alkaloids, bromocriptine; Suppress(L-dopa, ergot

Increase ( Domperidone, Metoclopramide, Methyldopa, Haloperidol, Phenothiazines) Dom-me-me-halo-pheno Which type of cancer is Gefitinib approved to treat? Non small cell lung cancer (get fit- non small)

Many drugs can cause an immunohemolytic anemia. Methyldopa may cause a positive Coombs test in as many as 20% of patients, along with hemolytic anemia. Other drugs with similar actions on red blood cells are penicillins, quinidine, procainamide, and sulfonamides. These form a stable or unstable hapten on the red cell surface, which induces an immune reaction [immunoglobulin G (IgG) antibodies] and leads to dissolution of the membrane. Hematologic Disorders and Cancer drugs causing gynaecomastia Digitalis INH (Isoniazid) Spironolactone Cimentidine Oestrogen Stilbestrol --- Diethylstilbestrol (DES) B2agonist......SMART

1)Salmeterol 2)Metaproterenol 3)Albuterol 4)Ritodrine 5)Terbutaline.

STREPTOMYCIN DRUG FOR TUBERCULOSIS PLAGUE (BUBONIC) TULAREMIA

STEVEN-JOHNSON SYNDROME LESS LAMOTRIGINE ETHOSUXIMIDE SULFONAMIDES STEVEN-JOHNSON SYNDROME

ITRACONONAZOLE used for BUS BLASTOMYCOSIS USELESS SPOROTRICOSIS For respiratory depression: "STOP" sedative/ hypnotics: trimethoprim opiate: polymyxin For direct cholinergic agonst & Rx that cases pulmonary disease! ABCMNP

acetylcholine, bethanachol, carbochol, methocholine, nicotine pilocarpine amphotericin, bleomycin, carbam nitrofurantoin, pulmonary disease,

Impromptu Atypical Antipsychotics "ROCK" Risperidone-Olanzapine-Clozapine-Kiss

PLATINum CYCLE MUST Be IN MECHanical PROtection Platins(cis and carbo) CYCLOphoshamide, MUST B IN Bus MUSTIN(car and lo) MECHlorethamine PROcarbazine All these are CCNS( cell cycle non-specific) ALKYLATING AGENTS

PacKliTAXEL--> TAXANES keep the spindle PACKED, prevents spindle disassembly. Vincristine and vinblastin Believe in ONE( V for one) tubulin i.e prevent assembly spindle assembly by inhibiting polymaerization of tubulin Dimers (though) these are obviously CCS (cell cycle specific) for the M phase Must b in MUSTINS and Busulphan

Insomnia treatment; "Falling Time TRIad and ZZzzzz"... Flurazepam(long), Temazepam(intermediate), TRIa BZNs). BUPRIOPION or BUSPIRONE... ?? antianXiety=buXpirone BuPROPERion = PROPER habits ( no smoking ) its used for smoking cessation.

LITHIUM Lithium/ leukocytosis Inhibits PIP2, cAMP, 5' deiodinase Teratogenic / Thiazide contraindicated as it increases reabsorption Hypothyroidism/ Hyponatremia increases toxicity Insipidus (Nephrogenic diabetes) Give Amiloride visUal dysfunction Movement disorders: CATS(Choreoathetosis, Ataxia, Tremors, Seizures) movements

if the patient is pregnant FASTly get away from the following...they are CE (contrendicated !) Floroqoinolones Aminoglycosides Sulfonamides Tetracyclines Clarythromycine Erythromycin estolate dont use 'safe ct' in pregnancy s-sulfonamide a-aminoglycoside f-flouroquinolones e-erythromycin c-clarithromycin t-tetracyclin this is new name of hydrochlorthiazide......... hyperGLUCothiazide G hyperglycemia L hyperlipedemia U hyper uricemia c hypercalcemia

conjugation has 4 types 1.glucoronidation 2.acetylation 3.glutathione 4.sulfation beta blockersdrugs starting with alphabits A to M are beta 1 selective (acebutolol, atenolol, esmolol, metoprolol. and those from N-T are non selective (pindalol, propranolol, nodalol, sotalol, timolol exceptions- labetalol and carvedilol which are both alpha and beta blocker

BBB- Bethanechol stimulates Bowel and Bladder.

Drugs causing Pulmonary Fibrosis Go BAN Me! Go-Gold B-Bleomycin/Busulphan/BCNU A-Amiodarone/Acyclovir/Azathioprine N-Nitrofurantoin Me-Melphalan/Methotrexate/Methysergide Benzodiazepines metabolized '' outside the liver '' : Oxazepam , Temazepam, Lorazepam.

The factory car probably ran over your TMX-fone man! fac- Cefaclor car- Loracarbef pro- Cefprozil ran- Ceforanide ur- Cefuroxime TMX- Cefotetan, Cefmetazole, Cefoxitin (Cephamycins) fon- Cefonicid man- Cephamandole

Drugs causing Megaloblastic Anemia: MAPLE M>Methotrexate A>AZT=Zidovudine P>Phenytoin (Fenytoin>Folate deficiency) L>Liver Disease (speaking of the MC drug Alcohol, think of Liver as well) E>Ethanol

hey opiates are esters and amines amide have i and so the drugs have 2 I s mepivacaine lidocaine bupivacaine etidocaine prilocaineand ropivacaine esters have no i and drugs have only one i benzocaine chloroprocaine cocaineand Tetracaine

Tricyclics E ach = Elavil V ictoms = Vivactil A = Aventyl T ough = Tofranil N eurotic = Norpramin

Pulmonary Edema M=Morphine A=aminophylline D=digoxin

So she 'screamnt' when she realized she has been abusing opioids.A mnemonic for the cns effects of morp S - Sedation C - Cough suppression,convulsions, R - Respiratory depression E - Euphoria A - Analgesia M - Myosis( but may cause medriasis in doses causing asphyxia) N - Nausea and vomiting T - Truncal rigidity(but especially occurs with fentanyl and its congeners)

Amphotericin B is becoming an important drug in the setting of immunosuppressed states like HIV-AIDS.A A- Anemia M- Muscle spasms P- Phlebitis H- Headaches,Hypotension,Hypokalemia T- Thrombocytopenia E- Emesis,Encephalopathy R- Respiratory strida I- Increased temperature(fever) C- Chills I- Immediate hypersensitivity(anaphylaxis) N- Nephrotoxicity - Important! B- Bronchospasm.

Captopril (an ACE inhibitor): side effects CAPTOPRIL: Cough Angioedema/ Agranulocystosis Proteinuria/ Potassium excess Taste changes Orthostatic hypotension Pregnancy contraindication/ Pancreatitis/ Pressure drop (first dose hypertension) Renal failure (and renal artery stenosis contraindication)/ Rash Indomethacin inhibition Leukopenia/ Liver toxicity

Beta-blockers: main contraindications, cautions ABCDE: Asthma Block (heart block) COPD Diabetes mellitus Electrolyte (hyperkalemia)

Ca++ channel blockers: uses CA++ MASH: Cerebral vasospasm/ CHF Angina Migranes Atrial flutter, fibrillation Supraventricular tachycardia Hypertension Alternatively: "CHASM": Cererbral vasospasm / CHF Hypertension Angina Suprventricular tachyarrhythmia Migranes

Amiodarone: action, side effects 6 P's: Prolongs action potential duration Photosensitivity Pigmentation of skin Peripheral neuropathy Pulmonary alveolitis and fibrosis Peripheral conversion of T4 to T3 is inhibited -> hypothyroidism

Patent ductus arteriosus: treatment "Come In and Close the door": INdomethacin is used to Close PDA.

Hypertension: treatment ABCD: ACE inhibitors/ AngII antagonists (sometimes Alpha agonists also) Beta blockers Calcium antagonists Diuretics (sometimes vasoDilators also)

Hepatic necrosis: drugs causing focal to massive necrosis "Very Angry Hepatocytes": Valproic acid Acetaminophen Halothane

Steroids: side effects BECLOMETHASONE: Buffalo hump Easy bruising Cataracts Larger appetite Obesity Moonface Euphoria Thin arms & legs Hypertension/ Hyperglycaemia Avascular necrosis of femoral head Skin thinning Osteoporosis Negative nitrogen balance Emotional liability

Steroid side effects CUSHINGOID: Cataracts Ulcers Skin: striae, thinning, bruising Hypertension/ Hirsutism/ Hyperglycemia Infections Necrosis, avascular necrosis of the femoral head Glycosuria Osteoporosis, obesity Immunosuppression Diabetes

Corticosteroids: adverse side effects CUSHINGS BAD MD: Cataracts Up all night (sleep disturbances) Suppression of HPA axis Hypertension/ buffalo Hump Infections Necrosis (avascular) Gain weight Striae Bone loss (osteoporosis) Acne Diabetes Myopathy, moon faces Depression and emotional changes Propythiouracil (PTU): mechanism It inhibits PTU: Peroxidase/ Peripheral deiodination Tyrosine iodination Union (coupling)

Gynaecomastia-causing drugs DISCOS: Digoxin Isoniazid Spironolactone Cimetidine Oestrogens Stilboestrol

K+ increasing agents K-BANK: K-sparing diuretic Beta blocker ACEI NSAID K supplement Lupus: drugs inducing it HIP: Hydralazine INH Procanimide

Nitrofurantoin: major side effects NitroFurAntoin: Neuropathy (peripheral neuropathy) Fibrosis (pulmonary fibrosis) Anemia (hemolytic anemia) Osmotic diuretics: members GUM: Glycerol Urea Mannitol Diuretics classification in order of site of action "COLT Pee:" In their sequential site of action along the nephron: Carbonic anhydrase inhibitors (at the proximal tubule) Osmotic diuretics (at the Loop of Henle) Loop diuretics (at the ascending loop) Thiazides (at the distal tubule) Potassium-sparing diuretics (at the collecting tubules) Diuretics make patient pee like a horse, hence "Colt Pee". Prazocin usage Prazocin sounds like an acronym of "praszz zour urine". Therefore Prazocin used for urinary retention in BPH. SIADH-inducing drugs ABCD: Analgesics: opioids, NSAIDs Barbiturates Cyclophosphamide/ Chlorpromazine/ Carbamazepine Diuretic (thiazide) Diuretics: thiazides: indications "CHIC to use thiazides": CHF Hypertension Insipidous Calcium calculi Diuretics: groups "Leak Over The CAN": Loop diuretics Osmotics Thiazides Carbonic anhydrase inhibitors Aldosterone inhibitors Na (sodium) channel blockers Note: "leak" is slang for urination and "can" is slang for a toilet.

-vir at start, middle or end means for virus":

Drugs: Abacavir, Acyclovir, Amprenavir, Cidofovir, Denavir, Efavirenz, Indavir, Invirase, Famvir, Gancic Ritonavir, Saquinavir, Valacyclovir, Viracept, Viramune, Zanamivir, Zovirax.

Sulfonamide: major side effects Sulfonamide side effects: Steven-Johnson syndrome Skin rash Solubility low (causes crystalluria) Serum albumin displaced (causes newborn kernicterus and potentiation of other serum albumin-binders like

Warfarin: interactions ACADEMIC QACS: Amiodarone Cimetidine Aspirin Dapsone Erythromycin Metronidazole Indomethacin Clofibrates Quinidine Azapropazone Ciprofloxacin Statins

Pupils in overdose: morphine vs. amphetamine "MorPHINE: Fine. AmPHETamine: Fat": Morphine overdose: pupils constricted (fine). Amphetamine overdose: pupils dilated (fat).

Atropine use: tachycardia or bradycardia "A goes with B": Atropine used clinically to treat Bradycardia.

Reserpine action Reserpine depletes the Reserves of catecholamines [and serotonin].

Botulism toxin: action, related bungarotoxin Action: "Botulism Bottles up the Ach so it can't be the released": Related bungarotoxin: "Botulism is related to Beta Bungarotoxin (beta-, not alpha-bungarotoxin--alpha has

Ipratropium: action Atropine is buried in the middle: iprAtropium, so it behaves like Atropine.

Succinylcholine: action, use Succinylcholine gets Stuck to Ach receptor, then Sucks ions in through open pore. You Suck stuff in through a mouth-tube, and drug is used for intubation.

Phenobarbitone: side effects Children are annoying (hyperkinesia, irritability, insomnia, aggression). Adults are dosy (sedation, dizziness, drowsiness).

Cholinergics (eg organophosphates): effects If you know these, you will be "LESS DUMB": Lacrimation Excitation of nicotinic synapses Salivation Sweating Diarrhea Urination Micturition Bronchoconstriction

Depression: 5 drugs causing it PROMS: Propranolol Reserpine Oral contraceptives Methyldopa Steroids

Benzodiazepines: actions "Ben SCAMs Pam into seduction not by brain but by muscle": Sedation anti-Convulsant anti-Anxiety Muscle relaxant Not by brain: No antipsychotic activity.

Cisplatin: major side effect, action "Ci-Splat-In": Major side effect: Splat (vomiting sound)--vomiting so severe that anti-nausea drug needed. Action: Goes Into the DNA strand.

"Bleo-Mycin Blows My DNA to bits": Bleomycin works by fragmenting DNA (blowing it to bits). My DNA signals that its used for cancer (targeting self cells).

Metabolism enzyme inducers "Randy's Black Car Goes Putt Putt and Smokes": Rifampin Barbiturates Carbamazepine Grisoefulvin Phenytoin Phenobarb Smoking cigarettes

Routes of entry: most rapid ways meds/toxins enter body "Stick it, Sniff it, Suck it, Soak it": Stick = Injection Sniff = inhalation Suck = ingestion Soak = absorption

Zero order kinetics drugs (most common ones) "PEAZ (sounds like pees) out a constant amount": Phenytoin Ethanol Aspirin Zero order Someone that pees out a constant amount describes zero order kinetics (always the same amount out)

Therapeutic dosage: toxicity values for most commonly monitored medications "The magic 2s": Digitalis (.5-1.5) Toxicity = 2. Lithium (.6-1.2) Toxicity = 2. Theophylline (10-20) Toxicity = 20. Dilantin (10-20) Toxicity = 20. APAP (1-30) Toxicity = 200.

Disulfiram-like reaction inducing drugs "PM PMT" as in Pre Medical Test in the PM: Procarbazine Metronidazole Cefo (Perazone, Mandole, Tetan).

page 1 -31 Common Conversions Memorizing these standard concentrations will make conversions easier. There is 1 mg of epinephrine in 1 mL of a 1:1000 solution. There are 40 mEq of potassium in 30 mL of a 10% potassium chloride solution. An 8.4% solution of sodium bicarbonate contains 1 mEq each of sodium and bicarbonate ions per mL. There are 154 mEq of sodium in 1000 mL of 0.9% sodium chloride. There are 50 grams of dextrose in 1000 mL of D5W. There are 1700 calories in 1000 ml of D50W (500 grams of dextrose). There are 400,000 units of penicillin in 250 mg. A nitroglycerin 0.4 mg sublingual tablet contains 1/150 grains.

Miscellaneous Review Lists The following lists are intended to provide a brief review. They are by no means comprehensive and should not be used to make medical recommendations Transdermal Systems Should Be Changed Accordingly Clonidine patch Estradiol patch Fentanyl patch Lidocaine patch Nicotine patch Nitroglycerin patch Oxybutynin patch Scopolamine patch Temperatures F = 1.8C + 32 A Common Vitamins and the Condition That Results From Their Deficiency Ascorbic acid (vitamin C) Cyanocobalamin (vitamin B12) Folic acid B9 Niacin (nicotinic acid, B3) Thiamine (vitamin B1) Vitamin D Biotin B7 Scurvy Pernicious anemia Megaloblastic anemia Megaloblastic anemia neural tube defects Pellegra Beriberi, Wernicke-Korsakoff syndrome Rickets Dermatitis, enteritis every 7 days once-twice weekly (depending on brand of product) every 3 days every day (remove for 12 hours each night) every day every day twice weekly every 3 days

Vitamin generic descriptor name

Vitamer chemical name(s) (list not complete)

Recommended dietary allowances (male, age 1970)

Deficiency disease

Upper Intake Level (UL/day) 3,000 g

Vitamin A

Retinoids (retinol, retinoids and carotenoids)

900 g

Night-blindness and Keratomalacia

Vitamin A

Retinoids (retinol, retinoids and carotenoids)

900 g

Night-blindness and Keratomalacia

3,000 g

Vitamin B1 Vitamin B2 Vitamin B3 Vitamin B5 Vitamin B6 Biotin B7

Thiamine Riboflavin Niacin, niacinamide Pantothenic acid Pyridoxine, pyridoxamine, pyridoxal Biotin

1.2 mg 1.3 mg 16.0 mg 5.0 mg 1.3-1.7 mg 30.0 g

The treatment of beriberi increases the need of the Riboflavin

Beriberi Ariboflavinosis Pellagra Paresthesia Anaemia

N/D N/D 35.0 mg N/D 100 mg N/D

Dermatitis, enteritis

Folic acid B9

Folic acid, folinic acid

400 g

Deficiency during pregnancy is associated with birth defects, such as 1,000 g neural tube defects Megaloblastic anaemia

Vitamin B12 Vitamin C Vitamin D Vitamin E Vitamin K

Cyanocobalamin, hydroxycobalamin, methylcobalamin Ascorbic acid Ergocalciferol, cholecalciferol Tocopherols, tocotrienols phylloquinone, menaquinones Mephyton

2.4 g 90.0 mg 5.0 g-10 g 15.0 mg 120 g

N/D 2,000 mg

Scurvy Rickets and Osteomalacia Deficiency is very rare; mild hemolytic anemia in newborn infants. Bleeding diathesis

50 g 1,000 mg N/D

Viruses and Antiviral Agents That Inhibit Them Cytomegalovirus (CMV) Cidofovir (Vistide) Ganciclovir (Cytovene) Foscarnet (Foscavir) Fomivirsen (Vitravene) Hepatitis B virus Adefovir dipivoxil Interferon alfa-2b (Intron A) Lamivudine (Epivir HBV) Hepatitis C virus Herpes simplex virus Interferon alfa-2b/ribavirin Pegylated interferon Acyclovir (Zovirax) Famciclovir (Famvir) Valacyclovir (Valtrex) Influenza A virus Influenza A and B virus Respiratory syncytial virus Varicella-zoster virus (VZV) Amantadine (Symmetrel) Rimantadine (Flumadine) Oseltamivir (Tamiflu) Zanamivir (Relenza) Ribavirin (Rebetron) Acyclovir (Zovirax) Famciclovir (Famvir) Valacyclovir (Valtrex) Common Medications and Their Antidotes Acetaminophen Acetylcysteine Aceta---Acetyl

Arsenic (As) Aspirin Benzodiazepines /diazepam Cisplatin Digoxin Dopamine Ethanol Heparin Iron Methanol Methotrexate Morphine (opiates) Naloxone Nitrogen mustard Organophosphates Warfarin Cyanide poisoning

Dimercaprol

Counteract As Dimer

Alkaline urine with NaHCO3 / Vitamin K Flumazenil Amifostine Digoxin immune fab Phentolamine fomepizole Protamine Deferoxamine fomepizole; or ethanol Leucovorin Naloxone hydromorphone Sodium thiosulfate Pralidoxime / 2-PAM Phytonadione / vitamin K Amyl Nitrite+ Sodium thiosulfate (Na2S2O4) leuco rescu metho acid and base Cis-Ami cis-amine

Essential: Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine Watch TV TILL PM Amino acids: Nonessential: Alanine Asparagine Aspartate Cysteine* Glutamate Glutamine* Glycine* Proline* Serine* Tyrosine* Arginine* Histidine* cysteine, taurine, tyrosine, histidine and arginine are semiessential amino acids in children,

Many amino acids are used to synthesize other molecules, for example: Tryptophan is a precursor of the neurotransmitter serotonin. Glycine is a precursor of porphyrins such as heme. Arginine is a precursor of nitric oxide. Ornithine and S-adenosylmethionine are precursors of polyamines. Aspartate, glycine and glutamine are precursors of nucleotides. AGG

Building blocks of all proteins: Alanine, Arginine, Asparagine, Aspartic acid, Cysteine, Cystine, Glutamic acid, Glutamine, Glycine, Histidine, Isoleucine, Leucine, Lysine, Methionine, Phenylalanine, Proline, Serine, Threonine, Tyrosine, Tryptophan, Valine Citrulline, Ornithine, Taurine, and GABA are present in the body but not in the proteins.

Glutathion

It is a peptide containing the aminoacids glutamic acid, cysteine, and glycine. It functions as a coenzyme in several oxidationreduction reactions. Glutathione serves as an antioxidant. It reacts with potentially harmful oxidizing agents and itself oxidized.

Tryptophan

Act as building blocks in protein biosynthesis. In addition, tryptophan functions as a biochemical precursor for Serotonin and Niacin;

Common Laboratory Tests and What They Indicate ANA titer AMES aPTT Coombs D-xylose Guaiac INR Prostate specific antigen Prothrombin time Reinsch Schillings Sweat test Tropronins Normal Lab Values of Electrolytes and Minerals Pulmonary fibrosis related drugs: bleomycin, bromocriptine, busulfan, pentamidine, tocaininide; carmustine, mitomycin (bleobromo-busul-penta-tacain Rheumatic diseases potential carcinogen; cancer producing capability Used to monitor heparin therapy Antibody screening for blood donor/recipient compatibility GI function Occult blood in the stool Used to monitor warfarin therapy Prostate cancer Used to monitor warfarin therapy Screen for heavy metals Vitamin B12 absorption (pernicious anemia) Cystic fibrosis Cardiac marker

Sodium Potassium Chloride Magnesium Calcium Phosphate Bicarbonate (HCO3 -) Uric acid Glucose

135147 mEq/L 3.55.0 mEq/L 95105 mEq/L 1.52.2 mEq/L 8.510.8 mg/dL 2.64.5 mg/dL 22-28 mEq/L 3-7 mg/dL ~5 mmol /L Normal: <180 mg/dL

Fasting test: < 100 mg/dL

Ascorbic acid causes a positive Coombs test. A. Methyldopa B. Penicillins C. Quinidine D. Procainamide

G6PD-hemolytic anemia

Certain oxidant drugs ( aspirin, quine, primaquine, chloroquine, chloramphenicol, dapsone, nitrofurantoin, nalidixic acid, sulfacetamide, sulfapyridine, sulfanilamide, sulfonamide, nitrofuran, nalidixic acid, probenecid, phenacetin, quinidine and dimercaptol, isosorbide dinitrate) may cause G6PD deficiency pts to hemolytic anemia. G6PD (glucose-6-phosphate dehydrogenase) is an enzyme necessary to maintain the reduce glutathione level in red blood cells. Immune hemolytic anemia is most commonly found with methyldopa, also including: Mefenamic acid, levodopa and streptomycin

Drugs That Have Been Associated With Folic Acid Deficiency Anemia

Folic acid deficiency Anemia is found in BMO PPPoST Barbiturates Methotrexate Oral contraceptives Phenytoin Primidone Pyrimethamine Sulfasalazine Trimethoprim

Ototoxicity drugs: salicylate, aminoglycoside antibiotics ( neomycin is the most oto- and nephro toxic), minocycline (a derivative of tetracycline); loop diuretics (furosemide, torsemide, ethacrynic acid >>bumetanide);

Ocular toxicity drugs: Amiodarone, chloroquine, chlorpromazine, hydroxychloroquine, corticosteroids (h intraocular pressure); phenothiazines (Chlorpromazine, thioridazine, -azine),

medications can trigger headaches

Nitrates (NTG, Nitroglycerin, Isordil, etc.). Calcium Channel Blockers (for example, procardia) Zantac (a medication given for acid) Hormone related drugs (Birth control pills, also Lupron, Provera) Alcohol containing remedies. Cold capsules and decongestants Caffeine containing medications (e.g. "esgic").

----- Drugs related to Weight Gain:

Antiepileptics (Valproic acid); 1 -receptor antagonist (doxazosin, prazosin, terazosin); Estrogens (estradiol, mestranol); progestins (megestrol acetate, norethindrone, norgestimate, Drospirenone); Androgens (testosterone, fluoxymesterone; oxymetholone, nandrolone decanoate, oxandrolone); Glucocorticoids (hydrocortisone, prednisolone, betamethasone, Budesonide); Oral antidibetics: sulfonylureas (chlorpropamide, gliclazide, gliquidone, glyburide, glipizide); meglitinides (repaglinide, nateglinide); thiazolidinediones (rosiglitazone, pioglitazone); Exceptions: Biguanides (Metformin, phenformin) and -glucosidase inhibitors (miglitol, Acarbose)--- No weight gain and basic; Antipsychotics (Typical: Chlorprothixene, Atypical: azine, idone--- Clozapine, Risperidone, Olanzapinehigh risk); Exceptions: Aripiprazole---low risk of weight gain; Antidepressants: TCAs (doxepin, imipramine, amitriptylineextreme risk); SSRIs (loss first then gain, fluoxetine; fluvoxamine); Dual action antidepressants (Mirtazapine); Exceptions: Sertraline --- No weight gain.

Drugs related to Cholestatic jaundice: Chlorpromazine, chlorpropamide, erythromycin estolate, trazodone, certain tricyclic antidepressants, sulindac, methyldopa

Drugs That Have Commonly Been Associated With Hepatic Failure HE Parental nutrition A(acetaminophen-alcohol) T(keToconazole) Isoniazid C(carbamazepine, cytarabine) Flucytosine Allopurinol INH L-asparaginase (sulfonyl-) Hepatic Failure is very important!! Ureas Rifampin Erythromycin is Very imPortant (VPA) Acetaminophen Alcohol Allopurinol Carbamazepine Cytarabine Erythromycin (estolate salt) Flucytosine Gancyclovir Isoniazid ---INH Ketoconazole L-asparaginase Methotrexate Niacin Oral contraceptives Parenteral nutrition Rifampin Sulfonylureas Valproate: Valproic acid (VPA) Flucytosine Erythromycin (estolate salt)

Drugs That Have Commonly Been Associated With Decreased Renal Function Am-Am-CCC- For- Gold- Nsay-Pentami Cispla Foscar and Penta SAID on Contrast media that I Am not Good at renal Cyclo Aminoglycosides Amphotericin B Cisplatin Contrast media Cyclosporine Drugs related to Hypertrichosis (excessive growth of hair) Foscarnet Gold salts NSAIDS Pentamidine DAMP Tamo shampoo, good for hair !!

Diazoxide, Acetazolamide, Minoxidil, Phenytoin, Tamoxifen Drugs That Have Been Associated With Lupus Erythematosus-like Reaction Etho-Iso-Nitro- Pro- Pheno-Sulfo; Hydra-Tetra-Peni-Quini-Methyl-Pheny LUP (peni, pheno, pheny, procainamide) U Sulfonamides Ethosuximide RY Tetracyclines Hydrolazine E Methyldopa ATOSUSL INH K(quinidine) E Reaction Ethosuximide Hydralazine Isoniazid Methyldopa Nitrofurantoin Penicillamine Phenothiazines Phenytoin Procainamide Quinidine Sulfonamides Tetracyclines

Agents produce disulfiram-like reactions Di-sulf meet phento cefo-sulfo-metro-phento cephalosporins cefoperazine, cefoperazone

Disulfiram is a pharmacologic adjunct in the treatment of alcoholism. When given to a person who has consumed ethanol, it produces flushing, headache, nausea, vomiting, sweating, hypotension, and confusion. The mechanism involves inhibition of aldehyde dehydrogenase; thus, acetaldehyde accumulates as a result of ethanol metabolism.

tolbutamide metronidazole nonselective -antagonist phentolamine chlorpropamide tolazamide sulfonylureas acetohexamide

glyburide glipizide glimepiride Drugs That Have Been Associated With increasing prolactin levels: Riserpine Trifluoperazine Domperidone Estrogens / TRH Haloperidol Methyldopa Metocloprmide Theophylline Domperidone (prokinetics) Used for increasing milk supply Metoclopramide Sulpiride (not availabe in canada) antipsychotic drugs effect orders: the major tranquilizers (phenothiazines), trifluoperazine (Stelazine), and haloperidol (Haldol); some antipsychotic medications; metoclopramide (Reglan), used to treat gastroesophageal reflux and the nausea caused by certain cancer drugs; and, less often, alpha-methyldopa and reserpine, used to control hypertension; and oestrogens and TRH (Thyrotropin-releasing hormone )

risperidone>haloperidol>olanzapine> ziprasidone> quetiapine>clozapine> aripiprazole Trifluoperazine

Compare in phenothiazines Group Autonomic Example Chlorpromazine Promazine Triflupromazine Levomepromazine Methotrimeprazine Mesoridazine Thioridazine Fluphenazine Perphenazine Flupentixol Prochlorperazine Trifluoperazine Sedative strong moderate strong extremely strong strong strong weak/moderate weak/moderate moderate moderate Extrapyramidal side-effect moderate moderate moderate/strong low weak weak strong strong strong strong

Aliphatic compounds

moderate

Piperidines

strong

Piperazines

weak

orthostatic hypotension is which drugs side effect? - Vasodilator: a-blocker: phenoxybenzamine, phentolamine / a1-blocker: prazosin, doxazosin, terazosin Hydralazine, minoxidil, diazoxide - cholinergic effect: Orthostatic Hypotension - guanethidine - TCAst: amitriptyline, doxepine; - MAOI: phenelzine, tranylcypromine Related drugs: - ACEI: benazepril, captopril, enalapril, fosinopril, lisinopril, ramipril, quinapril, moexipril - Organic nitrates: isosorbide dinitrate, isosorbide mononitrate, nitroglycerin (high dose) - Diuretic; levodopa; - opioid: morphine - Platelet inhibitor: dipyridamole (high dose) - Antipsychotic: chlorpromazine, thioridazine

Drugs That Have Been Associated With Pancreatitis

Alcohol L-asparaginase Azathioprine Cimetidine Dideoxyinosine (DDI) Estrogens Furosemide Glucocorticoids Mercaptopurine Drugs That Have Been Associated With Photosensitivity Reactions

Metronidazole Parenteral nutrition Pentamidine Ranitidine Sulfinamides Tetracycline Thiazides Valproate

Drug-induced photosensitivity reaction: - Phototoallergy: light makes a drug become antigenic or act as a hapten; - Phototoxic: light alters a drug to a toxic form - Thiazides, tetracyclines, phenothiazines, sulfonamides, and even sunscreens - Phenothizaines and riboflavin are extremely light sensive. Amiodarone Amitriptyline Doxepine Fluoxetine Furosemide Griseofulvin Isotretinoin Ketoprofen Nalidixic acid Drug-induced Parkinson's Disease May Be Caused by Butyrophenones (especially haldol) Heavy metal poisoning Phenothiazines (especially thorazine) Reserpine Naproxen Oral contraceptives Oral hypoglycemics Phenothiazines Piroxicam Riboflavin Sulfonamides Tetracycline Thiazides

Drugs That Have Been Associated With Hyperglycemia Amiodarone L-asparaginase Epinephrine Estrogens Glucocorticoids Lithium Drugs to Avoid in Pregnancy benzo; ergo; fluo; hormo; iso; metho; miso; ralo; Fina; tetra; tha; vita A; warfar; Benzodiazepines Ergotamine Finasteride Fluorouracil Fluoroquinolones Methotrexate Misoprostol Raloxifene Statins Tetracyclines Nicotinic acid Oral contraceptives Pentamidine Phenytoin Thyroid hormones

Hormonal agents Isotretinoin

Thalidomide Vitamin A palmitate Warfarin Atorvastatin Fluvastatin Lovastatin Pravastatin Simvastatin

FDA pregnancy category X rating

Thalidomide

Statins leflunomide leuprolide acetate levonorgestrel medroxyprogesterone acetate megestrol acetate menotropins mequinol mestranol methotrexate sodium methyltestosterone miglustat misoprostol (PGE1) nafarelin norethindrone noregestel oxandrolone oxymetholone plicamycin raloxifene ribavirin tazarotene testosterone thalidomide (anticancer drug) triptorelin urofollitropin warfarin sodium

acitretin amprenavir anisindione bexarotene bicalutamide bosentan cetrorelix acetate chorionic Gonadotropin clomiphene citrate diclofenac sodium dihyroergotamine dutasteride estradiol estrogens estropipate ethinyl finasteride fluorouracil flurazepam follitropin ganirelix acetate goserelin acetate histrelin acetate hydromorphone interferon alfa-2B Iodine 131 Tositumomab isotretinoin

a drug used in the treatment of liver spots

acitretin retinoids isotretinoin

Hormones

gonadotropin analogs GnRH agonist _relin

histrelin ganirelix goserelin nafarelin triptorelin

Drugs That Should Not Be Taken With Food Ampicillin Astemizole Cefaclor
Cetirizine

Didanosine Digoxin Diltiazem Etidronate Furosemide Indinavir

Isoniazid Labetalol Lansoprazole Levodopa Lithium Nimodipine Penicillamine Rifampin

Valacyclovir

Metoprolol Propranolol

Zafirlukast

drugs & meal

with meal: dicumarol, griseofulvin, metoprolol, morphine, phenytoin, propoxyphene; (Dic-grise-meto-mor-phen-pro: one disc greese meat and more, phen propox) without meal: ACE inhibitor( _prils), acetaminophen, antibiotics (tetracycline, penicillin), biphosphonates (pamidronate, alendronate, etidronate, risedronate, etidronate, ibandronate), ethanol, NSAIDs (e.g. aspirin, naproxen sodium....) ticlopidine, PDE5-Is (sildenafil, vardenafil)

Medications That Should Not Be Administered With Antacids Digoxin Fluoroquinolones Iron preparations Isoniazid Common Emulsifying Agents Used in Pharmaceuticals Include Acacia Agar Gelatin Methylcellulose Common Preservatives Used in Pharmaceuticals Include Benzalkonium chloride Benzyl alcohol Boric acid Chlorobutanol Disodium edetate Methylparaben Phenol Common Suspending Agents Used in Pharmaceuticals Include Alginic acid Carrageenin Common Pharmaceutical Substances and Their USP Names Burow's solution Dakin's solution Lime water Sweet oil Aluminum acetate solution (an astringent) Sodium hypochlorite solution (diluted bleach) Calcium hydroxide solution Olive oil Sodium Carboxymethylcellulose Phenylmercuric acetate Potasium sorbate Propylparaben Sodium bisulfite Sodium borate Thimersol Pectin Sodium lauryl sulfate Tragacanth Ketoconazole Quinidine Tetracycline Warfarin

Drugs That Are Highly Protein Bound: Barbiturates Clofibrate Salicylates

Bar-Clo- Sali-Sul -Tol _ War Sulfur/sulfonamides Tolbutamide Warfarin

Agents That Inhibit the P-450 Microsomal Enzyme System Allopurinol Anabolic agents Chloramphenicol Cimetidine Disulfiram Agents That Induce the P-450 Microsomal Enzyme System Alcohol Chloral hydrate Chlordiazepoxide Cortisone Imipramine Nicotine Phenobarbital Phenytoin Prednisone Testosterone Isoniazid Metronidazole Monoamine oxidase inhibitors Oral antidiabetic agents Warfarin

OTC Cough and Cold Products Commonly Contain the Following Analgesic Antihistamine Acetaminophen Brompheniramine Chlorpheniramine Clemastine Diphenhydramine Pyrilamine Triprolidine Antitussives Cough suppressant Codeine Dextromethorphan Diphenhydramine Decongestant Phenylephrine Phenylpropanolamine Pseudoephedrine

Expectorant

Ammonium chloride Guaifenesin Sodium citrate

Pharmaceutical References and What They Contain AHFS Drug Information (American Hospital Formulary Service) Merck Manual Merck Index Red Book List of diseases and how to treat Encyclopedia of chemicals, drugs, and biologicals Prices, lists of sugar-free, alcohol-free products pregnancy categories, photosensitivity information, etc. Compounding information Displays the structure of each of the drugs referenced

Remington's

English: 1:posterior chamber 2:ora serrata 3:ciliary muscle 4:ciliary zonules 5:canal of Schlemm 6:pupil 7:anterior chamber 8:cornea 9:iris 10:lens cortex 11:lens nucleus 12:ciliary process 13:conjunctiva ) 14:inferior oblique muscle 15:inferior rectus muscle 16:medial rectus muscle 17:retinal arteries and veins 18:optic disc 19:dura mater 20:central retinal artery 21:central retinal vein 22:optical nerve 23:vorticose vein 24:bulbar sheath 25:macula 26:fovea 27:sclera 28:choroid 29:superior rectus muscle 30:retina

English: 1:posterior chamber 2:ora serrata 3:ciliary muscle 4:ciliary zonules 5:canal of Schlemm 6:pupil 7:anterior chamber 8:cornea 9:iris 10:lens cortex 11:lens nucleus 12:ciliary process 13:conjunctiva ) 14:inferior oblique muscle 15:inferior rectus muscle 16:medial rectus muscle 17:retinal arteries and veins 18:optic disc 19:dura mater 20:central retinal artery 21:central retinal vein 22:optical nerve 23:vorticose vein 24:bulbar sheath 25:macula 26:fovea 27:sclera 28:choroid 29:superior rectus muscle 30:retina

Retina: is a light sensitive layer that lines the interior of the eye. The outer part of the retina is pigmented to block the passage of light. The inner part of the retina contain light sensitive cells know rods and cones. Conjunctiva covers the front of the eye and lines the inside of the eyelids. The mucous membrane that lines the inner surface of the eyelid and the exposed surface of the eyeball.

Macula lutea lies closest to the exact posterior pole of the eye; The macula or macula lutea (from Latin macula, "spot" + lutea, "yellow") is an oval yellow spot near the center of the retina of the human eye. It has a diameter of around 5 mm and is often histologically defined as having two or more layers of ganglion cells. Near its center is the fovea, a small pit that contains the largest concentration of cone cells in the eye and is responsible for central vision, and also contains the parafovea and perifovea. It is specialized for high acuity vision. Within the macula are the fovea and foveola which contain a high density of cones (photoreceptors with high acuity). In contrast to the rest of the retina, which is supplied by the retinal artery, the macula receives its blood supply from the choroid. Damage to the macula will result in loss of central vision,

Sympathetic (a1-aderenergic)
Iris sphincter muscle

Parasympathetic (muscarinic) Contraction miosis Sph-sphere---O ---miosis

Iris radial muscle

Contraction mydriasis Radialradiation--Contraction lens accommodate for near vision Dilation more light into the eye no effect on Urine pH furosemide torsemide bumetanide ethacrynic acid Constriction (pupil reflex-> less light into the eye) the other diuretics---- cause an alkaline urinary pH

Ciliary muscle Pupil result

loop diuretics

osmotic diuretic mannitol urea glycerin isosorbide

carbonic anhydrase inhibitors acetazolamide methazolamide dorzolamide topiramate

benzothiadiazide diuretics:

- thiazide; - azone chlorothiazide

Electrolyte imbalances; K+. Mg2+, Na+, Cl-, Ca2+ uric acid reabsorption in the proximal tubules can precipitate gouty attacks. Other side effects include rash, hglucose, dizziness, photosensitivity, hemolytic anemia hypo-BP, headache, lipids (hypercholesterolemia and hypersensitivity reaction).

HCTZ hydrochlorothiazide

cyclothiazide methyclothiazide

Electrolytes, blood glucose, and lipids need to be monitored periodically. NSAIDs (e.g., ibuprofen) interact to diminish the antihypertensive effects

gouty attacks. Other side effects include rash, hglucose, dizziness, photosensitivity, hemolytic anemia hypo-BP, headache, lipids (hypercholesterolemia and hypersensitivity reaction).

lipids need to be monitored periodically. NSAIDs (e.g., ibuprofen) interact to diminish the antihypertensive effects

quinethazone metolazone

High G L U Ca
sulfamoylbenzamides

indapamide chlorthalidone
potassium-sparing diuretics: Amilo Triam Spiro

Combination products

Aldactazide Aldactazide-50 Moduretic Dyazide Maxzide Maxzide-25 amiloride triamterene spironolactone

Sulfa allergies are common, hence medications containing sulfonamides are prescribed carefully.

sulfonamides

It is important to make a distinction between sulfa drugs and other sulfur-containing drugs and additives, such as sulfates and sulfites, which are chemically unrelated to the sulfonamide group, and do not cause the same hypersensitivity reactions seen in the sulfonamides.

Antibiotic sulfonamides; carbonic anhydrase inhibitors list class III antiarrhythmic agents Loop diuretics Antibiotic sulfonamides Sulfamethoxazole Sulfisoxazole Sulfadiazine Sulfacetamide sulfonamide group thiazide diuretics

Thiazide diuretics Sulfamoylbenzamides Sulfonamide anticonvulsant Sulfonylureas

Celecoxib Dofetilide Sulfasalazine topiramate Ibutilide sumatriptan Sulfonamide anticonvulsant Acetazolamide Methazolamide Sultiame Zonisamide also diuretics

sulfamoylbenzamides Chlorothiazide indapamide Hydrochlorothiazide chlorthalidone

Monosaccharides topiramate (anticonvulsant drug

NSAIDs Sulfasalazine loop diuretics Celecoxib Valdecoxib Bumetanide Furosemide Torsemide carbonic anhydrase inhibitors acetazolamide methazolamide dorzolamide class III antiarrhythmic age Dofetilide Ibutilide

sulfonylureas Glyburide (INN: Glibenclamide) Chlorpropamide ..

Dumitru's list Sulfonylureas: antidiabetics Chlorpropamide Antibiotic sulfonamides Sulfamethoxazole Sulfisoxazole Sulfadiazine Sulfacetamide Non-antibiotic sulfonamides Acetazolamide Bumetanide Celecoxib Chlorothiazide

First generation

Acetohexamide Chlorpropamide Tolbutamide Tolazamide Second generation Glipizide Gliclazide Glibenclamide (glyburide) Gliquidone Glyclopyramide Third generation Glimepiride

Tolazamide

Chlorpropamide Dorzolamide Furosemide Glyburide Hydrochlorothiazide Valdecoxib

Gliclazide

Anti-diabetic drug
1 Insulin 2 Secretagogues

See abouve; Triggering insulin release by direct action on the KATP channel of the pancreatic beta cells. The "second-generation" drugs are now more commonly used. They are more effective than first-generation drugs and have fewer side effects. All may cause weight gain & hypoglycemia. 2.1 Sulfonylureas Sulfonylureas bind strongly to plasma proteins. Sulfonylureas are only useful in Type II diabetes, as they work by stimulating endogenous release of insulin. They work best with patients over 40 years old, who have had diabetes mellitus for under ten years. They can not be used with type I diabetes, or diabetes of pregnancy. They can be safely used with metformin or -glitazones. (combination)

2.2 Meglitinides Repaglinide Nateglinide

Meglitinides help the pancreas produce insulin and are often called "short-acting secretagogues." By closing the potassium channels of the pancreatic beta cells, they open the calcium channels, hence enhancing insulin secretion. They are taken with meals to boost the insulin response to each meal. repaglinide (Prandin) - The maximum dosage is 16 mg/day, taken 0 to 30 minutes before meals. If a meal is skipped, the medication is also skipped. nateglinide (Starlix) - The maximum dosage is 360 mg/day, usually 120 mg three times a day (TID). It also follows the same recommendations as repaglinide. Adverse reactions include weight gain and hypoglycemia.

3 Sensitizers

Biguanides reduce hepatic glucose output and increase uptake of glucose by the periphery, including skeletal muscle. Although it must be used with caution in patients with impaired liver or kidney function, metformin has become the most commonly used agent for type 2 diabetes in children and teenagers. Amongst common diabetic drugs, metformin, a biguanide, is the only widely used oral drug that does not cause weight gain. 3.1 Biguanides Metformin metformin (Glucophage). Metformin may be the best choice for patients who also have heart failure. phenformin (DBI): used from 1960s through 1980s, withdrawn due to lactic acidosis risk. buformin: also withdrawn due to lactic acidosis risk. Metformin should be temporarily discontinued before any radiographic procedure involving intravenous iodinated contrast as patients are at an increased risk of lactic acidosis. Metformin is usually the first-line medication used for treatment of type-2 diabetes. Initial dosing is 500 mg twice daily, but can be increased up to 1000 mg twice daily. It is also available in combination with other oral diabetic medications.

3.2 Thiazolidinediones rosiglitazone pioglitazone

also known as "glitazones," bind to PPAR, a type of nuclear regulatory proteins involved in transcription of genes regulating glucose and fat metabolism. These PPARs act on Peroxysome Proliferator Responsive Elements (PPRE ). The PPREs influence insulin sensitive genes, which enhance production of mRNAs of insulin dependent enzymes. The final result is better use of glucose by the cells. rosiglitazone (Avandia) pioglitazone (Actos) troglitazone (Rezulin): used in 1990s, withdrawn due to hepatitis and liver damage risk. Weight gain and edema /Avoid in pts with heart failure

4 Alpha-glucosidase inhibitors miglitol acarbose

Not technically hypoglycemic agents because they do not have a direct effect on insulin secretion or sensitivity. These agents slow the digestion of starch in the small intestine, and can be matched more effectively by an impaired insulin response or sensitivity. These agents are effective by themselves only in the earliest stages of impaired glucose tolerance, but can be helpful in combination with other agents in type 2 diabetes. miglitol (Glyset) acarbose (Precose/Glucobay) Rarely used in the United States because of the severity of their side effects (flatulence and bloating) and more commonly prescribed in Europe. They do have the potential to cause weight loss by lowering the amount of sugar metabolized.

5 Peptide analogs 5.1 Incretin mimetics Incretins are insulin secretagogues. The two main candidate molecules that fulfill criteria for being an incretin are Glucagon-like peptide-1 (GLP-1) and Gastric inhibitory peptide (aka glucose-dependent Insulinotropic peptide or GIP). Both GLP-1 and GIP are rapidly inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4).

5.1.1 GLP agonists

Glucagon-like peptide (GLP) agonists bind to a membrane GLP receptor. As a consequence of this, insulin release from the pancreatic beta cells is increased. Endogenous GLP has a half life of only a few minutes; thus an analogue of GLP would not be practical. Exenatide

5.1.2 Gastric inhibitory peptide (GIP) analogs 5.2 DPP-4 inhibitors

None are FDA approved vildagliptin sitagliptin

5.3 Amylin analogues

Amylin agonist analogues slow gastric emptying and suppress glucagon. They have all the incretins actions except stimulation of insulin secretion. As of 2007, pramlintide is the only clinically available amylin analogue. Like insulin, it is administered by subcutaneous injection. The most frequent and severe adverse effect of pramlintide is nausea, which occurs mostly at the beginning of treatment and gradually reduces.

Tinnitus:

seen in conditions: Meniere disease, head injuries, otitis media, syphilis, temporomandibular-joint dysfunction and certain medications (salicylate, NSAIDs, aminoglycosides, loop diurectics, and chemotherapeutic agents)

Agents for weight control: Increase energy expenditure: Bitter orange, guarana seed, caffeine/ephedrine Modulate carbohydrate metabolism: chromium, ginseng [5dVinseN] Enhance satiety: guar gum, glucomannan, psyllium Increase fat oxidation or reduce fat synthesis: L-carnitine, hydroxycitric acid(HCA), green tea, vitamin B5, licorice, conjugated linoleic acid(CLA), pyruvate, calcium Block dietary fat absorption: chitosan Increase water elimination: dandelion, cascara Inhibit appetite: spirulina

OTC for sleeping aids Diphenhydramine: Blocks histamine-1 and muscarinic receptors, thus inducing sedation. Side effects: anticholinergic, dry mouth, blurred vision, constipation, urinary retention. rapid or irregular heartbeat tachycardia, mydriasis, photophobia, most common cardiac dysrhythmias associated with diphenhydramine overdose are sinus bradycardia, elongated S-T segment interval, and premature ventricular contraction Doxylamine: similar to diphenhydramine Melatonin: secreted by the pineal gland, has a sleep-phase-shifting effect on circadian rhythm given in the morning, the circadian phase is delayed; given in the evening, it will be advanced. Short half-life(30-50 min) so not good choice! Limited to 7-10 consecutive nights; combination with aspirin or acetaminophen as a nighttime analgesic

Valerian root: Kava: hepatotoxicity (hepatitis, cirrhosis, and liver failure), not recommended

Nicotine-replacement therapy (NRT) Gum, lozenges, and patches, only effective in pts is mentally ready to quit and not for the cessation of smokeless tobacco (chewing tobacco, cigars, pipes) For pts with acute cardiovascular disease (stroke, acute myocardial infarction, unstable angina), pregnant, breastfeeding women, absolute abstainment from nicotine should be recommended. Restricted to those over age 18. Pts with asthma or depression need consult physician before use NRT. Do not smoke while using NRT. NSAIDs: ibuprofen, naproxen, ketoprofen (OTC) - Contraindication in pts with bleeding disorders or peptic ulcers, - Extreme caution for during the last trimester of pregnancy: potential bleeding, prolonging or complicating delivery. - GI disturbances; decreased when taken with food or large dose of antiacids; - Renal toxicity during chronic administration: nephritic syndrome, hyperkalemia or interstitial nephritis

Common cold:
Etiology: the most contributing pathogens---coronaviruses respiratory virus (RSV), rhinoviruses Topical Decongestants: intranasal --- Ephedrine, naphazoline, phenylephrine, xylometazoline, oxymetazoline (limit use for 3-5 days to avoid to avoid rhinitis medicamentosa) Levmetamfetamine, currently found in Vicks Vapor inhalers, dose not cause rhinitis medicamentosa within a 7-day period; lacks vasopressor effect, better for pts with cardiac conditions, hypertension or diabetes than psedoephedrine, phenylephrine, xylometazoline, oxymetazoline

Oral decongestants

: Pseudoephedrine Phenylephrine Nasal stips

Antihistamines: -

1st generation: widely used in relief rhinorrhea and sneezing, but no effect on nasal congestion

Common OTC: brompheniramine, chlorpheniramine, clemastine, diphenhydramine, triprolidine, phenindamien, dexbrompheniramine. Side effects: dry mouth, blurred vision, difficulty in urination, constipation, irritability, and dizziness, Avoid in pts with narrow-angle glaucoma and benign prostatic hypertrophy, Cautions with driving and operating heavy machinery after taking the agents( sedation effects) , but children may experience paradoxical CNS stimulation

Expectorantsmucolytic agents, work to loosen sputum (phlegm) [flem] guaifenesin, for pts >2 years old

Antitussives : used for nonproductive cough Dextromethorphan Codeine: schedule C-V; not for children < 6 years of age; drowsiness, nausea and vomiting, excitement, abdominal discomfort, or worsening/aggrevation of constipation cautions in pts with pulmonary disease or shortness of breath; overdose may cause death from respiratory depression and cardiovascular collapse Diphenhydramine: antitussive (low dose) and antihistamine - not for children < 6 years of age; somnolence, sedation, and anticholinergic effects (dry mouth, blurred vision, difficulty in urination and constipation) Camphor and menthol : the only FDA approved topical antitussives

Analgesics: indicated for common cold symptoms when sore throat, myalgia, and/or headache exist. aspirin, acetaminophen, ibuprofen, naproxen sodium Combinations: antihitamines, decongestants, analgesics, expectorants, and antitussives useful for simplicity of dosing and adherence Complementary therapy: Zinc gluconate Vitamin C: reduce the frequency and the severity of common cold Echinacea

Allergic rhinitis

[rai5naitis ]

type I: IgE mediated immunological reaction

Antihistamines: 1st generation Chlorpheniramine, Diphenhydramine, Brompheniramine, Clemastine, Triprolidine, Phenindamine, Dexbrompheniramine Limited in continuous treatment, frequent dose and related sedation. High lipophilicity, easily cross the BBB to cause significant sedation; Other side effects: nightmares, anxiety, restlessness, unusual excitement, or irritability. 2ed generation: Loratadine advantage in their preferential peripheral H1-receptor binding, minimal CNS /sedative /anticholinerygic effect than1st generation.

Oral decongestants and ocular antihistamines as adjunctive treatment Ocular antihistamines: Pheniramine and antazoline in combination with decongestants (avoid use in pts with narrow-angle glaucoma) for eye conditions.

Cromolyn sodium: preventive measure, better 1 week before allergen contact.

Chlorpheniramine and intranasal cromolyn sodium are recommended for the relief of sneezing and rhinorrhea in pregnancy.

Systemic, second-generation Acrivastine Astemizole Cetirizine Loratadine Mizolastine Terfenadine Systemic, third-generation Levocetirizine Desloratadine Fexofenadine

Topical, second-generation Azelastine Levocabastine Olopatadine

withdrawn from most markets due to risk of cardiac arrhythmias and replaced with fexofenadine)

Constipation

: higher in elder people >65, more in women than in men

Causes: Diet( insufficient dietary fiber, inadequate fluid intake) lack of exercise, Poor bowel habits, Medications (narcotic analgesic, diuretic, anticholinergic: antidepressant, antihypertensive, antihistamine, phenothiazine, antispasmodic; iron supplement, Ca- or Al- anatacids, NSAIDs, histamine-2 receptor antagonists(H2RAs) such as ranitidine); antihypertensive, antihistamine, phenothiazine, antispasmodic; iron supplement, Ca- or Al- anatacids, NSAIDs, histamine-2 receptor antagonists(H2RAs) such as ranitidine); Pregnancy;

organic problems ( intestinal obstruction, tumor, inflammatory bowel disease, diverticulitis, hypothyroidism, hyperglycemia, irritable bowel syndrome, cerebrovascular disease, or Parkinson disease)

Drugs Natural (psyllium, Malt soup extract) or synthetic(methylcellulose, polycarbophil) polysaccharide derivatives that absorb water to soften the stool and increase bulk---stimulates peristalsis; work in both the small and large intestines; Bulk-forming laxatives onset is slow (12-24 and up to 72 hr) best for prevent rather than treat severe acute constipation side effects: abdominal cramping and flatulence Not for pts with obstructing bowel lesion, intestinal strictures, or Crohn disease

no more than 1 week treatment, but ok for long-term prevention

Saline laxatives: Mg citrate, Mg(OH)2, MgSO4, Na3PO4 Osmotic laxative: glycerin, lactulose,Sorbitol Saline and osmotic laxatives Should consume at 8 oz. of water with each dose to prevent possible dehydration Side effects: diarrhea and abdominal cramping; Work in the small and large intestines to stimulate bowel motility and h the secretion of fluids into the bowel Saline laxatives not for pts with hypertension or congestive Most fast action heart failure; severe kidney disease not use products containing Mg;

Chronic use can cause cathartic colon; Side effects: abdominal cramping, electrolyte and fluid deficiencies; enteric loss of protein, malabsorption; hypokalemia. Stimulant laxatives

Anthraquinone laxatives (senna, Ex-lax, Fletchers Castoria) may cause melanosis coli, discoloration, even carcinogenicity.

Bisacodyl: diphenylmethane derivative, enteric coated, should not be taken within 1 hr of ingesting antacids or milk; \ Castor oil: acts on small intestine, strong cathartic effect which can lead to dehydration; not for pregnant (induce premature labor)

Have a slow onset of action, used for prevention; Products: Dosusate Na / Ca / K Particularly useful in pts who must avoid straining to pass hard stools, such as who recently had a myocardial infarction or rectal surgery

Emollient laxatives

Mineral oil: taken on an empty stomach, and not at bedtime or recline after adm,.

Side effects: anal seepage()---itching and perianal discomfort;

Lubricant laxative

Can decrease absorption of fat-soluble vitamins; High risk of lipid pneumonitis in elderly, young debilitated, and dysphagic pts; Haptotoxicity;

Not for pts with rectal bleeding or appendicitis; or children < 6;

Bulk-forming agents can be used to treat constipation or chronic, watery diarrhea

Diarrhea:
Drug-induced Osmotic diarrhea: lactulose and magnesium containing antacids, and laxatives; Drug-induced motility diarrhea: acetylcholine (metoclopramide, bethanechol), digitalis, quinidine, antibiotics. Drug-induced secretory diarrhea: prostaglandins, antibiotics, colchicine, chemotherapeutic agents. Chronic diarrhea: longer than 2 weeks Protozoal organisms, food-induced (e.g., lactose intolerance), irritable bowel syndrome, malabsorption syndromes (celiac sprue, diverticulosis, short bowel syndrome), inflammatory bowel disease, pancreatic disease, and hyperthyroidism.

Treatment: Oral-replacement therapy: NaCl (90 mEq) KCl (20 mEq) NaHCO3 (30 mEq) Glucose (20 g) H2O (up to 1L) > 5 years old: 2 L/first 4 hr, then replace ongoing losses for mild, moderate (2-4 L /4 hr) < 5 years old: 50 mL/kg/first 4 hr, then replace ongoing losses for mild, moderate (100 mL/kg /4 hr) Drugs: Category 1: kaolin, bismuth subsalicylate, loperamide

Drugs causing agranulocytosis Acetaminophen Acetazolamide Acetylsalicylic acid Allopurinol -Lactam antibiotics Benzodiazepines Brompheniramine Carbamazepine Captopril Ceftriaxone Chloramphenicol Chlorpropamide Chlorpromazine Cimetidine Clindamycin Clomipramine Clozapine Dapsone

HYPERGLYCEMIA: Drug-Induced 2-adrenergic receptor agonists Ca2+-channel blockers Clonidine Diazoxide Diuretics Epinephrine Glucocorticosteroids H2-receptor blockers Heparin Marijuana Morphine Nalidixic acid Nicotine Oral contraceptives Pentamidine Phenytoin Sulfinpyrazone

OCULOTOXICITY: Drug-induced Antiinflammatory Agents Corticosteroids Cyclosporine

Gold salts, auranofin

Ibuprofen Indomethacin
Ketoprofen Phenylbutazone

Piroxicam Salicylates Antimicrobial Agents

Amiodaquine Clofazimine

Chloramphenicol
Chloroquine/hydroxychloroquine Diethylcarbamazine

Ethambutol Gentamicin Griseofulvin

Desipramine Doxycycline Ethacrynic acid Ethosuximide Fenoprofen Flucytosine Ganciclovir Gentamicin Gold salts Griseofulvin Hydralazine Hydroxychloroquine Ibuprofen Imipramine Indomethacin Isoniazid Levamisole Lincomycin Meprobamate Methazolamide Methimazole Metronidazole Nitrofurantoin Oxyphenbutazone
HYPOGLYCEMIA: Drug-Induced Angiotensin-converting enzyme inhibitors

Isoniazid

Minocycline Nalidixic acid

Nitrofurantoin

-adrenergic receptor antagonists Bromocriptine Calcium salts Clofibrate Ethanol Indomethacin Lithium salts Mebendazole Naproxen Pentamidine Pyridoxine Salicylates Sulbactam/ampicillin Sulfonamides Tetracycline Theophylline

Quinine Rifampin Streptomycin

Sulfonamides Suramin Tetracycline Vaccinations

Antineoplastic Agents BCNU/CCNU/MeCCNU

Busulfan

Carmustine Chlorambucil Cisplatin

Cyclophosphamide

Cytosine arabinoside Doxorubicin Fludarabine 5-fluorouracil Ifosfamide Methotrexate Mitotane Mitoxanthrone Nitrogen mustard Procarbazine Tamoxifen Vinca alkaloids Cardiovascular Agents Amiodarone Diazoxide Digitalis glycoside Ergot alkaloids Flecainide Guanethidine Metoprolol Minoxidil Nifedipine Propranolol Quinidine Reserpine Central Nervous System Agents Amantadine Barbiturates IMMUNIZATION: Agents Used in

Para-aminosalicyclic acid Bromocriptine Penicillamine Pentazocine Phenothiazines Phenylbutazone Phenytoin Primidone Procainamide Propranolol Propylthiouracil Pyrimethamine Quinine Rifampin Streptomycin Sulfa antibiotics Tocainide Tolbutamide Vancomycin Zidovudine Carbamazepine Ethchlorvynol Lithium Narcotic analgesics Phenothiazine Phenytoin Protriptyline Trimethadione Miscellaneous Agents Allopurinol Amantadine Clomiphene Dantrolene Deferoxamine Diphenhydramine Disulfiram Ganiumnitrate Isotretinoin Penicillamine Thiazide diuretics

Drugs used in the treatment of depression in Alzheimers disease

Monoamine Oxidase Tricyclic Inhibitors (MAOI) Antidepressants

Phenelzine Desipramine

Passive Immunization Antitoxins Botulism

Tranylcypromine Nortriptyline
Selective Serotonin Reuptake Inhibitors (SSRI)

Fluoxetine Paroxetine Sertraline Drugs used in the treatment of psychosis and agitation in Alzheimers disease are:
Classical Antipsychotics

Chlorpromazine Haloperidol Thioridazine

Atypical Antipsychotics

Diphtheria Tetanus Immunoglobulins Endotoxin (IgM) Hepatitis A or B Pertussis Poliomyelitis Rabies Rubella Tetanus Vaccinia Varicella

Active Immunization Bacterial Cholera Diphtheria Hemophilus Meningococci Pertussis Pneumococci Tetanus Tuberculosis (BCG) Typhoid Viral Hepatitis B Influenza Measles Mumps Poliomyelitis Rabies Rubella Smallpox Yellow fever MIGRAINE HEADACHES: Treatment of Drugs and Dosages Aspirin, 650 mg every 4 hours Aspirin, 650 mg with butalbital, 50 mg Aspirin, 300 mg, with caffeine, 50 mg, and butalbital, 50 mg Acetaminophen, 650 mg every 4 hours Acetaminophen, 325 mg, with butalbital, 50 mg Dihydroergotamine, 1 mg IM or IV at onset and every hour Ergotamine, 1 mg Ergotamine, 1 mg, plus caffeine, 100 mg Ergotamine, 2 mg, plus caffeine, 100 mg (suppository) Ibuprofen, 400800 mg three times a day Indomethacin, 50 mg three times a day Naproxen sodium, 550 mg, then 275 mg every 6 to 8 hours

Clozapine Risperidone
Benzodiazepines

Lorazepam Oxazepam Triazolam

Drugs used in the treatment of insomnia in Alzheimers disease are: Tricyclic Antidepressants

Nortriptyline Trazodone
Benzodiazepines

Lorazepam Oxazepam Triazolam

Antipsychotics

Chlorpromazine Haloperidol Thioridazine

Sumatriptan, 6 mg subcutaneously The medication to be chosen depends on the severity and/or frequency of attacks and the response of the patients. Ondansetron ACh Receptor Agonists Direct Acting Acetylcholine Bethanechol Carbachol Cevimeline Pilocarpine Suberylcholine Nicotine (in small doses) ACh Receptor Antagonists Antimuscarinic Agents Atropine Ipratropium Scopolamine Tiotropium

Cholinesterase inhibitors: Irreversible

Semi-permanently inhibit the enzyme acetylcholinesterase.

Ganglionic Blockers

Echothiophate Mecamylamine Isofluorophate Hexamethonium Organophosphate Insecticides (Malathion, Nicotine (in high doses) Parathion, Azinphos Methyl, Chlorpyrifos, among others) Organophosphate-containing nerve agents (e.g., Trimethaphan Sarin, VX) Neuromuscular Blockers Cholinesterase inhibitors: Reversible Many medications in Alzheimer's disease Donepezil Galantamine Rivastigmine Tacrine THC Edrophonium (differs myasthenic and cholinergic crisis) Neostigmine (in myasthenia gravis) Physostigmine (in glaucoma and anticholinergic drug overdoses) Pyridostigmine (in myasthenia gravis Carbamate insecticides (e.g., Aldicarb) Huperzine A
Reactivation of Acetylcholine Esterase

Atracurium Cisatracurium Doxacurium Metocurine Mivacurium Pancuronium Rocuronium Succinylcholine Tubocurarine Vecuronium HemiCholine dupogimine

Pralidoxime

Steroid-induced osteoporosis (SIOP) : prednisone ; or prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months. Alternate day use Medications associated with may not prevent this complication. osteoporosis: Barbiturates, phenytoin and some other enzyme-inducing antiepileptics: accelerate the metabolism of vitamin D. L-Thyroxine over-replacement : subclinical hypothyroidism.

Several drugs induce hypogonadism: aromatase inhibitors used in breast cancer, methotrexate and other antimetabolite drugs, depot progesterone and gonadotropin-releasing hormone agonists. Anticoagulants - long-term use of heparin and warfarin (and related coumarins) Proton pump inhibitors - these drugs inhibit the production of stomach acid then interferes with calcium absorption. Chronic phosphate binding may also occur with aluminium-containing antacids. Thiazolidinediones (used for diabetes) - rosiglitazone and possibly pioglitazone, inhibitors of PPAR Chronic lithium therapy has been associated with osteoporosis.[16]

The most important risk factors: advanced age (in both men and women) and female sex; estrogen deficiency Nonmodifiable following menopause is correlated with a rapid reduction in BMD, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect. Excess alcohol; Vitamin D deficiency; Tobacco smoking; High body mass index - being overweight protects against Potentially modifiable: osteoporosis; Malnutrition; Physical inactivity lead to significant bone loss. Excess physical activity; Heavy metals cadmium, lead; Soft drinks;

(A) glomerulus (B) descending loop of Henle (C) ascending loop of Henle (D) proximal tubule (E) distal tubule

acetazolamide (Diamox) works in the proximal tubule. Furosemide (Lasix), bumetanide (Bumex), ethacrynic acid (Edecrine) and torsemide (Demadex) work in the loop of Henle. Thiazide diuretics, such as metolazone (Mykrox, Zaroxolyn), chlorthalidone (Hygroton) and hydrochlorothiazide (Hydrodiuril, Microzide), block the reabsorption of sodium in the early distal tubule. Potassium-sparing(K-sparing) diuretics, such as amiloride (Midamor) (in combination with hydrochlorothiazide in Moduretic), triamterene (Dyrenium) (in combination with hydrochlorothiazide in Maxzide, Dyazide) and spironolactone (Aldactone) (in combination with hydrochlorothiazide in Aldactazide), act in the collecting duct /distal tubule, thereby preventing some of the exchange of sodium for potassium that occurs in this portion of the nephron. The K-sparing diuretics, Mende added, are sodium channel blockers.

The small intestine consists of the duodenum, jejunum and ileum. It is mainly responsible for the process of digestion and absorption of food. The surface area of the inside of the small intestine is increased by the presence of microvilli. The large intestine consists of the cecum, vermifoam, appendix, colon and rectum. It is mainly responsible for the absorption of water from the material passed through the small intestine.

Comparison of physical harm and dependence regarding various drugs (the British medical journal The Lancet Nutt D, King LA, Saulsbury W, Blakemore C (March 2007). "Development of a rational scale to assess the harm of drugs of potential misuse". Lancet 369 (9566): 104753. doi:10.1016/S0140-6736(07)60464-4. PMID 17382831

Table of Neurotransmitters
Transmitter Molecule Actions distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. also operates in many regions of the brain, but using different types of receptors. Derived From Site of Synthesis

Acetylcholine

Choline

CNS, parasympathetic nerves

a number of important functionsincluding regulation Serotonin of mood, sleep/wake cycles, and body 5-Hydroxytryptamine (5-HT) temperature. It is released during sunny weather, and also when eating chocolate or taking Prozac.

Tryptophan

CNS, chromaffin cells of the gut, enteric cells

GABA

fast inhibitory synapses in virtually every part of the brain; fast excitatory synapses in the brain and spinal cord; Also used at modifiable synapses which are thought to be the main memory-storage elements in the brain

Glutamate

CNS

Glutamate

CNS

Aspartate Inhibitory postsynaptic potential; Glycine is a required co-agonist along with glutamate for NMDA receptors and facilitate its excitatory. Histidine Tyrosine Tyrosine

CNS

Glycine

spinal cord

Histamine Epinephrine Norpinephrine synthesis pathway

hypothalamus adrenal medulla, some CNS cells CNS, sympathetic nerves

Dopamine synthesis pathway

plays a critical role in the reward system, but disfunction of the dopamine system is also implicated in Parkinson's Disease and schizophrenia.

Tyrosine

CNS

Adenosine ATP Nitric oxide, NO

ATP

CNS, periperal nerves sympathetic, sensory and enteric nerves CNS, gastrointestinal tract

Arginine

histamine receptor Type Location Function

H1

Causes vasodilation, bronchoconstriction, smooth muscle activation, separation of endothelial cells Found on smooth muscle, endothelium, and central (responsible for hives), and pain and itching due to insect stings; the primary receptors involved in nervous system tissue allergic rhinitis symptoms and motion sickness.

H2 H3

Located on parietal cells Found primarily in the basophils and in the bone marrow, also found on thymus, small intestine, spleen, and colon.

Primarily stimulate gastric acid secretion Decreased neurotransmitter release: histamine, acetylcholine, norepinephrine, serotonin

H4

Unknown physiological

Glycine

Biosynthetic intermediate: a building block to numerous natural products. In higher eukaryotes, D-Aminolevulinic acid, the key precursor to porphyrins, is biosynthesized from glycine and succinyl-CoA. Glycine provides the central C2N subunit of all purines.

Receptor type

Agonist potency order

Selected action of agonist Specific: smooth muscle contraction

1 (arterioles, intestine, bladder, uterus)

norepinephrine epinephrine >> isoprenaline

Common effects include: Vasoconstriction of arteries to heart (coronary arteries). Venoconstriction of veins (that supply to skin and mucosa) Decrease motility of smooth muscle in gastrointestinal tract Contraction of male genitalia during ejaculation

2 arterioles vein intestine male genitalia norepinephrine epinephrine >> isoprenaline

smooth muscle contraction and neurotransmitter inhibition; Common effects (see above) Specific: Mediates synaptic transmission in pre- and postsynaptic nerve terminals. h the release of acetylcholine and norepinephrine; Inhibition of lipolysis in adipose tissue. inhibition of insulin and glucagon release in pancreas; platelet aggregation contraction of sphincters of the gastrointestinal tract h Secretion from salivary gland relax gastrointestinal tract (presynaptic effect)

1 (heart, uterus)

isoprenaline > epinephrine = norepinephrine

Heart muscle contraction; stimulate viscous, amylase-filled secretions from salivary glands[2] Increase cardiac output: h heart rate in SA node (chronotropic effect); h atrial cardiac muscle contractility. (inotropic effect); h contractility and automaticity of ventricular cardiac muscle; h conduction and automaticity of atrioventricular node (AV node) . Renin release from juxtaglomerular cells . Lipolysis in adipose tissue. Receptor also present in cerebral cortex.

2 heart arterioles uterus intestine

isoprenaline > epinephrine >> norepinephrine

Smooth muscle relaxation; dilates blood vessels; striated muscle; Increase cardiac output (similar but less degree compared to 1); Digestive system: Glycogenolysis and gluconeogenesis in liver. Glycogenolysis and lactate release in skeletal muscle. Contract sphincters of GI tract. Insulin secretion from pancreas. Thickened secretions from salivary glands.

3 adipose tissue

isoprenaline = norepinephrine > epinephrine

Enhance lipolysis

Axon

Structure of myelinated axons.

Nature Reviews Neuroscience 4, 968-980 (December 2003) doi:10.1038/nrn1253

Myelin sheath

a | Myelinating glial cells, oligodendrocytes in the central nervous system (CNS) or Schwann cells in the peripheral nervous system (PNS), form the myelin sheath by enwrapping their membrane several times around the axon. Myelin covers the axon at intervals (internodes), leaving bare gaps the nodes of Ranvier. Oligodendrocytes can myelinate different axons and several internodes per axon, whereas Schwann cells myelinate a single internode in a single axon.

b | Schematic longitudinal cut of a myelinated fibre around the node of Ranvier showing a heminode. The node, paranode, juxtaparanode (JXP) and internode are labelled. The node is contacted by Schwann cell microvilli in the PNS or by processes from perinodal astrocytes in the CNS. Myelinated fibres in the PNS are covered by a basal lamina. The paranodal loops form a septate-like junction (SpJ) with the axon. The juxtaparanodal region resides beneath the compact myelin next to the paranode (PN). The internode extends from the juxtaparanodes and lies under the compact myelin.

c | Schematic cross-section of a myelinated nerve depicting the inner and outer mesaxons (IMA and OMA, respectively). d | Drawing of the specializations found along the internodes. A strand composed of paranodal molecules (Caspr, Contactin; red line) flanked by juxtaparanodal proteins (Caspr2, K+ channels and TAG-1; blue lines) extends along the internodal region (the juxtamesaxon) and below the SchmidtLanterman incisures (the juxtaincisure). In addition, Nf155 and ezrinradixinmoesin proteins, as well as connexins 29 and 32 are found at the glial side, opposite these axonal strands.

purkinje fibers

Heart's conducting system

The heart's conducting system consists of the sinoatrial node (SA node), atrioventicular node (AV node), the bundle of His, the bundle branches and the Purkinje fibers. The electrical impulse that causes rhythmic contraction of heart muscles arises in the SA node which is the intrinsic pacemaker of the heart. From the SA node, the impulse spreads over the atrial muscles causing atrial contraction. The impulse is also conducted to the atrioventicular (AV) node. From the AV node the electrical impulse is conducted to ventricular muscles via the bundle of His, the bundle branches and the Purkinje fibers. The bundle branches and the Purkinje fibers are collectively called the ventricular conduction system.

the impulse spreads over the atrial muscles causing atrial contraction. The impulse is also conducted to the atrioventicular (AV) node. From the AV node the electrical impulse is conducted to ventricular muscles via the bundle of His, the bundle branches and the Purkinje fibers. The bundle branches and the Purkinje fibers are collectively called the ventricular conduction system.

Overdose disease

Hypervitaminosis A

Hypervitaminosis A

Rare hypersensitive reactions resembling anaphylactic shock-- injection only; Drowsiness ? Liver damage (doses > 2g/day)[17] and other problems ? Impairment of proprioception, nerve damage (doses > 100 mg/day) ?

? Possible decrease in seizure threshhold

No known toxicity[21] Vitamin C megadosage Hypervitaminosis D

Increased congestive heart failure seen in one large randomized study.[24]

Increases coagulation in patients taking warfarin.[25]

17382831

Drugs page 1 -131

Antipsychotics

pharmacology

indication

adverse effects / drug interaction

_ azine; _apine; _idone

Typical antipsychotic First generation

antipsychotics might be used in to block D2 receptors in the dopamine pathways of the brain; with minimal effect on schizophrenia, mania, and delusional the serotonergic pathways, is considered a typical antipsychotic. disorder. Also used for Nausea;

EPS (extrapyramidal symptoms): tardive psychosis, acute dystonias, akathisia, pseudoparkinsonism (rigidity and tremor), tardive dyskinesia (after 1 y or more); NMS (Neuroleptic malignant syndrome): tachycardia, hypotension, impotence, lethargy, seizures, intense dreams or nightmares, and hyperprolactinaemia.

Butyrophenones

Haloperidol

(Haldol)

Schizophrenia: The most common symptoms:Delusion; hallucination; negative symptoms (affective flattening, Alogia, Anhedonia,Amotivation, apathy, Asocial behavior); Postitive symptoms: Delusions, hallucination, insomnia; disorganized speech, disorganized or catatonic behavior, The diagnosed for schizophrenia must include at least two of the above symptoms and presents for at least 1 month, with at least 6 months of continuous prodromal or residual symptoms.

Phenothiazines _ azine

Chlorpromazine (Thorazine)

used in the treatment of schizophrenia, hiccups and nausea. Long half-life, not good for old peoples. side-effect profile: anticholinergic effects(constipation, sedation, hypotension, and antiemetic properties); anxiolytic properties. EPS (akathisia and parkinsonian tremor, tardive dyskinesia), Neuroleptic malignant syndrome is a rare though potentially fatal; Cholestatic jaundice (fever, chills, anorexia, volmiting, myalgia);

Fluphenazine Perphenazine Prochlorperazine Thioridazine Trifluoperazine Mesoridazine Promazine Triflupromazine Levomepromazine Promethazine

(Prolixin) - Available in decanoate (long-acting) form (Trilafon) (Compazine) (Mellaril) (Stelazine) Pigemented retinopathy; NMS, tardive dyskinesia, extrapyramidal symptoms

(Vesprin) (Nozinan) (Phenergan)

Loxapine

a member of the dibenzoxazepine class and as a dibenzazepine derivative, it is structurally related to clozapine; Several researchers have argued that Loxapine may behave as an atypical antipsychotic. Loxapine may be metabolized by N-demethylation to amoxapine, a tricyclic antidepressant. Most significant side-effects of loxapine are excessive salivation and indifference to surroundings.

Group
Aliphatic compounds

Autonomic moderate

Example Chlorpromazine Promazine Triflupromazine Levomepromazine Methotrimeprazine Mesoridazine Thioridazine

Sedative strong moderate strong extremely strong strong strong weak/moderate weak/moderate moderate moderate

Extrapyramidal side-effect moderate moderate moderate/strong low weak weak strong----with "phe" and "flu" strong strong strong

Piperidines

strong

Piperazines

weak

Fluphenazine Perphenazine Flupentixol Prochlorperazine Trifluoperazine

Thioxanthenes _thixol or ene

Chlorprothixene

Chlorprothixene exerts strong blocking effects at the following postsynaptic receptors: 5-HT2 : anxiolysis, antipsychotic effects D1, D2, D3 : antipsychotic effects H1 : sedation, weight gain muscarinic : anticholinergic side effects, extrapyramidal side effects attenuated Alpha1 : hypotension, tachycardia (Depixol and Fluanxol) (Navane) (Clopixol & Acuphase)

the treatment of psychotic disorders (e.g. schizophrenia) and of acute mania occurring as part of bipolar disorders.

a high incidence of anticholinergic side effects.(dry mouth, massive hypotension and tachycardia, hyperhidrosis, substantial weight gain etc.) Normally cotreatment with another, more potent, antipsychotic agent is needed. weight gain ; a relatively high seizurogenic potential

Flupenthixol Thiothixene Zuclopenthixol

Atypical antipsychotic Second generation

_apine _idone

initial treatment. equally effective for the treatment of the positive symptoms. but offer additional benefit for the negative symptoms and cognitive deficits associated with schizophrenia; Atypical antipsychotics have a higher affinity for serotonin symptoms but a lower affinity for histamine, cholinergic muscarinic and alpha adrenergic receptors.

less EPS and hyperprolactinemia; weight gain and obesity-related diseases (hyperlipidemia, and hyperglycemia)

Clozapine (Clozaril)

risk of agranulocytosis (a severe decrease of white blood cells). a Clozapine has been shown to be the most effective drug in treating schizophrenia but due relatively high seizurogenic potential; Safer use of clozapine to its potential to cause many severe side effects, it is relegated to third-line use and only requires weekly blood monitoring for around five months followed used in patients after other anti-psychotics have failed. by four weekly testing thereafter.

Risperidone (Risperdal)

(FDA-approval: 1993) Available in oral tablets, dissolving tablets, liquid form, and extended Common: akathisia, anxiety, insomnia, low blood pressure, muscle release intramusclar injection. stiffness, muscle pain, sedation, sexual dysfunction, tremors, For the treatment of schizophrenia and bipolar disorder. It is the only drug agent available increased salivation, and stuffy nose; minimal to moderate weight for treatment of schizophrenia in children ages 1318; and for treatment of bipolar disorder gain. in youths ages 1018, joining lithium. Risperidone contains the functional groups of Occasionally breast tenderness and eventually lactation in both benzisoxazole and piperidine as part of its molecular structure. genders may occur. Potentially cause tardive dyskinesia (TD), extrapyramidal symptoms Many antipsychotics are known to increase prolactin because they inhibit dopamine. (EPS), and neuroleptic malignant syndrome (NMS). However, risperidone is known to increase prolactin to a greater extent than most other antipsychotics, such as quetiapine. It is thought that once risperidone raises prolactin, it may Trigger diabetes and more serious conditions of glucose cause non-cancerous tumors in the pituitary gland. metabolism, including ketoacidosis and hyperosmolar coma.

Olanzapine (Zyprexa)

(FDA-approval: 1996) Available in oral tablets, dissolving tablets, and intramuscular injection. Olanzapine has a higher affinity for 5-HT2 serotonin receptors than D2 dopamine receptors.

high risk of weight gain

Quetiapine (Seroquel)

used in the management of schizophrenia and bipolar I disorder, and off-label for a variety of other purposes, including insomnia and anxiety disorders. Common side effects: sedation, constipation, headache, dry mouth, weight gain (or loss). NMS, orthostatic hypotension, tardive dyskinesia, and cataract formation may occur in chronic use.

Ziprasidone

(Geodon) (FDA-approval: 2001) Available in oral capsules and intramuscular injection. Ziprasidone is hepatically metabolized by aldehyde oxidase. Minor metabolism occurs via cytochrome P450 3A4 (CYP3A4). Medication that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone. There are no known inducers or inhibitors of aldehyde reductase.

Aripiprazole Paliperidone

(Abilify) Available in oral tablets and dissolving tablets. (Invega) (FDA)-approval: 2006) Available in extended-release oral tablets.

low risk of weight gain

Asenapine FDA has accepted NDA as of November 26, 2007. [7] Iloperidone (Fanapta or Zomaril) FDA has accepted NDA as of November 27, 2007. [8] Sertindole (Serlect) (Not approved by the FDA for use in the USA). Zotepine (Not approved by the FDA for use in the USA). Amisulpride (Not approved by the FDA for use in the USA). Bifeprunox (Not approved by the FDA for use in the USA). Melperone Approved in Europe. Currently in clinical trial in the USA.

Third generation antipsychotics

Do not confuse with the proton pump inhibitors (such as omeprazole, pantoprazole, and lansoprazole),

Aripiprazole

Dosing 1 mg up to maximum of 30 mg has been used. Mechanism of action is thought to reduce susceptibility to metabolic symptoms seen in some other atypical antipsychotics. Approved for the treatment of schizophrenia, acute manic and mixed episodes associated with bipolar disorder, and depression. Common side effects: Akathisia, headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, lightheadedness, trouble sleeping, restlessness, sleepiness, shaking, and blurred vision.

others

Pimozide

Pimozide (sold as Orap) is an antipsychotic drug. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis it is even more potent than haloperidol. As it has severe side effects, it is considered a drug of last resort, typically prescribed only after the patient has failed to respond to other medications. It also has special neurologic indications for Tourette syndrome and resistant tics. The side effects include akathisia, tardive dyskinesia, neuroleptic malignant syndrome and long QT syndrome.

Antidepressive and antimanic agents

Tricyclic antidepressants

TCAs _pramine or _triptyline

Used for: Major depression; Obsessive compulsive disorder (OCD); Panic attacks with or without agoraphobia ; Narcolepsy; Premature ejaculation; Chronic pain with or without organic disease, particular headache of the tension type; enuresis (involuntary nightly urinating in sleep) in children and adolescents;

Tertiary amines:

the tertiary amines boost serotonin as well as nor-epinephrine (adrenergic) and produce more sedation, anticholinergic effects, and orthostatic hypotension.

amitriptyline

Amitriptyline inhibits serotonin and noradrenaline reuptake almost equally. It is used to prevent migranes, only in very small doses. It has the highest sedation property among all the antidepressants and may be more preferable to use for treatment of depression iwth anxiety disorder. Common side effects: dry mouth, extreme weight gain, drowsiness, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision and insomnia.

imipramine

affects numerous neurotransmitter systems know to be involved in the etiology of depression, anxiety , ADD/ADHD, enuresis and numerous other mental and physical conditions. Imipramine is similar in structure to some muscle relaxants. Nocturial enuresis: imipramine and desmopressin mechanism of action differs from other tricyclic antidepressants: only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamine. (strong : 5-HT2, Muscarinic, H1, H2, Alpha1; moderate : D2 ; weak : 5-HT1, Alpha2 ) the only effective drug against insomnia (it does not alter the normal sleep architecture;in particular, it does not suppress REM-sleep)

trimipramine

doxepin

As for all tricyclic antidepressants, concurrent use, or failure to allow a two week gap, with MAO inhibitors (e.g., phenelzine, tranylcypromine, etc.) may precipitate hyperpyretic crisis and/or severe convulsions; fatalities have occurred. generally indicated for the treatment of obsessive compulsive disorder of the brain. Fluvoxamine is also used in OCD. Also contraindicated in the acute recovery phase after myocardial infarction (e.g., heart attack). Hypersensitivity of TCA: the other structure related drugs such as Carbamazepine and cyclobenzaprine should be used carefully.

clomipramine lofepramine
opipramol

dosulepin hydrochloride

The most common side-effects are drowsiness and dry mouth as well as dry eyes.

Secondary amines:

Nor, De, Pro, Amo

The secondary amines act primarily on nor-epinephrine and tend to have a lower side-effect profile It is used in the treatment of major depression and childhood nocturnal enuresis (bedwetting). Also used for chronic illnesses such as chronic fatigue syndrome, chronic pain and migraines, and labile affect in some neurological conditions. Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma, and/or seizures, as well as those that have hyperthyroidism or are receiving thyroid medication.

nortriptyline

protriptyline desipramine

amoxapine

It is used in the treatment of depression, panic disorders and bipolar disorder. Amoxapine is a strong reuptake inhibitor of norepinephrine and weak reuptake inhibitor of serotonin. One of its major metabolites, 7-hydroxyamoxapine, has a dopamine receptor blocking effect, making this drug a common cause of neuroleptic malignant syndrome. Amoxapine is also associated with acute extra pyramidal symptoms and tardive dyskinesia. Adverse Effects: Amenorrhoea; Milk discharge; Drowsiness, dry mouth, blurred vision and constipaiton

Name

Norepinephrine reuptake inhibitor yes yes metabolite yes yes yes yes yes yes yes yes yes yes

Serotonin reuptake inhibitor yes yes yes

Dopamine antagonist

Histamine antagonist yes

amitriptyline (& butriptyline) amoxapine clomipramine desipramine dosulepin HCl doxepin imipramine (& dibenzepin) iprindole lofepramine nortriptyline opipramol protriptyline trimipramine
Tetracyclic antidepressants

metabolite

yes

yes yes yes

in order from most selective for nor-epinephrine to most selective for serotonin: lofepramine, nortriptyline, amitriptyline, imipramine, clomipramine

yes

It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake. Maprotiline It exerts blocking effects at : Strong : alpha1 / Moderate : 5-HT2, muscarinic, H1, D2 / Weak : alpha2 /Extremely weak : 5-HT1 Contraindications: Absolute (Hypersensitivity to Maprotiline or to other tri-/tetracyclic antidepressants ; Hypertrophy of the prostate gland with urine hesitancy; Closed Angle Glaucoma )

Contraindications: Absolute (Hypersensitivity to Maprotiline or to other tri-/tetracyclic antidepressants ; Hypertrophy of the prostate gland with urine hesitancy; Closed Angle Glaucoma )

Selective serotonin reuptake inhibitor

SSRIs _xetine; _talopram; _ine

A class of antidepressants used in the treatment of depression, anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia. SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, having little binding affinity for the noradrenaline and dopamine transporters.

SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, and diminished libido. On the other hand, the effect of SSRIs to slow down sexual stimulation may be used as treatment for premature ejaculation. One major contraindication of SSRIs is the concomitant use of MAOIs ---- likely to cause severe serotonin syndrome. It is also better to avoid taking pimozide. The atypical opioid analgesic tramadol hydrochloride can, in rare cases, produce seizures when taken in conjunction with an SSRI or tricyclic antidepressant. Liver impairment is another contraindication for medications of this type.

Available in CA: Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline

SSRIs may increase blood levels and risk of toxicities of certain medications: CYP2D6 inhibitors highly protein-bound medications like warfarin (coumadin) and digoxin / antiarrhythmic agents like propafenone (Rythmol) or flecainide (Tambocor) / beta blockers like metoprolol (Toprol xl) or propranolol (Inderal) / tricyclic antidepressants like amitriptyline (Elavil) (may increase risk of serotonin syndrome) / benzodiazepines like alprazolam (Xanax) or diazepam (Valium) / carbamazepine (Tegretol) / cisapride (Propulsid) / clozapine (Clozaril) / cyclosporin (Neoral) / haloperidol (Haldol) / phenytoin (Dilantin) / pimozide (Orap) / theophylline (Theo-dur) Certain drugs may increase toxicities of SSRIs: alcohol and other CNS depressants / diuretics (water pills) / MAOIs / sympathomimetic drugs like pseudoephedrine (Sudafed) / lithium / sibutramine (Meridia) / MDMA (ecstasy) / zolpidem (ambien) / Dextromethorphan

Serotonin Syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, or the recreational use of certain drugs. It is not a spontaneous drug reaction; it is a consequence of excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors.
Serotonin syndrome

The symptoms are often described as a clinical triad of abnormalities: Cognitive effects: mental confusion, hypomania, hallucinations, agitation, headache, coma. Autonomic effects: shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea,h risk of GI bleeding with NSAIDs; Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus ), tremor.

Citalopram is used to treat the symptoms of major depression, social anxiety disorder and panic disorder. citalopram Citalopram is a Pgp substrate (also venlafaxine, amitriptyline or paroxetine ) and is actively transported by Pgp from the brain. The efficacy of citalopram in people possessing a certain version of Pgp (genetic TT-allele) is likely to be diminished. This suggests that in non-responders to citalopram a switch to antidepressant which is not a Pgp substrate, such as fluoxetine or mirtazapine may be beneficial. It is a better choice for the elderly or comorbid patients. Citalopram should be taken with caution when using St John's wort and contraindicated in individuals taking MAOIs. Stereoisomer of citalopram, similar side effect but higher efficacy relative to other SSRIs

escitalopram dapoxetine

fluoxetine

First line treatment in children and alolescents. Major depression (including bipolar disorder depression and pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, anorexia nervosa, panic disorder, social phobia; and premenstrual dysphoric disorder, chronic fatigue syndrome, fibromyalgia, menopause, premature ejaculation. ( So many indications!!! ) The extremely slow elimination of fluoxetine and its active metabolite norfluoxetine: CYP450 inhibitors, they inhibit their own metabolism, so fluoxetine elimination half-life 1 to 3 days after a single dose and 4 to 6 days after long-term use. Norfluoxetine is even longer to16 days after long-term use;

SSRIs weight gain paroxetine

SSRIs comprise one of the major classes of antidepressants currently being prescribed by primary care physicians. At first, SSRIs were thought to be associated with weight loss and reduced appetite. For a while, they were even marketed as anti-obesity drugs. It is now known that long-term use of SSRIs is associated with weight gain. Discontinuation effects are particularly prevalent

Fluvoxamine was one of the first of the SSRI antidepressants to be launched (1984 Switzerland); most often used to treat obsessive-compulsive disorder (OCD). fluvoxamine It is also widely prescribed to treat major depression, and anxiety disorders such as Obsessive-Compulsive Spectrum Disorder, Panic Disorder, Social Phobia, and PostTraumatic Stress Disorder. and for children and adolescents with OCD.

decreased sex drive or ability, drowsiness, tiredness, diarrhea, dizziness or light-headedness, constipation, headache, nervousness, sleep problems, increased sweating, tremors, serious skin rash, nausea, vomiting, stomach pain, dry mouth, heart burn, loss of appetite, pins and needles, abnormal taste, increased heart beat, weight gain or loss, unusual bruising and other allergic problems such as difficulty breathing, fever, confusion, severe weakness, intense agitation or anxiety, restlessness, hypomania, mania, seizures. Delay ejaculation in a manner similar to but less than other SSRIs including fluoxetine, paroxetine and sertraline.

primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. In 2007 it was the most prescribed antidepressant on the US retail market, with 29,652,000 prescriptions. sertraline High rates of nausea, diarrhea, insomnia, and sexual side effects; however, it does not cause weight gain, and its effects on cognition are mild. In pregnant women taking sertraline, the drug was present in significant concentrations in fetal blood, and was also associated with a higher rate of various birth defects. Sertraline has been approved for the following indications: major depression, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder and social phobia (social anxiety disorder).

zimelidine

Serotonin-norepinephrine reuptake inhibitor (SNRIs)

They act on two neurotransmitters in the brain serotonin and norepinephrine, used in the treatment of major depression and other mood disorders. Also used to treat anxiety disorders, OCD, ADHD and chronic neuropathic pain.

As with the SSRIs, abrupt discontinuation of SNRI-medication usually leads to a discontinuation syndrome which could include states of anxiety and further symptoms. (slowly taper down the dose when discontinuing SNRIs.) Due to the effects of increased norepinephrine synaptic activity, these drugs are contraindicated in patients with hypertension, heart disease, or risk of stroke.

Venlafaxine

prescribed for the treatment of major depression and anxiety disorders, among other uses. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide, it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs.

Duloxetine

Available in USA and Europe since 2004

MAO inhibitors

Phenelzine Sele/ Rasa-giline Moclobe/Niala-mide Ipro- clozide/niazid Isocarboxazid Linezolid Toloxtone Tranylcypromine

Blocking the intraneuronal oxidative deamination of brain biogenic amines. Chronic inhibition of MAO ----down-regulaiton of central adrenergic and serotonergic receptors. More Cloth be mine

Depression, phobic anxiety and Interact with sympathomimietic drugs (reserpine, guanethidine) narcolepsy that was not responded to and with foods that have a high tyramine concentration such as other treatments. (last line) cheese, wine, and sausage. Hypertensive crises can result.

Moclobemide

Moclobemide is the only reversible and selective inhibitor of MAO-A that is currently available; Dietary precautions are not required at standord doses; Common S/N:Nausea, insomina, dizziness; Avoid sympathomimetics, meperidine (may cause hypertensive crisis); Caution with opioids, antihypertensives, antipsychotics, SSRIs, Selegiline, excessive tyramine, alcohol; reduce dose with cimetidine.

Phenelzine Drug interactions: Sympathomimetics (e.g. pseudoephedrine in cold remedies): Risk of hypertensive crisis; Meperidine: may cause agitation, hyperpyrexia, circulatory collapse; the same as moclobemide?? Reserpine, guanethidine, tricyclic antidepressants : Excitement / Increase in blood pressure and body temperature Levodopa (L-DOPA): Excitement / Hypertension Anticholinergics (Henbane, Datura): Risk of hallucination Antihistamines, barbiturates, ethanol, opioids: Action of these drugs prolonged - risk of respiratory depression Pethidine (Demerol, meperidine) :Risk of high fever, sweating, excitement, delirium, convulsions, respiratory depression (MAOIs retard metabolism of pethidine, but not its demethylation, therefore excess norpethidine is formed). Methylenedioxymethamphetamine (MDMA, "Ecstasy") :Risk of hypertensive crisis / Serotonin syndrome Dextromethorphan (DXM, cough-syrup) : Serotonin syndrome Imitrex/Sumatriptan, Migraine Medicine Side reactions: Interact with sympathomimietic drugs and with foods that have a high tyramine concentration such as cheese, wine, and sausage. Hypertensive crises can result.

Tranylcypromine

Selegiline

Rasagiline Nialamide

Side reactions: Iproniazid Interact with sympathomimietic drugs and with foods that have a high tyramine concentration such as cheese, wine, and sausage. Hypertensive crises can result. CNS effects: stimulation, tremors agitation, overactivity, hyperreflexia, mania,insomnia followed by weakness, fatigue, drowness Cardiovascular effects: postural hypotension GI effects: nausea, abdominal pain, and constipation Antimuscarinic effects: dry mouth, urinary retention, and constipation

Isocarboxazid

Iproclozide Toloxatone Linezolid Linezolid (Zyvox, Zyvoxid), an antibiotic of the oxazolidinone family, is a reversible, nonselective MAOI which has been known to induce serotonin syndrome post SSRI ingestion. Zyvox requires the same dietary precautions as other MAOI's Hypertensive crises: A hypertensive emergency is severe hypertension with acute impairment of an organ system (especially the central nervous system, cardiovascular system and/or the renal system) and the possibility of irreversible organ-damage. In case of a hypertensive emergency, the blood pressure should be lowered aggressively over minutes to hours with an antihypertensive agent. Dual action antidepressants Bupropion (pp) vs Busprione (spy) Both low side effects! Act by norepinephrine and dopamine reuptake inhibition, and nicotinic antagonist; First-line for major depression and also for smoking cessation; Favourable side effect profile and a low rate of sexual dysfunction; Contraindicated: histroy of anorexia or bulimia nervora or head trama; or a current seizure or prior seizure; Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (act on 5HT2 and 5HT3) (NaSSA). Directly act on noradrenergic system and indirectly on serotonin system; Mirtazapine and Maprotiline are the only tetracyclic antidepressants that have been approved by FDA to treat depression. Devoid of anticholinergic effects, serotonin-related side effects, and adrenergic side effects (orthostatic hypotension and sexual dysfunction). So it is relatively safe if an overdose is taken. Low rate of GI and sexual side effects; But associated with antihistaminic side effects (drowsiness and sedation) and weight gain;

Bupropion

Mirtazapine

Triazolopyridines

Not considered to be an SSRI, MAOI or tricyclic antidepressant.

Trazodone

Apsychoactive compound with sedative, anxiolytic, and antidepressant properties. Trazodone has less prominent anticholinergic (dry mouth, constipation, tachycardia) and adrenolytic (hypotension, male sexual problems) side effects than most tricyclic antidepressants. Distinct from tricyclic antidepressants and tetracyclic antidepressants, trazodone's antidepressant effects may be due to its antagonistic effects at 5-HT2 receptors. Trazodone is often used in conjunction with SSRI, like fluoxetine and has been noted to help with the anxiety that can result from beginning treatment with an SSRI anti-depressant. Trazodone has been prescribed to children as an aid to an SSRI.

Nefazodone

Nefazodone hydrochloride (trade name Serzone, Nefadar) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries(including the United States and Canada), due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death.

Anxiolytics and sedative hypnotics

SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetiene and sertraline) and SNRI (Venlafaxine); TCAs (imipramine, desipramine, clomipramine); Diazepines (alprazolam, clonazepam, lorazepam, diazepam) Dual action antidepressants (Mertazapine, bupropion) MAOIs (phenelzine, tranylcypromine, moclobemide)

Benzodiazepines

_zepam, _zolam

Benzodiazepines produce a range of effects from depressing to stimulating the CNS via The long-term use of benzodiazapines can cause physical modulating the GABAA receptor, with varying hypnotic, sedative, anxiolytic, anticonvulsant, dependence. muscle relaxant and amnesic properties, which are mediated by slowing down the CNS. Benzodiazepines are useful in treating anxiety, insomnia, agitation, seizures(lora- and dia-), Can increase the depressant effects of alcohol and other CNS and muscle spasms(Clona- ), alcohol withdrawal(chlordiazepoxide, dia-, lora-, oxa-). Also depressant drugs. used in preanesthetic medication.

3-OH, undergo phase II glucuronidation--- short-acting compounds(oxa-, lora-, tema-): half-life of less than 12 hours with few residual effects if taken before bedtime but rebound insomnia may occur and they might cause wake-time anxiety. Intermediate-acting compounds (alprazolam): half-life of 1224 hours with residual effects in the first half of the day. side half-life Long-acting compounds(without 3-OH---phase I metabolism: di, hala, alpra, flura, qua-zepam; ): a effects : greater than 24 hours. intermediate-acting short term treatment (up to 8 weeks) of panic disorder, with or without agoraphobia. Alprazolam is very effective in treating moderate to severe anxiety, essential tremor and panic attacks. also used to treat delirium tremens long-acting; May be used in Epilepsy / Anxiety disorders, Panic disorder / Initial treatment of mania, together with firstline drugs such as lithium, haloperidol or risperidone / Hyperexplexia / Restless legs syndrome Drowsiness / Dizziness Upset stomach Blurred vision Headache / Confusion / Depression Impaired coordination Changes in heart rate Trembling Weakness Amnesia Hangover effect (grogginess) Dreaming or nightmares Chest pain Vision changes Jaundice Paradoxical reactions

alprazolam

chlordiazepoxide

clonazepam

clorazepate

diazepam

long-acting

Dia-Flu-Qua -long DFQ

flurazepam quazepam lorazepam

the longest-acting long-acting

short-acting

Lora-Oxa-Triza-Tema---Short LOTT

oxazepam

short-acting; Metabolized mostly be Phase II reaction, safer than other drugs metabolized by Phase I in eldly patients.

trizaolam temazepam

short-acting short-acting

Azapirones

_pirone

serotonin receptor agonist; act by agonizing serotonin (specifically the 5-HT1A receptor), primarily in the hippocampus. Unlike benzodiazepines, azaspirodecanediones are not addictive and do not induce tolerance and with less side effects.

buspirone

Generalized anxiety disorder of mild to moderate intensity (not effective against other types such as obsessive-compulsive disorder); Augmentation of SSRI-treatment against depression; Attention-Deficit Hyperactivity Disorder (ADHD)

Most frequent: vertigo, headaches, nervousness, agitation, lightheadedness, nausea; Often (>1%) : drowsiness, insomnia, concentration disorders, confusion, depression, agitation, intestinal disorders, paresthesia , coordination disorders, tremors, disturbed vision, tinnitus, fatigue, weakness, Angina pectoris, sore throat, tachycardias, palpitations, dry mouth, pain in muscles and joints; diarrhea.

gepirone ipsapirone tiospirone

Barbiturates

Barbiturates bind to the GABA A receptor at the alpha subunit, (distinct from GABA itself and the benzodiazepine binding site). Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. Barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. The most widely used anticonvulsant worldwide and the oldest still commonly used (The WHO recommends its use as first-line for partial and generalized tonic-clonic seizures in developing countries). It also has sedative and hypnotic properties but has been superseded by the benzodiazepines for these indications. Sedation and hypnosis are the principal side effects of phenobarbital. CNS effects: dizziness, nystagmus and ataxia. In elderly patients, it may cause excitement and confusion while in children, it may result in paradoxical hyperactivity.

barbiturates is absolutely contraindicated in patients who have acute intermittent porphyria.

Barby not for Porphy These patients have a defect in regulation of -aminolevulinic acid synthetase; thus, administration of a barbiturate that increases this enzyme may cause a

dangerous increase in levels of porphyrins.

Phenobarbital (long-acting)

Indicated in the treatment of all types of seizures except absence seizures. Phenobarbital is no less effective at seizure control than more modern drugs but significantly less well tolerated. The first line choice for the treatment of neonatal seizures; The first line drugs for treatment of status epilepticus are fast acting benzodiazepines such as diazepam or lorazepam. If these fail then phenytoin may be used, with phenobarbital being an alternative in the U.S. and Canada. (intermediate) (intermediate) short short ultra-short ultra-short ultra-short also called: Methylphenobarbital a highly lipid-soluble barbiturate. It can, therefore, rapidly cross the blood-brain barrier and produce a rapid onset of action and a short duration. Methohexital is employed for the induction and maintenance of anesthesia. anesthesia

Amobarbital Butabarbital Pentobarbital Secobarbital

Thiopental Methohexital Thiamylal Mephobarbital
Carbamates

Meprobamate

Meprobamate (Miltown by Wallace Laboratories, Equanil by Wyeth, and Meprospan) is a carbamate derivative which is used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benzodiazepines. Arrhythmia, aplastic anemia, palpitation, tachycardia, dizziness, drowsiness and ataxia.

Anti-insomnia agents
Imidazopyridine

zolpidem

used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic that potentiates gammaaminobutyric acid (GABA). It works quickly (usually within 15 minutes) and has a short half-life (23 hours).

Piperidinediones

glutethimide

Glutethimide is a hypnotic sedative as a safe alternative to barbiturates to treat insomnia. It is a CYP2D6 enzyme inducer. When taken with codeine, it enables the body to convert higher amounts of the codeine (higher than the average 5 - 10%) to morphine. The general sedative effect also adds to the power of the combination. In these respects, glutethimide is a stronger booster of codeine and related opioids than is promethazine.

methyprylon

Aldehydes

paraldehyde chloral hydrate used to induce sleep in pediatric or geriatric patients

antiepileptics /anticonvulsants

also called antiepileptic drugs ( "AEDs"), a diverse group of pharmaceuticals used in epileptic seizures. Also increasingly being used the treatment of bipolar disorder (act as mood stabilizers). It can suppress the rapid and excessive firing of neurons that start a seizure. However, anticonvulsants themselves have been linked to lowered IQ in children. The major molecular targets of marketed anticonvulsant drugs are 1) voltage-gated sodium channels; 2) components of the GABA system, including GABA-A receptors, the GAT-1 GABA transporter, and GABA transaminase; and 3) voltage-gated calcium channels.

Generalized Tonic-clonic: carbamazepine, lamotrigine, phenytoin, valproic acid, (clobazam, levetracetam, topiramate)---alternative or add-on Canadian choices Absence (petit mal): ethosuximide, valproic acid; (clobazam, lamotrigine, levetracetam, topiramate)
Blue ones Myoclonic and Atonic : valproic acid; (clobazam, lamotrigine, levetracetam, topiramate) is the First choice

Partial (simple or complex) with or without 2 generalization: carbamazepine, lamotrigine, phenytoin, (clobazam,gabapentin, levetracetam, oxcarbazepine, phenobarbital, primidone, topiramate, valproic acid, vigabatrin) Generalized Tonic-clonic (grand mal): phenobarbital, phenytoin, primidone, carbamazepine; (PPP-Car) psychomotor: phenytoin, phenobarbital, primidone, carbamazepine (PPP-Car) Absence (petit mal): phynobarbital, ethosuximide, clonazepam, trimethadione, valproic acid;(PEClo-TV) Myoclonic : clonazepam (Myo----Clo) Partial: clorazepate, felbamate, gabapentin, lamotrigine (Clora-Fel-Gab-Lamo) status epilepticus: IV diazepam, phenytoin, phenobarbital (PP- IV-D); Dextrose 50% solution is normally indicated. nystagmus: (Phenytoin, Phenobarbital, Gabapentin)

Phenytoin DPH

Inhibits the spread of seizures at the motor cortex and block posttetanic potentiation of synaptic transmission; with effects on sodium channels and Ca-uptake in presynaptic terminals. Elimination: Zreo-order in high dose

Status epilepticus, generalized tonic, clonic, partial, focal motor seizures. Not effective for absence ~.

Infusion related (hypotension, cardiovascular collapse, CNS depression). Dose related (nystagmus, ataxia. slurred speech), Hematologic abnormalities (leukopenia, granulocytopenia, thrombocytopenia). Dermatological: Stevens-Johnson syndrome, lupus erythematosus, maculopapular rashes; Other common adverse effects: nystagmus, gingival hyperplasia, ataxia, hirsutism, hypertrichosis. Diplopia. NN, hepatotoxicity, hypersensitivity reactions Patients must be monitored closely during therapy.

D_D

Decreased levels with Cobalamin, rifampin, chronic alcohol ingestion, carbamazepine, valproic acid, clonazepam, phenobarbital. Increased levels with amiodarone, sulfonamides, isoniazid, fluconazole, disulfiram, chloramphenicol, propoxyphene, Unpredictable effects with VPA and PB, Decreased effectiveness of: Cobalamin, corticosteroids, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, quinidine, rifampin, theophylline, Vitamin D, warfarin, and enternal nutritional therapy.

Thought to be similar to phenytoin. and reduces polysynaptic responses. Carbamazepine (cross-hypersensitive)

Pain associated with trigeminal neuralgia;

"CBZ" used primarily in epilepsy and Antiseizure agent, related to tricyclic antidepressants; bipolar disorder.

Autoinduction metabolism property: increasing dose schizophrenia, Phantom limb syndrome, will increase metabolism Paroxysmal extreme pain disorder

Also used to treat ADD, ADHD,

Idiosyncratic aplastic anemia and agranulocytosis (can be fatal); leukopenia (usually mild, monitor closely), Dose related: GI upset. ataxia, diplopia, dizziness, drowsiness. Hypersensitivity reactions. / Tricyclic antidepressants and MAO inhibitors: nausea and vomiting( N&V) dizziness, drowsiness, unsteadiness

200 mg intial twice daily ---800-2000mg

Decreased levels with CYP450 enzyme inducers: DPH, PB. D_D Increased levels with erythromycin, itraconazole. propoxyphene, VPA. Decreased effectiveness of DPH, VPA, warfarin, oral contraceptives.

Contraindicated in: History of bone marrow suppression, hypersensitivity to CBZ or tricyclic antidepressants (chemically related). ( CBC and platelets measured) ; glaucoma

Valproic acid VPA

divalproes sodium

hlevels with enzyme inducers: DPH, CBZ. PB. CYP450 enzyme inhibitors (i.e., antidepressants) expected to have little effect. h levels of ethosuximide, tamotrigine, PB,

Complex partial, absence, generalized Hepatic failure (monitor LFTs prior to initiation and frequently tonic-clonic, myoclonic seizures. thereafter), pancreatitis. Dose related: NN, abdominal pain. Migraine headache prophylaxis, Tremor, somnolence, dizziness, astnenia, weight gain, alopecia, mania associated with bipolar thrombocytopenia, and hyperammonemia. disorder.

Both contraindicated in patients with: Hepatic disease; hypersensitiltity to drug; known urea cycle disorders. Phenobarbital PB Sodium effects similar to phenytoin, with effects on calcium and GABA. status epilepticus, partial, generalized Infusion related: hypotension (administer slowly), tonic-clonic seizures. Sedative somnolence[`sCmnElEns] , , CNS depression, ataxia. hypnotic. Hypersensitivity reactions. Paradoxic excitation for children.

Decreased levels with enzyme inducers (rifampin), pyridoxine, ethanol. Increased levels with Contraindicated in patients with: VPA, phenytoin; acetazolamide, chloramphenicol, cimetidine, furosemide; Hypersensitivity to barbiturates, hepatic dysfunction, porphyria, D_D Increased sedation with other CNS depressants. severe respiratory disease. Decreased effectiveness of warfarin, Cal, metronidazole, oral contraceptives.

Other informations of AEDs (may be repeated for some drugs)

Aldehydes Paraldehyde Aromatic allylic alcohols Stiripentol Barbiturates phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as lorazepam, diazepam or midazolam is usually tried first. One of the earliest anticonvulsants. Still used to treat status epilepticus, particularly where there are no resuscitation facilities. Stiripentol (2001 - limited availability). Indicated for the treatment of severe myoclonic epilepsy in infancy (SMEI).

Phenobarbital

Pyrimidinediones

Primidone

Primidone is an anticonvulsant whose active metabolites, phenobarbital (major) and phenylethylmalonamide (PEMA) (minor), are also anticonvulsants. It is used mainly to treat complex partial, simple partials, generalized tonic-clonic seizures, myoclonic, akinetic seizures and since the 1980s it has been a valuable alternative to propranolol in the treatment of essential tremor. Primidone has been occasionally used to treat long QT syndrome, cerebral palsy, and athetosis. Unlike other anticonvulsants such as carbamazepine and valproic acid, primidone is rarely used in the treatment of bipolar disorder or any other psychiatric problem.

Benzodiazepines

Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance and dependency. Of the many drugs in this class, only a few are used to treat epilepsy

delirium tremens Clobazam primary mechanism of action is via modulating GABA function in the brain, via the benzodiazepine receptor which in turn leads to enhanced GABAergic inhibition of neuronal firing. It also decreases the utilisation of 5-HT (serotonin) by neurons. Long-term use (more than 24 weeks) can lead to a number of problems, including muscle weakness and fatigue, tolerance, physical dependence and withdrawal symptoms upon discontinuation. Clonazepam may be prescribed for: Epilepsy / Anxiety disorders / Panic disorder / Initial treatment of mania (together with first line drugs such as lithium, haloperidol or risperidone) / Hyperexplexia / Restless legs syndrome / Off Label Use: muscle relaxant; sedative for sleep. Clorazepate Diazepam Midazolam Lorazepam Bromides Can be given rectally by trained care-givers. Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa. Given by injection in hospital. Potassium bromide (1857). The earliest effective treatment for epilepsy. There would not be a better drug for epilepsy until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.

Clonazepam

Carbamates Felbamate Carboxamides

(1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.

An anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat ADD, ADHD, schizophrenia, Phantom limb syndrome, Paroxysmal extreme pain disorder, and trigeminal neuralgia. Carbamazepine Carbamazepine can render many hormonal contraception products ineffective, due to its action as a cytochrome P450 enzyme inducer, which is the system that metabolizes many oral contraceptives. Common side effects include drowsiness, headaches and migraines, motor coordination impairment and/or upset stomach. Carbamazepine preparations typically greatly decrease a person's alcohol tolerance. Oxcarbazepine (1990). A derivative of carbamazepine that has similar efficacy but is better tolerated.

Fatty acids valproates valproic acid, sodium valproate, and divalproex sodium (1967). Vigabatrin Progabide Tiagabine (1996). (1989).

Fructose derivatives

Monosaccharides, anticonvulsant drug (1995). This drug is used to treat epilepsy in both children and adults. In many cases it can also be used as an antidepressant, most of the time for depressive realism. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delay). It is also approved for, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, although it is not FDA approved for this purpose.

Topiramate

Gaba analogs

Gabapentin

(1993). a medication originally developed for the In 2002, an indication was added for treating postherpetic neuralgia (neuropathic pain following shingles, treatment of epilepsy. Currently, gabapentin is widely other painful neuropathies, and nerve related pain). It is also effective in prevention of frequent migraine used to relieve pain, especially neuropathic pain. headaches, neuropathic pain and nystagmus.

Pregabalin

(2004).

Hydantoins ethotoin

phenytoin

Acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage gated sodium channels. It is also an option in the treatment of trigeminal neuralgia as well as certain cardiac arrhythmias. At therapeutic doses, phenytoin produces horizontal gaze nystagmus. At toxic doses, patients experience sedation, cerebellar ataxia, and ophthalmoparesis, as well as paradoxical seizures. As a CYP 450 inducer phenytoin causes a reduction in folic acid levels, predisposing patients to megaloblastic anemia. Phenytoin is a known teratogen. The syndrome consists of craniofacial anomalies which also been called the "fetal hydantoin syndrome."

mephenytoin fosphenytoin Water-soluble prodrug of phenytoin. Converted to phenytoin by bloodstream phosphatases, with a half-life of about 8 min in both adults and children. Indicated for pts who cannot take oral drugs and in the acute treatment for status epiepticus, IV or IM.

Oxazolidinediones Paramethadione

Trimethadione

used to treat epileptic conditions that are resistant to other treatments; recent studies For The Deaf's Center For Presbyacusis and Aging suggest that trimethadione, along with other oxazolidinedione anticonvulsant medications may be useful in treating sensorineural hearing loss cases like those of Iraq war veterans- if the drug's side effects, like dizziness, can be lessened by modifying the drug so it does not cross into the brain itself. If administered during pregnancy, fetal trimethadione syndrome may result causing Facial Dysmorphism(short upturned nose,slanted eyebrows), cardiac defects,Intra Uterine Growth Retardation,mental retardation. The fetal loss rate while using trimethadione has been reported to be as high as 87%.

Ethadione Propionates Beclamide Pyrrolidines _racetam Brivaracetam Levetiracetam Seletracetam (1999).

Succinimides _suximide

Ethosuximide Phensuximide Mesuximide Sulfonamides Acetazolamide (1953). Sultiame Methazolamide Zonisamide (2000). Triazines

(1955). Ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence drug, valproic acid.

For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine also acts as a mood stabilizer. Lamotrigine It is the first medication since lithium to be granted approval by FDA for the maintenance treatment of bipolar type I. Lamotrigine has relatively few side-effects and does not require blood monitoring in monotherapy.

Ureas Pheneturide

Phenacemide Valproylamides (amide derivatives of valproate)

As an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and less commonly major depression. It is also used to treat migraine headaches and schizophrenia. Valproic acid Common side effects are dyspepsia and/or weight gain. Less common are fatigue, peripheral edema, dizziness, drowsiness, hair loss, headaches, nausea, sedation and tremors. Valproic acid also causes hyperammonemia, which can lead to brain damage. Contraindicated in pregnancy due to its teratogenicity; overweight patients; Preexisting hepatic and/or renal damage or cancer, hepatitis, pancreatitis, end-stage AIDS HIV infection, bone marrow depression, urea cycle disorders, and coagulation hematological disorders are absolute contraindications.

Valpromide

A carboxamide derivative of valproic acid used in the treatment of epilepsy and some affective disorders. It is rapidly metabolised (80%) to valproic acid but has anticonvulsant properties itself. It may produce more stable plasma levels than valproic acid or sodium valproate and may be more effectively at preventing febrile seizures.

Valnoctamide

Diet

The ketogenic diet is a strict medically supervised diet that has an anticonvulsant effect. It is typically used in children with refractory epilepsy. a derivative of gamma-aminobutyric acid (GABA) primarily used to treat spasticity. , () Baclofen It is an agonist specific to mammalian GABAB receptors. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis, amyotrophic lateral sclerosis (Lou Gehrig's Disease) and trigeminal neuralgia. Its beneficial effects result from actions at spinal and supraspinal sites. Baclofen can also be used to treat hiccups.

Sodium oxybate

gamma-Hydroxybutyric acid; a naturally-occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also a neuroprotective therapeutic nutrient that is categorized as an illegal drug in a number of countries. It is currently regulated in the US and sold by Jazz Pharmaceuticals under the name Xyrem to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy.

Antiparkinsonian agents

Levodopa preparations: lebodopa/carbidopa; Dopamine Agonists: bromocriptine, pergolide, pramipexole, ropinirole; ---(bromo- pergo-prami-ropini ) MAO-B inhibitors: rasagiline, selegiline COMT inhibitors: entacapone; Therapeutic choices in Canada Anticholinergic Agents: benztropine, ethopropazine, procyclidine, trihexyphendidyl; NMDA Receptor Antagonisits: amantadine

dopaminergic agonists

levodopa Droxidopa Melevodopa Etilevodopa Bromocriptine

Carbidopa /levodopa ; benserazide /levodopa

an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors and Parkinson's disease. Pergolide is also used to treat the stiffness, tremors, spasms, and poor muscle control of Parkinson's disease, it was reported in 2003 to be associated with cardiac fibrosis and valvular dysfunction. Withdrawn from USA market, still available in Canada (2008). direct dopaminergic receptor agonists, mimic the activity of striatal dopamine

Pergolide

Pramipexole

Used for PD, restless legs syndrome (RLS); cluster headache or low libido experienced caused by SSRIs.

Ropinirole

Used for PD, restless legs syndrome Induce arthrenia (RLS)

Fenoldopam

that acts as a selective peripheral dopamine D1A receptor agonist; Fenoldopam is used as an antihypertensive agent postoperatively, and also via IV to treat hypertensive crisis; Not used for PD.

Enzyme inhibitors

carbidopa

Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC), an enzyme important in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to Dopamine (DA). Potentiate the effects of L-dopa

tolcapone Catechol-O-methyl transferase (COMT) inhibitors for the treatment of Parkinson's disease. When administered in conjunction with dopaminergic agents such as L-DOPA, it increases the bioavailability of these compounds by facilitating their passage across the blood-brain barrier. Entacapone

Cholinergic antagonists

atropine related; ( Etho- Benz- Trihexy-Procyc- ---- love Benz an anticholinergic drug principally used for the treatment of: Drug-induced parkinsonism, akathisia and acute dystonia; / PD; and Idiopathic or secondary dystonia.

benztropine

ethopropazine

Profenamine hydrochloride (INN, also known as ethopropazine) is a medication derived from phenothiazine. It is primarily used as an antidyskinetic to treat parkinsonism. It is sold under the trade names Parsidol in the United States, Parsidan in Canada and Parkin in Japan.

trihexyphenidyl

Trihexyphenidyl; an antimuscarinic class. It is a tertiary amine with alcohol, phenyl, and cyclohexyl moieties.The drug is available as the hydrochloride salt. Trihexyphenidyl is used in mono- and combination therapy. It is active in postencephalitic, arteriosclerotic, and idiopathic forms. The drug is also commonly used to treat extrapyramidal side effects occurring during antipsychotic treatment.

procyclidine

Procyclidine hydrochloride is an anticholinergic drug principally used for the treatment of: Drug-induced parkinsonism, akathisia and acute dystonia; Parkinson disease; and Idiopathic or secondary dystonia. used to treat muscle injuries, skeletal muscle tension and rigidity secondary to afflictions such prolapsed discs and degenerative soft tissue disease especially in the lower back, neck, and joints. and other causes of muscle spasms, to potentiate the action of opioid analgesics against moderate to severe neuropathic pain, and it is also used to treat Parkinson's disease. Biperiden is used for the adjunctive treatment of all forms of Parkinson's disease (postencephalitic, idiopathic, and arteriosclerotic). Biperiden has an atropinelike blocking effect on all peripheral structures which are parasympathetic-innervated (e.g. cardiovascular and visceral organs). It also has a prominent central blocking effect on M1 receptors. Contraindications: Hypersensitivity to biperiden; Narrow angle glaucoma; Ileus; It was approved for the treatment of Influenzavirus A in adults. It is also used to help reduce symptoms of Parkinson's disease and drug-induced EPS (extrapyramidal syndromes). Off-label uses: used to treat the characteristic fatigue often experienced by patients with multiple sclerosis. Low dose to treat ADHD; Also used to relieve SSRI-induced sexual dysfunction. Stimulate the release of dopamine from intact striatal dopaminergic terminals.

orphenadrine

biperiden

Antiviral agent amantadine

MAOIs

blocks the central catabolism of dopamine, increasing its availabity in the caudate-patamen. Selegiline
MAO-B selective

used for the treatment of early-stage PD, depression and senile dementia.

Rasagiline

drugs used for increasing milk supply

Prolactin levels are primarily regulated by inhibition: the presence of prolactin-inhibiting factors (dopamine is the principal one) keep prolactin levels in check. The drugs used for increasing milk supply work by blocking dopamine, which results in an increase in prolactin levels.

dopamine receptor antagonist

Prolactin levels are primarily regulated by inhibition: the presence of prolactin-inhibiting factors (dopamine is the principal one) keep prolactin levels in check. The drugs used for increasing milk supply work by blocking dopamine, which results in an increase in prolactin levels.

a potent dopamine receptor antagonist used for its antiemetic and prokinetic properties. Thus it is primarily used to treat nausea and vomiting, and to facilitate gastric emptying in patients with gastroparesis. Metoclopramide (Reglan) Prokinetic use Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb. Useful in the treatment of gastric stasis (e.g. after gastric surgery or diabetic gastroparesis). It is also used in gastroesophageal reflux disease (GERD/GORD). By inhibiting the action of prolactin-inhibiting hormone (i.e., dopamine), metoclopramide has been used to stimulate lactation.

Gastrointestinal problems: Domperidone is used, together with metoclopramide, cyclizine, and 5HT3 receptor antagonists (such as granisetron) for nausea and vomiting; effective in the treatment of gastroparesis, a stomach motility condition, and for paediatric Gastroesophageal reflux (infant vomiting). Parkinson's disease; Unlike metoclopramide, domperidone does not cross the blood-brain barrier. Domperidone Lactation: Domperidone, by acting as an anti-dopaminergic, results in increased prolactin secretion, and thus promotes lactation. Available in Canada. (Motilium) Anti-emetic: Domperidone is a first choice anti-emetic in most countries, together with metoclopramide. It is however not approved for prescription in the US.

Sulpiride

An anti-psychotic drug used mainly in the treatment of psychosis (e.g. schizophrenia) and depression. It is a substituted benzamide. Sulpiride is more commonly used in Europe and Japan. Levosulpiride is its purified levo isomer and is sold in India for similar purpose.So far it has not been approved in the US and Canada. The drug has strong chemical and clinical similarities to the novel anti-psychotic amisulpride.

Anti-ADHD agents

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurobehavioral developmental disorder affecting about 3-5% of the world's population. It typically presents during childhood, and is characterized by a persistent pattern of impulsiveness and inattention, with or without a component of hyperactivity.

First line treatments: stimulants (Methylphenidate, Dextroamphetamine, mixed salts amphetamine) Norepinephrine Reuptake inhibitors (atomoxetine); Therapeutic Choices Antidepreessants (bupropion), TCAs (desipramine, imipramine); 2ed or 3rd line options; in Canada 2-adrenergic agonists (clonidine), 2ed or 3rd line options; Atypical antipsychotics (risperidone) ; Natural Health Products: chamomile, valerian, melatonin, used in children who are restless, anxious, or sleep-dificult situations.

Amphetamine ( Adderall ) have warnings about potential for abuse, drug dependence, and sudden death.

Methylphenidate (MPH) is a prescription CNS stimulant commonly used to treat Attention-deficit hyperactivity disorder(ADHD). It is also one of the primary drugs used to treat the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. The drug is seeing early use to treat cancer-related fatigue. Methylphenidate Brand names of drugs that contain methylphenidate include Ritalin (Ritalina, Rilatine, Attenta, Methylin, Penid, Rubifen); and the sustained release tablets Concerta, Metadate CD, Methylin ER, Ritalin LA, and Ritalin-SR. Focalin is a preparation containing only dextro-methylphenidate. A newer way of taking methylphenidate is by using a transdermal patch (under the brand name Daytrana), similar to those used for hormone replacement therapy (HRT), nicotine release and pain relief (Fentanyl or Morphine).

Amphetamine

act by increasing levels of norepinephrine, serotonin, and dopamine in the brain. It includes prescription CNS drugs commonly used to treat attention-deficit hyperactivity disorder (ADHD) in adults and children; symptoms of traumatic brain injury and the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. Initially it was more popularly used to diminish the appetite and to control weight.

Dextroamphetamine

It is believed that the dextroamphetamine may actually be the primary chemical (compare to the "levo-isomer") responsible for most of the increased cognitive & focusing ability. It is the active metabolite of the recently introduced prodrug lisdexamfetamine and several older N-substituted amphetamine prodrugs used as anorectics, such as clobenzorex (Asenlix), benzphetamine (Didrex) and amphetaminil (Aponeuron).

Atomoxetine

Atomoxetine is a non-stimulant drug approved for the Classified as a norepinephrine (noradrenaline) reuptake inhibitor, atomoxetine is approved for use in treatment of attention-deficit hyperactivity disorder children, adolescents, and adults. However, its efficacy has not been studied in children under six years (ADHD). old. Its advantage over stimulants for the treatment of ADHD is that it has less abuse potential than stimulants, is not scheduled as a controlled substance and has proven in clinical trials to offer 24 hour It is sold in the form of the hydrochloride salt of coverage of symptoms associated with ADHD in adults and children. atomoxetine.

Bupropion, TCAs (Dedipramine, Imipramine, Nortriptyline) second or third-line options or as adjunctive therapy for the treatment ADHD in both children and Antidepressants adults; Less effective than stimulants in the management of ADHD in children; but may be benefit pts with comobid conditions such as depression, anxiety, enuresis or tic disorders;

2-adrenergic clonidine; used as second or third-line options or as adjunctive therapy for the treatment ADHD; reducing symptoms of aggression, impulsibity, overarousal and agonists hyperactivity, but have minimal effect on symptoms of inatention or poor concentration. Antipsychotics low doses of atypical antipsychotics (e.g., risperidone) may be moderately effective for the behavioural symptoms seen in hyperactive and impulsive children. Natural products chamomile, valerian, melatonin for recuding restless, anxious or sleep difficulties; The other antioxidants: Blue-green algae, Vitamin B, ginkgo biloba, pycnogenol, and evening primrose oil; is a medication used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy; Pemoline has some advantages over other stimulants in that it does not reduce the appetite or cause dry mouth, , it is a Schedule IV drug; but Dependence has only rarely been reported. Similar to Methylphenidate, the mechanism of action of Pemoline is to inhibit the reuptake of Dopamine and to increase the release of Dopamine and Norepinephrine in the central nervous system. Due to its Hepatotoxicity, Abbott Laboratories (Cylert marketer) had discontinued its production in March 2005.

Pemoline

Opioid Analgesics

its receptors are located in brain

Phenanthrenes

morphine

Side effects: BAD AMERICANS Bradycardia & hypotension Anorexia Diminished pupilary size Analgesics / Ameliorate cough reflex Miosis phenolic -OH group is extremely important for its Euphoria activity; Respiratory depression Morphine is primarily metabolized into morphine-3- Increased smooth muscle activity (biliary tract constriction) glucuronide (M3G) and M6G via glucuronidation by Constipation Ameliorate cough reflex phase II metabolism enzyme UDP-glucuronosyl Nausea and vomiting transferase-2B7 (UGT2B7). Sedations The cytochrome P450 (CYP) family of enzymes involved in phase I metabolism plays a lesser role. Not only does the metabolism occur in the liver but it sedation, constipation; may also take place in the brain and the kidneys. Additive sedation with other CNS depressants (e.g., alcohol), potential enhancement of opioid effects with lidocaine

Diacetylmorphine Heroin

Most drug dependence opioids

Common side effects of codeine: euphoria, itching, nausea, vomiting, drowsiness, dry mouth, miosis, orthostatic hypotension, urinary retention, depression and constipation. Another side effect commonly noticed is the lack of sexual drive and increased complications in erectile dysfunction.

hydromorphone Codeine is considered a prodrug, since it is Approved indications for codeine include: metabolised in vivo to the primary active compounds Cough, Diarrhea, Mild to severe pain, Irritable bowel syndrome morphine and codeine-6-glucuronide.

codeine

hydrocodone Withdrawal effects: As with other opiate based pain killers chronic use of codeine can cause a physical dependence to develop. If a person stops the medication too quickly they may experience withdrawal symptoms including craving, runny nose, yawning, sweating, restless sleep, weakness, stomach cramps, nausea, vomiting, diarrhea, muscle spasms, chills, irritability and pain. To minimise withdrawal symptoms long term users need to gradually reduce their codeine medication under the supervision of a healthcare professional. methadone strong potency

phenylheptylamines

moderate potency; It is used to treat mild to moderate pain and as an anti-tussive. It can be used Over dose symtoms: respiratory depression with cheyne stokes respiration, hypoxia, pinpoint pupil Dextro-propoxyphene to ease surgical pain both prophylactically and construction, pulmonary edema and circulatory collapse. palliatively. It is considered no more effective than aspirin in treating pain

Levomethadyl acetate

also known as levo--acetylmethadol (LAAM) is a synthetic opioid similar in structure to methadone. It has a long duration of action due to its active metabolites. LAAM is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone or buprenorphine. LAAM is not approved for use in Canada.

pheynylpiperidines

meperidine p-phenyl-N-alkylpiperidine

also called Pethidine (INN); a fast-acting opioid analgesic drug. It is quickly hydrolysed in the liver to pethidinic acid and is also demethylated to norpethidine which is toxic and has convulsant and hallucinogenic effects, and seizures can occur when used in renal failure; May cause tremors, hyperrreflexia, hallucinations. Avoid in liver disease and those who have received MAOIs within the last 14 days ( potentially life-threatening serotonin syndrome with nonselective MAOIs);

One of the most powerful opioid analgesics with a potency approximately 81 times that of morphine. The LD50 in humans, by intravenous injection in an opiate-naive individual (without tolerance), is 0.5-1 milligrams. It is also a highly abusable drug, and as a result, has been categorized as a Schedule II drug in the United States. fentanyl Fentanyls are extensively used for anesthesia and analgesia, most often in the operating room and intensive care unit. used IM or IV to promote analgesia during anesthesia. It is also available in a transmucosal (Fentanyl Oralet, Actiq) and transdermal (Duragesic) dosage form. Major side effects (more than 10% of patients) include diarrhea, nausea, constipation, dry mouth, somnolence, confusion, asthenia, and sweating; respiratory depression sufentanil
morphinan levorphanol

strong agonist with high oral bioavailability

Opioid peptides

Opioid Peptides are short sequences of amino acids which mimic the effect of opiates in the brain. Opioid peptides may be produced by the body itself, for example endorphins, or be absorbed from partially digested food (casomorphins, exorphins and rubiscolins). The effect of these peptides vary, but they all resemble opiates. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake. enkephalin endorphin dynorphin

Tramadol

a centrally acting analgesic, used for treating moderate to severe pain (acute, neruropathic pain); and most types of neuralgia, including trigeminal neuralgia; fibromyalgia. It is a synthetic agent, and although it is chemically unrelated to opioids, it does appear to have actions at the -opioid receptor as well as the noradrenergic and serotonergic systems.

Tapentadol

a centrally-acting analgesic with a unique dual mode of action as an agonist at the -opioid receptor and as a norepinephrine reuptake inhibitor. It is considered to have a potency between morphine and tramadol.

Opioid antagonists
nalbuphine partial agonist and antagonist actions Bu- Morphine; anta-morphine buprenorphine Buprenorphine (Buprenex) is a semi-synthetic opiate with partial agonist and antagonist actions. It is a List II drug of the Opium Law. As an analgesic, it is about 30 times as potent as morphine. It is administered intramuscularly or intravenously for the relief of moderate to severe pain.

nalorphine pure antagonist actions Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence.

naltrexone

naloxone

Naloxone has an extremely high affinity for -opioid receptors in the central nervous system. Naloxone is a -opioid receptor competitive antagonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at and -opioid receptors

General Anesthetics

Inhalational anaesthetics

Desflurane, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide.

Injection anaesthetics

Fentanyl citrate
Propofol Etomidate

Barbiturates thiopentone

methohexital /thiopental

and

M&A: bind post-synaptic GABA receptors ---open Clchannels --- inhibit APs

Benzodiazepines midazolam diazepam

Ketamine

pseudo-unconscious state; analgesia; associated with bizarre "emergence" phenomena: visual & auditory inhibits GABA--CNS overstimulation; also block CNS illusions, vivid dreams following anesthesia; h HR & BP; NMDA receptors Never use katamine alone! ( with diazepam)

Local Anesthetics: _ caine / _i_caine

Amino esters _ caine Benzocaine

ester type, generally short acting

Esters are prone to producing allergic reactions, which may necessitate the use of an Amide.

Chloroprocaine

a local anesthetic given by injection during surgical procedures and labor and delivery.

Cocaine Cyclomethycaine

Dimethocaine/Larocaine
Propoxycaine

Procaine
Proparacaine

It is used primarily to reduce the pain of intramuscular injection of penicillin, and is also used in dentistry. trade name Novocain----Novocaine

Tetracaine/Amethocaine

used topically and for spinal anesthesia; stays at the site of application and lasts longer than topical lidocaine

Amino amides _i_caine

amide type, generally longer acting---

Articaine
Bupivacaine Carticaine Cinchocaine /Dibucaine Etidocaine Levobupivacaine Lidocaine has a more rapid onset of action and longer duration of action than amino ester-type local anesthetics such as procaine. It is approximately 90% metabolized in the liver by CYP1A2 (and to a minor extent CYP3A4) to the pharmacologically-active metabolites monoethylglycinexylidide and glycinexylidide. The elimination half-life of lidocaine is approximately 1.52 hours in most patients. This may be prolonged in patients with hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes). longe duration (>24 h)

Lidocaine/Lignocaine

Mepivacaine Piperocaine Prilocaine Ropivacaine Trimecaine

Antihistaminics
H1-receptor antagonists

_amine, -astine, -zine, -tadine Mepyramine Ethylenediamines were the first group of clinically-effective H1-antihistamines developed.

Ethylenediamines (pyrilamine)

Antazoline

Ethanolamines

Carbinoxamine Doxylamine Clemastine Dimenhydrinate

Diphenhydramine was the prototypical agent in this group. Significant anticholinergic adverse effects, as well as sedation, are observed in this group but the incidence of gastrointestinal adverse effects is relatively low. [3] [6]

Diphenhydramine

Diphenhydramine is effective at treating EPS(extrapyramidal symptoms) or dystonic reactions associated with extended or high-dose antipsychotic or phenothiazine use, EPS or dystonic symptoms are due to dopamine antagonism and the subsequent central imbalance between dopamine and acetylcholine, These symptoms may be treated with anticholinergic agents, including antimuscarinic agents such as benztropine and trihexyphenidyl. Many providers prefer to use antihistamines because they are associated with less severe adverse reactions, Antihistamines, however, have different levels of anticholinergic activity, Diphenhydramine has a high anticholinergic profile, whereas tripelennamine, brompheniramine, cyproheptadine, and cetirizine have moderate to low anticholinergic profiles and would not be as effective at treating these reactions.

diphenhydramine is a potent anticholinergic agent; profound drowsiness as a very common side-effect, motor impairment (ataxia), dry mouth and throat, flushed skin, tachycardia, blurred vision at nearpoint owing to lack of accommodation (cycloplegia), photophobia, pupil dilation (mydriasis), urinary retention (ischuria), constipation, difficulty concentrating, short-term memory loss, visual disturbances, hallucinations, irritability, itchy skin, confusion, erectile dysfunction, and delirium. Severe, prolonged twitching and muscle spasm have also been experienced.

scopolamine

also known as levo-duboisine and hyoscine, is a tropane alkaloid drug with muscarinic antagonist effects.A transdermal scopolamine disc has an onset of action of 4 hours and provides 72 hours of continuous antiemetic coverage, This option would provide long-lasting antiemetic medication without the need for frequent dosing.

Pheniramine
(chlorpheniramine)

Chlorphenamine

Alkylamines

The isomerism is a significant factor in the activity of the agents in this group. E-triprolidine, for example, is 1000-fold more potent than Z-triprolidine. This difference relates to the positioning and fit of the molecules in the histamine H1-receptor binding site. Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical CNS stimulation.

Dexchlorpheniramine

Brompheniramine

Triprolidine Cyclizine Chlorcyclizine Hydroxyzine Meclizine structurally-related to the ethylenediamines and the ethanolamines, and produce significant anticholinergic adverse effects.

Piperazines

Meclizine is very helpful in preventing vertigo, motion sickness (nausea, vomiting, diziness), but it would require frequent dosing and its adverse effect profile may be augmented in elderly patient.

Meclizine

an antihistamine considered to be an antiemetic. Meclizine is less anticholinergic than many other antihistamines and other agents used for their anti-emetic and anti-puritic effects, also shares the anxiolytic, analgesic-sparing (potentiating), sedative, and other effects of its chemical relatives cyclizine and hydroxyzine to varying extents. Due to its possible anticholinergic action, meclizine should be used carefully with patients who suffer from asthma, glaucoma, or an enlarged prostate gland.

Promethazine Alimemazine (trimeprazine) Tricyclics and Tetracyclics Cyproheptadine Azatadine Ketotifen

These compounds differ from the phenothiazine antipsychotics in the ring-substitution and chain characteristics. (Nelson, 2002) They are also structurally-related to the tricyclic antidepressants (and tetracyclics), explaining the H1-antihistaminergic adverse effects of those three drug classes and also the poor tolerability profile of tricyclic H1-antihistamines. The second-generation H1-antihistamine loratadine was derived from compounds in this group.

Cyproheptadine

an antihistaminic and antiserotonergic agent. It acts as a 5-HT2 receptor antagonist and also blocks calcium channels. Used in the treatment of allergies (specifically hay fever) and is also used to stimulate appetite in underweight people (e.g. anorexia nervosa). For nightmares including nightmares related to post traumatic stress disorder. In the management of moderate to severe cases of serotonin syndrome (a complex of symptoms associated with the use of serotonergic drugs, such as SSRIs or stimulants), and in the disease carcinoid in which serotonin is overproduced by tumor cells; a preventative measure against migraine in children and adolescents.Can relieve SSRI-induced sexual dysfunction and drug-induced hyperhydrosis (excess sweating). It can be used in anorexia nervosa, pruritus, and headache in children. Renal impairment.

Systemic, second-generation

Acrivastine Astemizole

2ed generation antihistamines: less sedative properties; Should avoid concurrent with Erythromycin, Ketoconazole, Clarithromycin, Propulsid (may inhibit the metabolism of these antihistamines and increase the risk of severe cardiac toxicity and tachycardia. used to treat allergies, and marketed for its non-sedating properties. Droziness

Cetirizine

A major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, pruritus, hay fever, angioedema, and urticaria. Effective agent in Kimura's disease, which mostly occurs in young Asian men, affecting the lymph nodes and soft tissue of the head and neck in the form of tumor-like lesions. causes less sedation and psychomotor impairment (because it penetrates the blood brain barrier only to a slight extent.)

Loratadine

Most common side-effects: Drowsiness, headache, psychomotor impairment, and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances are the most common side effects.

Mizolastine Terfenadine withdrawn from most markets due to risk of cardiac arrhythmias and replaced with fexofenadine) Antihistamines: First generation: diphenhydramine, clemastine, brompheniramine, chlorpheniramine, hyroxyzine, azatadine, cyproheptadine, promethazine, trimeprazine; Second generation: loratadine, fexofenadine, cetirizine, desloratadine, doxepin, ketotifen

Treatment for Pruritus

Topical, second-generation

Azelastine

Levocabastine Olopatadine

2nd gen Alkylamine Acrivastine Tricyclic Olopatadine

Piperazine Cetirizine a prodrug, generally completely metabolised to the active form fexofenadine by the intestinal cytochrome P450 CYP3A4 isoform. Due to this presystemic gut wall metabolism terfenadine normally is not measurable in the plasma. Terfenadine itself, however, has a cardiotoxic effect in higher doses while its metabolites have not such effect.

Benzhydryl Terfenadine

Systemic, third-generation

Levocetirizine Desloratadine

Metabolite of terfenadine; does not readily cross the blood-brain barrier, and so causes less drowsiness than first-generation histamine-receptor antagonists. Fexofenadine Used in the treatment of allergic rhinitis, pruritus, hayfever and similar allergy symptoms.

Serotonin agonists
Their action is attributed to their binding to serotonin 5-HT1B and 5-HT1D receptors in cranial blood vessels (causing their constriction) and subsequent inhibition of pro-inflammatory neuropeptide release. Evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels.
5-HT1-receptor agonists

This leads to a decrease in the release of several peptides, including CGRP and substance P. 1. direct vasoconstriction, returning the blood vessel to its orignal diameter 2. by acting on neuronal receptors, it inhibits the release of additional vasodilating and pain-transmitting substances autacoid function) 3. direct antinociceptive action, preventing the firing of pain neurones directly

sumatriptan

tablets, solution for injection, and nasal inhalers. Sumatriptan was the first triptan available (in 1991),

migraine

rizatriptan naratriptan zolmitriptan almotriptan eletriptan frovatriptan

5-HT4-receptor agonists

Large doses of sumatriptan (200 mg/day) can cause sulfhemoglobinemia, a rare condition in which the blood changes from red to greenish-black, due to the integration of sulfur into the hemoglobin molecule[4]. If sumatriptan is discontinued, the condition reverses within a few weeks.

alosetron "diarrhea"-----tegaserod "constipation"

tegaserod
partial agonists

releasing of acetylcholine, increase GI motility and tone direct actions on the GI smooth muscle

constipation-prodorminant IBS

ergot alkaloids

CNS active drugs sanorexiants dexfenfluramine anxiolytics buspirone SSRIs fluxetine

depression block the ion-channel coupled 5-HT3-receptor, thus inhibiting the ability of serotonin to cause nause and or emesis both locally at the GI tract and centrally in the area postrema. both agonistic and antagonistic actibity at adrenergic, prevent postpartum hemorrhaging / dopaminergic, and serotonergic receptors

Serotonin antagonists
ergot alkaloids

ergonovine

dihydroergotamine

methysergide

bromocriptine

an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors and Parkinson's disease. Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly may all be caused by pituitary problems, such as hyperprolactinaemia, and therefore, these problems may be treated by this drug. Common side effects: associated with causing or worsening psychotic symptoms; breast engorgement ; syncope

Benzocycloheptane

The main medical use for pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid and amitryptyline. Pizotifen is a serotonin antagonist acting mainly at Side effects include sedation, dry mouth, drowsiness, increased appetite and weight gain. Occasionally it the 5-HT1, 5-HT2A and 5HT2C receptors. It also has may cause nausea or dizziness. In rare cases, anxiety, aggression and depression may also occur some activity as an antihistamine.

pizotifen

5-HT3-receptor antagonists

-setron

Antagonism of the 5-HT 3 receptor prevents stimulation of the chemoreceptor trigger zone and triggering of the vomiting center.

Prevention of nausea and vomiting, especially that associated with chemotherapy, surgical procedures, and radiotherapy

Well tolerated with few side effects. Headache, especially at higher doses, is the most common adverse effect. Others include dizziness, fatigue, constipation, GI upset, and elevations in hepatic transaminases.

ondansetron Few side effects. Very effective in combination with corticosteroids. 5-HT 3 antagonists are CYP450 substrates. Enzyme inducers ( rifampin, phenytoin) may increase 5-HT 3 antagonist clearance, and enzyme inhibitors ( cimetidine, allopurinol) may increase toxicity,

benzimidazoles granisetron

Very effective in combination with corticosteroids. dolasetron palonosetron alosetron

Slowing GI motility

inhibitors ( cimetidine, allopurinol) may increase toxicity,

diarrhea-prodorminant IBS
alosetron "diarrhea"-----tegaserod "constipation"

in pt. with diarrhea-associated IBS cause ischemic colitis and severe constipation(life-threatening complications)

Antiemetics

The major antiemetics serotonin antagonists, dopamine antagonists, anticholinergics, and antihistamines target the specific neurotransmitters through receptor antagonism.

5-HT3 receptor antagonists

block serotonin receptors in the central nervous system and gastrointestinal tract. As such, they can be used to treat post-operative and cytotoxic drug nausea & vomiting.

Dolasetron Granisetron Ondansetron Tropisetron Palonosetron

Dopamine antagonists

chlorperazine; azine; peridol/done; pramide

Domperidone Droperidol haloperidol chlorpromazine promethazine prochlorperazine. Metoclopramide Alizapride

(H1 histamine receptor antagonists), effective in many conditions, including motion sickness and severe morning sickness in pregnancy. Antihistamines (Reglan) by inhibiting stimulation of the chemoreceptor trigger zone; also enhances the rate of GI emptying and increases GI motility as a pro-kinetic, and is thus useful in gastrointestinal disease; however, it is poor in cytotoxic or post-op vomiting. So it can reduce the absorption of a number of drugs. Some of these drugs are limited in their usefullness by their extra-pyramidal and sedative side-effects.

Cyclizine Diphenhydramine Dimenhydrinate Meclizine Promethazine Hydroxyzine Cannabinoids used in patients with cachexia, cytotoxic nausea, and vomiting, or who are unresponsive to other agents.
(Pentazine, Phenergan, Promacot) (Gravol)

Cannabis (Marijuana). Most patients prefer smoked or vaporized cannabis over pharmaceutical versions because they do not contain all 66 cannabinoids that are in cannabis, many of which have medicinal applications. Medical marijuana is also much less expensive than related pharmaceuticals. CBD is a main cannabinoid not in Marinol or Cesamet. Dronabinol (Marinol). Ninety percent of sales are for cancer and AIDS patients. The other 10% of its sales thought to be for pain, Multiple Sclerosis and also for Alzheimer's disease. Dizziness, drowsiness, euphoria, ataxia and hallucination are reported side effects of the drug.

Nabilone (Cesamet). Put back on the market in late 2006. In the US, it is A Schedule II substance unlike Marinol which is Schedule III and cannabis which is Schedule I. Sativex is an oral spray containing THC and CBD. It is currently legal in Canada and a few countries in Europe but not in the U.S. Benzodiazepines Midazolam given at the onset of anesthesia has been shown in recent trials to be as effective as ondansetron, a 5HT3 antagonist in the prevention of post-operative nausea and vomiting. Further studies need to be undertaken. Lorazepam said to be very good as an adjunct treatment for nausea along with first line medications such as Compazine or Zofran.
Anticholinergics

scopolamine
Steroids

(also known as Hyoscine ) transdermal form

Dexamethasone given in low dose at the onset of a general anaesthetic for surgery is an effective anti-emetic.
The specific mechanism of action is not fully understood. NK1 receptor antagonist

Aprepitant Casopitant Investigational NK1 receptor antagonist

Other Trimethobenzamide

chemotherapy-induced emesis

thought to work on the CTZ (chemoreceptor trigger zones). It may mask symptoms and prolong the diagnosis of Reye's syndrome (nausea and vomiting) in children;

Ginger Emetrol also claimed to be an effective antiemetic. Propofol given intravenously. It has been used in an acute care setting in hospital as a rescue therapy for emesis. Peppermint claimed to help nausea or stomach pain when added into a tea or peppermint candies. Muscimol purported as such [1] Ajwain purported to be antiemetic. Also known as Bishop's weed, it is a popular spice in India, Ethiopia and Eritrea.

Antacids: aluminum hydroxide/magnesium hydroxide combinations; Antihistamines: dimenhydrinate, diphenhydramine, meclizine Nausea in adults Anticholinergics: scopolamine;
Therapeutic choices in Dopamine antagonists----Butyrophenones: haloperidol, droperidol Canada

Benzamides: domperidone, metoclopramide (also dopamine antagonists); Phenothiazines: chlorpromazine, perphenazine, prochlorperzaine, promethazine (--azines); Serotonin Antagonists: ondansetron;

Anticholinergic agents

a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. Antimuscarinic agents operate on the muscarinic acetylcholine receptors (The majority of anticholinergic drugs); Antinicotinic agents operate on the nicotinic acetylcholine receptors. An example of an anticholinergic is dicyclomine. Frequently, they reduce the effects mediated by acetylcholine on acetylcholine receptors in neurons through competitive inhibition. Therefore, their effects are reversible. Anticholinergics are classified according to the receptors that are affected:

a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. Antimuscarinic agents operate on the muscarinic acetylcholine receptors (The majority of anticholinergic drugs); Antinicotinic agents operate on the nicotinic acetylcholine receptors. An example of an anticholinergic is dicyclomine. Frequently, they reduce the effects mediated by acetylcholine on acetylcholine receptors in neurons through competitive inhibition. Therefore, their effects are reversible. Anticholinergics are classified according to the receptors that are affected:

Neuromuscular-blocking drug block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by acting Nicotinic blocking agents presynaptically via the inhibition of acetylcholine (ACh) synthesis or release, or by acting postsynaptically at the acetylcholine receptor. While there are drugs that act presynaptically (such as botulin toxin and tetrodotoxin), the clinically-relevant drugs work postsynaptically.
non-depolarizing All of these agents act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. competitive _curium / curonium / curarine/ Gallamine

d-tubocurarine Rapacuronium Mivacurium Atracurium Doxacurium Cisatracurium Vecuronium Rocuronium Pancuronium Tubocurarine Gallamine Pipecuronium

(Raplon) (Mivacron) (Tracrium) (Nuromax) (Nimbex) (Norcuron) (Zemuron) (Pavulon) (Jexin) (Flaxedil)

The main difference is in the reversal of these two types of neuromuscular-blocking drugs. Non-depolarizing blockers are reversed by acetylcholinesterase inhibitor drugs since they are competitive antagonists at the ACh receptor so can be reversed by increases in ACh. The depolarizing blockers already have ACh-like actions, so these agents will have prolonged effect under the influence of acetylcholinesterase inhibitors. Also, post-operative pain is associated with depolarizing blockers.

The tetanic fade is the failure of muscles to maintain a fused tetany at sufficiently-high frequencies of electrical stimulation. Non-depolarizing blockers will have this effect on patients. But depolarizing blockers will not.

Depolarizing succinylcholine

Suxamethonium chloride a medication widely used in emergency medicine and anesthesia to induce muscle relaxation, usually to make endotracheal intubation possible. Suxamethonium acts as a depolarizing neuromuscular blocker. It imitates the action of acetylcholine at the neuromuscular junction, acting on muscle type nicotinic receptors, but it is not degraded by acetylcholinesterase but by butyrylcholinesterase, a plasma cholinesterase. This hydrolysis by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase. May cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration; Cardiovascular effects; autonomic symptoms; may facilitate histamine release (hypotension, flushing, and tachycardia). Suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers. (risk for life-threatening complications, such as hyperkalemia and cardiac arrhythmias).

Side reaction:

Acetylcholinesterase inhibitors Ach-esterase-I

a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter acetylcholine.

Are used medicinally: To treat myasthenia gravis. In myasthenia gravis, they are used to increase neuromuscular transmission. To treat Alzheimer's disease To treat Lewy Body Dementia As an antidote to anticholinergic poisoning Occur naturally as venoms and poisons ; Are used as weapons in the form of nerve agents

Reversible inhibitor

Carbamates

Physostigmine

Physostigmine is used to treat myasthenia gravis, glaucoma and delayed gastric emptying. Because it is a tertiary amine, it can cross the blood-brain barrier and so it is also used to treat the CNS effects of atropine, scopolamine and other anticholinergic drug overdoses.

depression, overdose can cause a cholinergic syndrome

Neostigmine

It is used to improve muscle tone in people with myasthenia gravis and routinely, in anesthesia at the end of an operation, to reverse the effects of non-depolarizing muscle relaxants such as rocuronium and vecuronium. It can also be used for urinary retention resulting from general anaesthesia and to treat curariform drug toxicity. Another indication for use is the Ogilvie syndrome which is a pseudoobstruction of the colon in critically ill patients. Neostigmine will cause slowing of the heart rate (bradycardia), for this reason it is usually given along with a parasympatholytic drug such as atropine or glycopyrrolate.

Pyridostigmine Ambenonium Demarcarium Rivastigmine Phenanthrene derivatives Galantamine

Both used for treatment of dementia

Cholinergic syndrome Cholinergic too much you will get a SLUDGE (Salivation, Lacrimation, Urination, Defecation , Gastrointestinal upset, Emesis) is a syndrome of pathological effects indicative of massive discharge of the parasympathetic nervous system.

Piperidines Donepezil Tacrine tetrahydroaminoacridine (THA')

Edrophonium

Because its duration of action is only about 20 minutes, edrophonium (by the so-called Tensilon test) is used to differentiate myasthenic crisis from cholinergic crisis.

Irreversible organophosphate Metrifonate

One common cause of SLUDGE is exposure to organophosphorus insecticides, including parathion, malathion, and diazinon. These agents irreversibly phosphorylate acetylcholinesterase, thereby raising acetylcholine levels and causing SLUDGE. SLUD may be treated with Atropine or other anticholinergics. It has been proposed for use in treatment of Alzheimer's disease, but use for that purpose is not currently recommended.

muscle relaxant

Dantrolene

Dantrolene is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor. It is the only specific and effective treatment for malignant hyperthermia, a rare, life-threatening disorder triggered by general anesthesia. It is also used in the management of neuroleptic malignant syndrome, muscle spasticity (e.g. after strokes, in paraplegia, cerebral palsy, or patients with multiple sclerosis), ecstasy intoxication, serotonin syndrome, and 2,4-dinitrophenol poisoning

Parasympathomimetic drug

a drug or poison that acts by stimulating or mimicking the parasympathetic nervous system (PSNS). These chemicals are also called cholinergics because acetylcholine (ACh) is the neurotransmitter used by the PSNS. Chemicals in this family can act either directly by stimulating the nicotinic or muscarinic receptors, or indirectly by inhibiting cholinesterase, promoting acetylcholine release, or other mechanisms. These act by stimulating the nicotinic or muscarinic receptors. Choline esters Acetylcholine (all acetylcholine receptors) Bethanechol (M3 receptors) Carbachol (all muscarinic receptors and some nicotinic receptors) Methacholine (all muscarinic receptors, Chanllenge test for diagnosis of asthma)

Direct-acting

Plant alkaloids Nicotine Muscarine Pilocarpine (M3 receptors)

Indirect-acting

Indirect acting parasympathomimetic drugs may be either reversible cholinesterase inhibitors, irreversible cholinesterase inhibitors or drugs that promote ACh release or antiadrenergics. The latter inhibits the antagonistic system, the sympathetic nervous system. Donepezil Edrophonium Reversible cholinesterase Neostigmine Physostigmine inhibitors Pyridostigmine Rivastigmine Tacrine

clonidine (-receptor agonist, 2 > 1, giving negative feedback) propranolol (2 antagonist) Anti-adrenergics atenolol (1 antagonist) prazosin (1 antagonist) methyldopa (2 agonist giving negative feedback) Echothiophate Irreversible cholinesterase Isoflurophate inhibitors Malathion

ACh release promoters

Cisapride Metoclopramide

Donepezil

a centrally acting reversible acetylcholinesterase inhibitor. Its main therapeutic use is in the treatment of Alzheimer's disease where it is used to increase cortical acetylcholine. Its binding to the acetylcholinesterase can be seen at Proteopedia 1eve. It has an oral bioavailability of 100% and easily crosses the blood-brain barrier. Because it has a half life of about 70 hours, it can be taken once a day. Initial dose is 5 mg per day, which can be increased to 10 mg per day after an adjustment period of at least 4 weeks.

Muscarinic agonists

Action on eye, GI tract, urinary bladder; contraction of ciliary m./ detrusor m. / sphincter m. of iris, increased peristalsis, sphincter relaxation; enhances the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.

M1

M1-type muscarinic acetylcholine receptors play a role in cognitive processing. In Alzheimer disease (AD) amyloid formation may decrease the ability of these receptors to transmit their signals leading to decrease cholinergic activity. As these receptors themselves appear relatively unchanged in the disease process, they have become a potential therapeutic target when trying to improve cognitive function in patients with AD. In the form of pilocarpine muscarinic receptor agonists have been used medically for a long time. M3 agonists: Aceclidine, for glaucoma. Arecoline, an alkaloid present in the Betel nut. Pilocarpine is a drug that acts as a muscarinic receptor agonist that is used to treat glaucoma. Cevimeline (AF102B) (Evoxac) is a muscarinic agonist that is an Food and Drug Administration (FDA)-approved drug and used for the management of dry mouth in Sjgren's syndrome.

M3

pilocarpine

Pilocarpine has been used in the treatment of chronic open-angle and acute angle-closure glaucoma; dry mouth (xerostomia), Pilocarpine stimulates the secretion of large amounts of saliva and sweat. Side effects: excessive sweating, excessive salivation, bronchospasm, increased bronchial mucus secretion, bradycardia, hypotension, browache (when used as eye drops) and diarrhea. It can also result in miosis when used chronically as an eye drop.

Muscarinic antagonist

an agent that reduces the activity of the muscarinic acetylcholine receptor. Most of them are synthetic, but scopolamine and atropine are belladonna alkaloids, and are naturally extracted. contraindicated in:

Atropine (D/LHyoscyamine)

in anaesthesia; non-selective antagonism, CNS stimulation; It causes tachycardia by blocking vagal effects on the the action of Hyoscyamine twice as sinoatrial; potent as atropine

urinary retention tachycardia, but bradycardia (low dose); blurred vision xerostomia diminished sweating,

Side effects

ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, and possibly, notably in the elderly, extreme confusion, extreme dissociative hallucinations, and excitation. These latter effects are because atropine is able to cross the bloodbrain barrier. In overdoses, atropine is poisonous. Atropine is sometimes added to other potentially addictive drugs, particularly anti-diarrhea opioid drugs such as diphenoxylate or difenoxin where the secretion-reducing effects of the atropine can also aid the anti-diarrhea effects.

Increases firing of SA node, conduction through AV node, opposes vagus nerve, blocks acetylcholine receptor sites, decreases bronchiole secretions. Generally, atropine lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system. Therefore, it may cause swallowing difficulties and reduced secretions. Antispasmodic in gastrointestinal hypermotility; Antidote for organophosphate poisoning.

Anticholinergic toxidrome: The symptoms include blurred vision, choreoathetosis, coma, decreased bowel sounds, delirium, dry skin, fever, flushing, hallucinations, ileus, memory loss, mydriasis (dilated pupils), myoclonus, psychosis, seizures, and urinary retention. Complications include hypertension, hyperthermia, and tachycardia. Substances that may cause this toxidrome include antihistamines, atropine, benztropine, datura, tricyclic antidepressants, and scopolamine. Due to the characteristic appearance and behavior of patients with this toxidrome, they are colloquially described as "Hot as a Hare, Dry as a Bone, Red as a Beet, Mad as a Hatter, Blind as a Bat".

Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, and possibly, notably in the elderly, extreme confusion, extreme dissociative hallucinations, and excitation. Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause paradoxical bradycardia when given at very low doses, presumably as a result of central action in the CNS. Ophthalmic use: Topical atropine, used as a cycloplegic, to temporarily paralyze the accommodation reflex; and as a mydriatic to dilate the pupils. Resuscitation: Injections, used in the treatment of bradycardia, asystole and pulseless electrical activity (PEA) in cardiac arrest.

Ipratropium

in asthma and bronchitis non-selective antagonism, without any mucociliary excretion inhibition. allergic or viral rhinitis;

Tiotropium

long-acting, adm. once a day

Chronic obstructive pulmonary diseaseNot for relief of acute bronchospasm

Oxybutynin Tolterodine Flavoxate Solifenacin Darifenacin Scopolamine (L-Hyoscine) Tropicamide

increase bladder capacity and diminish frequency of uninhibited detrusor contractions; First-line

used for urinary incontinence

M3-selective

non-selective antagonism, CNS depression short acting non-selective antagonism, CNS depression

as atropine; motion sickness

as atropine; sedation

produce mydriasis and cycloplegia in may cause ocular hypertension diagnostics

Pirenzepine

M1 receptor-selective antagonist inhibits gastric secretion

in peptic ulcer (not much anymore)

(fewer than non-selective ones)

Diphenhydramine

used for extrapyramidal symptoms from typical antipsychotic medications motion sickness

Dimenhydrinate Dicyclomine Cyclopentolate Atropine methonitrate Trihexyphenidyl Mebeverine short acting non-selective antagonism, CNS depression

produce mydriasis and cycloplegia in may cause ocular hypertension diagnostics

antispasmodic in gastrointestinal non-selective antagonism, blocks transmission in ganglia hypermotility

Propantheline bromide

an antimuscarinic agent used for the treatment of excessive sweating (hyperhidrosis), cramps or spasms of the stomach, intestines (gut) or bladder, and involuntary urination (enuresis). It can also be used to control the symptoms of irritable bowel syndrome and similar conditions. Side effects include tachycardia, constipation, hypersensitivity to light, dry mouth, and urinary retention.

Benzatropine Ethopropazine

Reduces the effects of the relative central cholinergic Anti-Parkinsonian Drug excess that occurs as a result of dopamine deficiency.
Profenamine hydrochloride (INN, also known as ethopropazine) is a medication derived from phenothiazine. It is primarily used as an antidyskinetic to treat parkinsonism. It is sold under the trade names Parsidol in the United States, Parsidan in Canada Used for : Drug-induced parkinsonism, akathisia and acute dystonia; Parkinson disease; and Idiopathic or secondary dystonia.

Procyclidine

Prostaglandins PGs

PGA/ PGB /PGE .

synthesized from arachidonic acid by enzyme cyclooxygenase (COX) COX 1: daily synthesis prostaglandins COX 2: inflammatory response COX 3: thermoregulatory conrol and pain perception
impotence owing to erectile dysfunction

PGE1 analogs Aplrostadil

Misoprostol

a synthetic prostaglandin E1 (PGE1) analogue.

It can be used to prevent of NSAID-induced GI ulcers or to induce labor and as an abortifacient.

E1 - Alprostadil
PGE2 analogs Prostin E2 abortifacient effects to induce cerbical-ripening in pregnancy

Prepidil Cervidil
PGF2 analogs _ oprost

Carboprost Latanoprost Tracoprost bimatoprost unoprostone

PGI analog epoprostenol

abortifacient effects

high incidence of cardiovascular collapse caused its removal from US market

used topically to lower intraocular pressure in glaucoma

prostacyclin

emergent pulmonary hypertension

Leuktrienes

Leukotrienes are synthesized in the cell from arachidonic acid by 5-lipoxygenase. slow-reacting substance of anaphylaxis; powerful effect in bronchoconstriction, h vascular permeability and mucus secretion may be responsible for inflammatory response. Leukotrienes assist in the pathophysiology of asthma, causing or potentiating the following symptoms: airflow obstruction / increased secretion of mucus / mucosal accumulation / bronchoconstriction infiltration of inflammatory cells in the airway wall Platelet-activating factor(PAF), also known as an important mediator of bronchoconstriction.

leukotriene antagonists
lipoxygenase inhibitors

limited to treat ashma

Inhibit the SRSA (slow release substance of anaphylaxis) that is responsible for bronchospasm

block 5-lipoxygenase, inhibiting the synthetic pathway of leukotriene metabolism,

zileuton

used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies.[1] It is usually administered orally. Because of its method of operation, it is not useful for the treatment of acute asthma attacks. It does not interact with other allergy medications such as theophylline. Side effects include gastrointestinal disturbances, hypersensitivity reactions, sleep disorders and increased bleeding tendency, aside from many other generic adverse reactions.

block the actions of cysteinyl leukotrienes at the CysLT1 receptor on target cells such as bronchial smooth muscle. leukotriene antagonists _lukast These modifiers have been shown to improve asthma symptoms, reduce asthma exacerbations and limit markers of inflammation such as eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid. This demonstrates that they have anti-inflammatory properties.

zafirlukast

Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages. It is used for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. The reduction of the oral steroid dose, in some patients on ACCOLATE therapy, has been followed in rare cases by the occurrence of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes presenting as Churg Strauss Syndrome, a systemic eosinophilic vasculitis.

montelukast

Montelukast (Singulair), taken once daily, and Zyflo, taken four times per day.

Nonnarcotic analgesic-antipyretics weak acids, excretion influenced by urinary pH salicylates inhibit the enzyme cycloozygenase which is responsible for the formation of precursors of PGs and thromboxanes from arachidonic acid, and thus inhibit local prostaglandin synthesis. Low-intensity integumental pain, antipyretic, and anti-inflammatory

The action of aspirin results from both the acetyl and salicylate protions of the drug,

Used as analgesics for musculoskeletal pain, headache, neuralgias, myalgias, and spasmodic dysmenorrhea; Side effects: gastrointestinal bleeding; tinnitus (large doses), Reye's syndrome(in children), Overdose: potentially serious consequences, may cause significant morbidity and death. Mild intoxication: nausea and vomiting, abdominal pain, lethargy, and dizziness. More severe : hyperthermia, tachypnea, respiratory alkalosis, metabolic acidosis, hyperkalemia, hypoglycemia, hallucinations, confusion, seizure, cerebral edema, and coma. The most common cause of death following an aspirin overdose is cardiopulmonary arrest usually due to pulmonary edema.

aspirin

The only irreversibly inhibits cyclooxygenase by covalent acetylation of the enzyme; It can also inhibits COX in platelets in low doses---prevents the formation of thromboxane A2 (aggregating agent) -----indicated for prophylaxis of myocardial infarction

diflunisal

A loading dose is usually used. Primarily used to treat symptoms of arthritis.

methyl salicylate salsalate sodium thiosalicylate choline salicylate

Hypersensitivity: frequently in pts with nasal polyps; cross-reactivity with other NSAIDs occurs in >90% of people. With acetaminophen only 5%; Contraindication in pts with bleeding disorders or peptic ulcers, not for children or teenagers who have a viral illness: Reye syndrome Extreme caution for pregnancy: chronic high dose may potential bleeding, prolonging or complicating delivery.

D-D: salicylates potentiate the effect of anticoagulants and thrombolytic agents; potentiate the effect of hypoglycemics at high doses; potentiate the adverse GI reaction resulting from chronic alcohol or NSAIDs use; Competitively inhibit the metabolism of zidovudine, resulting their toxicity; Mesalazine (INN, BAN), or 5-aminosalicylic acid (5-ASA); Caffeine may enhance its analgesic effect.
It is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects.

mesalamine

sulfasalazine

A sulfa drug, a derivative of Mesalazine (5-ASA), used primarily as an anti-inflammatory agent in the treatment of IBD (ulcerative colitis and Crohn's disease) as well as for rheumatoid arthritis. It may be abbeviated SSZ. It is not a pain killer. It does this via reducing the synthesis of inflammatory mediators (eicosanoids and inflammatory cytokines). However, unlike glucocorticoids, sulfasalazine has no immunosuppressant action.

olsalazine

Olsalazine sodium (Dipentum) is a salicylate compound that is converted to 5-ASA in the colon. This exerts an anti-inflammatory effect useful in treating ulcerative colitis.

5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative colitis. Mesalazine is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects.

Mesalazine

As a derivative of salicylic acid, 5-ASA is also an antioxidant that traps free radicals, which are potentially damaging by-products of metabolism. 5-ASA is considered the active moiety of sulfasalazine, which is metabolized to it. It is formulated for oral ingestion as tablets or granules, and for rectal administration as rectal suppository, suspension or enemas. Commonly side effects: Diarrhea / Nausea / Cramping / Flatulence

p-aminophenol derivatives

acetaminophen

analgesic and antipyretic activity inhibit central prostaglandin synthesis through selectivity First-line therapy for osteroarthritis of for COX 3 / little or without activity on COX 1 or 2; the knee and hip No anti-inflammatory activity; safely in children with caricella or an and do not affect platelet function. influenza-type viral infection

relatively selective for COX3, no antiplatelet activity, lack of GI ulcerative effects, but profound hepatoxicity; Potential risk for chronic administration in pts with active alcoholism, hepatic disease, or viral hepatitis; may competitively inhibit the metabolism of zidovudine, increasing its toxicity.

pyrazolone derivatives

inhibit prostaglandin synthesis and sabilzie lysosomal membranes acute rheumatoid arthritic and acute gout when other therapeutic measures have failed. control hyperuricemia in the treatment of intermitent and chronic gout

analgesic, antipyretic, and anti-inflammatory effects, and also uricosuric activity

phenylbutazone oxyphenbutazone sulfinpyrazone

rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, secondary treatments in gouty arthritis

NSAIDs

anti-inflammatory effects by inhibiting the cyclooxygenase enzyme system and thus reduce local prostaglandin Increase in the risk of myocardial infarction; synthesis; analgesic and antipyretic effects; GI effects: Most NSAIDs are chiral mild uricosuric activity ; weak inhibitory activity for lipoxygenase, COX 2, leukocyte Nausea/Vomiting Dyspepsia Gastric ulceration/bleeding Diarrhea molecules; proliferation and migration and to stablize lysosomal NSAIDs never to be used in individuals with Inflammatory Bowel Disease (e.g., Crohn's Disease or membranes

Side reactions:

Non-steroid antiinflammatry drugs

Salicylates

Ulcerative Colitis)due to its tendency to cause gastric bleeding and form ulceration in the gastric lining. Pain relievers such as Tylenol (containing acetaminophen) or drugs containing codeine (which slows down bowel activity) are safer medications than ibuprofen for pain relief in IBD. Renal effects: Salt and fluid retention Hypertension These agents may also cause renal impairment, especially in combination with other nephrotoxic agents. Renal failure is especially a risk if the patient is also concomitantly taking an ACE inhibitor and a diuretic the so-called "triple whammy" effect. Photosensitivity: decarboxylation of the carboxylic acid moiety; ibuprofen is an exception Contrindication: concurrent peptic ulcer, or history of ulcer disease; allergy to indometacin, or other NSAIDs patients with nasal polyps reacting with an angioedema to other NSAIDs children under 2 y (with the exception of neonates with patent ductus arteriosus) severe pre-existing renal and liver damage caution: pre-existing bone marrow damage; bleeding tendencies of unknown origin (indometacin inhibits platelet aggregation); Parkinson's disease, epilepsy, psychotic disorders (indometacin may worsen these conditions); concurrent with potassium sparing diuretics.

Acetylsalicylic acid (Aspirin) Amoxiprin Benorylate/Benorilate Choline magnesium salicylate Diflunisal Ethenzamide Faislamine Methyl salicylate Magnesium salicylate Salicyl salicylate Salicylamide
Arylalkanoic acids

_fenac, _metacin Aceclofenac Acemethacin Alclofenac

Bromfenac Etodolac Nabumetone Oxametacin Proglumetacin Tolmetin

The name is derived from its chemical name: 2-(2,6-dichloranilino) phenylacetic acid; Diclofenac is used for musculoskeletal complaints, especially arthritis (rheumatoid arthritis, osteoarthritis, spondylarthritis, ankylosing spondylitis), gout attacks, and pain management in case of kidney stones and gallstones. Also used for acute migraines, red eye;mild to moderate post-operative or post-traumatic pain, such as postoperative cataract (particularly when inflammation is also present) and menstrual pain (dysmenorrhea).

Diclofenac

Indometacin

or indomethacin(USAN), Commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, It can be used for arthiritis (RA, OA, juvenile-, psoriatic-); gout, dysmenorrhea, headache in adults, orthostatic hypotension, tendinitis, nephrogenic diabetes insipidus, delay premature labor, sunburn, Indometacin also reduces plasma renin activity and aldosterone levels, and increases sodium and potassium retention, and enhances the effects of vasopressin. Together these may lead to: edema, hyperkalemia, hypernatremia, hypertension. Also hserum creatinine and more serious renal damage such as acute renal failure, chronic nephritis and nephrotic syndrome.

Sulindac

useful in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAID's except for drugs of the COX-2 inhibitor class.

2-Arylpropionic acids (profens) propionic acid derivatives

Ibuprofen, Ketoprofen, and Naproxen are the only NASAIDs available in OTC

Ibuprofen

It is used for relief of symptoms of arthritis, primary dysmenorrhea, fever, and as an analgesic, especially where there is an inflammatory component. Ibuprofen is known to have an antiplatelet effect, though it is relatively mild and short-lived when compared with that of aspirin. Ibuprofen is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.

Alminoprofen Benoxaprofen (withdrawn from the market) Carprofen Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuproxam Indoprofen Ketoprofen
(Actron, has been withdrawn from the market.)

Ketorolac

in the family of heterocyclic acetic acid derivatives; used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. Indicated for short-term management of pain. Can be given by IV, IM or oral route. It may reversibly inhibit the aggregation of platelets. Cefotetan, Ceforperazone, Moxalactam, Picamycin, Valproic acid may also inhibit the aggregation of platelets, concurrent use with ketorolac may increase the risk of bleeding; Gold-compound, methotrexate and Probenecid may increase the risk of nephrotoxicity. IV injection solution should avoid mixing with: morphine, meperidine, promethazine and hydroxyzine; precipitating may occur.

Loxoprofen Naproxen a non-narcotic, non-steroidal anti-inflammatory drug (NSAID), used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis. Chemically, it is a propionic acid derivative. It is available in 600 mg tablets. Normal adult dosage is 1200 mg daily, not to exceed 1800 mg per day. Safety and efficacy has been established in children over 6 years with juvenile rheumatoid arthritis only, and there is an increased risk of adverse reactions in the elderly population.

Oxaprozin

Pirprofen Suprofen Tiaprofenic acid

N-Arylanthranilic acids fenamic acids Mefenamic acid Flufenamic acid Meclofenamic acid Tolfenamic acid

Pyrazolidine derivatives Phenylbutazone Ampyrone Azapropazone Clofezone Kebuzone Metamizole Mofebutazone Oxyphenbutazone Phenazone Sulfinpyrazone Oxicams _oxicam

_azone

Piroxicam Droxicam Lornoxicam Meloxicam Tenoxicam

COX-2 inhibitors

used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; and act as an analgesic, especially where there is an inflammatory component. It is manufacturerd by Pfizer under the tradename Feldene

COX 2 inhibitors do not appear to cause as great an incidence of GI ulceration or antiplatelet effects as the nonselective NSAIDs. Celecoxib
FDA alert

But those drugs got alert or were withdrawn from the market due to an increased risk of myocardial infarction and stroke. May cause serious skin reactions

Etoricoxib Lumiracoxib Parecoxib Rofecoxib Valdecoxib

Sulphonanilides

FDA withdrawn TGA cancelled registration FDA withdrawn withdrawn from market withdrawn from market

Nimesulide (banned by several countries for the potential risk of hepatotoxicity)

Others

Licofelone Omega-3 fatty acids

Bismuth subsalicylate

used to treat nausea, heartburn, indigestion, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract. Commonly known as pink bismuth, it is the active ingredient in popular medications such as Pepto-Bismol and (modern) Kaopectate. As a derivative of salicylic acid, bismuth salicylate displays anti-inflammatory action and also acts as an antacid.

Agents for gout

Acute: NSAIDs, colchicine (first line) --phenylbutazone /oxyphybutazone (backup)

Chronic: allopurinol, probenecid; sulfinpyrazone (back-up);

Acute: colchicine; phenylbutazone,oxyphenbutazone (back-up)

alkaloid colchicine colchicine inhibits tubulin synthesis --- reducing the inflammatory response and reduces leukocyte lactic acid production

acute gout attacks

rescuces serum urate levels by blocking uric acid production. Comepetitively inhibits the enzyme xanthine oxidase;
isopurines allopurinol

Rash; hypersensitivity syndrome : fever, skin rash, eosinophilia, hepatitis, worsenend rectal function and Stevens-Johnson syndrome (SJS), and Toxic Epidermal Necrolysis Syndrome prevent the development or prograssion (TENS) . of chronic tophaceous gous. Decrease protrombin time
Sometimes used for alkalinizing the urine

so it will affect the metabolism of 6-mercaptopurine (6-MP) from conversion to uric acid Do not need drink more water to enhance its effect

Allopurinol can cause severe pancytopenia if given with azathioprine or mercaptopurine, due to inhibition of xanthine oxidase which metabolizes these drugs. CYP450 Inhibitors, may interact with theophillin, anticoagulants....

benzoic acid derivatives probenecid

inhibits the proximal tubular reabsorption of uric acid increasing uric acid excretion: The kidney's organic anion transporter (OAT) reclaims uric acid from the urine and returns it to the Side reactions: kidney stone, urinary lithiasis plasma. If probenecid (an organic acid) is administered to a patient, the OAT binds to probenecid instead of to uric acid, preventing the reabsorption of uric acid. As a result, more uric acid leaves the The use of aspirin alongside probenecid is contraindicated due to body in the urine, lowering the uric acid concentration in the plasma. This is an example of the way in aspirin's own tendency to increase uric acid excretion at high which competition between substrates transported across cell membranes has been put to use in plasma concentrations. medicine.

phenylbutazone
acute rheumatoid arthritic and acute gout when other therapeutic measures have failed. oxyphenbutazone

sulfinpyrazone

control hyperuricemia in the treatment of intermitent and chronic gout

probenecid
Uricosuric agents

Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. Generally, this effect is achieved by action on the proximal tubule. Primarily uricosuric drugs include probenecid, benzbromarone and sulfinpyrazone. Secondary: Drugs with other primary uses, that have some uricosuric properties, include guaifenesin, losartan,and fenofibrate. However, by increasing urinary uric acid levels these drugs may contribute to stones (calculi) in the kidneys and urinary system (see Uric acid nephrolithiasis). Thus use of these drugs is contraindicated in persons who already have a high urine concentration of uric acid (hyperuricosuria).

benzbromarone sulfinpyrazone

Antiuricosurics

Diuretics Aspirin

Antiuricosuric drugs raise serum uric acid levels at the expense of urine uric acid levels. These drugs include all diuretics and aspirin. These drugs are useful for treatment of hypouricemia and perhaps also hyperuricosuria but are contraindicated in persons with conditions including hyperuricemia and gout.

Adrenergic agonist

has effects similar to, or the same as, epinephrine (adrenaline). Thus, they are a kind of sympathomimetic agents. The five categories of adrenergic receptors are: 1, 2, 1, 2, and 3, and agonists vary in specificity between these receptors, and may be classified respectively.

Indirect action Tyramine Amphetamine Cocaine Ephedrine Mixed action Ephedrine Pseudoephedrine Norepinephrine

Direct action
Nonselective agonists: Oxymetazoline Xylometazoline Tetrahyrozoline _zoline

1 agonists:
Methoxamine Methylnorepinephrine

stimulates phospholipase C activity. (vasoconstriction and mydriasis; used as vasopressors, nasal decongestants and eye exams). Selected examples are:

Oxymetazoline

a selective alpha-1 agonist and partial alpha-2 agonist topical decongestant, used in the form of Oxymetazoline hydrochloride, Oxymetazoline is generally available as a nasal spray. It causes down-regulation of alpha-2 receptors, and therefore becomes less effective after a few doses. If overused it can cause a "rebound congestion" (rhinitis medicamentosa) where the mucosal surface of the sinuses are damaged due to ischemia, become swollen, and therefore become congested after the drug wears off.

Phenylephrine

2 agonists

inhibits adenylyl cyclase activity. (reduce brainstem vasomotor center-mediated SNS activation; used as antihypertensives, sedatives & treatment of opiate and alcohol withdrawal symptoms). Close-Guan- Men methyldopa (mixed alpha2-adrenergic and imidazoline-I1 receptor agonist) Its antihypertension action works by stimulating 2 receptors in the brain which decreases cardiac output and peripheral vascular resistance, lowering blood pressure.

Clonidine

Also used in some types of neuropathic pain, opioid detoxification, sleep hyperhidrosis, anaesthetic use, and off-label, to counter the side effects of stimulant medications such as methylphenidate or amphetamine. For insomnia, as well as for relief of menopausal symptoms. Used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD), for which it is administered in late afternoon or evening for sleep, and because it sometimes helps moderate ADHD-associated impulsive and oppositional behavior, and may reduce tics. Clonidine can also be used in the treatment of Tourette syndrome.

It is metabolized in the intestines and liver; its metabolite alpha-methylnorepineprine acts in the brain to stimulate alpha-adrenergic receptors and leads to a decrease in total peripheral resistance (TPR) and cardiac output. It is excreted in urine. Side effects: many possible side-effects (usually fewer if the dose is less than 1 g per day):

Methyldopa

Gastro-intestinal disturbances, Dry mouth, Bradycardia, Worsening of angina, Postural hypotension,first dose syncope, palpitations, Sedation, headaches, dizziness, Myalgia (muscle pain), arthralgia (joint pain) or paraesthesia (numbness); Nightmares, mild psychosis, depression; Parkinsonism; Bell's palsy; Abnormal liver functions tests and hepatitis; Pancreatitis; Haemolytic anaemia; Bone marrow suppression leading to thrombocytopenia (low platelets) or leucopenia (low white blood cells); Hypersensitivity reactions: lupus erythematosus-like syndrome, myocarditis (heart muscle inflammation), pericarditis and rashes; Ejaculatory failure, Impotence, decreased libido, gynecomastia (breast enlargement in men), hyperprolactinaemia and amenorrhoea; Note that if used in pregnant women, it may cause a positive Coombs test

Guanfacine

(preference for alpha2A-subtype of adrenoceptor); Do not confued with Guaifenesin

Guanabenz Guanoxabenz Guanethidine Xylazine

(most selective agonist for alpha2-adrenergic as opposed to imidazoline-I1) (metabolite of guanabenz) (periferal alpha2-receptor agonist)

tizanidine

It is a centrally acting -2 adrenergic agonist. It is used as a muscle relaxant and to treat the spasms (chronic spasticity) , cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or central nervous system. It is also prescribed off-label as a sleep aid, seizure inhibitor, and for some symptoms of fibromyalgia; Tizanidine may cause hypotension so caution is advised when it is used in patients who have a history of orthostatic hypotension; Use caution with this drug as it can be very strong even at the 2mg dose. Also use caution when switching from gel cap to tablet form and vice versa.

Other side effects: drug induced liver injury, with hallucinations. Visual hallucinations and delusion, If therapy needs to be discontinued, especially in patients who have been receiving high doses for long periods, the dose should be decreased slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia. Concomitant use of tizanidine and moderate or potent CYP450 1A2 inhibitors is contraindicated. Concomitant use of tizanidine with fluvoxamine, a potent CYP450 1A2 inhibitor in man, resulted in a 33-fold increase in the tizanidine AUC by fluvoxamine

Nonselective agonists

Its primary use is for bradycardia or heart block. By activating 1-receptors on the heart, it induces positive chronotropic, dromotropic, and inotropic effects. It can be used as an inhaled aerosol to treat asthma, although this is currently a rare treatment. Also available in IV and in sublingual pill form for treatment of asthma, chronic bronchitis and emphysema.

Isoproterenol

Used with caution, it can also be used to treat torsades de pointes, in conjunction with overdrive pacing and magnesium. The adverse effects : can produce an elevated heart rate (tachycardia), which predisposes patients to cardiac dysrhythmias. Other side effects include: nervousness, insomnia, restlessness, and headaches Contrindecated in patients with myocardial ischaemia.

1 agonists

stimulates adenylyl cyclase activity; opening of calcium channel. (cardiac stimulants; used to treat cardiogenic shock, acute heart failure, bradyarrhythmias).

Dobutamine

Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primarcy mechanism is direct stimulation of 1 receptors of the sympathetic nervous system. Primary side effects include those commonly seen for 1 active sympathomimetics: hypertension, angina, arrhythmia, and tachycardia.

Xamoterol

2 agonists _ terol (terenol) albuterol Clenbuterol Bitolterol Pirbuterol Fenoterol Formoterol Salmeterol Terbutaline

stimulates adenylyl cyclase activity; closing of calcium channel (smooth muscle relaxants; used to treat asthma and COPD). salbutamol: Ipratropium/albuterol Most side effects of beta-2 agonists result from their concurrent beta-1 activity, and include hin heart rate, h rise in systolic pressure, hdiastolic pressure, chest pain secondary to MI, and arrhythmia.
terol------ ---Asthma/COPD

May also cause fluid retention secondary to decrease in water clearance, which when added to the tachycardia and increased myocardial work, may result in cardiac failure. In addition, they increase gluconeogenesis in the liver and muscle resulting in hyperglycemia, which increases insulin requirements in diabetic patients.

Metaproterenol

Orciprenaline (INN)

The passage of beta-agonists through the placenta does occur and may be responsible for fetal tachycardia, as well as hypoglycemia or hyperglycemia at birth.

Cardiac glycosides and positive inotropes

SA node (sinoatrial node): the pacemaker of the heart. It generates nerve impulses that spread to the atrioventricular node (AV node), where the impulses are amplified and spead to other regions of the heart by nerves called Purkinje fibers.

Digitoxin
Glycosides

positive inotropic effects: increase myocardial contratility and efficiency, improve systemic circulation, improve renal perfusion, reduce edema

Digoxin

heart failure, atrial fibrillation, negative chronotropic effects: increase vagal tone of atrial flutter, SA node, diminished CNS sympathetic outflow from paroxysmal atrial tachycardia increased carotid sinus baroreceptor sensitivity, systemic arteriolar and venous constriction

early state: GI effects, CNS effects: headache, visual distubances, confusion, delirium, neuralgias , muscle weakness later state: serious cardiac disturbances (premature ventricular contractions, paroxysmal and nonparoxysmal atrial tachycardia, atrioventricular(AV) dissociation or block, ventricular tachycardia, and ventricular fibrillation)

The occurrence of adverse drug reactions is common (narrow therapeutic index) and concentration-dependent ( rare when plasma digoxin concentration is <0.8 g/L). They are also more common in hypokalemia patients, since digoxin normally competes with K+ ions for the same binding site on the Na+/K+ ATPase pump. Common adverse effects: loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos ----xanthopsia), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression, as well as a higher acute sense of sensual activities. Less frequent adverse effects: acute psychosis, delirium, amnesia, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, heart block but when systematically sought, the evidence for this is equivocal. Electrocardiogram (ECG) changes: ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of digoxin toxicity. Additionally, increased intracellular Ca2+ may cause a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation.

h digoxin levels: amidarone, quinidine, verapamil, propafenone, eryghromycin, clarithromycin, tetracycline, itraconazone, cyclosporine, ritonavir; h digoxin levels: antacids, cholestyramine, colestipol, sulfasalazine, neomycin, rifampin, St, John's wort; Beta-blockers, amiodarone, verapamil, diltiazem h risk of bradycardia Ouabain g-strophanthin, a poisonous cardiac glycoside.

Dipyridine derivatives Side effects: Thrombocytopenia, hepatotoxicity, arrhythmia, nausea, & vomiting; amrinone As type 3 pyridine phosphodiesterase inhibitor, acts by inhibiting the breakdown of both cAMP and cGMP; Precautions: May increase myocardial ischemia. Blood pressure, Classified as vasodilators; the positive inotropic pulse, and EKG should be constantly monitored. only for short-term treatment of CHF Amrinone should only be diluted with normal saline; no dextrose action like Digoxin, known as inodilators solutions should be used. positive inotropic effects:vasodilation and fall in vascular resistance, increased force of cardiac Furosemide should not be administered into an IV line delivering

action like Digoxin, known as inodilators milrinone positive inotropic effects:vasodilation and fall in vascular resistance, increased force of cardiac contraction, increased velocity of cardiac relaxtion,

only for short-term treatment of CHF Amrinone should only be diluted with normal saline; no dextrose solutions should be used. Furosemide should not be administered into an IV line delivering Amrinone. Contraindicated in pts with history of hypersensitivity to the drug;

inamrinone
ACE inhibitors

For myocardial ischemia

Angina pectoris, commonly known as angina, is severe chest pain due to ischemia (a lack of blood and hence oxygen supply) of the heart muscle, generally due to obstruction or spasm of the coronary arteries (the heart's blood vessels). Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries

antianginal agents nitrites

directly relax vascular smooth muscle (fast-acting amyl nitrite nitrates dilate epicardial: coronary arteries, consequently decreasing coronary vasospasm.

nitrates

Adverse reactions: Headache, postural hypotension. and syncope, tolerance develops and hypotension; Dizziness, facial flushing, nausea, and tachycardia also occur. Large doses of IV nitroglycerin acute anginal attacks: prophylaxis or will cause Methemoglobinemia long-term management coronary artery disease (CAD). D_D : The concurrent use of sildenafil (used for erectile dysfunction) is contraindicated due to potentiation of hypotensive effects of nitrates. Avoid concurrent use Ergot alkaloids (used for migraine headaches) may cause increased blood pressure and decreased antianginal effects of nitrates.

nitroglycerin

isosorbide

long acting decrease sympathetic-mediated myocardial stimulation. Negative inotropic and negative chronotropic effects reduce myocardial oxygen requirements

-adrenergic blockers

adjunctive prophylaxis of chronic stable angin pectoris in combination with nitrites and nitrates increase survive time in HF and myocardial infarction(MI) chronic stable angina pectoris and variant angina

Worsening of congestive HF, bradycardia and hypotension reduced kidney blood flow and decrease glomerular filtration, bronchospasm Labetalol, pindolol, acebutolol, as partial agonists, contraindicated in angina

propranolol

class I recomm. for HF peripheral arteriles dilate and total peripheral resistance decrases, increase oxygen delivery

calcium antagonists

verapamil nifedipine
Antiplatelet agents

aspirin ticlopidine
peripheral casodilators dipyridamole

platelet aggregation inhibitor

clopidogrel

Antiarrhythmic agents

IA/ III--- hQT; IB--- h QT IA /IC--- hQRS; II / IV--- h PR

fast-channel blockers
class IA

PDQ

block both Na channels and reduce K current; also prolong duration of action potential and increase effective refractory period. prolong repolarization; increase in the QRS interval and the QT interval

PVC (premature ventricular prolong QTc interval contraction), increase risk for torsade de pointes paroxysmal atrial tachycardia, AF, VT

Quinidine

Used in: acute and chronic ventricular and supraventricular arrhythmias,esp. paroxysmal supraventricular tachycardias (PSVTs), PVC, premature atrial contraction (PAC) and ventricular tachycardia;

cinchonism (headache, vertigo, tinnitus) thrombocytopenia GI upset(nausea, vomiting, diarrhea) hypotension and heart failure With a narrow therapeutic index(2-6 g/ml)

h serum levels of digoxin; severe orthostatic hypotension with vasodilators (e.g., nitroglycerin); phenytoin, rifampin, and barbiturates h its activity; D_D Nifedipine reduce its plasma levels; Antacids, sodium bicarbonate, socium acetazolamide h its levels; Produce additive hypoprothrombinemic effects with coumarin anticoagulants

IV Sodium lactate solution may reduce the cardio toxic effects of quinidine; Contraindicated in pts with complete AV block unless a ventricular pacemaker is in place

hypersensitivity reactions are the most severe adverse effects. GI upset (nausea, vomiting, diarrhea); hypotension and heart failure; hemolyticanemia; agranulocytosis; lupus-like syndrome procainamide Procainamide is used more frequently than quinidine May develop positive antinuclear antibody (ANA) titers and complain of rash, arthralgia , and because it can be adm. IV and in sustained-release arthritis, especially long-term use. oral preparations. With a narrow therapeutic index (4-10 g/ml) D_D amiodarone and cimetidine may increase its plasma levels. contraindicated in pts with: hypersensitivity to procaine and related drugs, myasthenia gravis, second- or third-degree AV block with no pacemaker, a history of procainamide-induced SLE, prolonged QT syndrome (torsades de pointes)

disopyramide

Used in : alternative for ventricular arrhythmias: PVC, moderate ventricular tachycardia

contraindicated in pts with cardiogenic shock or second- or third-degree AV block with no pacemaker; poorly tolerated due to its anticholinergic effects (urinary retention, dry mouth, blurred vision), Avoided in patients with CHF due to negative inotropic effects.

D_D

Phenytoin may increase its metabolism and recue therapeutoc efficacy.

class IB phen lido to me

Only for ventricular arrhythmias. inhibit Na channels and decrease the action potential duration and effective refractory period. Shorten repolarization

lidocaine

inhibit Na channels and decrease the action potential duration and effective refractory period. Shorten repolarization used for ventricular arrhythmias: esp. Minor side effects of lidocaine are drowsiness,dizziness, Decrease in the QT interval PVC and ventricular tachycardia; paresthesia, and euphoria. More serious side effects indude CN5 and cardiovascular effects. Have minimal effect on the rate of rise of phase 0 lidocaine is also used as a local anesthetic. Tocainide and mexiletine both have a high incidence of GI side effects (nausea and vomiting) and CNS side effects (dizziness, numbness, and paresthesias). Phenytoin may increase cardiodepressant effects of lidocaine; b-blockers may reduce lidocaine metabolism and leading drug-toxicity. Tocainide has a 15% incidence of rash and may cause Lidocaine is mostly cleared by hepatic metabolism, Any condition that impairs liver function or compromises liver blood flow may increase lidocaine levels. Lower infusion rates should be administered in patients with CHF, shock, advanced age, and liver cirrhosis. agranulocytosis. Pulmonary impairment: ~ fibrosis, ~ edema and pneumonia;

tocainide mexiletine

Both mexiletine and tocainide are well absorbed orally. Reduce first-pass liver metabolism

in pts failed in class I agent

contraindicated in pts with : phenytoin for digitalis-induced ventricular and sinus bradycardia or heart block; caustion in pts with supraventricular arrhythmias HF, renal or hepatic impariment, myocardial insufficiency, respiratory depression, or hypotension

phenytoin toxicity increases with concomitant adm. : diazepam, antihistamines, isoniazid, chloramphenicol, cimetidine, salicylates, sulfisoxazole, amiodarone, valproate; Carbamazepine may enhance phenytoin metabolism and reduce its plasma levels.

class IC

Flecainide Propafenone Moricizine

documented life-threatening ventricular arrhythmias

More Proper For Ventricular Arrhythmias

block Na channels; flecainide Strong depression depolarization Large increase in the QRS interval ; propafenone But no effect on repolarization or refractoriness

dizziness and nausea quite proarrhythmic, and additionally, these drugs should not be also used for AF and supraventricular used in patients with underlying heart disease, tachycardias without structural heart disease; Its use should be reserved for patients hypersensitivity reactions, lupus-like syndrome, agranulocytopenia, who have arrhythmias refractory to CNS disturbances, lightheadedness, gastrointestinal upset, a other treatments, metallic taste and bronchospasm. Cautions in pts with hepatic dysfunction, asthma, CHF, or bradycardia. perioral numbness and euphoria It undergoes extensive first-pass metabolism, has a bioavailability of 34-38 percent, and is 95 percent bound to plasma proteins. Moricizine is extensively metabolized and may have pharmacologically active metabolites.

moricizine

reduces fast inward sodium current, decreasing the action potential duration and effective refractory period, and increase the PR, QRS, QTe interval;

class II

b-blockers PEAN

decrease in heart rate and a prolongation in the PR interval (artial depolarization)

Propranolol

-adrenergic blockers, block catecholamine-induced supraventricular arrhythmias; stimulation of cardiac -receptors and depress tachyarrhythmias caused by depolarization of phase 4; catecholamine stimulation; Suppress severe centricular Decrease impulse conduction and lengthening the arrhythmias in prolonged QT refractory period. syndrome; digitalis-induced ventricular Slow the sinus rhythm without significantly changing arrhythmias, the QT or QRS intervals, reducing the heart rate and terminate certain ventricular myocardial oxygen demand. arrhythmias

Contraindicated in pts with: sinus bradycardia, second- or third-degree AV block with no pacemaker, cardiogenic shock; severe HF, or asthma; May lead to marked hypotension, exacerbation of CHF, left ventricular failure or cardiac arrest, hypoglycemia, and the signs of shock.

D_D

severe vasoconstriction may occur with epinephrine co-adm.; Digitalis can cause excessive bradycardia; Calcium-channel blockers( diltiazem, verapamil) and other negative inotropic and chronotropic drugs (disopyramide, quinidine) add to the myocardial depressant effects Morphine may h esmolol plasma levels. supraventricular tachycardias; Contraindicated in pts with sinus bradycardia, severe HF

Esmolol Acebutolol Nadolol

class III

inhibit outward K channels (prolongs action potential duration and repolarization) Amiodarone increase action potential duration by prolonging Sotalol repolarization via blockade of the delayed rectifier K Ibutilide current; no effect on myocardial contractility or Dofetilide conduction time. Bretylium increase in the QT interval

Amiodarone, lidocaine, and procainamide are commonly used conversion in VF (ventricular fibrillation). Of these, amiodarone recommended first.

All class III antiarrhythmics can cause QTc prolongation and increase risk of torsade de pointes

Also blocks Na and Ca channels; blocks beta-adrenergic receptors; impedes atrioventricular (AV) node conduction and slows heart rate amiodarone Used in : Conversion maintenance of AF to NSR; ventricular arrhythmias (~ fibrillation and pulseless ~ tarchycardia) NSR (normal sinus rhythm ) Reduce arrhythmic deaths in pts after an MI;

Hypo- or hyperthryroidism, bradycardia, corneal microdeposits or corneal verticillata, hepatotoxicity, GI upset, tremor, ataxia, pulmonary fibrosis; dermatologk reactions Life-threatening pulmonary toxicity may occur esp in pts receiveing >400 mg/day

D_D of amiodarone: May increase levels of digoxin (two-fold), procainamide, warfarin, quinidine, diltiazem, flecainide; May increase the pharmcological effcts of b-blockers, calcium-channel blockers, and warfarin

sotalol

Sotalol has nonselective beta-blocking activity and also prolongs phase 3 potential, which makes it classified as a type III rather than type II. Great oral absorption (90% to 100%); PO only

Ventricular arrhythmias; maintenance NSR after conversion from AF.

Fatigue, dyspnea, bradycardia, headache. Bronchospasm in patients with asthma or COPD

D_D : cautiously in pts receiving agents with cardiac-depressant properties; avoid with other prolonged-QT interval drugs Contraindicated in patients with renal impairment (CrCI rate of < 40 ml/min) Or prolonged QT interval (> 450 msec). Checked for normal renal function before initiating therapy. Relies on activation of slow inward sodium current to Raptid conversion of AF Arrhythmias (VT,supraventricular tachycardia), AV block; prolong action or atrial flutter (AFI) of recent onset to headache, hypotension, bradycardia potential and effective refractory period NSR IV only Administer in setting of continuous ECG monitoring (to identify acute ventricular arrhythmias) Headache, dizziness, insomnia, rash. nausea, diarrhea, dyspnea, arrhythmias (VT and torsade de pointes) Contraindicated in combination with medications that may increase its level (verapamil, cimetidine, ketoconazole, megestrol, trimethoprim, prochlorperazine). Avoid use with drugs that may prolong QT (cisapride phenothiazines, fluoroquinolones, bepridil. class I or III antiarrhythmic)

ibutilide

sulfonamides drugs

Great oral absorption (90% to 100%); PO only ; dofetilide Used in Conversion of Af/AFI to NSR

bretylium

class IV

Calcium-channel blockers (verapamil, diltiazem only, not the others)

The nondihydropyridine calcium channel blockers, block the slow inward current carried by calcium during phase 2, increase the effective refractory period and depress depolarization of phase 4;

verapamil

verapamil and diltiazem, have efficacy coconmitant adm. b-blockers or disopyramide may precipitate hear rates similar to that of adenosine, but failure; are considered second line, Quinidine may increase the risk of calcium-channel blocker-induced Intravenous Ca-channel blockers hypotension; have a few disadvantages, caution Rifampin may enhance the metabolism of Ca-channel blockers; by depressing the SA and AV nodes, reduced heart should be taken in hypotensive May inhibit theophylline and cyclosporine metabolism and may rate and patients. require reductions in their dosage. an increase in the PR interval.

Contraindicated in patients with: AV block, left ventricular dysfunction, severe hypotention, concomitant with IV b-blockers, atrial fibrillation with an accessory AV pathway; Cautiously in pts with CHF, sick sinus syndrome, MI, and hepatic or renal impairment; pts with slow heart rate or receiving digitalis glycosides diltiazem

others
Bepridil Atropine symtomatic sinus bradycardia and junctional rhythm

Digoxin

Arrhythmias, atrial fibrillation or flutter paroxysmal visual disturbances (blurred vision, yellow or green tinting, vagotonic response, increase AV nodel refractoriness atrial or nodal tachycardia "halos," red-green color blindness), Digoxin (cardiac glycoside) is a positive inotropic GI complaints (abdominal discomfort, nausea, vomiting, anorexia). agent that inhibits the Na+/K+ ATPase pump. and Used to improve cardiac output in causes an increase in intracellular sodium that allows CHF. Drug interactions: D_D the Na+/Ca 2+ exchanger to increase intracellular Amphotericin B or potassium-wasting diuretics (hypokalemia) calcium to increase contractility of the heart. Also used in atrial arrhythmias for rate may contribute to digoxin toxicity; Renally cleared. May undergo enterohepatic control. recycling. ACE-I, amiodarone, bepridil, diltiazem,quinidine, and verapamil Therapeutic plasma range: 0.5 to 2 g/L may increase digoxin levels.

Adenosine

Adverse reactions: Flushing, chest pain, and dyspnea often occur after adenosine administration, but acts at G-protein-coupled adenosine receptors to these discomforts are brief. Similarly, if hypotension occurs, it lasts only a few seconds. increase AV nodel refractoriness; slows the conduction and interrupts the re-entry pathways Warning: may provoke bronchospasm; there.fore. use adenosine with caution in patientswith obstructive through the AV node, restoring dysrhythmia to NSR. lung disease (e.g., emphysema and bronchitis) and avoid use in patients with asthma. Also, may result in brief periods of bradycardia or asystole and should be used cautiously in patients with sinus node Adenosine is only given IV and rapidly taken up by dysfunction. most types of cells and rapidly degraded by deamination or phosphorylation. Drug interactions: Methylxanthines(e.g., theophylline) and dipyridamole are adenosine antagonists.

Antihypertensive agents

Treat hypertensive emergencies: arteriolar and venous casodilator: nitroprusside or bosentan; arteriolar casodilator: diazoxide or hydralazine; Dual / -receptor blockers: labetalol, carvedilol; -receptor blockers: propranolol ganglionic-blocking agent: trimetaphan

Secondary and Drug-induced hypertension: Hyperaldosteronism: steroid or estrogen intake (including oral contraceptives); NSAIDs, nasal decongestants, TCAs, appetite suppressants, cyclosporine, erythropoietin, and MAO inhibitors ; Cushing syndrome: Pheochromocytoma: Primary aldosteronism; Renal artery stenosis;

Vasodilators without the sulfonamide group exhibit no diuretic activity

Used in acute hypertensive crisis; its oral form (Proglycem) is used in the management of hypoglycemia. pts with thiazide sensitivity cross-react to diazoxide; or with impaired cerebral or cardiac funtion; Transient hyperglycemia (caution in pts with diabetes); Hypotension, Potentiating edema (promotes Na / H2O retention) Because diazoxide is rapidly and extensively bound to serum protein, it must be administered by rapid IV injection (bolus). Repeated administration of the drug may cause sodium and water retention and the need for adjuvant diuretic therapy.

diazoxide

K channel activators, produce membrane hyperpolarization; direct actions on arterious but little on venous capacity

Minoxidil is a K-channel agonist. Relaxes arteriolar smooth muscle directly minoxidil Decreaseing peripheral resistance;

reflex activation of the sympathetic nervous system and an increase in heart rate, cardiac output, and renin secretion; Monitoring for fluid accumulation (Na /H2O retention) and sighs of cardiac dcompensation (combind with a sympatholytic agent and a potent diurectic will minimize these effects

Decreases renal vascular resistance while preserving its ability to slow or stop hair loss and promote hair regrowth. It is available over the counter for treatment of androgenic alopecia , among other baldness treatments, but measurable changes disappear renal blood flow within months after discontinuation of treatment.

nitroprusside

often administered intravenously to serves as a source of nitric oxide, a potent peripheral patients with a hypertensive vasodilator that affects both arterioles and venules emergency (acute hypertensive (venules more than arterioles). crisis).

Nitroprusside is contraindicated in patients with renal failure.

Hydralazine

a supplemental in combination with stimulate formation of EDRF(NO) to decrease arterial first-line therapy; resistance, relax both arterioles and veins First-lne for pregnant HPN

Common side effects: Diarrhea, Headache, Loss of appetite,Nausea or vomiting, fluid retention, Compensatory tachycardia (reflex). Pounding heartbeat, Postural hypotension, palpitations; Drug-Induced Lupus Erythematosus

peripheral sympatholytics

()

guanethidine

limiting the releasing of neurotransimitters from adrenergic neurons best avoid unless necessary; contraindicated in pts with a history of depression or peptic in low doses (0.05 mg) combined with ulcer; chlorothiazide

reserpine

depleting intraneuronal catecholamine storage sites

an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic behaviors; but it is rarely used today. Side effects: nasal congestion, nausea, vomiting, weight gain, gastric intolerance and ulceration, stomach cramps and diarrhea. Others: hypotension, bradycardia, worsen asthma, erectile dysfunction. Depression can occur at any dose and may be severe enough to lead to suicide.

Ganglinic-blocking agents

by blocking ganglionic transmission, reduce sympathetic activity, resulting in a hypotensive effect, indicated for hypertensive crisis

Hexamethonium It can act on receptors at pre-ganglionic sites in both the sympathetic and parasympathetic nervous system, which are both regulated (again, only pre-ganglionically) by nicotinic acetylcholine receptors. It acts as a non-depolarizing competitive antagonist Postganglionic sympathetic systems are usually regulated by norepinephrine or adrenaline (adrenergic at the nicotinic acetylcholine receptor, is short-acting, receptors), while parasympathetic systems are still acetylcholine based, but instead rely on muscarinic receptors (some post-ganglionic sympathetic neurons, such as those stimulating sweating, release and is given intravenously. acetylcholine). The organ system and adverse effects : combined sympatholytic (e.g. orthostatic hypotension and sexual dysfunction) parasympatholytic effects (e.g. constipation, urinary retention, glaucoma, blurry vision, decreased lacrymal secretion, dry mouth (xerostomia) effects. Postural hypotension is a common side effect

trimetaphan or trimethaphan

mecamylamine

nonselective -receptor antagonist phenoxybenzamine

phentolamine

orthostatic hypotension, tachycardia, inhibition of ejaculation, relieve vasospasm in Raynaud syndrome and for acute HPN emergencies resulting from miosis, and nasal congestion pheochromocytoma or from intake of MAO inhibitors or sympathomimetics. Mostly used for the control of hypertensive emergencies; also effective in cocaine induced hypertension, where generally avoid beta blockers and where calcium channel blockers are not effective.

1 -receptor antagonist

doxazosin prazosin
orally active and has a minimal effect on blocking postganglionic adrenergic receptors to relax cardiac function due to its alpha-1 both arterioles & veins; receptor selectivity. lower incidence of reflex tachycardia; Second line for HPN No adverse effect on serum lipids and other cardiac also useful in the symtomatic treatment risk factors of HPN (+ benign prostatic hyperplasia)

First-dose phenomenon: occurs within 30-90 min of first dose, similarly with postural hypotension, nausea, dizziness, headache, palpitations, fluid retention, and sweating. Should be limited to a small dose (1mg) and adm. just before bedtime. Others: nasal congestion, diarrhea, weight gain, peripheral edema, dry mouth, urinary urgency, constipation, and priapism( )

lower incidence of reflex tachycardia; No adverse effect on serum lipids and other cardiac risk factors

small dose (1mg) and adm. just before bedtime.

Second line for HPN also useful in the symtomatic treatment edema, dry mouth, urinary urgency, constipation, and priapism( of HPN (+ benign prostatic hyperplasia) )

Others: nasal congestion, diarrhea, weight gain, peripheral

terazosin

related

Tamsulosin

Sepcifically blocks the alpha 1 receptors in the prostate gland. It is indicated for treatment of BPH. The normal therapeutic dose of drug is 0.4 mg per day. It preferably should be taken after meals.

2 -receptor antagonist

Tolazoline

As a vasodilator it is used to treat spasms of peripheral blood vessels (as in acrocyanosis). Also as an antidote to reverse the severe peripheral vasoconstriction which can occur as a result of overdose with certain 5-HT2A agonist drugs

persistent neonatal pulmonary HPN

nonselective adrenoceptor antagonist (mixed)

carvedilol 1 + 2 + 1 labetalol

indicated in the management of congestive heart failure (CHF), as an adjunct to conventional treatments (ACE inhibitors and diuretics). The use of carvedilol has been shown to provide additional morbidity and mortality benefits in CHF

a racemic mixture of four isomers. the (S,S)- and (R,S)- forms are inactive. the (S,R)-isomer, is a powerful 1 blocker. the (R,R)-isomer, is a mixed nonselective blocker and selective 2 agonist. Used for HPN.

 -blockers

The most important adverse reactions are seen in asthmatics and COPD. In asthmatics, beta-blockers may lead to constriction of Beta-blockers competitively antagonize betathe airways via smooth muscle contraction. Although 1-selective receptors, leading to decreased calcium influx into Also used for controlling ventricular agents may have less of an effect, they should still be used myocardial cells, which in turn leads to both rate in AF, post-MI, CHF, angina, and cautiously. decreased heart rate (chronotropic effect) and hyperthyroidism. cardiac contractility (inotropic effect) The most common adverse effects are fatigue, bradycardia, The nonselective beta-blockers are hypotension, dizziness, nausea, diarrhea, and exercise intolerance. But relative cardioselectivity will lost as dosages are useful in the treatment of hepatic They are also associated with increased triglycerides and increased. No b-blocker is totally safe in pts with portal hypertension in patients with hyperglycemia. bronchospastic disease (asthma, chronic liver cirrhosis. obstructive pulmonary disease COPD) Other side effects seen are depression, sleep disturbance, and Topical agents are used to lower impotence. intraocular pressures in patients with The more lipophilic agents have more CNS adverse effects, such glaucoma. as drowsiness, nightmares, confusion, and depression.

Primarily as an antihypertensive agent.

Abrupt stoppage leads the risk for a withdrawal syndrome (exacerbated anginal attacks, myocardial infarction, BP rebound) Caution in pts with diabetes (mask hypoglycemic symptoms such as tachycardia), Raynaud phenomenon or peripheral vascular disease, nuerological disorders (esp. the lipid ones which can enter the CNS)

Drug interactions: An interaction at the level of cardiac activity may be seen, particularly with the calciumchannel blocker verapamil. This can lead to bradycardia and severely diminished cardiac output.

Nonselective CNMPPPT -receptor antagonist

propranolol

bradycardia, CHF, prophylaxis of angina pectoris, h airway resistance and serum triglycerides, blocking postganglionic adrenergic receptors. the supraventricular and ventricular most lipophilic agent which can penetrate the CNS, hHDL, cholesterol; blood dyscrasias , depression, dysrhythmias, migraine headaches, and is useful in treating migraines and anxiety, hallucinations, transient hearing loss; sudden withdrawn can be essential tremors, and anxiety. cardiotoxic owing to rebound synpathomimetic activity

carteolol nadolol metipranolol penbutolol pindolol The nonselective beta-blockers also have the disadvantage of masking hypoglycemic symptoms, especially in insulin-dependent diabetics. Contraindicated in patients with CHF, MI, DM congestive heart failure or myocardial infarct), bradycardia, diabetes mellitus.

Bronchospasms Nadolol allowed once-daily dosing (40-120 mg); Pindolol with high intrinsic sympathomimetic activity; Timolol effective in pts after an acute MI to prevent sudden death Blocking 2-receptors also leaves the alpha-mediated vasoconstriction unopposed and, as a result, may worsen Raynaud's disease or peripheral vascular disease. Less lipophilic beta-blockers are excreted more by the kidney and may require dosage adjustments in renal impairment.

timolol sotalol

1 -receptor antagonis AABBCEM

At low doses, metoprolol and atenolol predominantly antagonize the receptors on cardiac tissues with less activity on 2-receptors. Therefore, they are less likely to cause bronchospasm in patients with COPD or asthma. Beta-blockers with 1-antagonist activity may produce more vasodilation activity and have a higher incidence of postural dizziness, lightheadedness, and fatigue. combind with nadolol, possessing intrinsic sympathomimetic activity; hypertension angina pectoris, including unstable angina ventricular and atrial cardiac arrhythmia acute myocardial infarction in high-risk patients HTN, coronary heart disease, arrhythmias, angina (chest pain) and to treat and reduce the risk of heart complications following myocardial infarction (heart attack). also used to treat the symptoms of Graves Disease, until antithyroid medication can take effect. Oral: hypertension Ophthalmic: for glaucoma

acebutolol

atenolol

betaxolol

once-daily dosing 5-20mg

bisoprolol

once-daily dosing 2.5-10mg; no intrinsic sympathomimetic activity

Used for HTN, coronary heart disease, arrhythmias, ischemic heart diseases and treatment of myocardial infarction after the acute event. Patients with compensated congestive heart failure may be treated with Bisoprolol as a comedication (usually together with an ACE inhibitor, a diuretic and a digitalis-glycosid, if indicated).

celiprolol

Esmolol is given by slow intravenous injection. esmolol ultrashot duration of action used for HTN or tachycardia during or after surgical procedures; acute supraventricular tachycardia; used when aortic dissection is suspected.

metoprolol

2 -receptor antagonis butoxamine

It is used primarily in animal and tissue experiments to characterize beta-2 receptor involvement and identify beta-2 receptors.

The property of a drug (usually b-blockers) that produces partial agonist effect at the receptor similar to the cholinergic stimulation of the sympathetic
Intrinsic sympathomimetic activity nervous system. (ISA) Beta-blockers with ISA are beta-blockers that exert a partial agonism at the adrenergic receptor while simultaneously blocking the endogenous catecholamines

from binding to the receptor. Hence, they are less potent than catecholamines and other beta-agonists.

central 2-sympathomimetics

stimulating presynaptic 2-inhibitory receptors within CNS, resulting in a negative sympathetic outflow and lowered peripheral resistance Effective in pts with renal impairment (reduced dose and longer dosing interval); initial paradoxical increase in pressure, abrupt withdrawal syptoms, sedation and dry mouth, depression common adverse effects: orthostatic hypotension, fluid accumulation (in the absence of a diuretic), rebound HPN on abrupt withdrawal. Sedation is common in initial therapy but usually decrease with continued therapy; Others: Fever and other flu-like symtoms (represents hepatic dysfuntion, monitoring liver funtion), positive Coombs test, dry mouth, subtly decreased mental activity, sleep disturbances, depression, impotence, and lactation in either gender.

clonidine

methyldopa

guanabenz

cautiously with other sedating medications and in pts with severe coronary insufficiency, recent MI, cerebrovascular acident, and hepatic or renal disease. Common side effects: sedation, dry mouth, dizziness, reduced heart rate

guanfacine

calcium channel blockers

bind to L-type channels in cardiac and smooth muscle, and inhibit influx of calcium into cardiac muscle, which decreases contractility and rate. blockade effects in arterioles are more sensitive than veins

h levels of digoxin, carbamazepine, cyclosporine, theophylline; additive AV nodal block with concurrent beta-blockers

verapamil

AV node conduction hhh Myocardial contractility hh Peripheral vascular resistance hh Admistration: PO, IV Metabolism: liver(T1/2 3-7 hours) AV node conduction hh Myocardial contractility h Peripheral vascular resistance h Admistration: PO, IV Metabolism: liver(T1/2 3-7 hours)

Angina (vasospastic, chronic stable and unstable), HTN, arrhythmias, migraine prophylaxis

Sinus bradycardia, constipation, gingival hyperplasia D_D: beta-blockers (additive AV node suppression); Casupplements will reduce the therapeutic effect of verapamil; It will increase the plasma level of digoxin and its toxicity.

diltiazem

Angina (vasospastic, chronic stable and unstable), HTN, arrhythmias

Sinus bradycardia

nifedipine

AV node conduction 0 Myocardial contractility h Peripheral vascular resistance hhh Admistration: PO Metabolism: liver(T1/2 2-5 hours)

Vasospastic angina, HTN, nimodipine is used for subarachnoid hemorrhage

Facial flushing, peripheral edema, hypotension, headache, gingival hyperplasia , reflex tachycardia (palpitations, angina, myocardial infarct) Grapefruit juice may increase levels of some dihydropyridine agents

bepridil

AV node conduction h Myocardial contractility h Peripheral vascular resistance h Admistration: PO Metabolism: liver(T1/2 24 hours) unique in blocking both fast sodium channels / calcium channels in heart.

Chronic stable angina

Agranulocytosis, arrhythmias (torsade de pointes)

Dihydropyridine

amlodipine

Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance and arterial pressure, but are not used to treat angina because the vasodilation and hypotension can lead to reflex tachycardia (with the exception of amlodipine, which carries an indication to treat chronic stable angina as well as vasospastic angina) . This CCB class is easily identified by the suffix "-dipine". Common side effects: Dizziness, headache, redness in the face; Fluid buildup in the legs; Rapid heart rate or Slow heart rate; Constipation; Gingival overgrowth (hyperplasia) Contraindications of amlodipine: cardiogenic shock; unstable angina; significant aortic stenosis; breast feeding

felodipine isradipine nifedipine nicardipine nimodipine

With a high lipid solubility it can be used for cerebral spasm following subarachnoid hemorrhage. Common side effects: hypotention, tachycardia, peripheral edema and GI hemorrhage. (Calan, Isoptin) (Procorum, D600) (Cardizem)

Phenylalkylamine Verapamil

Gallopamil
Benzothiazepine Diltiazem

ACE inhibitors
angiotensin-coverting enzyme

block the conversion of A I to A II (the potent casoconstrictor), also lower aldosterone concentration (limits sodium retention) ACE-I are most commonly used for promoting vasodilatation and decreasing sodium hypertension, retention. diabetic nephropathy, CHF, and post-MI. captopril shortest-acting ACE inhibitor.

The most common adverse effects are hypotension, headache, fatigue, dizziness, hyperkalemia (serum levels should be monitored), and cough. Acute renal ischemia is normally reported due to profound inhibition of renin angiotensin system by ACE inhibitors.

Hypotension can be minimized by temporarily withholding or Especially for patients with compelling reducing the diuretic dose and/or starting the ACE-I at lower doses. indications (diabetes, postmyocardial The incidence of ACE inhibitor-induced cough ranges from 1 % infarction, high coronary disease risk, to 10% (dry. nonproductive, and not responsive to cough suppressants). It should resolve 1 to 4 days after discontinuing the chronic kidney disease, recurrent ACE-I. stroke prevention) Less common side effects are dysgeusia , rash, agranulocytosis, and angioedema . Patients should not be rechallenged with an ACE-I if they have a history of angioedema. Neutropenia is rare but serious; increasing incidence in patients with renal insufficiency or autoimmune disease.

enalapril

long-acting lisinopril

benazepril the only phosphonate-containing ACE inhibitor marketed. Both renal elimination and metabolism are important in the elimination of the drug and its active metabolites

fosinopril moexipril perindopril quinapril ramipril trandolapril

Warning: The use of ACE-I during the second and third trimesters of pregnancy can cause injury or death to the developing fetus. ACE inhibitors may cause blood dyscrasias in addition to cholestatic jaundice and acute renal failure. CPR P366

long-acting once-daily

Significant D_D: Antihypertensive effects may be deminished by NSAIDs (e.g., ibuprofen); Potassium-sparing diuretics increase serum potassium levels (need closely monitoring) Both ACE inhibitors and ARBs are contraindicated in patients with bilateral renal stenosis. (decreased blood flow to the glomerulus). ACE inhibitors or ARBs, the effects of angiotensin II are reduced, which leads to vasodilatation of the efferent arterioles. This will result in a decrease in pressure and glomerular filtration rate and a worsening of the renal function,

angiotensin II receptor block vasoconstriction and aldosterone-secreting effects similar to ACE-I. However, because ARBs do not block inhibitors the metabolism or increase the levels of bradykinin, they are less likely to be associated with nonrenin-angiotensin (blockers) effects such as cough and angioedema. ARBs predominantly eliminated via hepatic metabolism

Similar to ACE inhibitors. The most common side effects are cough, hypotension, headache, fatigue, dizziness, and hyperkalemia. The less cammon adverse reactions include dysgeusia, rash, diarrhea, agranulocytosis. and angioedema. Cough and angioedema occur less frequently than in ACE inhibitors, but precautions should be taken when initiating ARBs in

side effects are cough, hypotension, headache, fatigue, dizziness, and hyperkalemia. The less cammon adverse reactions include dysgeusia, rash, diarrhea, agranulocytosis. and angioedema. Cough and angioedema occur less frequently than in ACE ARBs have indications similar to those inhibitors, but precautions should be taken when initiating ARBs in for ACE inhibitors, but they are mainly someone who experienced angioedema with an ACE inhibitor because there is some cross-reactivity. used in patients who are unable to tolerate ACE inhibitors. Warning: Use during the second and third trimesters can cause injury or death to the developing fetus.

losartan

candesartan irbesartan telmisartan

valsartan

endothlin receptor bosentan antagonists

Diuretics
osmotic diuretic GUI Ma

Glycerin Urea Isosorbide Mannitol

oliguria and anuria highly polar, low renal threshold, limit tubular reabsorption of water and thus promote diuresis, cause an alkaline in urinary pH reduce cerebral edema: h intracranial pressure h intraocular pressure headache and blurred vision, increased blood volume that worsens CHF.

Related to osmotic but not diuretic

Can be used in the management of constipation when cognitively impaired or bedbound; Glycerin is also the same in this use. It is a synthetic disaccharide, is an analog of lactose. Unlike lactose, which is hydrolyzed enzymatically to its monosaccharide components, oral doses of lactulose pass to the colon virtually unchanged. In the colon, bacteria chemically convert the lactulose to low-molecularweight acids and carbon dioxide. The acids produce an osmotic effect that Lactulose draws water into the colon and makes the stools more watery. They also permit ammonia in the body to be converted to ammonium ion in the acidic colon and allow it to be eliminated in the stool. It is also used in the treatment of hepatic encephalopathy, a complication of liver disease.

carbonic anhydrase inhibitors Sulfonamides

_zolamide

noncompetitively inhibit the enzyme carbonic anhydrase, result in sodium bicarbonate diuresis (block the formation of H+ and HCO3- from CO2 and H2O). ----bicarbonate is excreted in the urine. cause an alkaline urinary pH; Acts on proximal tubule

reduce edema(adjunct) reduce intraocular pressure alkalinize the urine, enhancing excreaion of acidic drugs and their metabolites treat motor disorders

Cl-, numbness and tingling in the fingers and toes, and taste alterations (parageusia), especially for carbonated drinks. Some may also experience blurred vision but this usually disappears shortly after stopping the medication. Acetazolamide also increases the risk of developing calcium oxalate and calcium phosphate kidney stones.

acetazolamide

is also used to treat glaucoma, epileptic seizures, benign intracranial hypertension (pseudotumor cerebri), altitude sickness, cystinuria, and dural ectasia. Acetazolamide is available as a generic drug.

methazolamide dorzolamide

benzothiadiazide diuretics

_thiazide; thazone, lazone Electrolyte imbalances: Low K, Mg, Na, Cl, High Ca Thiazide diuretics: chronic edema, hypertension congestive HF( adjunct) HTN, adjunct to loop diuretics for edema. K+. Mg2+, Na+, Cl-, Ca2+ High: GLUC (glucse, Lipid, Uric acid, Ca) h uric acid reabsorption in the proximal tubules can precipitate gouty attacks. Other side effects: rash, hglucose, dizziness, photosensitivity,

chlorothiazide

hydrochlorothiazide HCTZ

directly inhibit NaCl reabsorption, cause an alkaline urinary pH

Inhibits reabsorption of NaCl in the ascending loop of Henle and the But not used in renal failure pts early distal convoluted tubules (DCT)

cyclothiazide quinethazone methyclothiazide metolazone

sulfamoylbenzamides

adjunct to loop diuretics for edema. Inhibits reabsorption of NaCl in the ascending loop of Henle and the But not used in renal failure pts early distal convoluted tubules (DCT) (also as early distal tubules)

h uric acid reabsorption in the proximal tubules can precipitate gouty attacks. Other side effects: rash, hglucose, dizziness, photosensitivity, hBP, headache, h lipids (hypercholesterolemia and hypersensitivity reaction). Electrolytes, blood glucose, and lipids need to be monitored periodically. NSAIDs (e.g., ibuprofen) interact to diminish the antihypertensive effects

similar to benzothiadiazide diuretics indapamide

chlorthalidone

a thiazide-like diuretic because it acts similarly to the thiazides but does not contain the benzothiadiazine molecular structure; Compared with other medications of the thiazide class, chlorthalidone has the longest duration of action, but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema. Unlike loop diuretics, chlorthalidone efficacy is diminished in patients with certain renal diseaes (e.g. Chronic Renal Disease).

Mild hypokalemia is often without symptoms, although it may cause a small elevation of blood pressure, and can occasionally provoke cardiac arrhythmias. Moderate hypokalemia may cause muscular weakness, myalgia, and muscle cramps (owing to disturbed function of the skeletal muscles), and constipation (from disturbed function of smooth muscles). symptoms of Severe hypokalemia: flaccid paralysis, hyporeflexia, and tetany may result. There are reports of rhabdomyolysis occurring with profound hypokalemia. hypokalemia Respiratory depression from severe impairment of skeletal muscle function is not uncommon. Some electrocardiographic (ECG) findings associated with hypokalemia are flattened T waves, U waves, ST segment depression, and prolongation of the QT interval.

Furosemide Torsemide Bumetanide Ethacrynic acid loop diuretics Fur Etha Tor Bume

inhibit the cotransport of Na, K, Cl from the luminal edema from congestive HF, hepatic filtrate, no change in urinary pH cirrhosis and renal disease, pulmonary edema and ascites Inhibits reabsorption of NaCI in the thick ascending limb of the loop of Henle ; Edema HTN in patients withCrCl < 30-50 NSAIDs (e.g., ibuprofen) interact to diminish the ml/min antihypertensive effects

fluid and solute imbalances: dehydration, hypokalemia, hyperuricemia, hypercalciuria, and azotemia;may also cause hypocalcemia. CNS effects: headache, vertigo, blurred vision Hematologic effects: thrombocytopenia and agranulocytosis CV effects: orthostatic hypotension GI effects: nausea, vomitting, diarrhea Leg cramps Hypercholesterolemia and hypertriglyceridemia Sulfonamide-type hypersensitivety reaction

Contraindication Diuretics that act on the distal tubule (thiazides and potassium-sparing diuretics) lose their effectiveness when CrCl decreases to less than 30 to 50 mL/min. The loop diuretics are more potent and retain their effectiveness at low CrCl (> 5 mL/min)

furosemide

Ototoxicity may occur with furosemide at high infusion rates. (Bumetanide is the least) D-D: Aminoglycoside antibiotics such as Gentamicin acts by inhibiting the Na-K-2Cl symporter in the thick Aspirin and other salicylates ; ascending limb of the loop of Henle. Other diuretics (e.g. ethacrynic acid, hydrochlorothiazide) used in the treatment of hypertension, congestive Indomethacin heart failure and edema. Lithium Synergistic effects with other antihypertensives (e.g. Doxazosin) Sucralfate

bumetanide

Bumetanide is 40 times more potent than furosemide (for patients with normal renal function). used in patients in whom high doses of furosemide are ineffective. The drug is often used for weight loss, but also to mask other drugs or steroids.

ethacrynic acid torsemide adjunctive therapy to treat edema/hypertension treat or prevent hypokalemia

potassium-sparing diuretics Eple- Ami-Tri-Spi---SEAT for sharing K

act on the late distal tubule and collecting duct,

hBP, hK+, constipation, and nausea. Gynecomastia can occur with spironolactone. Gynaecomastia [7dVinEkEu5mAstiE] h K+ most often occurs in patients with renal impairment or in combination with ACE-Inhibitors.

amiloride

They disrupt sodium exchange with K and H by blocking Na channels and decreasing the driving force for secretion of K and H cause an alkaline urinary pH and h K

triamterene

contraindicated in pts with kidney stones or hepatic disease.

Cometitive inhibitors of aldosterone, act on the late distal tubule and collecting duct, decreasing K secretion; Used primarily to treat acne; acute coronary syndromes; ascites; edema; heart failure; hypokalimia; renal impairment; hypertension (with HCTZ) spironolactone

systolic heart failure; hepatic cirrhosis and ascites , hypokalemia, and Conn's syndrome as well as high blood pressure, low-renin hypertension; Other side effects: ataxia, erectile dysfunction, drowsiness and Hirsutism, and a common component in hormone therapy for male-to-female transsexual rashes. and transgendered people; hair loss and acne in women and as a topical medication for treatment of male baldness.

hyperkalemia, gynecomastia or gynaecomastia menstrual irregularities associated with an increased risk of bleeding from the stomach and duodenum;

Eplerenone

gynecomastia or gynaecomastia related drugs: potassium-sparing diuretics; cemetidine; Androgens and Flutamide(antiandrogen); Menotropins hMG

Symptoms are fairly nonspecific and generally include malaise, palpitations and muscle weakness; mild hyperventilation may indicate a compensatory Symptoms of response to metabolic acidosis, which is one of the possible causes of hyperkalemia. other symptoms (paresthesias, bradycardia, fatigue, flaccid paralysis of hyperkalemia the extremities, shock).

Pamabrom is a diuretic product included in retail drugs available in over-the-counter medications. The active diuretic ingredient is 8-bromotheophylline. pamabrom It is also available in combination with acetaminophen (paracetamol) for menstrual relief. The acetaminophen helps reduce menstrual pains and the pamabrom reduces associated bloating. The acetaminophen/pamabrom combination is also marketed as a pain reliever for pain associated with back ache, headache, and muscle ache and can be used as a mild muscle relaxant.

Action orders & sites

Combination products

--- Proximal tubule Osmotic / Carbonic anhydrase inhibitors loop + thiazide HCTZ 25 mg spironlactone and 25 mg HCTZ

--- Henle's Loop ---Loop

--- Distal Tubule ---Thiazdie

---Late DT & Collecting Duct ---K-sparing

Aldactazide Aldactazide-50 Moduretic Dyazide Maxzide Maxzide-25

5 mg amiloride plus 50 mg HCTZ 37.5 mg triamterene and 50 mg HCTZ 75 mg trizmeterene and 50 mg HCTZ 37.5 mg trizmeterene and 25 mg HCTZ

antihyperlipidemic agents
nonabsorbable agents

increase catabolism

colesevelam hydrochloride
hydrophilic water-soluble resins cholestryamine chloride colestipol hydrochloride

bile acid sequestrants GI distress increase the efficiency of lipoprotein removal

absorbable agents

GI distress, skin rash, leukopenia Contraindicated in pts with: liver disease; active peptic ulcer disease (PUD); arterial bleeding; caution use in diabetes; and gout

nicotinic acid

Niacin--- vitamin B3, Inhibit VLDL secretion

flushing; hblood sugar and uric acid; GI upset; liver toxicity

gemfibrozil
Fibric acid _fibrate

fenofibrate clofibrate bezafibrate

reduce lipoprotein production, h VLDL catabolism, PPAR agonist

Contraindicated in pts with: liver or severe renal disease; primary biliary cirrhosis; preexisting gallbladder disease

GI upset, dyspepsia,gallstones, hLFTs, myopathy D_DWarfarin /Cyclosporine / Statins

Inhibit rate-limiting step in cholesterol synthesis

HMG CoA reductase inhibitors

(Stastins)

Simvastatin causes the greatest percentage increase in HDL

Contraindicated in pts with: Liver disease; pregnancy and lactation

Myopathy (rare) hLFTs (rare) D_D: Macrolide antibiotics Cyclosporine / Digoxin / Nefazodone Azole antifungals / HIV protease inhibitors Amiodarone / Warfarin Fibric acids / Niacin

Lovastatin

Atorvastatin

(Lipitor, Pfizer), Common side effects: myalgia, mild transient GI symptoms (diarrhea, constipation, passing gas), elevated hepatic transaminase concentrations, headache, insomnia, joint pain, and/or dizziness. Rare: Myopathy and rhabdomyolysis. Risk is increased in patients with renal impairment, serious concurrent illness; and/or concomitant use of drugs which inhibit CYP3A4. The main clinical advantage of Lipitor over Simvastatin is that it is not metabolised by certain liver enzymes, and thus its blood concentration is not increased when combined with grapefruit juice which inhibits these enzymes. It was used to treat hypercholesterolemia and to prevent cardiovascular disease. It has also been shown to exhibit antiviral activity against Hepatitis

Fluvastatin

Pravastatin

Simvastatin

Common side effects: abdominal pain, diarrhea, indigestion, and a general feeling of weakness. Rare side effects: joint pain, memory loss, and muscle cramps. D_D: intake of grapefruit lows metabolization of simvastatin; when simvastatin is used with amiodarone can lead to kidney failure or death,

cholesterol absorption inhibitor

ezetimibe

Used to lower cholesterol levels by decreasing cholesterol absorption in the intestine. It may be used alone when other cholesterol-lowering medications are not tolerated, or together with statins (e.g. ezetimibe/simvastatin, marketed as Vytorin and Inegy) when cholesterol levels are unable to be controlled on statins alone. Side effects: headache and/or diarrhea; Others: myalgia and/or raised liver function test (ALT/AST); hypersensitivity reactions (rash, angioedema) or myopathy.

Bile acid sepuestrants

cholestryamine colestipol solesevalam

EPA eicosapentaenoic acid DHA docosahexaenoic acid

Bind to bile acids in gut

GI:constipation.bloating, abdominal pain Contraindicated in pts with: ibioavailability of coadministered drugs; Complete biliary obstruction; severely separate other drugs at least 1 hr before elevated TG or 4-6 hr after

Resins HMG-CoA-Is Niacin Fibrates Ezetimibe

LDL hh hhh hh h--hh hh hh

h h hh hh h

HDL TG (triglycerides) h (the only appropriate for children(>2) / pregnant / lactating women h---hh(Atorva-/Rosuva have the greast TG-lowering effect hh hhh Greatest in HDL increasing Greatest in TG lowering

anticoagulant

heparin
low molecular weight heparin( DENT---parin LMWH)

inhibition of thrombin by antithrombin III preventing the conversion of fibrinogen to fibrin

Avoid IM route (may produce a high risk of hematoma) antidote is protamine (basic)

Differences from unfractionated heparin include: Average molecular weight: heparin is about 20000 Da and LMWH is about 3000 Da Once-daily dosing, rather than a continuous infusion of unfractionated heparin No need for monitoring of the APTT coagulation parameter Possibly a smaller risk of bleeding; Smaller risk of osteoporosis in long-term use Smaller risk of heparin-induced thrombocytopenia (HIT), a feared side-effect of heparin. The anticoagulant effects of heparin are typically reversible with protamine sulfate, while the effect on LMWH is limited Has less of an effect on thrombin compared to heparin, but maintains the same effect on Factor Xa. Carefully used in pts with hypersensitivity to heparin; It can also elevate AST, caution in pts with liver disease and pulmonary emlolism.

Dalteparin Enoxaparin Nadroparin Tinzaparin ..

others

danaparoid lepirudin argatroban bivalirudin drotrecogin fondaparinux

Hyperkalaemia: LMWH can cause hypoaldosteronism, which may result in hyperkalaemia. Potassium should be monitored before and during treatment, particularly in patients at risk of high potassium e.g. renal impairment, ACE inhibitors, Angiotension II receptor blockers, potassium sparing diuretics etc. Heparin induced thrombocytopenia (HIT): is a rare side effect of LMWH. HIT predisposes patients to an increased risk of VTE. Platelet count should be performed before treatment is started and during treatment. Danaparoid, Lepirudin and Argatroban are appoved for treatment of HIT in Canada.

Coumarin derivatives Warfarin decrease blood coagulation by inhibiting vitamin K epoxide reductase, an enzyme that recycles oxidated vitamin K to its reduced form hydroquinone after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VII. For this reason, drugs in this class are also referred to as vitamin K antagonists. Hemorrhage: The risks of bleeding increased when combined with antiplatelet drugs (clopidogrel, aspirin), or otherNSAIDs, or in Highly protein bound and extensively metabolized in the liver, susceptible to significant drug elderly patients and hemodialysis patients; bleeding may be treated interactions; contraindicated in pregnancy; with Vitamin K( phytonadion) Others: anorexia, urticaria, purpura, alopecia Rare but complicated: Warfarin necrosis: Osteoporosis: Purple toe syndrome: result from small deposits of cholesterol breaking loose and flowing into the blood vessels in the skin of the feet, which causes a blueish purple color and may be painful.

warfarin

D_D: interacts with many commonly-used drugs, and the metabolism of warfarin varies greatly between patients. Highly protein bound drugs can displace warfarin from albumin and cause an increase in INR; Antibiotics, such as metronidazole or the macrolides, will greatly increase the effect of warfarin by reducing the metabolism of warfarin; Broad-spectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel, which make significant quantities of vitamin K, thus potentiating the effect of warfarin; Hypothyroidism h the effects of warfarin; hyperthyroidism boosts the anticoagulant effect; Excessive use of alcohol h metabolism of warfarin and can elevate the INR; dicumarol non-prothrombopenic anticagulant citrate dextrose

with Vitamin K( phytonadion) Others: anorexia, urticaria, purpura, alopecia Rare but complicated: Warfarin necrosis: Osteoporosis: Purple toe syndrome: result from small deposits of cholesterol breaking loose and flowing into the blood vessels in the skin of the feet, which causes a blueish purple color and may be painful.

Unlike Dicumarol, Warfarin and Aisindione (prothrombopenic, competitively inhibit Vitamin K and hepatic production of prothrombin), they act by other mechanisms. The citrate chelates with calcium ions and acts as an anticoagulant. It is used for anticoagulation and preparation of whole blood for transfusion.

The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. Prothrombin time The reference range for PT is usually around 1215 seconds; the normal range for the INR is 0.81.2. PT measures the extrinsic pathway including factors II, V, VII, X and fibrinogen. It is used in conjunction with the activated partial thromboplastin time (aPTT, 25-39 seconds) which measures both the intrinsic pathway (now referred to as the contact activation pathway) and the common coagulation pathways. aPTT is also used to monitor the treatment effects with heparin.

Antiplatelet agents
aspirin

aspi- abci- efpti- tiroficilopy- dipy- trepro-

ticlopidine

an inhibitor of platelet aggregation that is administered orally, with food, in doses of 250 mg twice daily. Patients using this drug should have a complete blood count (CBC) with differential performed every two weeks for three months to detect neutropenia (decreased number of white blood cells). The drug's antiplatelet effects are not maximal until at least 8 to 11 days of therapy have been completed. specific factor Xa inhibitors a platelet aggregation inhibitor mainly used during and after coronary artery procedures like angioplasty to prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. Its mechanism of action is inhibition of glycoprotein IIb/IIIa; While Abciximab has a short plasma half life, due to its strong affinity for its receptor on the platelets, it may occupy some receptors for weeks. In practice, platelet aggregation gradually returns to normal about 24 to 48 hours after discontinuation of the drug.

Fondaparinux

abciximab

tirofiban eptifibatide anagrelide cilostazol anagre--not coagulate

treprostinil

Treprostinil is a synthetic analogue of prostacyclin, used to treat pulmonary hypertension. As an analogue of prostacyclin PGI2, treprostinil effects vasodilation, which in turn lowers the blood pressure. Treprostinil also inhibits platelet aggregation, though the role this phenomenon may play in relation to pulmonary hypertension has yet to be determined.

85% of patients report pain at the infusion site. Other side effects: headache, diarrhea, nausea, rash, jaw pain, vasodilatation, dizziness, edema (swelling), pruritus (itching), and hypotension.

dipyridamole

It inhibits the cellular reuptake of adenosine into platelets, red blood cells and endothelial cells leading to increased extracellular concentrations of adenosine. It also inhibits the enzyme adenosine deaminase which normally breaks down adenosine into inosine. This inhibition leads to further increased levels of extracellular adenosine. Dipyridamole also inhibits the phosphodiesterase enzymes A thienopyridine compound; used in treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It works by blocking a receptor called P2Y12. Adverse effects include hemorrhage.

Clopidogrel

Its combination with ASA was used in acute coronary syndromes, may also be used in acute ischemic stroke; stable angina; Used as secondary prevention for ischemic stroke, myocardial infarction, and pretreatment in percutaneous coronary intervention;

Thrombolytic agents _eplase _kinase

alteplase reteplase tenecteplase streptokinase anistreplase urokinase

used in myocardial infarction (heart attack), ischemic strokes, deep vein thrombosis and pulmonary embolism to clear a blocked artery and avoid permanent damage to the perfused tissue (e.g. myocardium, brain, leg) and death. A less frequent use is to clear blocked catheters that are used in long-term medical therapy.

The tissue plasminogen activator produced by recombinant DNA technology. It is used in the management of acute myocardial infarction (AMI), acute ischemic stroke, and pulmonary embolism.

It is used intravenously in the management of AMI patients in order to lyse thrombi obstructing coronary arteries. It is administered as soon as possible after the onset of AMI.

Hemorrhagic stroke is a rare but serious complication of Once injected into the circulation, alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This and assists in reopening a blocked blood vessel. thrombolytic therapy. If a patient has had thrombolysis before, an allergy against the thrombolytic drug may have developed (especially after streptokinase).

antianemic agents
iron preparations sodium ferric gluconate

iron sucrose iron dextran ferrous sulfate frrrous gluconate ferrous fumarate
cyanocobalamin Vitamin B12

folic acid
glycoproteins

_epoetin _grastim epoetin darbepoetin filgrastim pegfilgrastim sargramostim

oprelvekin interluekin 11

Pituitary Hormones
posterior pituitary hormones

oxytocin vasopressin
anterior pituitary hormones

stimulates uterine contraction and plays an important roal in the induction of labor. vasopressor and antidiuretic hormone (ADH) activity, acts on the distal renal tubular epithelium, where it promotes the reabsorption of water.

FLAT PiG FSH LH

A FLAT PEG in the front (FSH, LH, ACTH, TSH, Prolactin, Endorphin and GH) follicle stimulating hormone Luteinizing hormone adrenocorticotropic hormone ACTH, stimulating the adrenal cortex to produce and secrete adrenocorticosterioids thyroid-stimulating hormone TSH thyrotropin-releasing hormone associated with lactation sustain the corpus luteum in pregnancy sustain the corpus luteum in pregnancy for the diagnosis and differnentiation of primary and secondary adrenal insufficiency

ACTH (corticotropin thyrotropin TRH prolactin

Endorphin

growth hormon

somatotropin, stimulate protein, carbohydrate, and lipid metabolism to promote increased cell, organ, connective tissue, and skeletal growth, causing a rapid increase in the overall rate of linear growth

long-term treatment of children whose gowth failure

pituitary gonadotropin analogs human menopausal gonadotropin hMG, obtained from induce ovulation and pregnancy in the urine of postmenopausal women, procuce ovarian anovulatory infertile women; In men, follicular growth and induce ovulation by FSH-like / LH-like to induce spermatogenesis activity,

menotropins hMG

hypersensitivity, gynecomastia

urofollitropin

FSH-like, obtained from the urine of postmenopausal women severe water intoxication with convulsions and coma after slow infusion; uterine hypertonicity postpartum hemorrhage nausea, vomiting, and anaphylaxic Fetal effects: bradycardia, neonatal jaundice, cardiac dysrhythmias, and premature ventricular contracions

hCG

LH-like, obtained from the urine of pregnant women

promote delivery, to controll postpartum bleeding or hemorrhage

Goserelin Acetate

an injectable gonadotropin releasing hormone super-agonist (GnRH agonist) also known as an LHRH agonist. It stops the production of sex hormones (testosterone and oestrogen). Goserelin Acetate is used to treat hormone-sensitive cancers of the prostate and breast (in pre-/perimenopausal women) and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, goserelin is used in assisted reproduction and in the treatment of precocious puberty.

Histrelin Acetate Leuprorelin Triptorelin

Gonadal hormones

estrogen

bond to estrogen receptor, induce its comformational change which increases its affinity for DNA and alters the production of mRNA and ultimately leads to either oral contraceptives (combination with an increase or decrease in enzyme or protein progestins) synthesis. treatment of menopausal sumptoms: (casomotor disorder, urogenital atrophy, psychological disorder) acne osteoporosis (both senile and postmenopausal) prostate cancer mestranol The 3-methyl ether of ethinylestradiol. It was the estrogen used in many of the first oral contraceptives. It is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70%

GI effects: distress, nausea, vomiting, anorexia and diarrhea cardiovascular effects: hypertension, and thromboembolic diseases, stroke, and myocardial infarction fluid and electrolyte disturbances, fluid retention and increased triglyceride level an increased incidence of endometrial cancer and hepatic adenomas

weak in oral adm. estradiol

in equilibrium with estrone( converted to estriol before excretion)

estradiol cypionate or calerate ethinyl estradiol

Estrogen excess: Nausea, vomiting /Fluid retention, weight gain, edema /hbreast size or tenderness / Skin discoloration (cholasma)/white or yellowish vaginal discharge /Hypertension / Cyclic headache /Heavy flow, hypermenorrhea /Increased risk thrombus, blood clot Estrogen deficiency: BTB days 1-9 / Vasomotor symptoms / Nervousness, irritability / Decreased libido / Atrophic vaginitis

conjugated estrogens

premarin cenestin menest enjuvia estropipate antiestrogen _mifene

clomiphene

Indicated to ovulatory dysfunction women to induce ovulation. It has estrogenic and antiestrogenic activity, It combines with estrogen receptors. Through negative feedback mechanism, the hypothalamus and pituitary are stimualted to increase secretion of FSH and LH and then stimulant ovulation; Recommended dose: 50 mg/day five days. Side effects: blurred vision, spots or flashes, posterior capsular cataract, spasm of retinal atteriole, and uterine bleeding.

tamoxifen citrate competitively binding estrogen receptors in breast tissue, and then inhibit the action of estrogen toremifene citrate

treat estrogen-dependent breast cancer for the treatment of both early and advanced ER+ (estrogen receptor positive) breast cancer in pre- and post-menopausal women

It is a known carcinogen; endometrial changes, including cancer; rapid h triglyceride concentration in the blood; steatorrhoeic hepatosis or steatosis hepatis; a reduction of libido;

fulvestrant

competitively binding estrogen receptors and preventing estrogen receptor dimerization in target tissue.

a class of medication that acts on the estrogen receptor. A characteristic that selective estrogen distinguishes these substances from pure receptor agonists and antagonists is that receptor modulator (SERM) their action is different in various tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues. _xifene/fen Phytoserms are scientificaly accepted SERMs from a botanical source.

The actions of SERMs on various tissues: Bone turnover, postmenopausal osteoporosis respond favorably to most SERMs. Breast - all SERMs decrease breast cancer risk, and tamoxifen are commonly used. Cholesterol and triglycerides - levels respond favorably to SERMs. Deep venous thrombosis - the risk may be elevated in at least some SERMs. Hot flashes are increased by some SERMs. Pituitary gland - clomifene blocks estrogen action, leading to an increase of follicle-stimulating hormone. Uterus - tamoxifen may increase endometrial carcinoma risk, but raloxifene and femarelle do not. Data on toremifene and clomifene is insufficient.

raloxifene

an oral SERM that has oestrogenic actions on bone and antiestrogenic actions on the uterus and breast.

It is used in the prevention of osteoporosis in postmenopausal women. Raloxifene reduces the risk of hormone-positive breast cancer and vertebral fractures

Common side effects: hot flashes and leg cramps. Others: serious blood clots to form in the legs, lungs, or eyes; leg swelling/pain, trouble breathing, chest pain, vision changes.

Raloxifene is contraindicated in lactating women or women who are or may become pregnant, in women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis and in women known to be hypersensitive to raloxifene. This may take hours which not only includer paramedic history, but also idiomatically. afimoxifene (4-hydroxytamoxifen) arzoxifene bazedoxifene clomifene femarelle (DT56a) lasofoxifene ormeloxifene tamoxifen toremifene used for contraception used for breast cancer used in anovulation used for managing menopause symptoms and maintaining bone health

Aromatase inhibitors

_trozole

Selective nonsteroidal inhibitors of aromatase which is responsible for the conversion of androgens to estrogens

Anastrozole binds reversibly to the aromatase enzyme through competitive inhibition. anastrozole Commonly indicated in the treatment of breast cancer in post-menopausal women; Combined with OC or a progestin is useful in reducing the risk of developing ovarian cysts; It is also used to relieve endometriosis pain; effective in the off-label use of reducing estrogens (in particular and more importantly, estradiol) in men; it is frequently used in the treatment of children with growth disorder to stop or slow the onset of puberty. Side effects: Bone weakness.

letrozole

Side effects: Bone weakness. exemestane

progestin
progesterone synthetic
17- OH medroxyprogesterone acetate

oral contraceptive agents menstrual disorder: dysfunctional uterine bleeding, dysmenorrhea endometrisis

gynecological effects: irregular menses, breakthrough bleeding, and amenorrhea weight gain and edema exacerbation of breast carcinoma

megestrol acetate

Indicated for advance breast cancer and endometrium cancer. Weight gain is a common side effect. And it is also useful as an appetite stimulant agent in HIV pts (800 mg/day) Common progestational side effects

19 -de methyl 17- ethinyl group

norethindrone norethynodrel norgestresl levonorgestrel

common adr: breakthrough bleeding

contraceptive agents in combination with ethinyl estradiol

Progestin excess (also see androgenic effects): Dysmenorrhea, amenorrhea [ei7menE5ri:E] Hypertension Candida vaginitis Weight gain and edema Breast tenderness Exacerbation of breast carcinoma

PlanB, emergency contraception preven( with ethinyl estradiol

Progestin excess: h LDL, h HDL cholesterol happetite, weight gain hacne, oily skin, hirsutism, hair loss htenderness hdepression, fatigue ilibido Progestin deficiency: BTB days 10-21 Amenorrhea Heavy flow/clots

ethynodiol diacetate

norgestimate Desogestrel norelgestromin etonogestrel

orally active prodrug( deacetylated and oxidized to norgestrel prodrug

Drospirenone

An analog to spironolactone; it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic. With its activities similar to spironolactone it may lead to less water retention and breast tenderness while improving skin appearance (less acne).

Seasonale

91-day cycle extended oral contraception

antiprogestin

mifepristone

inhibit the action of progestins by competitively binding progestin receptors

Used in termianation of intrauterine pregnancy (through 49 days), 2 days after adm. Misoprostol is adm. for inducing uterine contractions

Combined Oral Contraceptives (COC)

MOA: COCs decrease ovulation and sperm and egg transport and implantation. The estrogen component alters FSH (follicle stimulating hormone) and LH (Ieutinizing hormone) release, accelerates egg transport, and alters the endometrium so that it is unsuitable for implantation. Progestins alter FSH and LH release, thicken cervical mucous to reduce sperm and egg transport, inhibit enzymes necessary for fertilization, and also alter the endometrium so that it is unsuitable for implantation.

A family history of breast cancer does not preclude the use of COCs, In general, COC use does not increase the risk for breast cancer and may diminish the risk for endometrial, colorectal. and ovarian cancer

Monophasic formulations

contain a constant dose of estrogen and progestin,

COC use is not recommended, however, in patients who have a current or past history of breast, hepatic, or cervical cancer. COC use may increase the risk for cervical dysplasia and cancer with more than 1 year of use. It also may increase the risk for hepatic cancer and gallbladder disease. Benefits of short-term COC use may include improved cycle regularity, less dysmenorrhea, fewer premenstrual symptoms, less irregular bleeding and blood loss, reduced risk for ectopic pregnancy and functional ovarian cysts, and possible reduction in acne. Long-term benefits of COC use may include a reduced risk for pelvic inflammatory disease (PID), benign breast disease, and improved bone mineral density and lipid profile n HDL),

Triphasic formulations

contain varying doses of progestin (generally increasing) every 7 days, and either a stable or a variable amount of estrogen every 7 days. No uniform

Progestin-only contraceptives

Patients who have contraindications to estrogen or who experience intolerable side effects

less effective than COC pills, and are associated with a greater incidence of dysmenorrhea, amenorrhea, irregular menses, and break-through bleeding (BTB)

Non-oral formulations

allow for lower doses of hormones to be used and bypass first-pass metabolism, thereby limiting the production of factors produced by the liver (e,g., fibrinogen, Creactive protein)

IM injectable DMPA ((depo-medroxyprogesterone acetate surgically placed subdermal implant surgically placed intrauterine system transdermal patch vaginal ring Monthly IM injectable

reversible bone loss.

androgens

Tesosterone is converted to DHT which bind to an androgen receptor in the nucleus, and thus increase the production of mRNA and ultimately leads to either androgen-replacement therapy an increase in enzyme or protein synthesis. breast cancer / endometriosis female hypopituitarism, with estrogen therapy anabolic therapy, in patients with negative nitrogen balance anemia converted to DHT by 5-reductase

fluid retention increased LDL and decreased HDL cholesterol levels, increase risk of artherosclerosis and coronary artery disease psychological changes liver disorders development of masculine features in female decreased fertility in male

androgenic effects _rone----

testosterone

testosterone 17 enanthate testosterone cypionate Most of these side effects are dose-dependent, the most common being elevated blood pressure, especially in those with pre-existing hypertension,and harmful changes in cholesterol levels: some steroids cause an increase in LDL cholesterol and a decrease in used to treat men with a testosterone deficiency. It is also used in women to treat breast cancer, breast pain, swelling due to pregnancy, and with the addition of estrogen it can treat HDL cholesterol. symptoms of menopause. Androgenic side effects (excess): hLDL, h HDL cholesterol h appetite, weight gain h acne, oily skin, hirsutism, hair loss h tenderness h depression, fatigue h libido Also called methyldihydrotestosterone, is the 17-methylated version of dihydrotestosterone (DHT). It is an orally bioavailable androgenic steroid that is highly androgenic while only Alterations in the structure of the heart, such as enlargement and slightly anabolic. It is incapable of aromatization and is not an agonist of the progesterone thickening of the left ventricle: hypertension, cardiac arrhythmias, receptor. congestive heart failure, heart attacks, and sudden cardiac death. Indicated for the treatment of chronic wasting disease, negative nitrogen balance and osteoporosis. Liver toxicity and cholestatic jaundice are common side effects. High doses of oral anabolic steroid compounds can cause liver damage; Pelionis hepatitis male-specific side effect: Gynecomastia: Development of breast tissue in males; Reduced sexual function and temporary infertility; testicular atrophy; Female-specific side effects include increases in body hair, deepening of the voice, enlarged clitoris, and temporary decreases in menstrual cycles. severe side effects in adolescents:prematurely stop the lengthening of bones resulting in stunted growth; accelerated bone maturation, increased frequency and duration of erections, and premature sexual development.

methyltestosterone

fluoxymesterone

Mestanolone

anabolic effects _long---- Grow long ---anabolic

oxymetholone

oxymetholone is the strongest androgenic steroid available. primary clinical applications include treatment of osteoporosis and anaemia, as well as stimulating muscle growth in undernourished or underdeveloped patients. Also used in treating HIV wasting syndrome. Schedule III drug oxymetholone is the strongest androgenic steroid available.

nandrolone decanoate oxandrolone

others

testolactone a derivative of the synthetic steroid ethisterone, a modified testosterone (17alpha-ethinyl testosterone). Danazol has been used - mostly off-label - for other indications, namely in the management of menorrhagia, fibrocystic breast disease, immune thrombocytopenic purpura and of hereditary angioedema. and occasionally used to treat endometriosis , usually when all other hormone therapies have not helped. Though danazol prevents pregnancy, it is not licenced for use as a contraceptive agent.

danazol

antiandrogens _lutamide

for prostate cancer

Flutamide

gynecomastia Tamoxifen can partially counteract this effect.

Bicalutamide Nilutamide is an antiandrogen medication used in the treatment of advanced stage prostate cancer. Nilutamide blocks the androgen receptor, preventing its interaction with testosterone. A delay in adaption to the dark, ranging from seconds to a few minutes; tinted glasses will reduce this effect.

Nilutamide

5 -reductase inhibitors

competitive inhibit 5 -reductase, reduce DHT

Benign prostatic heperplasia BPH

Antihistamines, nasal decongestants and parasympatholytic drugs (such as dephenhydramien, phenylephrine, atropine) can precipitate urinary retention, and should be avoided by pts suffering from BPH

androgenic alopecia at one fifth the dose used in BPH; finasteride Minoxidil is also used in alopecia; dutasteride

DHT

DHT, 5-Dihydrotestosterone, it is crucial to virilization and is necessary to mitigate estrogen's effects in men. It is responsible for the formation of male sexspecific characteristics and other characteristics generally attributed to males, including facial and body hair growth, and deepening of the voice. DHT may also play a crucial role in both sex drive and the growth of muscle tissue. DHT cannot be converted by the enzyme aromatase to estradiol. DHT is the primary contributing factor in male-pattern baldness; also participates in the development of acne.

Retinoid

The retinoids are related chemically to vitamin A and used in medicine, primarily due to the way they regulate epithelial cell growth. Its functions throughout the body includes roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes. Research is also being done into their ability to treat skin cancers. Currently 9-cis retinoic acid may be used topically to help treat skin lesions from Kaposi's sarcoma. First generation retinoids: retinol, retinal, tretinoin (retinoic acid, Retin-A), isotretinoin and alitretinoin. Second generation retinoids: etretinate and its metabolite acitretin. Third generation retinoids: tazarotene , bexarotene and Adapalene.

It is a retinoid and derives from vitamin A and is found in small quantities naturally in the body.
Isotretinoin

Adverse drug reactions resembling vitamin A toxicity: Mild acne flare, dryness of skin, lips and mucous membranes, dry mouth, infection of the cuticles, cheilitis, itch, skin fragility, skin peeling, Used for the treatment of severe acne. It is sometimes used as a chemotherapy medication rash, flushing, photosensitivity, nose bleeds, dry eyes, eye irritation, for prevention and treatment of certain skin cancers. In some cases, it is used to treat conjunctivitis, reduced tolerance to contact lenses, hyperlipidaemia, Harlequin type ichthyosis. raised liver enzymes, headaches, hair thinning , myalgia and/or arthralgia, back pain. Sometimes fetal abnormalities; pregnant X rating; administered orally;

A second generation retinoid. It is taken orally, and is typically used for psoriasis. It is a metabolite of etretinate, which was used prior to the introduction of acitretin. Etretinate was discontinued because it had a narrow therapeutic index as well as a long elimination half-life (t1/2=120 days), making dosing difficult. In contrast, acitretin's half-life is approximately 2 days. It is necessary to adjust the dosage in renal impairment patients. acitretin Teratogenicity: Because acitretin can be reverse metabolised into etretinate which has a long half life, women must avoid becoming pregnant for at least 2 years after discontinuing acitretin. Therefore, not recommended at for women of child bearing age with risk becoming pregnant. Acitretin is the least toxic systemic treatment for psoriasis. It is an oral retinoid of choice used in the treatment of severe resistant psoriasis.

A prescription topical retinoid sold as a cream or gel. This medication is approved for treatment of psoriasis, acne, and sun damaged skin (photodamage). It is commonly sold in two concentrations: 0.05% and 0.1%. Tazarotene Common side effects include worsening of acne, dry skin, itchiness, redness and in some cases extreme drying and cracking of skin. For most patients these side effects are uncomfortable but mild and decrease markedly after the first 24 weeks of use.

Indicated for the topical treatment of acne vulgaris. Adapalene Adapalene has been shown to enhance the efficacy of topical clindamycin. Unlike Retin-A, adapalene has also been shown to retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure.

Adrenocorticosteroids

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior.

1. Topical steroids for use topically on the skin, eye, and mucous membranes. 2. Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchii, and lungs. 3. Oral forms - such as prednisone and prednisolone. 4. Systemic forms - available in injectibles for use intravenously and parenteral routes.

Group A: (short to medium acting glucocorticoids) Hydrocortisone, Hydrocortisone acetate, Cortisone acetate, Tixocortol pivalate, Prednisolone, Methyprednisolone, and Prednisone. Group B: Group C: Triamcinolone acetonide, Triamcinolone alcohol, Mometasone, Amcinonide, Budesonide, Desonide, Fluocinonide, Fluocinolone acetonide, and Halcinonide. Betamethasone, Betamethasone sodium phosphate, Dexamethasone, Dexamethasone sodium phosphate, and Fluocortolone.

Group D: Hydrocortisone-17-butyrate, Hydrocortisone-17-valerate, Aclometasone dipropionate, Betamethasone valerate, Betamethasone dipropionate, Prednicarbate, Clobetasone-17-butyrate, Clobetasol-17-propionate, Fluocortolone caproate, Fluocortolone pivalate, and Fluprednidene acetate.

Dexamethasone and Betamethasone are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia. used in the treatment of joint pain or inflammation (arthritis), temporal arteritis, dermatitis, allergic reactions, asthma, hepatitis, systemic lupus erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency. Topical formulations for treatment of skin, eye diseases (uveitis) or inflammatory bowel disease are available. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g. ondansetron).

Synthetic glucocorticoids

Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side effects are hypertension, hypernatremia, hypokalemia, without causing peripheral edema, metabolic alkalosis and connective tissue weakness (Werner, 2005). Corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC).

Glucocorticoids

anti-inflammation, protein-catabolic, immunosuppress, control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.

Glucocorticoids may be used in low doses in adrenal insufficiency. In much higher doses, glucocorticoids are used to suppress various allergic, inflammatory, and autoimmune disorders. They are also administered as posttransplantory immunosuppressants to prevent the acute transplant rejection and the graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. Side effects: Suppression of pituitary-adrenal integrity

graft-versus-host disease. Nevertheless, they do not prevent an infection and also inhibit later reparative processes. cortisone hydrocortisone formed in the middle(fasiccular) layer of the adrenal cortex C-11- O essential for glucocorticoid activity prednisone prednisolone C-1 and C-2 double bond, increase gluco-act Side effects: Suppression of pituitary-adrenal integrity GI effects: peptic ulcer, GI hemorrhage, ulcerative esophagitis, acute pancreatitis CNS effects: such as headache, vertigo, increase introcular and intracranial pressures, cataracts; muscle weakness, psychological disturbances (uephoria, dysphoria, depression and suicidal tendencies) Cardiovascular effects: edema and hypertension; fluid retention; dexamethasone C9 fluorination incrases mineralo- and gluco-act weight gain, osteroporosis, heperglycemia, flushed face and neck, acne, hirsutism, cushingoid " moom face" and "buffalo hump" and increased susceptibility to infection; The combination of clinical problems produced by prolonged, excess glucocorticoids, whether synthetic or endogenous, is termed Cushing's syndrome. (caused by high levels of cortisol in the blood )

C6 fluorination incrases gluco-act

endogenous, is termed Cushing's syndrome. (caused by high levels of cortisol in the blood ) betamethasone dexamethasone 17 -OH with 16 -OH or Me incrases gluco-act but abolish mineralo-act

triamcinolone acetonide fluorometholone

17/ 16 isopropylidenedioxygroup or an acetate ester in C21 enhances topical absorption

Triamcinolone differs from most glucocorticoids because it does not increase appetite.

used after laser-based refractive surgery. Fluorometholone acetate ophthalmic suspension is indicated for use in the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye.

Budesonide

Budesonide is a glucocorticoid steroid for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis. Additionally, it is used for inflammatory bowel disease.

Side effects of glucocorticoids (review version): immunosuppression hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance; caution in those with diabetes mellitus; cardiovascular effects: edema and hepertension; fluid retention; increased skin fragility, easy bruising; reduced bone density (osteoporosis, osteonecrosis, higher fracture risk, slower fracture repair); weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; adrenal insufficiency (if used for long time and stopped suddenly without a taper) muscle breakdown (proteolysis), weakness; reduced muscle mass and repair; expansion of malar fat pads and dilation of small blood vessels in skin anovulation, irregularity of menstrual periods growth failure, pubertal delay increased plasma amino acids, increased urea formation; negative nitrogen balance excitatory effect on central nervous system (euphoria, psychosis) glaucoma due to increased cranial pressure; cataracts

Comparative steroid potencies

Name Hydrocortisone (Cortisol)
Cortisone acetate

Glucocorticoid potency 1 0.8 3.5-5 4 5-7.5 25-80

Mineralocorticoid potency 1 0.8 0.8 0.8 0.5 0

Duration of action (t1/2 in hours) 8 oral 8, intramuscular 18+ 16-36 16-36 18-40 36-54

Prednisone Prednisolone Methylprednisolone Dexamethasone

Betamethasone Triamcinolone Beclometasone Fludrocortisone acetate DOCA Aldosterone

25-30 5 8 puffs 4 times a day equals 14 mg oral prednisone once a day 15 0 (Deoxy-corticosterone acetate) 0.3

0 0 200 20 200-1000

36-54 12-36 -

Mineralocorticoids

Na retaining / K excreting: control electrolyte and water levels, mainly by promoting sodium retention in the kidney.

aldosterone

Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water. It is formed in the outer (glomerular) layer of the adrenal cortex, the prototypical minralocorticoid. Aldosterone is part of the renin-angiotensin system. Spironolactone lower blood pressure by blocking the aldosterone receptor.

fludrocortisone acetate

With moderate glucocorticoid potency and much greater mineralocorticoid potency. Used to treat Addison disease and the classic salt wasting (21-hydroxylase deficiency) form of congenital adrenal hyperplasia. It has been used in the treatment of cerebral salt wasting and orthostatic intolerance.

mineralocorticoids receptor antagonists

spironolactone

diuretics similar to spironolactone, though it may be more specific for the mineralocorticoid receptor and is used as an adjunct in the specifically marketed for reducing cardiovascular risk management of chronic heart failure in patients following myocardial infarction

eplerenone

contraindicated in patients with hyperkalemia, severe renal impairment (creatinine Cl less than 30 ml/min), or severe hepatic impairment (Child-Pugh C).

Thyroid hormones

regualte growth and development , calorigenic and metabolic activity, through sensitization of beta-adrenergic receptors hance positive inotropic and chronotropic effects on the myocardium

TRH is secreted by the hypothalamus and stimulates the release of TSH from anterior Hepothalamicpituitary. Thyrotropin(TSH) stimulates the thyroid gland to produce T4 and T3. These pituitary-thyroid hormones regulate their own sysnthesis by binding to specific sites in the anterior pituitary feedback system and inhibiting the release TSH.

Bile acid sequestrants(BAS), calcium, ferrous sulfate, sucralfate, iron, and aluminum hydroxide antacids can decrease the abosrption of thyroid hormones. Take hormone 14 hr after taking those drugs phenytoin, carbamazepine, and rifampin accelertae thyroid metabolism. ( increase the dose of the thyroid hormone needed).

levo---4 letters---T4 Levo

levothyroxine T4

T4 / T3 in a ratio of 4:1; hypothyroidism: T4 less potent than T3 but longer duration of action myxedema (6-7 day versus 1-2 days); myxedema coma, cretinism , D_D: carefully with cholestyramine (acidic), simple goiter carbamazepine, cimetidine

side effects, mostly similar to hyperthyroidism: weight loss / tremor headache / upset stomach vomiting / diarrhea stomach cramps / nervousness irritability / insomnia excessive sweating increased appetite fever / changes in menstrual cycle sensitivity to heat temporary hair loss, particularly in children during the first month of therapy

lio--- 3 letters-T3

liothyronine T3

L-isomer of triiodothyronine (T3), a form of thyroid hormone used to treat hypothyroidism and myxedema coma. Liothyronine is the most potent form of thyroid hormone. In comparison to levothyroxine (T4), liothyronine has a faster onset of action as well as a shorter biological half-life, which may be due to less plasma protein binding to thyroxinebinding globulin and transthyretin.

sodium salts of T3/T4 Liotrix Thyroid USP Thyrotropin (TSH) Thyroxine

inhibitors

4:1 mixture of levothroxine sodium to liothyronine sodium

an adjunct in the detection and treatment of thyroid cancer

used in hyperthyroidism Graves diease and toxic adenoma K or Na iodide Lugol solution radioactive iodine used before thyroid surgery to make the thyroid gland firmer and reduce its size High concentration of iodide Used in older pts or with heart disease inhibit the enzyme iodoperoxidase

thiourylenes

propylthiouracil (PTU)

Agranulocytosis- leukopenia; 6-N-Propylthiouracil (PROP) is a thioamide drug used to Infectious lesions of the throat, the GI tract and skin with an overall feeling treat hyperthyroidism by decreasing the amount of thyroid it is used in hyperthyroidism, including of illness and fever. hormone produced by the thyroid gland. A decrease in blood platelets (thrombocytopenia); Graves disease. PTU inhibits the enzyme thyroperoxidase, to prevent adding iodide to the tyrosine residues on the hormone it has a risk of causing precursor thyroglobulin, thus forming thyroxine. PTU also agranulocytosis as a side effect. acts by inhibiting the enzyme 5'-deiodinase prevent converting T4 to the active form T3. PTU is generally well-tolerated ; The most common side effects: rash, itching, hives, abnormal hair loss, and skin pigmentation. Others: Swelling, nausea, vomiting, heartburn, loss of taste, joint or muscle aches, numbness and headache, allergic reactions, and hair whitening.

methimazole

Thioamides inhibit many steps in the synthesis of thyroid hormones, including the addition of iodide to thyroglobulin by the enzyme thyroperoxidase, a necessary step in the synthesis of thyroxine. Notably, they do not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate. Side effects: agranulocytosis, thrombocytopenia, and agranulocytopenia, it is contraindicated in pregnancy

antidiabetic agents

Type 1/2; Gestational diabetes mellitus (GDM), secondary DM

Type 1: beta cell destruction---absolute insulin deficiency; often immune mediated, but occasionally idioathic; prestents as acute metabolic symptoms of relative short duration in a child, adolescent or young adult; Ketoacidosis if untreated; the presentation may be more gradual in older individuals. In North America, 5-10 % of all patients with diabetes Type 2: insulin resistance combined with insulin deficiency, either can be predominant; presents as chorinic complications and increasingly frequent; prevalence in certain ethnic groups (aboriginal populaitons and obese children and adolesents) Gestational diabetes: glucose intolerance in pregnancy; insulin is the only choice for pregnant

Atypical antipsychotic agents: clozapine, olanzapine, quetiapine, risperidone, ziprasidone; beta-adrenergic agonists: atenolol, metoprolol, propranolol;...... Drugs that can cause Thiazide diuretics: hydrochlorothiazide, cyclothiazide, methyclothiazide, quinethazone, metolazone dysglycemia Protease inhibitors: _navir---- indinavir, ritonavir, tipranavir....... Glucocorticoids: Hydrocortisone, Betamethasone, Prednisone,Triamcinolone...... Others: Diazoxide; Interferon alfa; Nicotinic acid; Pentamidine; Phenytoin

insulin

secreted by -cells of the pancreas, a 51 amino acid protein composed of two polylpeptide chains; The purity of insulin can be measured by the content of proinsulin.

insulin-dependent diabetes hypoglycemia, sweating, tachycardia, hunger, mellitus(IDDM) that cannot be insulin shock with hypoglycemic conculsions controlled by diet alone hypersensitivity reacions or non-IDDM that cannot be controlled local irritation at the inject sites: lipoatrophy and lipohypertropy by diet or oral antidiabetic agents (rotate site of an injection needed) stress-induced hyperglycemia

used in Type 1 DM; life-threatening hyperkalemia;

short-acting

A shorter 15-30 min onset, 3-4 hr duration; 15 min before or after the initiation of a meal; have a lower propensity to cause hypoglycemia, thus recuding the need for snacks between meals lispro insulin insulin aspart insulin glulisine reversed in Lys29 and Pro28 of the B chain replaced the Pro28 with Asp of the B chain Asn3---Lysine Lys29---Glu the only type that can be given intravenously, soluble and prepared at neutral pH, it can be mixed with most other insulins (except glargine and detemir---long-acting insulin)

regular insulin
intermediate-acting

NPH
combination product: lispro/aspart insulin

Neutral Protamine Hagedorn insulin: the presence of protamine, along with low concentration of Zn, enhance the aggregation of insulin into dimers and hexamers after subcutaneous injection and prolongs its duration. neutral protamine lispro(NPL) / neutral protamine aspart(NPA) 30 / 70 U/ ml

long-acting

insulin glargine insulin detemir Lente Insulin Ultralente

a decreased solubility at physiological pH, precipitation and delayed absorption after subcutaneous injection and increased duration of action. Once dayly adm.

Oral Antidiabetic Agents

amide; ride; tide; formin; glitazone;glinide;

an adjunt to diet in treating NIDDM contraindicated in pregnancy that cannot be controlled by diet alone acidic diabetics: meglitinides / sulfonylureas / thiazolidinediones basic diabetics: -glucosidase inhibitors / biguanide: acrobose / metformin--no weight gain

Sulfonylureas

_amide _zide _ride gli- /gly2ed Gen. tolbutamide

acidic compounds, block ATP sensitive K channels, which stimulates the release of insulin form pnacreatic cells ( K channel blcokers)

type 2 DM; require some islet function. useless in type 1

Chlorpropamide can also be used in diabetes insipidus to reduce polyuria.

Weight gain,

chlorpropamide
Chlorpropamide can also be used in diabetes insipidus to reduce polyuria.

Weight gain, Hypoglycemia (esp. in patients with renal or hepatic insufficiency who are taking longer-acting agents chlopropamide GI effects: nausea, vomiting , diarrhea, constipation Hypersensitivity: skin rash, cross-sensitivity with compounds containing the benzene sulfonamide functional group( sulfanilamide antibacterial, thiazides, loop diuretics and carbonic anhydrase inhibitors) blood dyscrasias: leukopenia, thrombocytopenia, agranulocytosis, hemolytic anemia cholestatic jaundice

tolazamide
first generation

First-generation: disulfiram-like effects

gliclazide

acetohexamide

glyburide

more lipid soluble and potent than first generation

hyponatremia (mainly with chlorpropamide) contraindicated in type 1 and pregnancy

second generation

glipizide

Second-generation: hypoglycemia

gliquidone

Third generation

glimepiride

basic compund, Biguanide _formin do not stimulate the release of insulin, no hypoglycemia increase in insulin action in peripheral tissues inhibition of gluconeogenesis; increase glucose transport across skeletal muscle cell membrances inhibit hepatic gluconeogenesis Can potentiate the hypoglycemic effects of insulin and sulfonylureas; Metformin

Do not cause hypoglycemia matallic taste GI effects: epigastric distress, nausea, vomiting , diarrhea, anorexia; Most grave ADR: lactic acidosis

The combination of use of metformin and iodinated contrast media are contraindicated as it increases the risk of lactic acidosis; also avoid in pts with hepatic impairment or renal impairment; previous lactic acidosis; not associated with Weight gain but annoying with lactic acidosis

phenformin

fatal lactic acidosis( withdrawn from market in 1977

basic compund
-glucosidase inhibitors

Lowers postprandial blood glucose levels by delaying absorption of carbohydrates. Do not significantly inhibit intestinal lactase; inhibit the digestion of carbohydrates in the small intestine and therefore decrease the postprandial rise in glucose levels

Rarely cause hypoglycemia No weight gain; GI effects: diarrhea, abdominal pain, cramps,nausea; Contraindicated in pts with irritable bowel syndrome or IBD

monosaccharides miglitol

not available in Canada Do not cause hypoglycemia, but can potentiate the hypoglycemic effects of insulin and sulfonylureas; May elevate the serum transaminase enzyme level---monitoring AST level.

smaller compound, better absorbed and fewer GI effects glucose or dextrose is used for treatment hypoglycemia caused by acarbose (the digestion of sucrose is impaired by acrarbose, so table sugar is not suitable)

polysaccharides acarbose

Meglitinides

_glinide

acidic compounds stimulate release of insulin, more rapid onset of action and a shorter duration of action

no effect on type 1

Weight gain, Contraindicated in type 1 and pregnancy hepoglycemia upper respiratory infection, rhinitis and bronchitis headache and back pain hepoglycemia

repaglinide nateglinide

lowering postprandial glucose levels; Should be taken only with meals

Thiazolidinediones

_glitazone

acidic compounds bind to nuclear peroxisome proliferator-activated receptors(PPARs) involved in transcription of insulin-responsive genes and in regulation of adipocyte differentiation and lipid metabolism, enance the synthesis and translocation of glucose transporter proteins, enhance insulin sensitivity, and cause a favotable redistribution of fat. Active only when insulin is present; (no effect for type 1)

GI effects: epigastric distress, nausea, vomiting , diarrhea, abdominal fullness decrease in hemoglocin and white blood count during the first 4-8 weeks of therapy( reversible) upper respiratory infection, rhinitis and bronchitis headache weight gain and edema Avoid in pts with heart failure

rosiglitazone Do not cause hypoglycemia, but can potentiate the hypoglycemic effects of insulin and sulfonylureas; pioglitazone troglitazone withdrawn from market

D_D: cholestyramine, colestid, may reduce its absorption by 79%; Terfenadine may also reduce its serum levels.

hepatotoxicity (rare but can be severe and fatal,

Intestinal Lipase Inhibitors

Orlistat

treade name Xenical, OTC as alli, inhibitor of pancreatic lipases, an enzyme that breaks down triglycerides in the intestine. Should not be used as monotherapy for glycemic control. A drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake. The primary side effects of the drug are gastrointestinal-related, and include steatorrheathat is, oily, loose stools; because orlistat blocks some of the dietary fat from being absorbed, the fat is excreted unchanged in the feces, fecal incontinence, frequent or urgent bowel movements, and flatulence.

peptide mimetics

_tide

an adjunt therapy in combination with insulin or oral antidiabetic agents binds and activates the human GLP-1 receptor, stimulate glucose-dependent insulin synthesis, enhances insulin secretion by the pancreatic cells, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying CNS effects: asthenia , dizziness, restlessness, jittery effects GI effects: epigastric distress, nausea, vomiting , diarrhea, anorexia and gastroesophageal reflux metabolic effects: hepoglycemia and excess sweating( hyperhidrosis or diaphoresis

exenatide

inprove glycemic control in patients with type 2 diabetes who have not been adequately controlled by oral antidiabetic agents

pramlintide

slows gastric emptying, does not alter the overall absorption of nutrients; suppression of postprandial glucagon secretion and modulates central process, resulting in a decreased appetide and caloric intake

allergic reaction CNS effects: fatigue, dizziness, headache adjunct to mealtime insulin in patients GI effects: abdominal pain, anorexia, nausea, vomiting with both type 1 / 2 Arthralgia respiratory effects: cough and pharyngitis

anti-insulin Glucagon

Glucagon is a polypeptide secreted by the pancreas. It acts to enhance gluconeogenesis and glycogenolysis, thereby causing higher levels of glucose in the blood. Glucagon is used to treat severe hypoglycemia. It is generally administered intramuscularly or intravenously. -glucosidase inhibitors, biguanide and thiazolidinediones normally have lower chances of hypoglycemia because it is generally associtated with excessive secretion of insulin rather than a low intake of glucose. Those drugs do not stimulate the release insulin. Adrenergic manifestations: Shakiness, anxiety, nervousness, tremor; Palpitations, tachycardia; Sweating, feeling of warmth (diaphoresis); Pallor, coldness, clamminess; Dilated pupils (mydriasis); Feeling of numbness "pins and needles" (parasthaesia) in the fingers; Glucagon manifestations: Hunger, borborygmus; Nausea, vomiting, abdominal discomfort; Headache

Symptoms of Hypoglycemia

Neuroglycopenic manifestations: Abnormal mentation, impaired judgement; Nonspecific dysphoria, anxiety, moodiness, depression, crying; Negativism, irritability, belligerence, combativeness, rage; Personality change, emotional lability; Fatigue, weakness, apathy, lethargy, daydreaming, sleep; Confusion, amnesia, dizziness, delirium; Staring, "glassy" look, blurred vision, double vision; Automatic behavior, also known as automatism; Difficulty speaking, slurred speech; Ataxia, incoordination, sometimes mistaken for "drunkenness"; Focal or general motor deficit, paralysis, hemiparesis; Paresthesia, headache; Stupor, coma, abnormal breathing; Generalized or focal seizures;

drug interactions:

(also see above review Diabetes is the leading cause of renal failure in the world, ACEIs (enalapril, etc) reduces the risks of renal insufficiency by 50% and ends point death associated version) with diabetes. thiazide diuretics h in blood glucose levels by altering carbohydrate metabolism

-blockers

petentiate hypoglycemia by inhibiting flycogenolysis and glucagon release can also promote hyperglycemia by inhibiting insulin secretion and decreasing tissue sensitivity to insulin can mask the sighs of hypoglycemia by blunting the reflex tachycardia h the efficacy of antidibetic agents by promoteing insulin resistance; glucocorticoids produce metabolic effects that are opposite those of insulin

oral contraceptives

glucocorticoids phenytoin
sympathomimetics

corticotropin ACTH salicylates isoniazid angrogens anabolic steroids MAOIs

4-Fluoroquinolones specific interactions

cause hypoglycemia ( only in diabetic patients monoamine oxidase inhibitors ciprofloxacin, ofloxacin stimulate insulin secretion and can contribute to hypoglycemia cause alterations in blood glucose levels: hypoglycemia / hyperglycemia

sulfonylureas

highly plasma protein bound, oxidatively metabolized by cytochrome P450 enzymes, may have interactions with: drugs capable of causing plasma protein displacement: fibrates, sulfonamides, phenylbutazone Potassium channel openers: minoxidil and diazoxide drugs capable of inducing or inhibiting cyctochrome P450 enzymes increased risk of lactic acidosis and acute renal failure can occur if metromin is co-administered with: cationic drugs: amiloride, cimetidine, dofetilide, midodrine,morphine, procainamide, quinidine, quinine, ranitidine, triamterene, cancomycin, may interfere with the renal tubular secretion of merformin; iodinated contrast materials corticosteroids similar as sulfonylureas

biguanide

meglitinides
thiazolidinediones

-glucosidase inhibitors

may impair the oral absorption of digoxin

peptide mimetics

decrease the rate and extent of oral absorption of other drugs owing to their ability to slow gastric emptying. Avoid co-administration with drugs that significantly alter gastric motility:antimuscarinics pramlintide and insulin should not be mixed together but rather administered as separate injections

carbohydrate intolerence of varying severity during pregnancy; It is associated with increased risk of macrosomia (high birth weight), neonatal hypoglycemia, hyperbilirubinemia, hypocalcemia and polycythemia. May also increase the risk of childhood obesity and diabetes in the offspring and the mother.
Gestational Diabetes

insulin only

Usually detected towards the end of the second trimester based on the abnormal response to a 75 g oral glucose tolerance test. Should discontinue all oral antihyperglycemic agents, ACE inhibitors, and ARBs before conception; Optimize glycemic control with diet, if necessary insulin.

Agents for Asthma

Inhaled 2-agonists

albuterol
short-acting bitolerol

pritbuterol formoterol
long-acting

Onset of action: 5-15 min 2-selective adrenergic agonists that induce Duration of action: 2-3 hr broncodilation through activation of adenylate cyclase, causing an increase in cAMP levels and resulting in smooth muscle relaxation in the airways. Onset of action: 15 min (formoterol); 15-30 min (salmeterol) Duration of action: 12 hr

Tachycardia, skeletal muscle tremor,CNS tremor, hypokalemia, hyperglycemia, prolonged QT, interval(in overdose), hypotension

salmeterol salbutamol
Mast cell stabilizers (inhaled)

cromolyn

Block early and late reaction to allergen. Stabilize mast cell membranes and inhibit activation and release of inflammatory mediators from eosinophils and epithelial cells, inhibiting bronchoconstriction caused by exercise and cold dry air. Onset of action: 10-15 min Duration of action: 1-2 hr

Cromolyn sodium (Intal, Nasalcrom, Opticrom) is a drug with anti-asthmatic, antiallergy, and mast cell stabilizing activity. It has no bronchodilator or anti-inflammatory activity.Cromolyn products are used prophylactically to treat bronchial asthma, allergic rhinitis, and mastocytosis. Cromolyn is effective in antigen-induced asthma, occupation-exposure asthma, and in some cases of intrinsic asthma. Cromolyn should not be used in treating acute asthmatic attacks. Administration of cromolyn by inhalation is most effective in treating patients.

nedocromil

Corticosteroids (inhaled)

beclomethasone

budesonide flunisolide fluticasone triamcinolone

Beclomethasone is generally reserved for patients in whom bronchodilators and other nonsteroidal medications have not been Onset of action; 7-14 days; full effect totally successful in controlling asthmatic attacks. When used with a may not be realized for 6-8 wk. bronchodilator administered by inhalation, the beclomethasone dipropionate should be administered several minutes after the Adverse effects minimized by bronchodilator in order to enhance the penetration of the administering with a spacer and by Block late reaction to allergen and reduce airway beclomethasone into the bronchial tree. rinsing the oral cavity with water -after hyperresponsive-ness, Inhibit production of cytokines inhalation. responsible for initiation of inflammatory cascade, Cough, dysphonia, ora candidiasis (thrush). High doses may cause systemic effects (e.g., adrenal and growth suppression, osteoporosis, skin thinning, and cataracts).

Leukotriene modifiers ~receptor antagonists montelukast

_lukast

Headache, abdominal pain, hepatotoxicity ( 2%), Churg-Strauss syndrome (rare).

zafirlukast

5-lipoxygenase inhibitor

zileuton

Headache, hepatotoxicity (12%) Abdominal pain, nausea. Churg-Strauss syndrome (rare).

Bronchodilators

Albuterol Levalbuterol Clenbuterol 2-agonists Pirbuterol Anticholinergics Salmeterol Elphedrine

Bronchodilators are substances that dilate the bronchi and bronchioles, decreasing airway resistance and thereby facilitating airflow. most useful in obstructive lung diseases, of which asthma and chronic obstructive pulmonary disease are the most common conditions. they might be useful in bronchiolitis. They are often prescribed but of unproven significance in restrictive lung diseases.

Side-effects: increased heart rate; hyperactivity; feeling nervous, shaky, or over-excited; and, very rarely, upset stomach or difficulty sleeping.

Serevent (salmeterol) Ventolin (salbutamol = albuterol) Xopenex (levosalbutamol = levalbuterol)

Primatene (ephedrine) Proventil (salbutamol = albuterol)

Oral - Long-acting albuterol is available in pill or syrup form. Effective for 12 hours, albuterol is particularly helpful for nighttime asthma symptoms. Because this medication requires high dosing, there tend to be increased side-effects. Therefore it is not Spiropent (clenbuterol) commonly prescribed.
Accu-Hale Maxair (pirbuterol)

Ritodrine

used for smooth muscle relaxation;

Anticholinergics

ipratropium bromide

Only available as an inhalant, ipratropium bromide It can take a full hour to begin working Most common side-effect: Dry throat . relieves acute or new asthma symptoms. Because it and plays a minor role in asthma has no effect on asthma symptoms when used alone, treatment. If the medication gets in contact with the eyes, it may cause blurred it is most often paired with a short-acting 2-agonist. vision for a brief time.

It acts by blocking muscarinic receptors in the lung, inhibiting bronchoconstriction and mucus secretion.

It is a non-selective muscarinic antagonist, and does not diffuse into the blood, which prevents systemic side effects. Ipratropium is a derivative of atropine but is a quaternary amine and therefore does not cross the blood-brain barrier, which prevents central side effects (anticholinergic syndrome). Ipratropium is considered a short-acting bronchodilator.

Salbutamol

Ipratropium combined with albuterol (salbutamol) (trade names Combivent and Duoneb) Ipratropium combined with fenoterol (trade names Duovent and Berodual N)

for the management of chronic obstructive pulmonary disease (COPD) and asthma. for the management of asthma.

Dry mouth and sedation have been reported.

Berodual N

Xanthine

A group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in treating the symptoms of asthma. They only inhibit the actions of sleepinessinducing adenosine, making them somewhat less effective as stimulants than sympathomimetic amines. Due to widespread effects, the therapeutic range of xanthines is narrow, (merely a second-line asthma treatment). The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia. Methylated xanthine derivatives include caffeine, paraxanthine, theophylline, and theobromine which inhibit phosphodiesterase and antagonise adenosine. Xanthines are also found very rarely as constituents of nucleic acids.

theophylline (dimethylxanthine

The main actions: relaxing bronchial smooth muscle increasing heart muscle contractility and efficiency: positive inotropic increasing heart rate: positive chronotropic increasing blood pressure increasing renal blood flow some anti-inflammatory effects central nervous system stimulatory effect mainly on the medullary respiratory center.

used in therapy for respiratory diseases : COPD or asthma; D_D: Cimetidine and Phenytoin, Erythromycin, Ciprofloxacin, Oral contraceptives), Its toxicity is increased by erythromycin, cimetidine, and fluoroquinolones. It can reach toxic levels when taken with fatty meals, an effect called dose dumping. Narrow therapeutic index (monitored to avoid toxicity). Cause nausea, diarrhea, increase in heart rate, arrhythmias, and CNS excitation (headaches, insomnia, irritability, dizziness and lightheadedness) .

Pentoxifylline

Pentoxifylline is a PDE4 inhibitor increasing intracellular cAMP and stimulating PKA activity. It is also a known inhibitor of Tumor necrosis factor-alpha. It is used to treat intermittent claudication resulting from obstructed arteries in the limbs, and vascular dementia. It was also used in alcoholic heptatitis and renal impairment; Pentoxifylline improves blood flow through blood vessels and therefore helps with blood circulation in the arms and legs. For conservative treatment of Peyronie's disease and neuropathic injuries.

Additionally, as a PDE inhibitor, Pentoxifylline may be useful as a treatment for erectile dysfunction. It also helps prevent strokes, can be used in managing sickle cell disease and improves blood flow to the brain. Pentoxifylline has also been used to treat nausea and headaches in the mountains (altitude sickness), and has been shown to reduce mortality in acute alcoholic and non-alcoholic steatohepatitis, presumably through its ability to inhibit TNF-alpha.

Interferons Opioids TNF binding proteins Mycophenolate

Anticancer drugs antineoplastic

The majority of chemotherapeutic drugs: alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way. Some newer agents don't directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors e.g. imatinib mesylate (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors).

M: mitotic-I s G1: pre-aspa S: antimetab G2: bleo-etopo

Phase-specific agents: M (mitotic inhibitors: Vinca alkaloids; taxanes); G1 (Asparaginase; Prednisone) S (antimetabolites); G2 (Bleomycin; etoposide) Phase-nonspecific agents: (alkylating agents, antitumor antibiotics) Cell cycle-nonspecific agents: (carmustine, lomustine, radiation) Bone marrow suppression (myelosuppression, dose-limiting: neutropenia, febrile neutropenia; thromboctopenia, anemia) Dermatological toxicity (alopecia; ulceration or necrosis by vesicant chemotheraphy drugs(dactinomycin, daunorubicin, doxorubicin, idarubicin, mechlorethamine, mitomycin, vinblastine, vincristine, and vinorelbine), skin changes) GI toxicities ( nausea and vomiting which may be acute, delayed, or anticipatory; stomatitis)

Tumor lysis syndrome (TLS, the intracellular products from the lysis of cells may lead to renal failure and cardiac arrhythmias; including the uric acid, potassium, and phosphate. It can be prevented by alkalinizing the urine by allopurinol or rasburicase) Hypercalcemia / Chills and fever Pulmonary toxicity ( generally irreversible and may be fatal)---- bleomycin, busulfan, carmustine, mitomycin

Cardiac toxicity (daunorubicin, doxorubicin,epirubicin, mitoxantrone; Dexrazoxane as a

cardioprotective agent may be used with doxorubicin);

Hypersensitivity reactions (asparaginase, carboplatin, cisplatin, etoposide, paclitaxel, teniposide) Neurotoxicity (Cincristine, cisplatin, cytarabine, methotrexate) Hemorrhagic cystitis (cyclophosphamide, ifosfamide)

Renal toxicity Hepatotoxicity Secondary malignancies; Infertility cyclo-ifo collapse hemo

Alkylating agents
Nitrogen mustards Chlorambucil Chlormethine

___mustin---paltin---sulfan---bazine---quone---amide---

Cyclophosphamide

also known as cytophosphane, from the oxazophorines group. It is used to treat various types of cancer and some autoimmune disorders as immunosuppressive agent. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity.

Hemorrhagic cyctitis (irritation of the lining of the bladder by acrolein, a metabolite of these two drugs)

Ifosfamide

Trofosfamide Melphalan Bendamustine Uramustine

Nitrosoureas

_mustine Carmustine being investigated for use in the treatment of melanoma

Fotemustine Lomustine Nimustine Prednimustine Ranimustine Semustine Streptozocin

Streptozocin is an alkylating agent with the capacity to cross-link DNA, thereby inhibiting its synthesis. It is a nitrosourea-like antibiotic that contains a glucosamine moiety that allows it to be selectively taken up by the cells of the islets of Langerhans. Consequently, it can be useful in treating metastatic islet cell carcinoma.

Platinum (alkylating-like)

_platin Carboplatin A platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. Platinum complexes are formed in cells, which bind and cause Crosslinking of DNA-- ultimately triggering apoptosis.

Cisplatin

Side reactions

Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the pts' creatinine clearance is reduced. Neurotoxicity (nerve damage); Nausea and vomiting: Cisplatin is one of the most emetogenic chemotherapy agents, but this is managed with prophylactic antiemetics (e.g. ondansetron, granisetron, etc.) in combination with corticosteroids. . Ototoxicity (hearing loss): Other ototoxicity drugs (such as the aminoglycoside antibiotic class) should be avoided co-admn. Alopecia (hair loss): this is generally not a major problem in patients treated with cisplatin. Electrolyte disturbance: hypomagnesaemia, hypokalaemia and hypocalcaemia.

Nedaplatin Oxaliplatin Triplatin tetranitrate Satraplatin

Alkyl sulfonates

_sulfan

Busulfan Mannosulfan Treosulfan

Hydrazines

Procarbazine
Triazenes

Dacarbazine Temozolomide
Aziridines

used for the treatment of Grade IV astrocytoma -- an aggressive brain tumor, also known as glioblastoma multiforme.

Carboquone ThioTEPA Triaziquone Triethylenemelamine

Antitumor antibiotics

Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) Anthracenediones (Mitoxantrone, Pixantrone) Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) Hydroxyurea

Anthracycline

_rubicin

Intercalation into DNA, which leads to blockade of DNA and RNA synthesis; DNA strand breaks; free radical formation. (Daunomycin) used to acute myeloid leukemia and acute lymphocytic leukemia, initially isolated from Streptomyces peucetius. Used to treat a wide range of cancers, including: leukemias, lymphomas, breast, uterine, ovarian, and lung cancers.

main adverse effects are heart damage (dose related, myocardial toxicity/cardiotoxicity), and vomiting. Caution in pts with CHF

Daunorubicin

Daunorubicin Doxorubicin Doxorubicin Epirubicin Idarubicin Valrubicin

(liposomal) (Adriamycin) (liposomal)

Cardiotoxicity (increased risk when lifetime cumulative dose equivalent to doxorubicin 400-550 mg/m 2 is exceeded), alopecia, vesicant, nausea/vomiting (moderate to high emetogenic potential for doses> 60 mg), mucositis, myelosuppression (primarily leukopenia, nadir 10 to 14 days).

used only to treat bladder cancer Pulmonary fibrosis related drugs: bleomycin, bromocriptine, busulfan, carmustine, mitomycin,pentamidine, tocaininide; (bleo-bromo-busul-penta-tacain

Pulmonary fibrosis related drugs: bleomycin, bromocriptine, busulfan, carmustine, mitomycin,pentamidine, tocaininide; (bleo-bromo-busul-penta-tacain structural analogs of naturally occurring substrates for biochemical ractions----inhibit DNA synthesis by acting as false substitutions

Antimetabolites

Folic acid (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed) Purine (Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine)----rabine, ribine Pyrimidine (Cytarabine, Decitabine, Fluorouracil/Capecitabine, Floxuridine, Gemcitabine, Enocitabine, Sapacitabine) --tabine

Methotrexate

autoimmune diseases: ankylosing MTX, is an antimetabolite and antifolate drug used in spondylitis, Crohn's disease, treatment of cancer and autoimmune diseases. psoriasis, psoriatic arthritis, rheumatoid arthritis, and scleroderma It acts by inhibiting the metabolism of folic acid. (disease-modifying antirheumatic drugs).DMARDs Methotrexate replaced the more powerful and toxic antifolate aminopterin, and the two should not be A parallel use with TNF blockers as confused with each other. infliximab or etanercept has been shown to markedly improve symptoms.

side effects: anemia, neutropenia, increased risk of bruising, nausea and vomiting, dermatitis and diarrhea. hepatitis, and increased risk of pulmonary fibrosis may occur. The higher doses can cause toxic effects to the rapidly-dividing cells of bone marrow and gastrointestinal mucosa. Highly teratogenic drug (Pregnancy Category X There is a risk of a severe adverse reaction if penicillin is prescribed alongside methotrexate.

Azacytidine 5-Fluorouracil Pentostatin Fludarabine Gemcitabine 5-FU; Side effects: myelosuppression, mucositis, dermatitis, diarrhea and cardiac toxicity. Do not confused with HMG CoA reductase inhibitors (Stastins: -astatin ----lovastatin

Mitotic inhibitors

Taxanes (Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine) Ixabepilone

Vin-taxel stop mito

Taxane Docetaxel

inhibition cell division by promoting microtubule assembly and stabilization,

Indicated for breast cancer and non-small lung cancer. Closely monitored for abnormal liver function and neutropenia (bilirubin, SGOT/SGPT, CBC); Reported severe fluid retention or edema, caution in pts with CHF;

Paclitaxel

Before initiating therapy, the pts need to be pretreated with corticosteroid, diphenhydramine, or H2-receptor antagonists to prevent the hypersensitivity reactions that are generally associated with the use of Taxels; Complete AV block, syncope, angioedema, and dyspnea are reported side effects of the drug.

Vinca alkaloids Vinblastine

arrest cell division by preventing microtubule formation

breast cancer non-small cell lung cancer.

Vincristine Vinorelbine

Low incidence of nausea and vomiting. (10%)

Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan)

topoisomerase inhibitors

Podophyllum (Etoposide, Teniposide) a topoisomerase 1 inhibitor. It is used to treat ovarian Topotecan is the first topoisomerase cancer and lung cancer, as well as other cancer inhibitor for oral use. types. IV, Oral admn.

Topotecan

Etoposide

an inhibitor of the enzyme topoisomerase II. Chemotherapy for malignancies such as Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, non-lymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.

Enzymes asparaginase

Pegasparaginase
Protein tyrosine kinase inhibitors

Axitinib Bosutinib Cediranib Dasatinib Erlotinib Gefitinib Imatinib Lapatinib Lestaurtinib Nilotinib Semaxanib Sorafenib Sunitinib Vandetanib Imatinib mesylate Erlotinib

Cyclin-dependent kinase inhibitors

Alvocidib Seliciclib
Hormones Tamoxifen

Estradiol tesosterone
Photosensitizers Aminolevulinic acid/Methyl aminolevulinate Efaproxiral Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin) Others

tretinoin (ARTA) Arsenic trioxide bortezomib bexarotene

all-trans retinoic acid

acute leukemia, APL

proteosome inhibitor

multiple myeloma mantle cell lymphoma.

thalidomide

as an angiogenesis inhibitor by interfering with the growth of new blood vessels needed for tumor growth and survial; inhibits the production of tumor necrosis factor alpha (TNF-a) production --- causes oxidative damage to DNA; stimulate human T cells. Used in multiple myeloma

Biological response modigiers

cytokine

soluble factors secreted or released by cells that affect the acitvity of other cells and/or the secreting cell itself. Generally act as regulatory or hematopoietic growth factors

monoclonal antibodies _zumab

bevacizumab alemtuzumab Gemtuzumab ozogamicin Ibritumomab tiuxetan Efalizumab

identify cancer-specific antigens binding to the cancer cells, allowing immune system to eliminate those cells.

Receptor tyrosine kinase (Cetuximab, Panitumumab, Trastuzumab) CD20 (Rituximab, Tositumomab) other (Alemtuzumab, Bevacizumab, Edrecolomab, Gemtuzumab) metastatic colon cancer

plaque psoriasis a monoclonal antibody made by Genentech / Novartis and used mainly in allergy-related asthma therapy, with the purpose of reducing allergic hypersensitivity. Xolair (Omalizumab) is a recombinant DNA-derived humanized IgG1k monoclonal antibody that selectively binds to human immunoglobulin E (IgE). IgE is commonly involved with allergies when present in high amounts in the body. Titanium dioxide is the most widely used white pigment because of its brightness and very high refractive index (n=2.7), in which it is surpassed only by a few other materials.

Omalizumab

Titanium dioxide

Immunosuppressive agents

Calcineurin inhibitors

cyclosporine

widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection in transplants of skin, heart, kidney, liver, lung, pancreas, bone marrow and small intestine. Also used in inflammatory bowel disease; psoriasis, renal impairment, rheumatoid arthritis;

D_D of cyclosporine: CYP inducers: phenytoin, phenobarbital, caramazepine, Rifampin, isoniazid, St. John's Wort CYP inhibitors: Ketocinazole, fluconazole, itraconazole, erythromycin, Josamycin, Verapamil, Diltiazem, Nicardipine, Grapefruit juice;

tacrolimus
antimetabolites

Azathioprine Mycophenolic acid

Methotrexate

Glucocorticoids suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and IFN-, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation. glucocorticoids Glucocorticoids do however not only reduce T cell proliferation, another well known effect is glucocorticoid induced apoptosis. The effect is more prominent in immature T cells that still reside in the thymus, but also affect peripheral T cells.

cytostatics

Cytostatics inhibit cell division. In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells. Due to their highest effectiveness, purine analogs are most frequently administered.

Alkylating agents

nitrogen mustards (cyclophosphamide), nitrosoureas, platinum compounds, and others. Cyclophosphamide is probably the most potent immunosuppressive compound. folic acid analogues, such as methotrexate purine analogues such as azathioprine and mercaptopurine pyrimidine analogues protein synthesis inhibitors.

Antimetabolites

Methotrexate

As a folic acid analogue it act as an antagonist. It binds dihydrofolate reductase and prevents synthesis of tetrahydrofolate. It is used in the treatment of autoimmune diseases (for example rheumatoid arthritis) and in transplantations. It may raise the uric acid concentration, should be carefully used in pts with gout.

Azathioprine

The main immunosuppressive cytotoxic substance. It is extensively used to control transplant rejection reactions. It is nonenzymatically cleaved to mercaptopurine, that acts as a purine analogue and an inhibitor of DNA synthesis. Mercaptopurine itself can also be administered directly. By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It is also efficient in the treatment of autoimmune diseases.

Cytotoxic antibiotics

actinomycin is the most important. It is used in kidney transplantations. Other cytotoxic antibiotics are anthracyclines, mitomycin C, bleomycin, mithramycin.

antibodies Polyclonal antibodies Monoclonal antibodies T-cell receptor directed antibodies IL-2 receptor directed antibodies

used as a quick and potent immunosuppression method to prevent the acute rejection reaction.

drugs acting on immunophilins

Calcineurin inhibitors

cyclosporine or ciclosporin

widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection in transplants of skin, heart, kidney, liver, lung, pancreas, bone marrow and small intestine. Also used in inflammatory bowel disease; psoriasis, renal impairment, rheumatoid arthritis and many other autoimmune disorders. D_D of cyclosporine:

Ciclosporin interacts with a wide variety of other drugs and other substances including grapefruit juice. There have been studies into the use of grapefruit juice to increase the blood level of cyclosporin. Side effects: gum hyperplasia, convulsions, peptic ulcers, pancreatitis, fever, vomiting, diarrhea, confusion, breathing difficulties, numbness and tingling, pruritus, high blood pressure, potassium retention and possibly hyperkalemia, kidney and liver dysfunction (nephrotoxicity & hepatotoxicity), and obviously an increased vulnerability to opportunistic fungal and viral infections.

CYP inducers: Phenytoin, Phenobarbital, Caramazepine, Rifampin, Isoniazid, St. John's Wort CYP inhibitors: Ketocinazole, fluconazole, itraconazole, erythromycin, Josamycin, Verapamil, Diltiazem, Nicardipine, Grapefruit juice;

Tacrolimus

Side effects can be severe and include blurred vision, liver and kidney problems (it is nephrotoxic), seizures, tremors, hypertension, hypomagnesemia, diabetes mellitus, hyperkalemia, itching, insomnia, confusion, loss of appetite, hyperglycemia, weakness, Used particularly in the liver and kidney Use in treating ulcerative colitis depression, cramps, and neuropathy, as well as potentially transplantations, also in heart, lung and heart/lung increasing the severity of existing fungal or infectious conditions transplants. It binds to an immunophilin, followed by Dermatological use:in the treatment of such as herpes zoster or polyoma viral infections. the binding of the complex to calcineurin and the eczema, particularly atopic dermatitis. inhibition of its phosphatase activity--- prevents the Tacrolimus and a related drug for eczema (pimecrolimus) were cell from transitioning from the G0 into G1 phase of Tacrolimus ointment is used primarily suspected of carrying a cancer risk, though the matter is still a the cell cycle. Tacrolimus is more potent than to treat atopic dermatitis subject of controversy. cyclosporin and has less-pronounced side-effects. A fungal product (Streptomyces tsukubaensis). It is a Immunosuppresion following macrolide lactone and acts by inhibiting calcineurin. transplantation

TNF- inhibitor

Thalidomide Alkylating agents

nitrogen mustards cyclophosphamide nitrosoureas platinum compounds

Antibodies

-mab Muromonab-CD3

monoclonal OKT3

Daclizumab Basiliximab Efalizumab

Polyclonal

used to treat psoriasis. a recombinant humanized monoclonal antibody that binds to CD11a and acts as an immunosuppressant. It is administered once weekly by subcutaneous injection. Anti-thymocyte globulin Anti-lymphocyte globulin

Fusion protein

.-cept Abatacept Aflibercept Alefacept Belatacept Rilonacept TNF inhibitor Etanercept Etanercept indicated for polymyalgia rheumatica, psoriasis, Severe Rheumatoid Arthritis

mTOR

.-rolimus

Mammalian target of rapamycin Sirolimus Deforolimus Everolimus Temsirolimus Zotarolimus

Corticosteroids

Prednisone Methylprdnisolone

H 2 -Receptor Antagonists

To block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonist are used in the treatment of dyspepsia, although they have largely been surpassed in popularity by the more effective proton pump inhibitors. In the United States, all four FDA-approved members of the groupcimetidine, ranitidine, famotidine, and nizatidineare available over the counter in relatively low doses. Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists.

H2-antagonists are clinically used in the treatment of acid-related Gastrointestinal conditions: Peptic ulcer disease (PUD) Gastroesophageal reflux disease (GERD) Dyspepsia Prevention of stress ulcer (a specific indication of ranitidine)

generally well-tolerated (except for cimetidine) Infrequent ADRs include hypotension. Rare ADRs include: headache, tiredness, dizziness, confusion, diarrhea, constipation, and rash. In long-term use of H2 blockers appeared to increase the risk of cognitive decline

Cimetidine

Cimetidine is an inhibitor of the P450 enzymes CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. By reducing the metabolism of drugs through these enzymes, cimetidine may increase their serum concentrations to toxic levels. Many drugs are affected, including warfarin, theophylline, phenytoin, lidocaine, quinidine, propranolol, labetalol, metoprolol, tricyclic antidepressants, some benzodiazepines, dihydropyridine calcium channel blockers, sulfonylureas, metronidazole, and some recreational drugs such as ethanol and MDMA. Cimetidine should be used with caution in cases of hepatic impairment and cardiovascular disease Cimetidine may also cause gynecomastia in males, loss of libido, and impotence, which are reversible upon discontinuation.

Ranitidine

longer-acting H2-receptor antagonists

Ranitidine is not as potent a CYP inhibitor as cimetidine, although it still shares several of the latter's interactions (such as with warfarin, theophylline, phenytoin, metoprolol, and midazolam).

Famotidine

Famotidine has negligible effect on the CYP system, and appears to have no significant interactions.

Nizatidine

Gastroesophageal reflux disease (GERD)

also called Gastro-oesophageal reflux disease (GORD), defined as chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus. This is commonly due to transient or permanent changes in the barrier between the esophagus and the stomac. If the reflux reaches the throat, it is called laryngopharyngeal reflux disease. The most-common symptoms: heartburn, regurgitation, trouble swallowing (dysphagia), and chest pain; Pain with swallowing (odynophagia), excessive salivation, and nausea also may occur. GERD sometimes causes injury of the esophagus: Reflux esophagitis; Esophageal strictures; Barrett's esophagus; Esophageal adenocarcinomaa rare form of cancer.

PPIs proton pump inhibitors

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (gastric proton pump) of the gastric parietal cell. Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%. They are the most potent inhibitors of acid secretion available today. Structurally, the vast majority of these drugs are benzimidazole derivatives

Common adverse effects include: headache, nausea, diarrhea, abdominal pain, fatigue, dizziness. Infrequent adverse effects include: rash, itch, flatulence, constipation. Decreased cyanocobalamin (vitamin B12) absorption may occur with long-term use. Rarely PPI cause idiosyncratic reactions such as erythema multiforme, pancreatitis, Stevens Johnson syndrome and acute interstitial nephritis.

These drugs are utilized in the treatment of many conditions such as: Dyspepsia Peptic ulcer disease (PUD) Gastroesophageal reflux disease (GORD/GERD) Laryngopharyngeal Reflux Disease Barrett's esophagus prevention of stress gastritis Gastrinomas and other conditions that cause hypersecretion of acid Zollinger-Ellison syndrome (brand names: Losec, Prilosec, Zegerid, ocid) Omeprazole

PPIs reduce absorption of antifungals (itraconazole and ketoconazole) and possibly h plasma concentrations of Digoxin and Cilostazol (risk of toxicity) Absorption of PPIs possibly reduced by: sucralfate / ampicillin / bisacodyl / delavirdine fluvoxamine / iron salts theophylline voriconazole / aminophylline and theophylline astemizole

_prozole

Omeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole in penicillin-hypersensitive patients) in the 7-14 day eradication triple therapy for Helicobacter pylori.

Lansoprazole

(brand names: Prevacid, Zoton, Inhibitol)

Esomeprazole

(brand names: Nexium) Can cause serious abdominal pain and or serious muscle spasms induced by alchohol. DO NOT TAKE WITH DEPRESSION PILLS

Pantoprazole

(brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan)

Rabeprazole

(brand names: Rabecid, Aciphex, Pariet, Rabeloc)

hypersensitivity to Rabeprazole, substituted benzimidazoles or any of components of its pharmaceutical forms. pregnancy lactation

Sucrose sulfate-aluminium Sucralfate complex

an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Sulcrate in Canada. Sucralfate is also used for the treatment of GERD and stress ulcers. Unlike the other classes of medications used for treatment of peptic ulcers, sucralfate is a sucrose sulfate-aluminium complex that binds to the hydrochloric acid in the stomach and acts like an acid buffer with cytoprotective properties. The most common side effects: constipation and bezoar formation. Less commonly reported: flatulence, cephalalgia (headache), hypophosphatemia, and xerostomia (dry mouth).

Prokinetics

Used on the digestive system. It includes all drugs whose primary effect is to augment the speed of intestinal transit, by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm. They are mostly used to treat or prevent pathological gastroesophageal reflux, or to speed up absorption of certain other drugs. Some of them can also be used to help in the treatment of nausea or other symptoms associated with dyspepsia.

8 prokinetics:

-mide or -pride: Domp- Erythro- ItoMetoBenza- Cisa- MosaPrucaBCDE IMMP

These drugs may increase acetylcholine concentrations by inhibiting dopamine D2 receptors and acetylcholinesterase. Higher acetylcholine would increase GI peristalsis and further increase the lower esophageal sphincter pressure, thereby stimulating gastric motility and accelerating gastric emptying and improve gastro-duodenal coordination. Some of these drugs may or may not have affinity for the 5-HT4 receptors depending on their class such as some benzamides like cisapride and mosapride which are 5-HT4 agonists. The affinity of cisapride for 5-HT4 receptors in the heart has been implicated as a potential cause of cardiac arrhythmias.

Domperidone

Dopamine antagonists; used orally, rectally or intravenously, generally to suppress nausea and vomiting. It has also Can prolong QT interval; GI effects; hyperprolactinemia, drowness, been used to stimulate lactation. restlessness Parkinson's disease: does not cross the blood-brain barrier. Used to treat: (Reglan) bind to dopamine D2 receptors where it is a Anorexia nervosa, headache in adults and children; nausea and vomiting in pregnancy and cancer pts; receptor antagonist, palliative care, persistent hiccoughs, renal impairment

Metoclopramide

Also a mixed 5-HT3 receptor antagonist / 5-HT4 receptor agonist.

Metoclopramide is also used to treat heartburn caused by GERD; and useful in the treatment of gastric stasis. Also commonly used in diabetic gastroparesis. Can prolong QT interval; GI effects; hyperprolactinemia, drowness, restlessness

Erythromycin Benzamide Prucalopride Cisapride Mosapride Itopride (withdrawn for human use in the US) Heart burn

Bismuth subsalicylate

used to treat nausea, heartburn, indigestion, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract. Commonly known as pink bismuth, it is the active ingredient in popular medications such as Pepto-Bismol and (modern) Kaopectate. As a derivative of salicylic acid, bismuth salicylate displays anti-inflammatory action and also acts as an antacid.

Phosphodiesterase inhibitor

A drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), by the respective PDE subtype(s).

Non-selective PDEIs

caffeine, a minor stimulant theophylline, a bronchodilator IBMX (3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research

PDE1 selective inhibitors Vinpocetine

PDE2 selective inhibitors

EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) Enoximone used clinically for short-term treatment of cardiac failure(CHF). These drugs mimic sympathetic stimulation and increase cardiac output. PDE3 is sometimes referred to as cGMP-inhibited phosphodiesterase. PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells. PDE4 inhibitors have proven potential as anti-inflammatory drugs, especially in inflammatory pulmonary diseases such as asthma, COPD and rhinitis. They suppress the release of cytokines and other inflammatory signals and inhibit the production of reactive oxygen species. PDE4 inhibitors may have antidepressive effects[5] and have also recently been proposed for use as antipsychotics.

PDE3 selective inhibitors Milrinone

Amrinone Mesembrine Rolipram Ibudilast Pentoxifylline

PDE4 selective inhibitors

Ibudilast

a neuroprotective and bronchodilator drug used mainly in the treatment of asthma and stroke. It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor depending on the dose.

Pentoxifylline

Pentoxifylline is a xanthine derivative (see above); a drug that potentially enhances circulation and may have applicability in treatment of diabetes, fibrotic disorders, peripheral nerve damage, peripheral vascular and microvascular injuries; As a hemorrheologic agent, it can affect the blood viscosity.

PDE5 inhibitors _afil ---fill for ED

A phosphodiesterase type 5 inhibitor is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. These drugs are used in the treatment of erectile dysfunction, and were the first effective oral treatment available for the condition. Because PDE5 is also present in the arterial wall smooth muscle within the lungs, PDE5 inhibitors have also been explored for the treatment of pulmonary hypertension, a disease in which blood vessels in the lungs become abnormally narrow.

sildenafil Viagra

The occurrence ADRs with PDE5 inhibitors appears to be dose related. Headache is a very common ADR, occurring in >10% of patients. Other common ADRs include: dizziness, flushing, dyspepsia, nasal congestion or rhinitis.[2] A warning about possible sudden hearing loss and anterior optic neuropathy would be added to drug labels of PDE5 inhibitors. Organic nitrates are contraindicated when used with sildenafil. PDE5 inhibitors are contraindicated in those taking nitrate medication. They are also contraindicated in men for whom sexual intercourse is inadvisable due to cardiovascular risk factors.

tadalafil

vardenafil

PDE5 inhibitors are primarily metabolised by the cytochrome P450 enzyme CYP3A4. The potential exists for adverse drug interactions with other drugs which inhibit or induce CYP3A4, including HIV protease inhibitors, ketoconazole, itraconazole, and other anti-hypertensive drugs such as Nitro-spray (due to its capacity to diminish blood pressure).

Alprostadil

the pharmaceutical name for prostaglandin E1. and normally relaxes teh smooth muscles of the ductus arteriosus and has vasodilatory properties. It is used as a drug in the treatment of erectile dysfunction. It is indicated to temporarily maintain the potency of ductus arteriosus until surgery can be performed (IV indomethacin is also an option); Side effects: apnea, cardia arrest, flushing, fever and sepsis;

Proteasome inhibitor

drugs that block the action of proteasomes, cellular complexes that break down proteins, like the p53 protein. Proteasome inhibitors are being studied in the treatment of cancer. In 2003, bortezomib was the first proteasome inhibitor to be approved for use in the U.S.

Bortezomib

The first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease. Bortezomib is associated with peripheral neuropathy in 30% of patients; occasionally, it can be painful. This can be worse in patients with pre-existing neuropathy. In addition, myelosuppression as neutropenia and thrombocytopenia can also occur and be dose limiting.

Disulfiram

Aphrodisiac drugs
Testosterone

An aphrodisiac is a substance which is used in the belief that it increases sexual desire. [7AfrEu5diziAk]

Yohimbine

Yohimbine Hydrochloride is a selective competitive alpha-2 adrenergic receptor antagonist. The alpha-2 receptor is responsible for sensing adrenaline and noradrenaline and telling the body to decrease its production as part of a negative feedback loop. It is a prescription medicine that has been used to treat erectile dysfunction.

Bremelanotide Stimulants affecting the dopamine system such as cocaine and amphetamines (e.g. methamphetamine, aka crystal meth) are frequently associated with hyperarousal and hypersexuality, though both may impair sexual functioning, particularly with long term use. A newer dopamine reuptake inhibitor MDPV has also been noted to have characteristic hypersexual effects.

Others

Pramipexole

Some directly acting dopamine agonists may also cause increased libido, although they can also cause various side effects. Pramipexole is the only dopamine agonist used in medicine as an aphrodisiac, and is sometimes prescribed to counteract the decrease in libido associated with SSRI antidepressant drugs.

Anorexiants

Sibutramine (Meridia), mazindol (Sanorex, Mazanor), and benzphetamine (Didrex) are central nervous system stimulants used as anorexiants, ie, they are used to reduce appetite and used for obesity. mechanism: serotonin/NE reuptake inhibitor; phentermine: also dopamine release phentermine side effect: heart rate, blood pressue, constipation, dry mouth, headache, insomnia _propion drug interaction: MAOI (selegiline and rasagiline) ; SSRI (fluoxetine); Serotonin agonist (sumatriptan-used for migraine); erythromycin, cimetidine)

CYP450 ( ketoconazole,

phentermine

It is approved as an appetite suppressant to help reduce weight in obese patients when used short-term and combined with exercise, diet, and behavioral modification. It is typically prescribed for individuals who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.

Benzphetamine

Benzphetamine (brand name Didrex) is an anti-obesity drug marketed under this brand in the USA by Pharmacia. Benzphetamine is used as a short term adjunct in management of exogenous obesity. It is closely related to amphetamine. It works on the hypothalamus portion of the brain to release norepinephrine, a neurotransmitter that signals a fight-or-flight response, reducing hunger.It works outside the brain to release epinephrine or adrenaline causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction.

Diethylpropion sympathomimetic drugs that have a mild appetite-suppressant effect and can be used for short-term induction of weight loss. Bupropion Satiety enhancers

Sibutramine

trade name Meridia in the U.S. and Canada, an orally administered agent for the treatment of obesity, as an appetite suppressant. It is a centrally-acting serotonin-norepinephrine reuptake inhibitor, It is classified as a Schedule IV controlled substance in the United States.

orlistat

Act as lipase inhibitor which is responsible for breakdown fat into smaller moleculars. Also an adjunt therapy in diabetes. side effect: oil spotting; flatulence with discharge; fecal urgency; increased with defecation, b-carotene, carotenoid absorption Contraindication: cholestasis patient

Mazindol

Mazindol is a central nervous system stimulant. It is used in short-term (i.e., a few weeks) treatment of exogenous obesity, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a BMI 30, or in patients with a BMI 27 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia.

DMARDs

DMARDs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to NSAIDs, which refers to agents that treat the inflammation but not the underlying cause. Disease-modifying Although their use was first propagated in rheumatoid arthritis (hence their name) the term has come to include many other diseases, such as Crohn's disease, antirheumatic drug lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP), myasthenia gravis and various others. Many of these are autoimmune disorders, but others, such as ulcerative colitis, are not.

Hydroxychloroquine (HCQ) Methotrexate (MTX)

Azathioprine (AZA) Sulfasalazine (SSZ)

adalimumab

TNF inhibitor; a fully human monoclonal antibody, Used for: rheumatoid or psoriatic arthritis, ankylosing spondylitis, Crohn's disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis. Side effects: serious and sometimes fatal blood disorders; serious infections including include TB (tuberculosis) and infections caused by viruses, fungi, or bacteria; Purine synthesis inhibitor (antimalarials) (Cyclosporin A) inhibit calcineurin Reducing numbers of T-lymphocytes etc. TNF inhibitor (sodium aurothiomalate, auranofin) TNF inhibitor Pyrimidine synthesis inhibitor (MTX) Antifolate 5-LO inhibitor (SSZ) used in active moderate to severe rheumatoid arthritis and psoriatic arthritis

azathioprine hydroxychloroquine chloroquine cyclosporine D-penicillamine etanercept gold salts infliximab leflunomide methotrexate minocycline sulfasalazine

Related

Anakinra

an interleukin-1 receptor antagonist. It antagonizes the inflammation and pain associated with R. arthritis. The recommended dose of the drug is 100 mg SC daily. Erythema, pruritus, rash and pain are commonly reported side effects of the lung.

Bisphosphonates

also called: diphosphonates) are a class of drugs that inhibit osteoclast action and the resorption of bone. Its uses include the prevention and treatment of osteoporosis, osteitis deformans ("Paget's disease of bone"), bone metastasis (with or without hypercalcaemia), multiple myeloma, osteogenesis imperfecta and other conditions that feature bone fragility. Bisphosphonates, when attached to bone tissue, are "ingested" by osteoclasts, the bone cell that breaks down bone tissue.

Non-nitrogenous

The non-nitrogenous bisphosphonates(disphosphonates) are metabolised in the cell to compounds that replace the terminal pyrophosphate moiety of ATP, forming a nonfunctional molecule that competes with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone. Etidronate Clodronate Tiludronate (Didronel) - 1 (potency relative to that of etidronate) (Bonefos, Loron) - 10 (Skelid) - 10

Nitrogenous

Nitrogenous bisphosphonates act on bone metabolism by binding and blocking the enzyme farnesyl diphosphate synthase (FPPS) in the HMG-CoA reductase pathway (also known as the mevalonate pathway. Pamidronate (APD, Aredia) - 100 Disruption of the HMG CoA-reductase pathway at the level of FPPS prevents the formation of two metabolites (farnesol and geranylgeraniol) that are essential for connecting some small proteins to the cell membrane. This phenomenon is known as prenylation, and is important for proper sub-cellular protein trafficking (see "lipid anchored protein" for the principles of this phenomenon).[4] While inhibition of protein prenylation may affect many proteins found in an osteoclast, disruption to the lipid modification of Ras, Rho, Rac proteins has been speculated to underlie the effects of bisphosphonates. These proteins can affect both osteoclastogenesis, cell survival, and cytoskeletal dynamics. In particular, the cytoskeleton is vital for maintaining the "ruffled border" that is required for contact between a resorbing osteoclast and a bone surface. Statins are another class of drugs that inhibit the HMG-CoA reductase pathway. Unlike bisphosphonates, statins do not bind to bone surfaces with high affinity, and are thus not specific for bone. Nevertheless, some studies have reported a decreased rate of fracture (an indicator of osteoporosis) and/or an increased bone mineral density in statin users. The overall efficacy of statins in the treatment osteoporosis remains controversial.

Neridronate - 100

Olpadronate - 500 Alendronate (Fosamax) - 500 Ibandronate (Bonviva) - 1000 Risedronate (Actonel) - 2000

Zoledronate

(Zometa, Aclasta) - 10000 Used to prevent skeletal fractures, hypercalcemia of Flu-like symptoms are commonly experienced after the first zoledronate infusion, malignancy; prevent recurring fractures; Paget's disease of bone; postmenopausal osteoporosis.

Lactase enzyme Lactase enzyme is effective in treating symptoms of lactose intolerance. These symptoms are most evident shortly after consuming a lactose-containing food and may include bloating and diarrhea. Lactase enzyme is available as a liquid (Lactaid), caplets (Lactaid), capsules (Lactrase), or as chewable tablets (Dairy Ease). It is also added to some commercial dairy products.

Dihydrotachysterol

is a synthetic product of tachysterol, a substance similar to vitamin D. It is used in combination with calcium and parathyroid hormone in the treatment of hypoparathyroidism. It is activated in the liver that does not require renal hydroxylation like vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). DHT has a rapid onset of action (2 hours), a shorter half-life, and a greater effect on mineralization of bone salts than does vitamin D.

Desmopressin acetate

Desmopressin acetate (DDAVP) is the synthetic analog of naturally occurring human antidiuretic hormone (ADH) produced by the posterior pituitary gland. It is administered intranasally for the treatment of primary nocturnal enuresis. A single dose of the drug will produce an antidiuretic effect lasting from 8 to 20 hours. Desmopressin can be used to promote the release of von Willebrand factor and factor VIII in patients with coagulation disorders such as type I von Willebrand disease, mild hemophilia A, and thrombocytopenia. It is not effective in the treatment of hemophilia B or severe hemophilia A. Desmopressin is also used to reduce urine production in central diabetes insipidus patients.

Lypressin

Lypressin (Diapid) is a synthetic vasopressin analog possessing antidiuretic activity without producing a pressor or oxytocic effect. It is used clinically in the management of symptoms of diabetes insipidus. Lypressin is administered as a nasal spray.

Permethrin

Permethrin (Nix, Elimite) is a topical scabicide and pediculocide. It acts by disrupting the nerve cell membranes of parasites, resulting in their paralysis. Permethrin is widely used as an insect repellent. It belongs to the family of pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to harm most mammals or birds. It generally has a low mammalian toxicity and is poorly absorbed by skin.

Dyphylline

Dyphylline is a theophylline derivative. These agents act by inhibiting the enzyme phosphodiesterase, thereby increasing cyclicAMP levels and producing bronchodilation.

Loperamide, a synthetic piperidine derivative, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically. Loperamide Loperamide is an opioid receptor agonist and acts on the -opioid receptors in the myenteric plexus large intestines; it does not affect the CNS like other opioids. Treatment should be avoided in the presence of fever or if the stool is bloody. Treatment is not recommended for patients who could suffer detrimental effects from rebound constipation. If there is a suspicion of diarrhea associated with organisms that can penetrate the intestinal walls, such as E. coli O157:H7 or salmonella, loperamide is contraindicated.

Also glyceryl guaiacolate, is an expectorant drug sold OTC and usually taken by mouth to assist the bringing up ("expectoration") of phlegm from the airways in acute respiratory tract infections. guaifenesin The principal use of guaifenesin is in the treatment of coughing, but the drug has numerous other uses, including the thickened bronchial mucosa characteristic of asthma, gout (as a uricosuric, increasing excretion of uric acid from the blood serum into the urine), fibromyalgia; also widely used by women to facilitiate conception by thinning and increasing the amount of cervical mucus; Opera singers sometimes refer to guaifenesin as the "wonder drug" for its ability to promote secondary mucosal secretion in the respiratory system.

Rasburicase (brand names: Elitek in the US ) is a recombinant version of a urate oxidase enzyme that occurs in many mammals but not in humans. It has been used to reduce risk of hyperuricemia. It is approved for use by FDA for the prevention and treatment of tumor lysis syndrome (TLS) in patients receiving chemotherapy for hematologic cancers such as leukemias and lymphomas. Rasburicase Rasburicase catalyses the conversion of uric acid to allantoin. Allantoin is an inactive metabolite of purine metabolism, and is 5 to 10 times more soluble than uric acid, so renal excretion is more effective. Rasburicase is unique as a treatment and prevention for renal failure associated with TLS in that it catalyses the metabolism of existing uric acid. Other options prevent uric acid formation.

Phenazopyridine

Phenazopyridine is a chemical which, when secreted into the urine, has a specifical local analgesic effect. It is often used to alleviate the pain, irritation, discomfort, or urgency caused by urinary tract infections, surgery, or injury to the urinary tract. Dangerous and prohibited for G6PD deficiency patients. A distinct color change in the urine, typically to a dark orange to reddish color. This effect is common and harmless, and indeed a key indicator of the presence of the drug in the body. Users of phenazopyridine are warned not to wear contact lenses, as phenazopyridine has been known to permanently discolor contact lenses and fabrics. Others: headaches, upset stomach (especially when not taken with food), or dizziness; a pigment change in the skin or eyes, to a noticeable yellowish color; fever, confusion, shortness of breath, skin rash, and swelling of the face, fingers, feet, or legs.

Clofazimine

Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy (MDT) for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and Mycobacterium avium paratuberculosis infection in Crohn's disease patients May cause pink-to-brownish skin pitmentation within a few weeks of the initiation of therapy. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum (ENL).

Drugs

TCAs _pramine or _triptyline

Secondary amines:

Selective serotonin reuptake inhibitor SSRIs _xetine; _talopram; _ine

serotonin agonists or antagonists 5-HT1-receptor agonists used for migraine

sumatriptan rizatriptan naratriptan zolmitriptan almotriptan eletriptan frovatriptan

PPIs proton pump inhibitors

prazole Omeprazole (brand names: Losec, Prilosec, Zegerid, ocid)

Lansoprazole (brand names: Prevacid, Zoton, Inhibitol) Esomeprazole (brand names: Nexium) Pantoprazole (brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan) Rabeprazole (brand names: Rabecid, Aciphex, Pariet, Rabeloc)

ACE inhibitors angiotensin-coverting enzyme

captopril enalapril lisinopril benazepril fosinopril moexipril perindopril quinapril ramipril trandolapril

ARBs angiotensin II receptor blockers

_sartan losartan candesartan irbesartan telmisartan valsartan

endothlin receptor bosentan antagonists

HMG CoA reductase inhibitors (Stastins)

lovastatin Atorvastatin Fluvastatin Pravastatin Simvastatin

COX-2 inhibitors

Celecoxib Etoricoxib Parecoxib

MAO inhibitors

Iso-Phe; Tranyl-Selegi; Moclobe

Phenelzine Sele/ Rasa-giline Moclobe/Niala-mide Ipro- clozide/niazid Isocarboxazid Linezolid Tranylcypromine

Phenelzine Tranylcypromine Moclobemide Selegiline Isocarboxazid

Nonselective: non-reversible (Isocarboxazid, Iproclozide, Iproniazid, Nialamide, Phenelzine) reversible (Tranylcypromine)---- long time use can make it irreversible MAOA (N/S): Clorgiline Minaprine RIMAs (Befloxatone, Brofaromine, Cimoxatone, Harmaline, Moclobemide (reversible), Pirlindole, Toloxatone) MAOB (D): Rasagiline Selegiline Pargyline

oral antidiabetic agents

amide; ride; tide; formin; glitazone;glinide;

sulfonylureas tolbutamide chlorpropamide first generation tolazamide acetohexamide glyburide second generation glipizide glimepiride meglitinides repaglinide nateglinide thiazolidinediones rosiglitazone pioglitazone troglitazone biguanide Metformin phenformin -glucosidase inhibitors monosaccharides miglitol polysaccharides acarbose

peptide mimetics exenatide pramlintide

PDE5 inhibitors

_afil ---fill for ED sildenafil tadalafil vardenafil

macrolides----- 30 S or 50S

Antiarrhythmic agents
class IA

class IB

class IC

class II

class III

class IV

others

Hypercalcemia CHIMPANZEES.

Caused by Calcium ingestion (milk-alkali syndrome), Hyperparathyroid, Hyperthyroid, Iatrogenic (thiazides), Multiple myeloma , Pagets disease, Addisons disease, Neoplasms, Zollinger-Ellison syndrome, Excess vitamin D, Excess vitamin A, Sarcoidosis.

Treatment for selected psychiatric conditions Psychiatric condition Alcohol withdrawal Anorexia/bulimia Anxiety Drug Benzodiazepines SSRIs Barbiturates Benzodiazepines

Buspirone MAO inhibitors ADHD Methylphenidate (Ritalin) Amphetamine Atypical depression MAO inhibitors Bipolar disorder Mood stabilizers: Lithium Valproic acid Carbamazepine Depression SSRIs TCAs Depression with insomnia Trazodone Mirtazapine Obsessive-compulsive disorder Panic disorder Schizophrenia Tourettes syndrome SSRIs

TCAs Buspirone Antipsychotics Antipsychotics (haloperidol)

Neuromuscular-blocking drug block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by Nicotinic blocking agents acting presynaptically via the inhibition of acetylcholine (ACh) synthesis or release, or by acting postsynaptically at the acetylcholine receptor. While there are drugs that act presynaptically (such as botulin toxin and tetrodotoxin), the clinically-relevant drugs work postsynaptically.

non-depolarizing All of these agents act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. competitive _curium / curonium / curarine/ Gallamine

d-tubocurarine Rapacuronium (Raplon) Mivacurium (Mivacron) Atracurium (Tracrium) Doxacurium (Nuromax) Pipecuronium

Ca 2+ channel blockers

verapamil diltiazem bepridil

Treprostinil Tadalafil Rasburicase

a synthetic analogue of prostacyclin, used to treat pulmonary hypertension. erectile dysfunction hyperuricemia

Drugs Anticonvulsants Phenytoin (DPH

Carbamazepine

Valproic acid divalproes sodium Phenobarbital(PB

Antiplatelet agents
aspirin cilostazol ticlopidine treprostinil Fondaparinux dipyridamole abciximab Clopidogrel anagrelide tirofiban eptifibatide

Thrombolytic agents
alteplase reteplase tenecteplase streptokinase anistreplase urokinase

Antipsychotics

Typical antipsychotic First generation

to block D2 receptors in the dopamine pathways of the brain; with minimal effect on the serotonergic pathways, is considered a typical antipsychotic.

Butyrophenones

Haloperidol (Haldol)

Phenothiazines _ azine

Chlorpromazine (Thorazine)

Fluphenazine (Prolixin) - Available in decanoate (long-acting) form Perphenazine Prochlorperazine (Compazine) Thioridazine (Mellaril) Trifluoperazine (Stelazine) Mesoridazine Promazine Triflupromazine (Vesprin) Levomepromazine (Nozinan) Promethazine (Phenergan)

Loxapine

Group Autonomic

Aliphatic compounds

moderate

Piperidines strong

Piperazines weak

Thioxanthenes _thixol or ene

Chlorprothixene

Flupenthixol (Depixol and Fluanxol) Thiothixene (Navane) Zuclopenthixol (Clopixol & Acuphase)

Atypical antipsychotic Second generation

_apine _idone

Clozapine (Clozaril)

Risperidone (Risperdal)

Olanzapine (Zyprexa)

Quetiapine (Seroquel)

Ziprasidone

Aripiprazole Paliperidone Asenapine FDA has accepted NDA as of November 26, 2007. [7] Iloperidone (Fanapta or Zomaril) FDA has accepted NDA as of November 27, 2007. [8] Sertindole (Serlect) (Not approved by the FDA for use in the USA).

Zotepine (Not approved by the FDA for use in the USA). Amisulpride (Not approved by the FDA for use in the USA). Bifeprunox (Not approved by the FDA for use in the USA). Melperone Approved in Europe. Currently in clinical trial in the USA.

Third generation antipsychotics

Aripiprazole

others

Pimozide

Antidepressive and antimanic agents

Tricyclic antidepressants

TCAs _pramine or _triptyline

Tertiary amines:

amitriptyline

imipramine

trimipramine

doxepin

clomipramine lofepramine opipramol

dosulepin hydrochloride

Secondary amines:

Nor, De, Pro, Amo

nortriptyline

protriptyline desipramine

amoxapine

Tetracyclic antidepressants

Maprotiline

Selective serotonin reuptake inhibitor

SSRIs _xetine; _talopram; _ine

Available in CA: Citalopram Escitalopram Fluoxetine Fluvoxamine Paroxetine Sertraline

Serotonin syndrome

citalopram

escitalopram dapoxetine

fluoxetine

SSRIs weight gain paroxetine

fluvoxamine

sertraline

zimelidine

Serotonin-norepinephrine reuptake inhibitor (SNRIs)

Venlafaxine

Duloxetine

MAO inhibitors

Phenelzine Sele/ Rasa-giline Moclobe/Niala-mide Ipro- clozide/niazid Isocarboxazid Linezolid Toloxtone Tranylcypromine

Moclobemide

Phenelzine

Tranylcypromine

Selegiline

Rasagiline Nialamide Iproniazid

Isocarboxazid

Iproclozide Toloxatone

Linezolid

Dual action antidepressants

Bupropion

Mirtazapine

Triazolopyridines

Trazodone

Nefazodone

Anxiolytics and sedative hypnotics

Benzodiazepines

_zepam, _zolam

alprazolam

chlordiazepoxide

clonazepam

clorazepate

diazepam

flurazepam quazepam lorazepam oxazepam trizaolam temazepam

Azapirones

_pirone

buspirone

gepirone ipsapirone tiospirone

Barbiturates

Barby not for Porphy

Phenobarbital (long-acting)

Amobarbital Butabarbital Pentobarbital Secobarbital

Thiopental

Methohexital Thiamylal Mephobarbital

Carbamates

Meprobamate

Anti-insomnia agents
Imidazopyridine

zolpidem

Piperidinediones

glutethimide

methyprylon
Aldehydes

paraldehyde chloral hydrate

antiepileptics /anticonvulsants

Generalized Tonic-clonic: carbamazepine, lamotrigine, phenytoin, valproic acid, (clobazam, levetracetam, topiramate)---alternative or add-on Canadian choices Absence (petit mal): ethosuximide, valproic acid; (clonazam, lamotrigine, levetracetam, topiramate)
Blue ones Myoclonic and Atonic : valproic acid; (clonazam, lamotrigine, levetracetam, topiramate) ---First choice

Partial (simple or complex) with or without 2 generalization: carbamazepine, lamotrigine, phenytoin, (clobazam,gabapentin, levetracetam, oxcarbazepine, phenobarbital, primidone, topiramate, valproic acid, vigabatrin)

Generalized Tonic-clonic (grand mal): phenobarbital, phenytoin, primidone, carbamazepine; (PPP-Car) psychomotor: phenytoin, phenobarbital, primidone, carbamazepine (PPP-Car) Absence (petit mal): phynobarbital, ethosuximide, clonazepam, trimethadione, valproic acid;(PEClo-TV) Myoclonic : clonazepam (Myo----Clo) Partial: clorazepate, felbamate, gabapentin, lamotrigine (Clora-Fel-Gab-Lamo) status epilepticus: IV diazepam, phenytoin, phenobarbital (PP- IV-D); Dextrose 50% solution is normally indicated.

Phenytoin DPH

D_D

Carbamazepine

200 mg intial twice daily ---800-2000mg

D_D

Valproic acid

VPA

divalproes sodium

Phenobarbital PB

D_D

Other informations of AEDs

Aldehydes Paraldehyde Aromatic allylic alcohols Stiripentol Barbiturates

Phenobarbital

Pyrimidinediones

Primidone

Benzodiazepines

delirium tremens Clobazam

Clonazepam

Clorazepate Diazepam Midazolam Lorazepam Bromides

Carbamates Felbamate Carboxamides

Carbamazepine

Oxcarbazepine

Fatty acids The valproates valproic acid, sodium valproate, and divalproex sodium (1967). Vigabatrin Progabide Tiagabine

Fructose derivatives

Topiramate

Gaba analogs

Gabapentin

Pregabalin

Hydantoins ethotoin

phenytoin

mephenytoin fosphenytoin

Oxazolidinediones Paramethadione

Trimethadione

Ethadione Propionates Beclamide Pyrrolidines _racetam Brivaracetam Levetiracetam Seletracetam

Succinimides _suximide

Ethosuximide Phensuximide Mesuximide Sulfonamides Acetazolamide (1953). Sultiame Methazolamide Zonisamide (2000). Triazines

Lamotrigine

Ureas Pheneturide Phenacemide Valproylamides (amide derivatives of valproate)

Valproic acid

Valpromide

Valnoctamide

Diet

Baclofen

Sodium oxybate

Antiparkinsonian agents
dopaminergic agonists

levodopa Droxidopa Melevodopa Etilevodopa Bromocriptine

Pergolide

Pramipexole

Ropinirole

Fenoldopam

Enzyme inhibitors

carbidopa

tolcapone Entacapone

Cholinergic antagonists

benztropine

trihexyphenidyl

procyclidine

orphenadrine

biperiden

Antiviral agent amantadine

MAOIs

selegiline
MAO-B Is

rasagiline

drugs used for increasing milk supply dopamine receptor antagonist

Metoclopramide (Reglan)

Domperidone (Motilium)

Sulpiride

Anti-ADHD agents

Therapeutic Choices in Canada

Methylphenidate

Amphetamine

Dextroamphetamine

Atomoxetine

Antidepressants

2-adrenergic agonists Antipsychotics Natural products

Pemoline

Opioid Analgesics

Phenanthrenes

morphine

Diacetylmorphine Heroin hydromorphone codeine hydrocodone

phenylheptylamines

methadone

Dextro-propoxyphene

Levomethadyl acetate

pheynylpiperidines

meperidine

p-phenyl-N-alkylpiperidine

fentanyl

sufentanil
morphinan levorphanol

Opioid peptides

enkephalin endorphin dynorphin

Tramadol

Tapentadol

Opioid antagonists
nalbuphine

buprenorphine

nalorphine

naltrexone

naloxone

General Anesthetics
Inhalational anaesthetics

Desflurane, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide.

Injection anaesthetics

Fentanyl citrate
Propofol Etomidate

methohexital
Barbiturates thiopentone

and

/thiopental

Benzodiazepines midazolam diazepam

Ketamine

Local Anesthetics: _ caine / _i_caine

Amino esters _ caine Benzocaine

Chloroprocaine

Cocaine Cyclomethycaine

Dimethocaine/Larocaine
Propoxycaine

Procaine
Proparacaine

Tetracaine/Amethocaine

Amino amides _i_caine

Articaine
Bupivacaine Carticaine Cinchocaine /Dibucaine Etidocaine Levobupivacaine

Lidocaine/Lignocaine

Mepivacaine Piperocaine Prilocaine Ropivacaine Trimecaine

Antihistaminics
H1-receptor antagonists

Ethylenediamines (pyrilamine)

Mepyramine Antazoline

Ethanolamines

Carbinoxamine Doxylamine Clemastine Dimenhydrinate

Diphenhydramine

scopolamine

Pheniramine
(chlorpheniramine)

Chlorphenamine

Alkylamines Dexchlorpheniramine Brompheniramine

Triprolidine Cyclizine Chlorcyclizine Piperazines Hydroxyzine Meclizine

Meclizine

Promethazine Alimemazine (trimeprazine) Tricyclics and Tetracyclics Cyproheptadine Azatadine Ketotifen

Cyproheptadine

Systemic, second-generation

Acrivastine Astemizole

Cetirizine

Loratadine

Mizolastine Terfenadine Treatment for Pruritus

Topical, second-generation

Azelastine Levocabastine Olopatadine

2nd gen Alkylamine Acrivastine Tricyclic Olopatadine Piperazine Cetirizine

Benzhydryl Terfenadine

Systemic, third-generation

Levocetirizine Desloratadine

Fexofenadine

Serotonin agonists

5-HT1-receptor agonists

sumatriptan

rizatriptan naratriptan zolmitriptan almotriptan eletriptan frovatriptan

5-HT4-receptor agonists

tegaserod
partial agonists

ergot alkaloids
CNS active drugs sanorexiants dexfenfluramine anxiolytics buspirone SSRIs fluxetine

Serotonin antagonists

ergot alkaloids

ergonovine
dihydroergotamine

methysergide

bromocriptine

Benzocycloheptane

pizotifen

5-HT3-receptor antagonists

-setron

ondansetron

benzimidazoles granisetron

dolasetron palonosetron alosetron

Antiemetics

5-HT3 receptor antagonists

Dolasetron Granisetron Ondansetron Tropisetron Palonosetron

Dopamine antagonists

Domperidone Droperidol haloperidol chlorpromazine promethazine prochlorperazine. Metoclopramide Alizapride

Antihistamines

Cyclizine Diphenhydramine Dimenhydrinate Meclizine Promethazine Hydroxyzine Cannabinoids

Cannabis (Marijuana). Most patients prefer smoked or vaporized cannabis over pharmaceutical versions because they do not contain all 66 cannabinoids that are in cannabis, many of which have medicinal applications. Medical marijuana is also much less expensive than related pharmaceuticals. CBD is a main cannabinoid not in Marinol or Cesamet. Dronabinol (Marinol). Ninety percent of sales are for cancer and AIDS patients. The other 10% of its sales thought to be for pain, Multiple Sclerosis and also for Alzheimer's disease. Dizziness, drowsiness, euphoria, ataxia and hallucination are reported side effects of the drug. Nabilone (Cesamet). Put back on the market in late 2006. In the US, it is A Schedule II substance unlike Marinol which is Schedule III and cannabis which is Schedule I.

Sativex is an oral spray containing THC and CBD. It is currently legal in Canada and a few countries in Europe but not in the U.S. Benzodiazepines Midazolam given at the onset of anesthesia has been shown in recent trials to be as effective as ondansetron, a 5HT3 antagonist in the prevention of post-operative nausea and vomiting. Further studies need to be undertaken. Lorazepam said to be very good as an adjunct treatment for nausea along with first line medications such as Compazine or Zofran.
Anticholinergics

Hyoscine
Steroids

Dexamethasone given in low dose at the onset of a general anaesthetic for surgery is an effective anti-emetic.

NK1 receptor antagonist

Aprepitant Casopitant Investigational NK1 receptor antagonist

Other Trimethobenzamide

Ginger Emetrol also claimed to be an effective antiemetic. Propofol given intravenously. It has been used in an acute care setting in hospital as a rescue therapy for emesis. Peppermint claimed to help nausea or stomach pain when added into a tea or peppermint candies. Muscimol purported as such [1] Ajwain purported to be antiemetic. Also known as Bishop's weed, it is a popular spice in India, Ethiopia and Eritrea. Antacids: aluminum hydroxide/magnesium hydroxide combinations; Antihistamines: dimenhydrinate, diphenhydramine, meclizine Nausea in adults Anticholinergics: scopolamine; Benzamides: domperidone, metoclopramide (also dopamine antagonists); Therapeutic choices in Dopamine antagonists----Butyrophenones: haloperidol, droperidol Canada Phenothiazines: chlorpromazine, perphenazine, prochlorperzaine, promethazine (--azines); Serotonin Antagonists: ondansetron;

Anticholinergic agents

Neuromuscular-blocking drug block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by Nicotinic blocking agents acting presynaptically via the inhibition of acetylcholine (ACh) synthesis or release, or by acting postsynaptically at the acetylcholine receptor. While there are drugs that act presynaptically (such as botulin toxin and tetrodotoxin), the clinically-relevant drugs work postsynaptically.
non-depolarizing All of these agents act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. competitive _curium / curonium / curarine/ Gallamine

d-tubocurarine Rapacuronium Mivacurium Atracurium Doxacurium Cisatracurium Vecuronium Rocuronium Pancuronium Tubocurarine Gallamine Pipecuronium

Depolarizing succinylcholine

Side reaction:

Acetylcholinesterase inhibitors Ach-esterase-I

Reversible inhibitor
Carbamates

Physostigmine

Neostigmine

Pyridostigmine Ambenonium Demarcarium Rivastigmine Phenanthrene derivatives Galantamine Piperidines Donepezil Tacrine tetrahydroaminoacridine (THA')

Edrophonium

Irreversible

organophosphate Metrifonate

Muscarinic agonists

M1

M3

Muscarinic antagonist

Atropine (D/LHyoscyamine)

Side effects

Increases firing of SA node, conduction through AV node, opposes vagus nerve, blocks acetylcholine receptor sites, decreases bronchiole secretions. Generally, atropine lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system. Therefore, it may cause swallowing difficulties and reduced secretions. Antispasmodic in gastrointestinal hypermotility; Antidote for organophosphate poisoning.

Adverse reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, and possibly, notably in the elderly, extreme confusion, extreme dissociative hallucinations, and excitation. Although atropine treats bradycardia (slow heart rate) in emergency settings, it can cause paradoxical bradycardia when given at very low doses, presumably as a result of central action in the CNS. Ophthalmic use: Topical atropine, used as a cycloplegic, to temporarily paralyze the accommodation reflex; and as a mydriatic to dilate the pupils. Resuscitation: Injections, used in the treatment of bradycardia, asystole and pulseless electrical activity (PEA) in cardiac arrest.

Ipratropium

Tiotropium

Oxybutynin Tolterodine Flavoxate Solifenacin Darifenacin Scopolamine (L-Hyoscine)

Tropicamide

Pirenzepine

Diphenhydramine

Dimenhydrinate Dicyclomine Cyclopentolate Atropine methonitrate Trihexyphenidyl Mebeverine

Propantheline bromide

Benzatropine Ethopropazine

Procyclidine

Prostaglandins

PGA/ PGB /PGE .

PGE1 analogs Aplrostadil

Misoprostol

PGE2 analogs Prostin E2

Prepidil Cervidil
PGF2 analogs _ oprost

Carboprost Latanoprost Tracoprost bimatoprost unoprostone

PGI analog epoprostenol

prostacyclin

Leuktrienes

leukotriene antagonists
lipoxygenase inhibitors

zileuton

leukotriene antagonists _lukast

zafirlukast

montelukast

Nonnarcotic analgesic-antipyretics

salicylates

aspirin

diflunisal

methyl salicylate salsalate

sodium thiosalicylate choline salicylate

mesalamine

sulfasalazine

olsalazine

Mesalazine

p-aminophenol derivatives

acetaminophen

pyrazolone derivatives

phenylbutazone oxyphenbutazone sulfinpyrazone

Non-steroid antiinflammatry drugs

NSAIDs

Most NSAIDs are chiral molecules;

Salicylates

Acetylsalicylic acid (Aspirin) Amoxiprin Benorylate/Benorilate Choline magnesium salicylate Diflunisal Ethenzamide Faislamine Methyl salicylate Magnesium salicylate Salicyl salicylate Salicylamide
Arylalkanoic acids

_fenac, _metacin Aceclofenac Acemethacin Alclofenac Bromfenac Etodolac Nabumetone Oxametacin Proglumetacin Tolmetin

Diclofenac

Indometacin

Sulindac

2-Arylpropionic acids (profens) propionic acid derivatives

Ibuprofen

Alminoprofen Benoxaprofen (withdrawn from the market) Carprofen Dexibuprofen Dexketoprofen Fenbufen Fenoprofen Flunoxaprofen Flurbiprofen Ibuproxam Indoprofen Ketoprofen

Ketorolac

Loxoprofen Naproxen

Oxaprozin

Pirprofen Suprofen Tiaprofenic acid

N-Arylanthranilic acids fenamic acids Mefenamic acid Flufenamic acid Meclofenamic acid Tolfenamic acid Pyrazolidine derivatives Phenylbutazone Ampyrone Azapropazone Clofezone Kebuzone Metamizole Mofebutazone Oxyphenbutazone Phenazone Sulfinpyrazone Oxicams _oxicam

Piroxicam

Droxicam Lornoxicam Meloxicam Tenoxicam

COX-2 inhibitors

Celecoxib

Etoricoxib Lumiracoxib Parecoxib Rofecoxib Valdecoxib

Sulphonanilides

Nimesulide (banned by several countries for the potential risk of hepatotoxicity)

Others

Licofelone Omega-3 fatty acids

Bismuth subsalicylate

Agents for gout

alkaloid colchicine colchicine

isopurines allopurinol

benzoic acid derivatives probenecid

phenylbutazone
oxyphenbutazone

sulfinpyrazone

probenecid
Uricosuric agents

benzbromarone sulfinpyrazone

Antiuricosurics

Diuretics Aspirin

Adrenergic agonist

Indirect action Tyramine Amphetamine Cocaine Ephedrine Mixed action Ephedrine Pseudoephedrine Norepinephrine

Direct action
Nonselective agonists: Oxymetazoline Xylometazoline Tetrahyrozoline

1 agonists:
Methoxamine Methylnorepinephrine

Oxymetazoline

Phenylephrine

2 agonists

Clonidine

Methyldopa

Guanfacine

Guanabenz Guanoxabenz Guanethidine Xylazine

tizanidine

Nonselective agonists

Isoproterenol

1 agonists

Dobutamine

Xamoterol

2 agonists _ terol (terenol) albuterol Clenbuterol Bitolterol Pirbuterol Fenoterol Formoterol Salmeterol Terbutaline

Metaproterenol

Cardiac glycosides and positive inotropes

Digitoxin
Glycosides

Digoxin

Ouabain

Dipyridine derivatives

amrinone

milrinone

inamrinone
ACE inhibitors

For myocardial ischemia

antianginal agents nitrites

amyl nitrite
nitrates

nitroglycerin

isosorbide

-adrenergic blockers

propranolol

calcium antagonists

verapamil nifedipine
Antiplatelet agents

aspirin ticlopidine
peripheral casodilators dipyridamole

clopidogrel

Antiarrhythmic agents

fast-channel blockers
class IA

PDQ

Quinidine

D_D

procainamide

disopyramide

D_D
class IB phen lido to me

lidocaine

tocainide mexiletine

phenytoin

class IC

Flecainide Propafenone Moricizine

flecainide

propafenone

moricizine

class II

b-blockers PEAN

Propranolol

D_D

Esmolol Acebutolol Nadolol

class III

Amiodarone Sotalol Ibutilide Dofetilide Bretylium

amiodarone

sotalol

D_D :

ibutilide

sulfonamides drugs

dofetilide

bretylium

class IV

verapamil

diltiazem

others
Bepridil Atropine

Digoxin

Adenosine

Antihypertensive agents

Vasodilators

diazoxide

diazoxide

minoxidil

nitroprusside

Hydralazine

peripheral sympatholytics guanethidine

reserpine

Ganglinic-blocking agents

Hexamethonium

trimetaphan or trimethaphan

mecamylamine

nonselective -receptor antagonist phenoxybenzamine

phentolamine

1 -receptor antagonist

doxazosin

prazosin

terazosin

related

Tamsulosin

2 -receptor antagonist

Tolazoline

nonselective adrenoceptor antagonist (mixed)

carvedilol

labetalol

-blockers

Abrupt stoppage leads the risk for a withdrawal syndrome (exacerbated anginal attacks, myocardial infarction, BP rebound) Caution in pts with diabetes (mask hypoglycemic symptoms such as tachycardia), Raynaud phenomenon or peripheral vascular disease, nuerological disorders (esp. the lipid ones which can enter the CNS)

Nonselective CNMPPPT -receptor antagonist

propranolol

carteolol nadolol metipranolol penbutolol pindolol

timolol sotalol

1 -receptor antagonis AABBCEM

acebutolol

atenolol

betaxolol

bisoprolol

celiprolol

esmolol

metoprolol

2 -receptor antagonis butoxamine

Intrinsic sympathomimetic activity (ISA)

central 2-sympathomimetics

clonidine

methyldopa

guanabenz

guanfacine

calcium channel blockers

verapamil

diltiazem

nifedipine

bepridil

Dihydropyridine

amlodipine

felodipine isradipine nifedipine nicardipine nimodipine

Phenylalkylamine Verapamil

Gallopamil
Benzothiazepine Diltiazem

ACE inhibitors
angiotensin-coverting enzyme

captopril

enalapril

long-acting lisinopril

benazepril fosinopril moexipril perindopril quinapril ramipril trandolapril

long-acting once-daily

Both ACE inhibitors and ARBs are contraindicated in patients with bilateral renal stenosis. (decreased blood flow to the glomerulus). ACE inhibitors or ARBs, the effects of angiotensin II are reduced, which leads to vasodilatation of the efferent arterioles. This will result in a decrease in pressure and glomerular filtration rate and a worsening of the renal function,

angiotensin II receptor block vasoconstriction and aldosterone-secreting effects similar to ACE-I. However, because ARBs do not block the metabolism or increase the levels of bradykinin, they are less inhibitors likely to be associated with nonrenin-angiotensin effects such as cough and angioedema. (blockers) ARBs predominantly eliminated via hepatic metabolism

losartan

candesartan irbesartan telmisartan valsartan

endothlin receptor bosentan antagonists

Diuretics
osmotic diuretic GUI Ma

Glycerin Urea Isosorbide Mannitol

Related to osmotic but not diuretic

Lactulose

carbonic anhydrase inhibitors Sulfonamides

_zolamide

acetazolamide

methazolamide dorzolamide

benzothiadiazide diuretics

chlorothiazide

hydrochlorothiazide HCTZ

cyclothiazide quinethazone methyclothiazide metolazone

sulfamoylbenzamides

indapamide

chlorthalidone

symptoms of hypokalemia

Furosemide Torsemide Bumetanide Ethacrynic acid loop diuretics Fur Etha Tor Bume

furosemide

bumetanide

ethacrynic acid torsemide

potassium-sparing diuretics Ami-Tri-Spi

amiloride

triamterene

spironolactone

Symptoms of hyperkalemia

pamabrom

Action orders & sites

Combination products

Aldactazide Aldactazide-50 Moduretic Dyazide Maxzide Maxzide-25

antihyperlipidemic agents
nonabsorbable agents

colesevelam hydrochloride
hydrophilic water-soluble resins cholestryamine chloride colestipol hydrochloride

absorbable agents

nicotinic acid

gemfibrozil
Fibric acid _fibrate

fenofibrate clofibrate bezafibrate

HMG CoA reductase inhibitors

(Stastins)

Lovastatin

Atorvastatin

Fluvastatin

Pravastatin

Simvastatin

cholesterol absorption inhibitor

ezetimibe

Bile acid sepuestrants

cholestryamine colestipol solesevalam

EPA eicosapentaenoic acid DHA docosahexaenoic acid

anticoagulant
heparin
low molecular weight heparin( DENT---parin LMWH)

Dalteparin Enoxaparin Nadroparin Tinzaparin ..

others

danaparoid lepirudin argatroban bivalirudin drotrecogin fondaparinux

Coumarin derivatives

warfarin

D_D: interacts with many commonly-used drugs, and the metabolism of warfarin varies greatly between patients. Highly protein bound drugs can displace warfarin from albumin and cause an increase in INR; Antibiotics, such as metronidazole or the macrolides, will greatly increase the effect of warfarin by reducing the metabolism of warfarin; Broad-spectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel, which make significant quantities of vitamin K, thus potentiating the effect of warfarin; Hypothyroidism h the effects of warfarin; hyperthyroidism boosts the anticoagulant effect; Excessive use of alcohol h metabolism of warfarin and can elevate the INR;

dicumarol non-prothrombopenic anticagulant citrate dextrose

Prothrombin time

Antiplatelet agents
aspirin

ticlopidine

Fondaparinux

abciximab

tirofiban eptifibatide anagrelide cilostazol

treprostinil

dipyridamole

Clopidogrel

Thrombolytic agents _kinase

_eplase

alteplase reteplase tenecteplase streptokinase anistreplase urokinase

antianemic agents
iron preparations sodium ferric gluconate

iron sucrose iron dextran ferrous sulfate frrrous gluconate ferrous fumarate
cyanocobalamin Vitamin B12

folic acid
glycoproteins

_epoetin _grastim epoetin darbepoetin filgrastim pegfilgrastim sargramostim

oprelvekin interluekin 11

Pituitary Hormones
posterior pituitary hormones

oxytocin vasopressin

anterior pituitary hormones

FLAT PiG FSH LH ACTH (corticotropin thyrotropin TRH prolactin

Endorphin

growth hormon

pituitary gonadotropin analogs

menotropins hMG urofollitropin

hCG

Goserelin Acetate

Histrelin Acetate Leuprorelin

Triptorelin

Gonadal hormones

estrogen

weak in oral adm. estradiol estradiol cypionate or calerate ethinyl estradiol

mestranol

conjugated estrogens

premarin cenestin menest enjuvia estropipate antiestrogen _mifene

clomiphene

tamoxifen citrate

toremifene citrate

fulvestrant

selective estrogen a class of medication that acts on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various receptor modulator (SERM) tissues, thereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues. _xifene/fen Phytoserms are scientificaly accepted SERMs from a botanical source.

raloxifene

afimoxifene (4-hydroxytamoxifen) arzoxifene bazedoxifene clomifene femarelle (DT56a) lasofoxifene

ormeloxifene tamoxifen toremifene

Aromatase inhibitors

_trozole

anastrozole

letrozole exemestane

progestin
progesterone synthetic
17- OH medroxyprogesterone acetate

megestrol acetate

19 17- ethinyl group

norethindrone norethynodrel norgestresl levonorgestrel

ethynodiol diacetate

norgestimate Desogestrel norelgestromin etonogestrel

Drospirenone

Seasonale

antiprogestin

mifepristone

Combined Oral Contraceptives (COC)

MOA: COCs decrease ovulation and sperm and egg transport and implantation. The estrogen component alters FSH (follicle stimulating hormone) and LH (Ieutinizing hormone) release, accelerates egg transport, and alters the endometrium so that it is unsuitable for implantation. Progestins alter FSH and LH release, thicken cervical mucous to reduce sperm and egg transport, inhibit enzymes necessary for fertilization, and also alter the endometrium so that it is unsuitable for implantation.

Monophasic formulations

Triphasic formulations

Progestin-only contraceptives

Non-oral formulations

allow for lower doses of hormones to be used and bypass first-pass metabolism, thereby limiting the production of factors produced by the liver (e,g., fibrinogen, Creactive protein)

IM injectable DMPA ((depo-medroxyprogesterone acetate surgically placed subdermal implant surgically placed intrauterine system transdermal patch vaginal ring Monthly IM injectable

androgens

androgenic effects _rone----

testosterone

testosterone 17 enanthate testosterone cypionate

methyltestosterone

fluoxymesterone

Mestanolone

anabolic effects _long---- Grow long ---anabolic

oxymetholone

nandrolone decanoate oxandrolone

others

testolactone

danazol

antiandrogens _lutamide

Flutamide

Bicalutamide

Nilutamide

5 -reductase inhibitors

finasteride

dutasteride

DHT

Retinoid

Isotretinoin

acitretin

Tazarotene

Adapalene

Adrenocorticosteroids

Group A: (short to medium acting glucocorticoids) Hydrocortisone, Hydrocortisone acetate, Cortisone acetate, Tixocortol pivalate, Prednisolone, Methyprednisolone, and Prednisone. Group B: Group C: Triamcinolone acetonide, Triamcinolone alcohol, Mometasone, Amcinonide, Budesonide, Desonide, Fluocinonide, Fluocinolone acetonide, and Halcinonide. Betamethasone, Betamethasone sodium phosphate, Dexamethasone, Dexamethasone sodium phosphate, and Fluocortolone.

Group D: Hydrocortisone-17-butyrate, Hydrocortisone-17-valerate, Aclometasone dipropionate, Betamethasone valerate, Betamethasone dipropionate, Prednicarbate, Clobetasone-17butyrate, Clobetasol-17-propionate, Fluocortolone caproate, Fluocortolone pivalate, and Fluprednidene acetate.

Synthetic glucocorticoids

Glucocorticoids

cortisone hydrocortisone

prednisone prednisolone

dexamethasone

betamethasone dexamethasone

triamcinolone acetonide fluorometholone

Budesonide

Side effects of glucocorticoids (review version): immunosuppression hyperglycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance; caution in those with diabetes mellitus; cardiovascular effects: edema and hepertension; fluid retention; increased skin fragility, easy bruising; reduced bone density (osteoporosis, osteonecrosis , higher fracture risk, slower fracture repair); weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; adrenal insufficiency (if used for long time and stopped suddenly without a taper) muscle breakdown (proteolysis), weakness; reduced muscle mass and repair; expansion of malar fat pads and dilation of small blood vessels in skin anovulation, irregularity of menstrual periods growth failure, pubertal delay increased plasma amino acids, increased urea formation; negative nitrogen balance excitatory effect on central nervous system (euphoria, psychosis) glaucoma due to increased cranial pressure; cataracts

weight gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; adrenal insufficiency (if used for long time and stopped suddenly without a taper) muscle breakdown (proteolysis), weakness; reduced muscle mass and repair; expansion of malar fat pads and dilation of small blood vessels in skin anovulation, irregularity of menstrual periods growth failure, pubertal delay increased plasma amino acids, increased urea formation; negative nitrogen balance excitatory effect on central nervous system (euphoria, psychosis) glaucoma due to increased cranial pressure; cataracts

Comparative steroid potencies

Name Hydrocortisone (Cortisol)
Cortisone acetate

Prednisone Prednisolone Methylprednisolone Dexamethasone Betamethasone Triamcinolone Beclometasone Fludrocortisone acetate DOCA Aldosterone

Mineralocorticoids

aldosterone

fludrocortisone acetate

mineralocorticoids receptor antagonists

spironolactone eplerenone

Thyroid hormones

Hepothalamicpituitary-thyroid feedback system

levo---4 letters---T4 Levo

levothyroxine T4

lio--- 3 letters-T3

liothyronine T3

sodium salts of T3/T4 Liotrix Thyroid USP Thyrotropin (TSH) Thyroxine

inhibitors

K or Na iodide Lugol solution

radioactive iodine
thiourylenes

propylthiouracil (PTU)

methimazole

antidiabetic agents

Drugs that can cause dysglycemia

insulin

short-acting

lispro insulin insulin aspart insulin glulisine

regular insulin
intermediate-acting

NPH
combination product: lispro/aspart insulin

long-acting

insulin glargine insulin detemir Lente Insulin Ultralente

Oral Antidiabetic Agents

Sulfonylureas

_amide _zide _ride gli- /gly2ed Gen. tolbutamide chlorpropamide tolazamide

first generation

gliclazide

acetohexamide

glyburide

second generation

glipizide

gliquidone

Third generation

glimepiride

Biguanide

_formin

Metformin

phenformin

-glucosidase inhibitors

monosaccharides miglitol

polysaccharides acarbose

Meglitinides

_glinide

repaglinide nateglinide

Thiazolidinediones

_glitazone

rosiglitazone

pioglitazone troglitazone

Intestinal Lipase Inhibitors

Orlistat

peptide mimetics

_tide exenatide

pramlintide

anti-insulin Glucagon

Symptoms of Hypoglycemia

specific interactions

sulfonylureas

biguanide

meglitinides
thiazolidinediones

-glucosidase inhibitors

peptide mimetics

Gestational Diabetes

insulin only

Agents for Asthma

Inhaled 2-agonists

albuterol
short-acting bitolerol

pritbuterol formoterol
long-acting

salmeterol salbutamol
Mast cell stabilizers (inhaled)

cromolyn

nedocromil

Corticosteroids (inhaled)

beclomethasone

budesonide flunisolide fluticasone triamcinolone

Leukotriene modifiers ~receptor antagonists montelukast

zafirlukast
5-lipoxygenase inhibitor

zileuton

Bronchodilators

Albuterol Levalbuterol Clenbuterol 2-agonists Pirbuterol Anticholinergics Salmeterol Elphedrine

Serevent (salmeterol) Ventolin (salbutamol = albuterol) Xopenex (levosalbutamol = levalbuterol)

Ritodrine

Anticholinergics

ipratropium bromide

Salbutamol

Berodual N

Xanthine

A group of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in treating the symptoms of asthma. They only inhibit the actions of sleepinessinducing adenosine, making them somewhat less effective as stimulants than sympathomimetic amines. Due to widespread effects, the therapeutic range of xanthines is narrow, (merely a second-line asthma treatment). The therapeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia. Methylated xanthine derivatives include caffeine, paraxanthine, theophylline, and theobromine which inhibit phosphodiesterase and antagonise adenosine. Xanthines are also found very rarely as constituents of nucleic acids.

theophylline (dimethylxanthine

Pentoxifylline

Interferons Opioids TNF binding proteins Mycophenolate

Anticancer drugs antineoplastic

M: mitotic-I s G1: pre-aspa S: antimetab G2: bleo-etopo

Alkylating agents
Nitrogen mustards Chlorambucil Chlormethine

Cyclophosphamide

Ifosfamide Trofosfamide Melphalan Bendamustine Uramustine

Nitrosoureas

_mustine Carmustine

Fotemustine Lomustine Nimustine Prednimustine Ranimustine Semustine

Streptozocin

Platinum (alkylating-like)

_platin Carboplatin

Cisplatin

Side reactions

Nedaplatin Oxaliplatin Triplatin tetranitrate Satraplatin

Alkyl sulfonates

_sulfan Busulfan Mannosulfan Treosulfan

Hydrazines

Procarbazine
Triazenes

Dacarbazine Temozolomide
Aziridines

Carboquone ThioTEPA Triaziquone Triethylenemelamine

Antitumor antibiotics

Anthracycline

_rubicin

Daunorubicin

Daunorubicin Doxorubicin Doxorubicin Epirubicin Idarubicin Valrubicin

structural analogs of naturally occurring substrates for biochemical ractions----inhibit DNA synthesis by acting as false substitutions

Antimetabolites

Folic acid (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed) Purine (Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine)----rabine, ribine Pyrimidine (Cytarabine, Decitabine, Fluorouracil/Capecitabine, Floxuridine, Gemcitabine, Enocitabine, Sapacitabine) --tabine

Methotrexate

Azacytidine 5-Fluorouracil Pentostatin Fludarabine Gemcitabine

Mitotic inhibitors

Taxanes (Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) Vinca alkaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine) Ixabepilone

Vin-taxel stop mito

Taxane Docetaxel

Paclitaxel

Vinca alkaloids Vinblastine

Vincristine Vinorelbine

topoisomerase inhibitors

Topotecan

Etoposide

Enzymes asparaginase

Pegasparaginase
Protein tyrosine kinase inhibitors

Imatinib mesylate Erlotinib

Cyclin-dependent kinase inhibitors

Alvocidib Seliciclib
Hormones Tamoxifen

Estradiol tesosterone
Photosensitizers Aminolevulinic acid/Methyl aminolevulinate Efaproxiral Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin) Others

tretinoin (ARTA) Arsenic trioxide

bortezomib bexarotene

thalidomide

Biological response modigiers

cytokine

monoclonal antibodies _zumab

bevacizumab alemtuzumab Gemtuzumab ozogamicin Ibritumomab tiuxetan Efalizumab

Omalizumab

Titanium dioxide

Immunosuppressive agents

Calcineurin inhibitors

cyclosporine

tacrolimus
antimetabolites

Azathioprine Mycophenolic acid Methotrexate

glucocorticoids

cytostatics

Alkylating agents

Antimetabolites

Methotrexate

Azathioprine

Cytotoxic antibiotics

antibodies Polyclonal antibodies Monoclonal antibodies T-cell receptor directed antibodies IL-2 receptor directed antibodies

drugs acting on immunophilins

Calcineurin inhibitors

cyclosporine or ciclosporin

Tacrolimus

TNF- inhibitor

Thalidomide Alkylating agents

nitrogen mustards cyclophosphamide nitrosoureas platinum compounds

Antibodies

.
monoclonal OKT3

-mab

Daclizumab Basiliximab Efalizumab

Polyclonal

Fusion protein

.-cept

mTOR

.-rolimus

Corticosteroids

Prednisone Methylprdnisolone

H 2 -Receptor Antagonists

Cimetidine

Ranitidine

Famotidine

Nizatidine

Gastroesophageal reflux disease (GERD)

PPIs proton pump inhibitors

Omeprazole

Lansoprazole

Esomeprazole

Pantoprazole

Rabeprazole

Sucrose sulfate-aluminium Sucralfate complex

Prokinetics

8 prokinetics: -mide or -pride: Domp- Erythro- Ito- MetoBenza- Cisa- Mosa- PrucaBCDE IMMP

Domperidone

Metoclopramide

Erythromycin Benzamide Prucalopride Cisapride Mosapride

Itopride

Bismuth subsalicylate

Phosphodiesterase inhibitor

Non-selective PDEIs

PDE1 selective inhibitors Vinpocetine

PDE2 selective inhibitors

PDE3 selective inhibitors Milrinone

Enoximone Amrinone Mesembrine Rolipram Ibudilast Pentoxifylline

PDE4 selective inhibitors

Ibudilast

Pentoxifylline

PDE5 inhibitors _afil ---fill for ED

sildenafil Viagra

tadalafil

vardenafil

Alprostadil

Proteasome inhibitor

Bortezomib

Disulfiram

Aphrodisiac drugs

Testosterone

Yohimbine

Bremelanotide

Others

Pramipexole

Anorexiants

phentermine

Benzphetamine

Diethylpropion Bupropion Satiety enhancers

Sibutramine

orlistat

Mazindol

Benzphetamine

DMARDs

Disease-modifying antirheumatic drug

adalimumab

azathioprine hydroxychloroquine chloroquine cyclosporine

D-penicillamine etanercept gold salts infliximab leflunomide methotrexate minocycline sulfasalazine

Anakinra

Bisphosphonates

Non-nitrogenous

Etidronate Clodronate Tiludronate

Nitrogenous

Pamidronate (APD, Aredia) - 100

Neridronate - 100

Olpadronate - 500 Alendronate (Fosamax) - 500 Ibandronate (Bonviva) - 1000 Risedronate (Actonel) - 2000

Zoledronate

Lactase enzyme

Dihydrotachysterol

Desmopressin acetate

Permethrin

Lypressin

Dyphylline

Loperamide

guaifenesin

Phenazopyridine

Clofazimine

page 1-141 (take note of 249) pharmacology

amitriptyline imipramine trimipramine doxepin clomipramine opipramol lofepramine lofepramine dosulepin hydrochloride

selcetive inhibit Norepinephrine reuptake; less side effects nortriptyline desipramine protriptyline amoxapine
citalopram escitalopram dapoxetine fluoxetine paroxetine fluvoxamine sertraline zimelidine

antiemetics
5-HT3-receptor antagonists

-setron anti- serotonin receptor 3 ondansetron granisetron dolasetron palonosetron alosetron

ole (brand names: Losec, Prilosec, Zegerid, ocid)

zole (brand names: Prevacid, Zoton, Inhibitol) azole (brand names: Nexium) zole (brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan) zole (brand names: Rabecid, Aciphex, Pariet, Rabeloc)

a dual endothelin receptor antagonist important in the treatment of pulmonary artery hypertension (PAH).

Rofecoxib (withdrawn from market) (FDA alert) Valdecoxib (withdrawn from market ) FDA withdrawn Lumiracoxib TGA cancelled registration; FDA withdrawn

Depression, phobic anxiety and narcolepsy that was not responded to other treatments. (last line)

Interact with sympathomimietic drugs and with foods that have a high tyramine concentration such as cheese, wine, and sausage. Hypertensive cries can result.

ctive: non-reversible (Isocarboxazid, Iproclozide, Iproniazid, Nialamide, Phenelzine) reversible (Tranylcypromine)---- long time use can make it irreversible N/S): Clorgiline Minaprine RIMAs (Befloxatone, Brofaromine, Cimoxatone, Harmaline, Moclobemide (reversible), Pirlindole, Toloxatone) D): Rasagiline Selegiline Pargyline

ride; tide; glitazone;glinide;

The preferred initial regimens for AIDS (HAART): efavirenz (NNRTI) + zidovudine (NRTI) + lamivudine (NRTI) efavirenz + tenofovir (NtRTI) + emtricitabine (NRTI) lopinavir (PI) boosted with ritonavir (PI) + zidovudine + lamivudine lopinavir boosted with ritonavir + tenofovir + emtricitabine. Indinavir is a specific inhibitor of HIV-1 proteases. Cross-resistance can occur with other protease inhibitors.

ides----- 30 S or 50S;

chloramphenicol -----50S;

Gentamicin and tetracyclines-----30S ribosomal subunit

fast-channel blockers PDQ procainamide disopyramide quenidine phen lido to me lidocaine tocainide mexiletine phenytoin Flecainide Propafenone Moricizine

flecainide propafenone moricizine b-blockers PEAN

Propranolol Esmolol Acebutolol Nadolol Amiodarone Sotalol Ibutilide Dofetilide Bretylium amiodarone sotalol

ibutilide dofetilide bretylium

verapamil diltiazem bepridil Atropine Digoxin adenosine

by Calcium ingestion (milk-alkali syndrome), Hyperparathyroid, Hyperthyroid, Iatrogenic (thiazides), myeloma , Pagets disease, Addisons disease, Neoplasms, Zollinger-Ellison syndrome, Excess vitamin D, vitamin A, Sarcoidosis.

nt for selected psychiatric conditions Drug Benzodiazepines SSRIs Barbiturates Benzodiazepines

ric condition withdrawal a/bulimia

Buspirone MAO inhibitors Methylphenidate (Ritalin) Amphetamine depression MAO inhibitors disorder Mood stabilizers: Lithium Valproic acid Carbamazepine ion SSRIs TCAs ion with insomnia Trazodone Mirtazapine SSRIs

ve-compulsive disorder

sorder

hrenia s syndrome

TCAs Buspirone Antipsychotics Antipsychotics (haloperidol)

uscular-blocking drug block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by resynaptically via the inhibition of acetylcholine (ACh) synthesis or release, or by acting postsynaptically at the acetylcholine receptor. While there are drugs that act ptically (such as botulin toxin and tetrodotoxin), the clinically-relevant drugs work postsynaptically.

ese agents act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. _curium / curonium / curarine/ Gallamine Cisatracurium (Nimbex) Vecuronium (Norcuron) Rocuronium (Zemuron) Pancuronium (Pavulon) Tubocurarine (Jexin) Gallamine (Flaxedil)

etic analogue of prostacyclin, used to treat pulmonary hypertension.

dysfunction

pharmacology
Appears to block posttetanic potentiation of synaptic transmission; with effects on sodium channels.

Thought to be similar to phenytoin. and reduces polysynaptic responses. antiseizure agent, related to tricyclic antidepressants

Sodium effects similar to phenytoin, with effects on calcium and GABA.

_eplase _kinase

_ azine; _apine; _idone

D2 receptors in the dopamine pathways of the brain; with minimal effect on the serotonergic pathways, is considered a typical antipsychotic.

used in the treatment of schizophrenia, hiccups and nausea. side-effect profile: anticholinergic effects (constipation, sedation, hypotension, and antiemetic properties); anxiolytic properties. Extrapyramidal side-effects (evolution--- 4h acute dystonia; 4d akinesia; 4 wk akathisia; 4 month tardive dyskinesia; parkinsonian tremor), Neuroleptic malignant syndrome (rigidity, myoglobinuria, autoniomic instability, hyperpyrexia, treat with dantroene and dopamine agonists)is a rare though potentially fatal; Cholestatic jaundice (fever, chills, anorexia, volmiting, myalgia);

azine (Prolixin) - Available in decanoate (long-acting) form (Trilafon)

perazine (Compazine)

erazine (Stelazine)

mazine (Vesprin) promazine (Nozinan) hazine (Phenergan)

a member of the dibenzoxazepine class and as a dibenzazepine derivative, it is structurally related to clozapine; Several researchers have argued that Loxapine may behave as an atypical antipsychotic. Loxapine may be metabolized by N-demethylation to amoxapine, a tricyclic antidepressant. Most significant side-effects of loxapine are excessive salivation and indifference to surroundings.

Example

Chlorpromazine Promazine Triflupromazine Levomepromazine Methotrimeprazine Mesoridazine Thioridazine Fluphenazine Perphenazine Flupentixol Prochlorperazine Trifluoperazine

Chlorprothixene exerts strong blocking effects at the following postsynaptic receptors: 5-HT2 : anxiolysis, antipsychotic effects D1, D2, D3 : antipsychotic effects H1 : sedation, weight gain muscarinic : anticholinergic side effects, extrapyramidal side effects attenuated Alpha1 : hypotension, tachycardia

hixol (Depixol and Fluanxol)

nthixol (Clopixol & Acuphase)

initial treatment. equally effective for the treatment of the positive symptoms. but offer additional benefit for the negative symptoms and cognitive deficits associated with schizophrenia; Atypical antipsychotics have a higher affinity for serotonin symptoms but a lower affinity for histamine, cholinergic muscarinic and alpha adrenergic receptors.

Clozapine has been shown to be the most effective drug in treating schizophrenia but due to its potential to cause many severe side effects, it is relegated to third-line use and only used in patients after other anti-psychotics have failed. Side effects: agranulocytosis (requires weekly WBC monitoring);

(FDA-approval: 1993) Available in oral tablets, dissolving tablets, liquid form, and extended release intramusclar injection. For the treatment of schizophrenia and bipolar disorder. It is the only drug agent available for treatment of schizophrenia in children ages 1318; and for treatment of bipolar disorder in youths ages 1018, joining lithium. Risperidone contains the functional groups of benzisoxazole and piperidine as part of its molecular structure. Many antipsychotics are known to increase prolactin because they inhibit dopamine. However, risperidone is known to increase prolactin to a greater extent than most other antipsychotics, such as quetiapine. It is thought that once risperidone raises prolactin, it may cause non-cancerous tumors in the pituitary gland.

(FDA-approval: 1996) Available in oral tablets, dissolving tablets, and intramuscular injection. Olanzapine has a higher affinity for 5-HT2 serotonin receptors than D2 dopamine receptors. It is also used for OCD, anxiety disorder, depression, mania, Tourette's syndrome;

used in the management of schizophrenia and bipolar I disorder, and off-label for a variety of other purposes, including insomnia and anxiety disorders. Common side effects: sedation, constipation, headache, dry mouth, weight gain (or loss). NMS, orthostatic hypotension, tardive dyskinesia, and cataract formation may occur in chronic use.

(Geodon) (FDA-approval: 2001) Available in oral capsules and intramuscular injection. Ziprasidone is hepatically metabolized by aldehyde oxidase. Minor metabolism occurs via cytochrome P450 3A4 (CYP3A4). Medication that induce (e.g. carbamazepine) or inhibit (e.g. ketoconazole) CYP3A4 have been shown to decrease and increase, respectively, blood levels of ziprasidone. There are no known inducers or inhibitors of aldehyde reductase.

(Abilify) Available in oral tablets and dissolving tablets. (Invega) (FDA)-approval: 2006) Available in extended-release oral tablets.

ne FDA has accepted NDA as of November 26, 2007. [7]

one (Fanapta or Zomaril) FDA has accepted NDA as of November 27, 2007. [8]

le (Serlect) (Not approved by the FDA for use in the USA).

e (Not approved by the FDA for use in the USA).

ride (Not approved by the FDA for use in the USA).

ox (Not approved by the FDA for use in the USA).

ne Approved in Europe. Currently in clinical trial in the USA.

Do not confuse with the proton pump inhibitors (such as omeprazole, pantoprazole, and lansoprazole),

Dosing 1 mg up to maximum of 30 mg has been used. Mechanism of action is thought to reduce susceptibility to metabolic symptoms seen in some other atypical antipsychotics. Approved for the treatment of schizophrenia, acute manic and mixed episodes associated with bipolar disorder, and depression. Common side effects: Akathisia, headache, unusual tiredness or weakness, nausea, vomiting, an uncomfortable feeling in the stomach, constipation, lightheadedness, trouble sleeping, restlessness, sleepiness, shaking, and blurred vision.

Pimozide (sold as Orap) is an antipsychotic drug. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis it is even more potent than haloperidol. As it has severe side effects, it is considered a drug of last resort, typically prescribed only after the patient has failed to respond to other medications. It also has special neurologic indications for Tourette syndrome and resistant tics. The side effects include akathisia, tardive dyskinesia, neuroleptic malignant syndrome and long QT syndrome.

agents

the tertiary amines boost serotonin as well as nor-epinephrine (adrenergic) and produce more sedation, anticholinergic effects, and orthostatic hypotension.

Amitriptyline inhibits serotonin and noradrenaline reuptake almost equally. It is used to prevent migranes, only in very small doses. It has the highest sedation property among all the antidepressants and may be more preferable to use for treatment of depression iwth anxiety disorder. Common side effects: dry mouth, extreme weight gain, drowsiness, muscle stiffness, nausea, constipation, nervousness, dizziness, blurred vision and insomnia.

affects numerous neurotransmitter systems know to be involved in the etiology of depression, anxiety , ADD/ADHD, enuresis and numerous other mental and physical conditions. Imipramine is similar in structure to some muscle relaxants. Nocturial enuresis: imipramine and desmopressin mechanism of action differs from other tricyclic antidepressants: only a moderate reuptake inhibitor of norepinephrine, and a weak reuptake inhibitor of serotonin and dopamine. (strong : 5-HT2, Muscarinic, H1, H2, Alpha1; moderate : D2 ; weak : 5-HT1, Alpha2 ) the only effective drug against insomnia (it does not alter the normal sleep architecture;in particular, it does not suppress REM-sleep)

generally indicated for the treatment of obsessive compulsive disorder of the brain. Fluvoxamine is also used in OCD.

The secondary amines act primarily on nor-epinephrine and tend to have a lower side-effect profile It is used in the treatment of major depression and childhood nocturnal enuresis (bedwetting). Also used for chronic illnesses such as chronic fatigue syndrome, chronic pain and migraines, and labile affect in some neurological conditions. Closer monitoring is required for those with a history of cardiovascular disease, stroke, glaucoma, and/or seizures, as well as those that have hyperthyroidism or are receiving thyroid medication.

It is used in the treatment of depression, panic disorders and bipolar disorder. Amoxapine is a strong reuptake inhibitor of norepinephrine and weak reuptake inhibitor of serotonin. One of its major metabolites, 7-hydroxyamoxapine, has a dopamine receptor blocking effect, making this drug a common cause of neuroleptic malignant syndrome. Amoxapine is also associated with acute extra pyramidal symptoms and tardive dyskinesia. Adverse Effects: Amenorrhoea; Milk discharge; Drowsiness, dry mouth, blurred vision and constipaiton

It is a strong norepinephrine reuptake inhibitor with only weak effects on serotonin and dopamine reuptake. It exerts blocking effects at : Strong : alpha1 / Moderate : 5-HT2, muscarinic, H1, D2 / Weak : alpha2 /Extremely weak : 5-HT1 Contraindications: Absolute (Hypersensitivity to Maprotiline or to other tri-/tetracyclic antidepressants ; Hypertrophy of the prostate gland with urine hesitancy; Closed Angle Glaucoma )

A class of antidepressants used in the treatment of depression, anxiety disorders, and some personality disorders. They are also typically effective and used in treating premature ejaculation problems as well as some cases of insomnia. SSRIs increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake into the presynaptic cell, increasing the level of serotonin available to bind to the postsynaptic receptor. They have varying degrees of selectivity for the other monoamine transporters, having little binding affinity for the noradrenaline and dopamine transporters. SSRIs can cause various types of sexual dysfunction such as anorgasmia, erectile dysfunction, and diminished libido. On the other hand, the effect of SSRIs to slow down sexual stimulation may be used as treatment for premature ejaculation. One major contraindication of SSRIs is the concomitant use of MAOIs ---- likely to cause severe serotonin syndrome. It is also better to avoid taking pimozide. The atypical opioid analgesic tramadol hydrochloride can, in rare cases, produce seizures when taken in conjunction with an SSRI or tricyclic antidepressant. Liver impairment is another contraindication for medications of this type.

SSRIs may increase blood levels and risk of toxicities of certain medications: CYP2D6 inhibitors highly protein-bound medications like warfarin (coumadin) and digoxin / antiarrhythmic agents like propafenone (Rythmol) or flecainide (Tambocor) / beta blockers like metoprolol (Toprol xl) or propranolol (Inderal) / tricyclic antidepressants like amitriptyline (Elavil) (may increase risk of serotonin syndrome) / benzodiazepines like alprazolam (Xanax) or diazepam (Valium) / carbamazepine (Tegretol) / cisapride (Propulsid) / clozapine (Clozaril) / cyclosporin (Neoral) / haloperidol (Haldol) / phenytoin (Dilantin) / pimozide (Orap) / theophylline (Theo-dur) Certain drugs may increase toxicities of SSRIs: alcohol and other CNS depressants / diuretics (water pills) / MAOIs / sympathomimetic drugs like pseudoephedrine (Sudafed) / lithium / sibutramine (Meridia) / MDMA (ecstasy) / zolpidem (ambien) / Dextromethorphan

Serotonin Syndrome is a potentially life-threatening adverse drug reaction that may occur following therapeutic drug use, inadvertent interactions between drugs, or the recreational use of certain drugs. It is not a spontaneous drug reaction; it is a consequence of excess serotonergic activity at central nervous system (CNS) and peripheral serotonin receptors. The symptoms are often described as a clinical triad of abnormalities: Cognitive effects: mental confusion, hypomania, hallucinations, agitation, headache, coma. Autonomic effects: shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea,h risk of GI bleeding with NSAIDs; Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus,), tremor.

Citalopram is used to treat the symptoms of major depression, social anxiety disorder and panic disorder. Citalopram is a Pgp substrate (also venlafaxine, amitriptyline or paroxetine ) and is actively transported by Pgp from the brain. The efficacy of citalopram in people possessing a certain version of Pgp (genetic TT-allele) is likely to be diminished. This suggests that in non-responders to citalopram a switch to antidepressant which is not a Pgp substrate, such as fluoxetine or mirtazapine may be beneficial. It is a better choice for the elderly or comorbid patients. Citalopram should be taken with caution when using St John's wort and contraindicated in individuals taking MAOIs. Stereoisomer of citalopram, similar side effect but higher efficacy relative to other SSRIs

First line treatment in children and alolescents. Major depression (includingbipolar disorder depression and pediatric depression), obsessive-compulsive disorder (in both adult and pediatric populations), bulimia nervosa, anorexia nervosa, panic disorder, social phobia; and premenstrual dysphoric disorder, chronic fatigue syndrome, fibromyalgia, menopause, premature ejaculation. The extremely slow elimination of fluoxetine and its active metabolite norfluoxetine: CYP450 inhibitors, they inhibit their own metabolism, so fluoxetine elimination half-life 1 to 3 days after a single dose and 4 to 6 days after long-term use. Norfluoxetine is even longer to16 days after long-term use;

SSRIs comprise one of the major classes of antidepressants currently being prescribed by primary care physicians. At first, SSRIs were thought to be associated with weight loss and reduced appetite. For a while, they were even marketed as anti-obesity drugs. It is now known that long-term use of SSRIs is associated with weight gain. Discontinuation effects are particularly prevalent

Fluvoxamine was one of the first of the SSRI antidepressants to be launched (1984 - Switzerland); most often used to treat obsessive-compulsive disorder (OCD). It is also widely prescribed to treat major depression, and anxiety disorders such as Obsessive-Compulsive Spectrum Disorder, Panic Disorder, Social Phobia, and Post-Traumatic Stress Disorder. and for children and adolescents with OCD.

primarily used to treat major depression in adult outpatients as well as obsessive-compulsive, panic and social anxiety disorders in both adults and children. In 2007 it was the most prescribed antidepressant on the US retail market, with 29,652,000 prescriptions. high rates of nausea, diarrhea, insomnia, and sexual side effects; however, it does not cause weight gain, and its effects on cognition are mild. In pregnant women taking sertraline, the drug was present in significant concentrations in fetal blood, and was also associated with a higher rate of various birth defects. Sertraline has been approved for the following indications: major depression, obsessive-compulsive disorder (OCD), posttraumatic stress disorder (PTSD), premenstrual dysphoric disorder (PMDD), panic disorder and social phobia (social anxiety disorder).

They act on two neurotransmitters in the brain serotonin and norepinephrine, used in the treatment of major depression and other mood disorders. Also used to treat anxiety disorders, OCD, ADHD and chronic neuropathic pain.

As with the SSRIs, abrupt discontinuation of SNRI-medication usually leads to a discontinuation syndrome which could include states of anxiety and further symptoms. (slowly taper down the dose when discontinuing SNRIs.) Due to the effects of increased norepinephrine synaptic activity, these drugs are contraindicated in patients with hypertension, heart disease, or risk of stroke.

prescribed for the treatment of major depression and anxiety disorders, among other uses. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide, it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs.

Available in USA and Europe since 2004

Blocking the intraneuronal oxidative deamination of brain biogenic amines. Chronic inhibition of MAO ----down-regulaiton of central adrenergic and serotonergic receptors.

Moclobemide is the only reversible and selective inhibitor of MAO-A that is currently available; Dietary precautions are not required at standord doses; Common S/N:Nausea, insomina, dizziness; Avoid sympathomimetics, mepetidine; Caution with opioids, antihypertensives, antipsychotics, SSRIs, Selegiline, excessive tyramine, alcohol; reduce dose with cimetidine.

Drug interactions: Sympathomimetics (e.g. pseudoephedrine in cold remedies): Risk of hypertensive crisis; Mepridine: may cause agitation, hyperpyrexia, circulatory collapse; ??? is it the same as moclobemide?? Reserpine, guanethidine, tricyclic antidepressants : Excitement / Increase in blood pressure and body temperature Levodopa (L-DOPA): Excitement / Hypertension Anticholinergics (Henbane, Datura): Risk of hallucination Antihistamines, barbiturates, ethanol, opioids: Action of these drugs prolonged - risk of respiratory depression Pethidine (Demerol) :Risk of high fever, sweating, excitement, delirium, convulsions, respiratory depression (MAOIs retard metabolism of pethidine, but not its demethylation, therefore excess norpethidine is formed). Methylenedioxymethamphetamine (MDMA, "Ecstasy") :Risk of hypertensive crisis / Serotonin syndrome Dextromethorphan (DXM, cough-syrup) : Serotonin syndrome Imitrex/Sumatriptan, Migraine Medicine Side reactions: Interact with sympathomimietic drugs and with foods that have a high tyramine concentration such as cheese, wine, and sausage. Hypertensive crises can result. CNS effects: stimulation, tremors agitation, overactivity, hyperreflexia, mania,insomnia followed by weakness, fatigue, drowness Cardiovascular effects: postural hypotension GI effects: nausea, abdominal pain, and constipation Antimuscarinic effects: dry mouth, urinary retention, and constipation

Linezolid (Zyvox, Zyvoxid), an antibiotic of the oxazolidinone family, is a reversible, nonselective MAOI which has been known to induce serotonin syndrome post SSRI ingestion. Zyvox requires the same dietary precautions as other MAOI's

Act by norepinephrine and dopamine reuptake inhibition, and nicotinic antagonist; First-line for major depression and also for smoking cessation; Favourable side effect profile and a low rate of sexual dysfunction; Contraindicated: histroy of anorexia or bulimia nervora or head trama; or a current seizure or prior seizure; Mirtazapine has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (act on 5HT2 and 5HT3) (NaSSA). Directly act on noradrenergic system and indirectly on serotonin system; Mirtazapine and Maprotiline are the only tetracyclic antidepressants that have been approved by FDA to treat depression. Devoid of anticholinergic effects, serotonin-related side effects, and adrenergic side effects (orthostatic hypotension and sexual dysfunction). So it is relatively safe if an overdose is taken. Low rate of GI and sexual side effects; But associated with antihistaminic side effects (drowsiness and sedation) and weight gain;

Not considered to be an SSRI, MAOI or tricyclic antidepressant.

Apsychoactive compound with sedative, anxiolytic, and antidepressant properties. Trazodone has less prominent anticholinergic (dry mouth, constipation, tachycardia) and adrenolytic (hypotension, male sexual problems) side effects than most tricyclic antidepressants. Distinct from tricyclic antidepressants and tetracyclic antidepressants, trazodone's antidepressant effects may be due to its antagonistic effects at 5-HT2 receptors. Trazodone is often used in conjunction with SSRI, like fluoxetine and has been noted to help with the anxiety that can result from beginning treatment with an SSRI anti-depressant. Trazodone has been prescribed to children as an aid to an SSRI.

Nefazodone hydrochloride (trade name Serzone, Nefadar) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries(including the United States and Canada), due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death.

SSRIs (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetiene and sertraline) and SNRI (Venlafaxine); TCAs (imipramine, desipramine, clomipramine); Diazepines (alprazolam, clonazepam, lorazepam, diazepam) Dual action antidepressants (Mertazapine, bupropion) MAOIs (phenelzine, tranylcypromine, moclobemide)

Benzodiazepines produce a range of effects from depressing to stimulating the CNS via modulating the GABAA receptor, with varying hypnotic, sedative, anxiolytic, anticonvulsant, muscle relaxant and amnesic properties, which are mediated by slowing down the CNS. Benzodiazepines are useful in treating anxiety, insomnia, agitation, seizures(lora- and dia-), and muscle spasms(Clona- ), alcohol withdrawal(chlordiazepoxide, dia-, lora-, oxa-). Also used in preanesthetic medication.

3-OH, undergo phase II glucuronidation--- short-acting compounds(oxa-, lora-, tema-): half-life of less than 12 hours with few residual effects if taken before bedtime but rebound insomnia may occur and they might cause wake-time anxiety. Intermediate-acting compounds (alprazolam): half-life of 1224 hours with residual effects in the first half of the day. Long-acting compounds(without 3-OH---phase I metabolism: di, hala, alpra, flura, qua-zepam; ): a half-life greater than 24 hours. intermediate-acting short term treatment (up to 8 weeks) of panic disorder, with or without agoraphobia. Alprazolam is very effective in treating moderate to severe anxiety, essential tremor and panic attacks.

also used to treat delirium tremens

long-acting; May be used in Epilepsy / Anxiety disorders, Panic disorder / Initial treatment of mania, together with firstline drugs such as lithium, haloperidol or risperidone / Hyperexplexia / Restless legs syndrome

long-acting

the longest-acting long-acting

short-acting

short-acting; Metabolized mostly be Phase II reaction, safer than other drugs metabolized by Phase I in eldly patients. short-acting short-acting

serotonin receptor agonist; act by agonizing serotonin (specifically the 5-HT1A receptor), primarily in the hippocampus. Unlike benzodiazepines, azaspirodecanediones are not addictive and do not induce tolerance and with less side effects

Generalized anxiety disorder of mild to moderate intensity (not effective against other types such as obsessive-compulsive disorder); Augmentation of SSRI-treatment against depression; Attention-Deficit Hyperactivity Disorder (ADHD)

Barbiturates bind to the GABA A receptor at the alpha subunit, (distinct from GABA itself and the benzodiazepine binding site). Like benzodiazepines, barbiturates potentiate the effect of GABA at this receptor. Barbiturates also block the AMPA receptor, a subtype of glutamate receptor. Glutamate is the principal excitatory neurotransmitter in the mammalian CNS. The most widely used anticonvulsant worldwide and the oldest still commonly used (The WHO recommends its use as first-line for partial and generalized tonic-clonic seizures in developing countries). It also has sedative and hypnotic properties but has been superseded by the benzodiazepines for these indications. Sedation and hypnosis are the principal side effects of phenobarbital. CNS effects: dizziness, nystagmus and ataxia. In elderly patients, it may cause excitement and confusion while in children, it may result in paradoxical hyperactivity. barbiturates is absolutely contraindicated in patients who have acute intermittent porphyria. These patients have a defect in regulation of -aminolevulinic acid synthetase; thus, administration of a barbiturate that increases this enzyme may cause a dangerous increase in levels of porphyrins.

Indicated in the treatment of all types of seizures except absence seizures. Phenobarbital is no less effective at seizure control than more modern drugs but significantly less well tolerated. The first line choice for the treatment of neonatal seizures; The first line drugs for treatment of status epilepticus are fast acting benzodiazepines such as diazepam or lorazepam. If these fail then phenytoin may be used, with phenobarbital being an alternative in the U.S. and Canada. (intermediate) (intermediate) short short ultra-short

ultra-short ultra-short also called: Methylphenobarbital

Meprobamate (Miltown by Wallace Laboratories, Equanil by Wyeth, and Meprospan) is a carbamate derivative which is used as an anxiolytic drug. It was the best-selling minor tranquilizer for a time, but has largely been replaced by the benzodiazepines. Arrhythmia, aplastic anemia, palpitation, tachycardia, dizziness, drowsiness and ataxia.

used for the short-term treatment of insomnia, as well as some brain disorders. It is a short-acting nonbenzodiazepine hypnotic that potentiates gammaaminobutyric acid (GABA). It works quickly (usually within 15 minutes) and has a short half-life (23 hours).

Glutethimide is a hypnotic sedative as a safe alternative to barbiturates to treat insomnia. It is a CYP2D6 enzyme inducer. When taken with codeine, it enables the body to convert higher amounts of the codeine (higher than the average 5 - 10%) to morphine. The general sedative effect also adds to the power of the combination. In these respects, glutethimide is a stronger booster of codeine and related opioids than is promethazine.

used to induce sleep in pediatric or geriatric patients

also called antiepileptic drugs ( "AEDs"), a diverse group of pharmaceuticals used in epileptic seizures. Also increasingly being used the treatment of bipolar disorder (act as mood stabilizers). It can suppress the rapid and excessive firing of neurons that start a seizure. However, anticonvulsants themselves have been linked to lowered IQ in children. The major molecular targets of marketed anticonvulsant drugs are 1) voltage-gated sodium channels; 2) components of the GABA system, including GABA-A receptors, the GAT-1 GABA transporter, and GABA transaminase; and 3) voltage-gated calcium channels.

ized Tonic-clonic: carbamazepine, lamotrigine, phenytoin, valproic acid, (clobazam, levetracetam, topiramate)---alternative or add-on

e (petit mal): ethosuximide, valproic acid; (clonazam, lamotrigine, levetracetam, topiramate)

nic and Atonic : valproic acid; (clonazam, lamotrigine, levetracetam, topiramate)

simple or complex) with or without 2 generalization: carbamazepine, lamotrigine, phenytoin, (clobazam,gabapentin, levetracetam, oxcarbazepine, phenobarbital, ne, topiramate, valproic acid, vigabatrin)

ized Tonic-clonic (grand mal): phenobarbital, phenytoin, primidone, carbamazepine; (PPP-Car) motor: phenytoin, phenobarbital, primidone, carbamazepine (PPP-Car)

e (petit mal): phynobarbital, ethosuximide, clonazepam, trimethadione, valproic acid;(PEClo-TV) ic : clonazepam (Myo----Clo) clorazepate, felbamate, gabapentin, lamotrigine (Clora-Fel-Gab-Lamo)

epilepticus: IV diazepam, phenytoin, phenobarbital (PP- IV-D); Dextrose 50% solution is normally indicated.

Inhibits the spread of seizures at the motor cortex and block posttetanic potentiation of synaptic transmission; with effects on sodium channels and Ca-uptake in presynaptic terminals. Elimination: Zreo-order in high dose

Decreased levels with Cobalamin, rifampin, chronic alcohol ingestion, carbamazepine, valproic acid, clonazepam, phenobarbital. Increased levels with amiodarone, sulfonamides, isoniazid, fluconazole, disulfiram, chloramphenicol, propoxyphene, Unpredictable effects with VPA and PB, Decreased effectiveness of: Cobalamin, corticosteroids, digitoxin, doxycycline, estrogens, furosemide, oral contraceptives, quinidine, rifampin, theophylline, Vitamin D, warfarin, and enternal nutritional therapy.

Thought to be similar to phenytoin. and reduces polysynaptic responses. antiseizure agent, related to tricyclic antidepressants; Autoinduction metabolism property: increasing dose will increase metabolism

Decreased levels with CYP450 enzyme inducers: DPH, PB. Increased levels with erythromycin, itraconazole. propoxyphene, VPA. Decreased effectiveness of DPH, VPA, warfarin, oral contraceptives.

hlevels with enzyme inducers: DPH, CBZ. PB. CYP450 enzyme inhibitors (i.e., antidepressants) expected to have little effect. h levels of ethosuximide, tamotrigine, PB,

Sodium effects similar to phenytoin, with effects on calcium and GABA.

Decreased levels with enzyme inducers (rifampin), pyridoxine, ethanol. Increased levels with VPA, phenytoin; acetazolamide, chloramphenicol, cimetidine, furosemide; Increased sedation with other CNS depressants. Decreased effectiveness of warfarin, Cal, metronidazole, oral contraceptives.

informations of AEDs
One of the earliest anticonvulsants. Still used to treat status epilepticus, particularly where there are no resuscitation facilities. Stiripentol (2001 - limited availability). Indicated for the treatment of severe myoclonic epilepsy in infancy (SMEI).

phenobarbital is rarely used to treat epilepsy in new patients since there are other effective drugs that are less sedating. Phenobarbital sodium injection can be used to stop acute convulsions or status epilepticus, but a benzodiazepine such as lorazepam, diazepam or midazolam is usually tried first.

Primidone is an anticonvulsant whose active metabolites, phenobarbital (major) and phenylethylmalonamide (PEMA) (minor), are also anticonvulsants. It is used mainly to treat complex partial, simple partials, generalized tonic-clonic seizures, myoclonic, akinetic seizures and since the 1980s it has been a valuable alternative to propranolol in the treatment of essential tremor. Primidone has been occasionally used to treat long QT syndrome, cerebral palsy, and athetosis. Unlike other anticonvulsants such as carbamazepine and valproic acid, primidone is rarely used in the treatment of bipolar disorder or any other psychiatric problem.

Benzodiazepines act as a central nervous system depressant. The relative strength of each of these properties in any given benzodiazepine varies greatly and influences the indications for which it is prescribed. Long-term use can be problematic due to the development of tolerance and dependency. Of the many drugs in this class, only a few are used to treat epilepsy

primary mechanism of action is via modulating GABA function in the brain, via the benzodiazepine receptor which in turn leads to enhanced GABAergic inhibition of neuronal firing. It also decreases the utilisation of 5-HT (serotonin) by neurons. Long-term use (more than 24 weeks) can lead to a number of problems, including muscle weakness and fatigue, tolerance, physical dependence and withdrawal symptoms upon discontinuation. Clonazepam may be prescribed for: Epilepsy / Anxiety disorders / Panic disorder / Initial treatment of mania, together with firstline drugs such as lithium, haloperidol or risperidone / Hyperexplexia / Restless legs syndrome / Use as a muscle relaxant (Off Label Use) / Use as a sedative for sleep (Off Label Use).

Can be given rectally by trained care-givers. Increasingly being used as an alternative to diazepam. This water-soluble drug is squirted into the side of the mouth but not swallowed. It is rapidly absorbed by the buccal mucosa. Given by injection in hospital. Potassium bromide (1857). The earliest effective treatment for epilepsy. There would not be a better drug for epilepsy until phenobarbital in 1912. It is still used as an anticonvulsant for dogs and cats.

(1993). This effective anticonvulsant has had its usage severely restricted due to rare but life-threatening side effects.

An anticonvulsant and mood stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder. It is also used to treat ADD, ADHD, schizophrenia, Phantom limb syndrome, Paroxysmal extreme pain disorder, and trigeminal neuralgia. Carbamazepine can render many hormonal contraception products ineffective, due to its action as a cytochrome P450 enzyme inducer, which is the system that metabolizes many oral contraceptives. Common side effects include drowsiness, headaches and migraines, motor coordination impairment and/or upset stomach. Carbamazepine preparations typically greatly decrease a person's alcohol tolerance.

(1990). A derivative of carbamazepine that has similar efficacy but is better tolerated.

proates valproic acid, sodium valproate, and divalproex sodium (1967). (1989).

(1996).

Monosaccharides, anticonvulsant drug (1995). This drug is used to treat epilepsy in both children and adults. In many cases it can also be used as an antidepressant, most of the time for depressive realism. In children it is also indicated for treatment of Lennox-Gastaut syndrome (a disorder that causes seizures and developmental delay). It is also approved for, and now most frequently prescribed for, the prevention of migraines. It has been used by psychiatrists to treat bipolar disorder, although it is not FDA approved for this purpose.

(1993). a medication originally developed for the treatment of epilepsy. Currently, gabapentin is widely used to relieve pain, especially neuropathic pain.

(2004).

Acts to dampen the unwanted, runaway brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage gated sodium channels. It is also an option in the treatment of trigeminal neuralgia as well as certain cardiac arrhythmias. At therapeutic doses, phenytoin produces horizontal gaze nystagmus. At toxic doses, patients experience sedation, cerebellar ataxia, and ophthalmoparesis, as well as paradoxical seizures. As a CYP 450 inducer phenytoin causes a reduction in folic acid levels, predisposing patients to megaloblastic anemia. Phenytoin is a known teratogen. The syndrome consists of craniofacial anomalies which also been called the "fetal hydantoin syndrome."

Water-soluble prodrug of phenytoin. Converted to phenytoin by bloodstream phosphatases, with a half-life of about 8 min in both adults and children. Indicated for pts who cannot take oral drugs and in the acute treatment for status epiepticus, IV or IM.

used to treat epileptic conditions that are resistant to other treatments; recent studies For The Deaf's Center For Presbyacusis and Aging suggest that trimethadione, along with other oxazolidinedione anticonvulsant medications may be useful in treating sensorineural hearing loss cases like those of Iraq war veterans- if the drug's side effects, like dizziness, can be lessened by modifying the drug so it does not cross into the brain itself. If administered during pregnancy, fetal trimethadione syndrome may result causing Facial Dysmorphism(short upturned nose,slanted eyebrows), cardiac defects,Intra Uterine Growth Retardation,mental retardation. The fetal loss rate while using trimethadione has been reported to be as high as 87%.

(1999).

(1955). For absense seizures. Ethosuximide is considered the first choice drug for treating absence seizures in part because it lacks the idiosyncratic hepatotoxicity of the alternative anti-absence drug, valproic acid.

For epilepsy it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. Lamotrigine also acts as a mood stabilizer. It is the first medication since lithium to be granted approval by FDA for the maintenance treatment of bipolar type I. Lamotrigine has relatively few side-effects and does not require blood monitoring in monotherapy.

As an anticonvulsant and mood-stabilizing drug, primarily in the treatment of epilepsy, bipolar disorder, and less commonly major depression. It is also used to treat migraine headaches and schizophrenia. Common side effects are dyspepsia and/or weight gain. Less common are fatigue, peripheral edema, dizziness, drowsiness, hair loss, headaches, nausea, sedation and tremors. Valproic acid also causes hyperammonemia, which can lead to brain damage. Contraindicated in pregnancy due to its teratogenicity; overweight patients; Preexisting hepatic and/or renal damage or cancer, hepatitis, pancreatitis, end-stage AIDS HIV infection, bone marrow depression, urea cycle disorders, and coagulation hematological disorders are absolute contraindications.

A carboxamide derivative of valproic acid used in the treatment of epilepsy and some affective disorders. It is rapidly metabolised (80%) to valproic acid but has anticonvulsant properties itself. It may produce more stable plasma levels than valproic acid or sodium valproate and may be more effectively at preventing febrile seizures.

The ketogenic diet is a strict medically supervised diet that has an anticonvulsant effect. It is typically used in children with refractory epilepsy. a derivative of gamma-aminobutyric acid (GABA) primarily used to treat spasticity. , () It is an agonist specific to mammalian GABAB receptors. It is used for the treatment of spastic movement, especially in instances of spinal cord injury, spastic diplegia, multiple sclerosis, amyotrophic lateral sclerosis (Lou Gehrig's Disease) and trigeminal neuralgia. Its beneficial effects result from actions at spinal and supraspinal sites. Baclofen can also be used to treat hiccups.

gamma-Hydroxybutyric acid; a naturally-occurring substance found in the central nervous system, wine, beef, small citrus fruits, and almost all animals in small amounts. It is also a neuroprotective therapeutic nutrient that is categorized as an illegal drug in a number of countries.[2] It is currently regulated in the US and sold by Jazz Pharmaceuticals under the name Xyrem[3] to treat cataplexy and excessive daytime sleepiness in patients with narcolepsy.

Levodopa preparations: lebodopa/carbidopa; Dopamine Agonists: bromocriptine, pergolide, pramipexole, ropinirole; MAO-B inhibitors: rasagiline, selegiline COMT inhibitors: entacapone; Anticholinergic Agents: benztropine, ethopropazine, procyclidine, trihexyphendidyl; NMDA Receptor Antagonisits: amantadine Carbidopa /levodopa ; benserazide /levodopa

direct dopaminergic receptor agonists, mimic the activity of striatal dopamine

direct dopaminergic receptor agonists, mimic the activity of striatal dopamine

that acts as a selective peripheral dopamine D1A receptor agonist; Fenoldopam is used as an antihypertensive agent postoperatively, and also via IV to treat hypertensive crisis; Not used for PD.

Carbidopa inhibits aromatic-L-amino-acid decarboxylase (DOPA Decarboxylase or DDC), an enzyme important in the biosynthesis of L-tryptophan to serotonin and in the biosynthesis of L-DOPA to Dopamine (DA). Potentiate the effects of L-dopa

Catechol-O-methyl transferase (COMT) inhibitors for the treatment of Parkinson's disease. When administered in conjunction with dopaminergic agents such as L-DOPA, it increases the bioavailability of these compounds by facilitating their passage across the blood-brain barrier.

atropine related an anticholinergic drug principally used for the treatment of: Drug-induced parkinsonism, akathisia and acute dystonia; / PD; and Idiopathic or secondary dystonia.

Trihexyphenidyl; an antimuscarinic class. It is a tertiary amine with alcohol, phenyl, and cyclohexyl moieties.The drug is available as the hydrochloride salt. Trihexyphenidyl is used in mono- and combination therapy. It is active in postencephalitic, arteriosclerotic, and idiopathic forms. The drug is also commonly used to treat extrapyramidal side effects occurring during antipsychotic treatment.

Procyclidine hydrochloride is an anticholinergic drug principally used for the treatment of: Drug-induced parkinsonism, akathisia and acute dystonia; Parkinson disease; and Idiopathic or secondary dystonia. used to treat muscle injuries, skeletal muscle tension and rigidity secondary to afflictions such prolapsed discs and degenerative soft tissue disease especially in the lower back, neck, and joints. and other causes of muscle spasms, to potentiate the action of opioid analgesics against moderate to severe neuropathic pain, and it is also used to treat Parkinson's disease.

It was approved for the treatment of Influenzavirus A in adults. It is also used to help reduce symptoms of Parkinson's disease and drug-induced extrapyramidal syndromes. Off-label uses: used to treat the characteristic fatigue often experienced by patients with multiple sclerosis. Low dose to treat ADHD; Also used to relieve SSRI-induced sexual dysfunction. Stimulate the release of dopamine from intact striatal dopaminergic terminals.

blocks the central catabolism of dopamine, increasing its availabity in the caudate-patamen. used for the treatment of early-stage PD, depression and senile dementia.

Prolactin levels are primarily regulated by inhibition: the presence of prolactin-inhibiting factors (dopamine is the principal one) keep prolactin levels in check. The drugs used for increasing milk supply work by blocking dopamine, which results in an increase in prolactin levels.

a potent dopamine receptor antagonist used for its antiemetic and prokinetic properties. Thus it is primarily used to treat nausea and vomiting, and to facilitate gastric emptying in patients with gastroparesis. Prokinetic use Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb. Useful in the treatment of gastric stasis (e.g. after gastric surgery or diabetic gastroparesis). It is also used in gastroesophageal reflux disease (GERD/GORD). By inhibiting the action of prolactin-inhibiting hormone (i.e., dopamine), metoclopramide has been used to stimulate lactation.

Gastrointestinal problems: Domperidone is used, together with metoclopramide, cyclizine, and 5HT3 receptor antagonists (such as granisetron) for nausea and vomiting; effective in the treatment of gastroparesis, a stomach motility condition, and for paediatric Gastroesophageal reflux (infant vomiting). Parkinson's disease; Unlike metoclopramide, domperidone does not cross the blood-brain barrier. Lactation: Domperidone, by acting as an anti-dopaminergic, results in increased prolactin secretion, and thus promotes lactation. Available in Canada. Anti-emetic: Domperidone is a first choice anti-emetic in most countries, together with metoclopramide. It is however not approved for prescription in the US.

An anti-psychotic drug used mainly in the treatment of psychosis (e.g. schizophrenia) and depression. It is a substituted benzamide. Sulpiride is more commonly used in Europe and Japan. Levosulpiride is its purified levo isomer and is sold in India for similar purpose.So far it has not been approved in the US and Canada. The drug has strong chemical and clinical similarities to the novel anti-psychotic amisulpride.

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurobehavioral developmental disorder affecting about 3-5% of the world's population. It typically presents during childhood, and is characterized by a persistent pattern of impulsiveness and inattention, with or without a component of hyperactivity.

First line treatments: stimulants (Methylphenidate, Dextroamphetamine, mixed salts amphetamine) Norepinephrine Reuptake inhibitors (atomoxetine); Antidepreessants (bupropion), TCAs (desipramine, imipramine); 2ed or 3rd line options; 2-adrenergic agonists (clonidine), 2ed or 3rd line options; Atypical antipsychotics (risperidone) ; Natural Health Products: chamomile, valerian, melatonin, used in children who are restless, anxious, or sleep-dificult situations. Amphetamine ( Adderall ) have warnings about potential for abuse, drug dependence, and sudden death. Methylphenidate (MPH) is a prescription CNS stimulant commonly used to treat Attention-deficit hyperactivity disorder(ADHD). It is also one of the primary drugs used to treat the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. The drug is seeing early use to treat cancer-related fatigue. Brand names of drugs that contain methylphenidate include Ritalin (Ritalina, Rilatine, Attenta, Methylin, Penid, Rubifen); and the sustained release tablets Concerta, Metadate CD, Methylin ER, Ritalin LA, and Ritalin-SR. Focalin is a preparation containing only dextro-methylphenidate. A newer way of taking methylphenidate is by using a transdermal patch (under the brand name Daytrana), similar to those used for hormone replacement therapy (HRT), nicotine release and pain relief (Fentanyl or Morphine).

act by increasing levels of norepinephrine, serotonin, and dopamine in the brain. It includes prescription CNS drugs commonly used to treat attention-deficit hyperactivity disorder (ADHD) in adults and children; symptoms of traumatic brain injury and the daytime drowsiness symptoms of narcolepsy and chronic fatigue syndrome. Initially it was more popularly used to diminish the appetite and to control weight.

It is believed that the dextroamphetamine may actually be the primary chemical (compare to the "levo-isomer") responsible for most of the increased cognitive & focusing ability. It is the active metabolite of the recently introduced prodrug lisdexamfetamine and several older N-substituted amphetamine prodrugs used as anorectics, such as clobenzorex (Asenlix), benzphetamine (Didrex) and amphetaminil (Aponeuron).

Atomoxetine is a non-stimulant drug approved for the treatment of attention-deficit hyperactivity disorder (ADHD). It is sold in the form of the hydrochloride salt of atomoxetine.

Bupropion, TCAs (Dedipramine, Imipramine, Nortriptyline) second or third-line options or as adjunctive therapy for the treatment ADHD in both children and adults; Less effective than stimulants in the management of ADHD in children; but may be benefit pts with comobid conditions such as depression, anxiety, enuresis or tic disorders;

clonidine; used as second or third-line options or as adjunctive therapy for the treatment ADHD; reducing symptoms of aggression, impulsibity, overarousal and hyperactivity, but have minimal effect on symptoms of inatention or poor concentration. low doses of atypical antipsychotics (e.g., risperidone) may be moderately effective for the behavioural symptoms seen in hyperactive and impulsive children. chamomile, valerian, melatonin for recuding restless, anxious or sleep difficulties; The other antioxidants: Blue-green algae, Vitamin B, ginkgo biloba, pycnogenol, and evening primrose oil; is a medication used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy; Pemoline has some advantages over other stimulants in that it does not reduce the appetite or cause dry mouth, , it is a Schedule IV drug; but Dependence has only rarely been reported. Similar to Methylphenidate, the mechanism of action of Pemoline is to inhibit the reuptake of Dopamine and to increase the release of Dopamine and Norepinephrine in the central nervous system. Due to its Hepatotoxicity, Abbott Laboratories (Cylert marketer) had discontinued its production in March 2005.

its receptors are located in brain

phenolic -OH group is extremely important for its activity; Morphine is primarily metabolized into morphine-3-glucuronide (M3G) and M6G via glucuronidation by phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 (UGT2B7). The cytochrome P450 (CYP) family of enzymes involved in phase I metabolism plays a lesser role. Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys.

phenolic -OH group is extremely important for its activity; Morphine is primarily metabolized into morphine-3-glucuronide (M3G) and M6G via glucuronidation by phase II metabolism enzyme UDP-glucuronosyl transferase-2B7 (UGT2B7). The cytochrome P450 (CYP) family of enzymes involved in phase I metabolism plays a lesser role. Not only does the metabolism occur in the liver but it may also take place in the brain and the kidneys.

Codeine is considered a prodrug, since it is metabolised in vivo to the primary active compounds morphine and codeine-6-glucuronide.

strong potency

moderate potency; It is used to treat mild to moderate pain and as an anti-tussive. It can be used to ease surgical pain both prophylactically and palliatively. It is considered no more effective than aspirin in treating pain

also known as levo--acetylmethadol (LAAM) is a synthetic opioid similar in structure to methadone. It has a long duration of action due to its active metabolites. LAAM is indicated as a second-line treatment for the treatment and management of opioid dependence if patients fail to respond to drugs like methadone or buprenorphine. LAAM is not approved for use in Canada.

also called Pethidine (INN); a fast-acting opioid analgesic drug. It is quickly hydrolysed in the liver to pethidinic acid and is also demethylated to norpethidine which is toxic and has convulsant and hallucinogenic effects, and seizures can occur when used in renal failure; May cause tremors, hyperrreflexia, hallucinations. Avoid in liver disease and those who have received MAOIs within the last 14 days ( potentially life-threatening serotonin syndrome with nonselective MAOIs);

One of the most powerful opioid analgesics with a potency approximately 81 times that of morphine. The LD50 in humans, by intravenous injection in an opiate-naive individual (without tolerance), is 0.5-1 milligrams. It is also a highly abusable drug, and as a result, has been categorized as a Schedule II drug in the United States. Fentanyls are extensively used for anesthesia and analgesia, most often in the operating room and intensive care unit. used IM or IV to promote analgesia during anesthesia. It is also available in a transmucosal (Fentanyl Oralet, Actiq) and transdermal (Duragesic) dosage form. Major side effects (more than 10% of patients) include diarrhea, nausea, constipation, dry mouth, somnolence, confusion, asthenia, and sweating; respiratory depression

strong agonist with high oral bioavailability

Opioid Peptides are short sequences of amino acids which mimic the effect of opiates in the brain. Opioid peptides may be produced by the body itself, for example endorphins, or be absorbed from partially digested food (casomorphins, exorphins and rubiscolins). The effect of these peptides vary, but they all resemble opiates. Brain opioid peptide systems are known to play an important role in motivation, emotion, attachment behaviour, the response to stress and pain, and the control of food intake.

a centrally acting analgesic, used for treating moderate to severe pain (acute, neruropathic pain); and most types of neuralgia, including trigeminal neuralgia; fibromyalgia. It is a synthetic agent, and although it is chemically unrelated to opioids, it does appear to have actions at the -opioid receptor as well as the noradrenergic and serotonergic systems.

a centrally-acting analgesic with a unique dual mode of action as an agonist at the -opioid receptor and as a norepinephrine reuptake inhibitor. It is considered to have a potency between morphine and tramadol.

partial agonist and antagonist actions Bu- Morphine; anta-morphine Buprenorphine (Buprenex) is a semi-synthetic opiate with partial agonist and antagonist actions. It is a List II drug of the Opium Law. As an analgesic, it is about 30 times as potent as morphine. It is administered intramuscularly or intravenously for the relief of moderate to severe pain.

pure antagonist actions Naltrexone is an opioid receptor antagonist used primarily in the management of alcohol dependence and opioid dependence.

Naloxone has an extremely high affinity for -opioid receptors in the central nervous system. Naloxone is a -opioid receptor competitive antagonist, and its rapid blockade of those receptors often produces rapid onset of withdrawal symptoms. Naloxone also has an antagonist action, though with a lower affinity, at - and -opioid receptors

ne, isoflurane and sevoflurane are the most widely used volatile anaesthetics today. They are often combined with nitrous oxide.

M&A: bind post-synaptic GABA receptors ---open Cl- channels --- inhibit APs

inhibits GABA--CNS overstimulation; also block CNS NMDA receptors

ester type, generally short acting

a local anesthetic given by injection during surgical procedures and labor and delivery.

ocaine/Larocaine

It is used primarily to reduce the pain of intramuscular injection of penicillin, and is also used in dentistry. trade name Novocain----Novocaine

ine/Amethocaine

amide type, generally longer acting

longe duration (>24 h)

aine /Dibucaine

Lidocaine has a more rapid onset of action and longer duration of action than amino ester-type local anesthetics such as procaine. It is approximately 90% metabolized in the liver by CYP1A2 (and to a minor extent CYP3A4) to the pharmacologically-active metabolites monoethylglycinexylidide and glycinexylidide. The elimination half-life of lidocaine is approximately 1.52 hours in most patients. This may be prolonged in patients with hepatic impairment (average 343 minutes) or congestive heart failure (average 136 minutes).

_amine, -astine, -zine, -tadine Ethylenediamines were the first group of clinically-effective H1-antihistamines developed.

Diphenhydramine was the prototypical agent in this group. Significant anticholinergic adverse effects, as well as sedation, are observed in this group but the incidence of gastrointestinal adverse effects is relatively low. [3] [6]

Diphenhydramine is effective at treating EPS(extrapyramidal symptoms) or dystonic reactions associated with extended or high-dose antipsychotic or phenothiazine use, EPS or dystonic symptoms are due to dopamine antagonism and the subsequent central imbalance between dopamine and acetylcholine, These symptoms may be treated with anticholinergic agents, including antimuscarinic agents such as benztropine and trihexyphenidyl. Many providers prefer to use antihistamines because they are associated with less severe adverse reactions, Antihistamines, however, have different levels of anticholinergic activity, Diphenhydramine has a high anticholinergic profile, whereas tripelennamine, brompheniramine, cyproheptadine, and cetirizine have moderate to low anticholinergic profiles and would not be as effective at treating these reactions.

diphenhydramine is a potent anticholinergic agent; profound drowsiness as a very common side-effect, motor impairment (ataxia), dry mouth and throat, flushed skin, tachycardia, blurred vision at nearpoint owing to lack of accommodation (cycloplegia), photophobia, pupil dilation (mydriasis), urinary retention (ischuria), constipation, difficulty concentrating, short-term memory loss, visual disturbances, hallucinations, irritability, itchy skin, confusion, erectile dysfunction, and delirium. Severe, prolonged twitching and muscle spasm have also been experienced.

A transdermal scopolamine disc has an onset of action of 4 hours and provides 72 hours of continuous antiemetic coverage, This option would provide long-lasting antiemetic medication without the need for frequent dosing.

The isomerism is a significant factor in the activity of the agents in this group. E-triprolidine, for example, is 1000-fold more potent than Z-triprolidine. This difference relates to the positioning and fit of the molecules in the histamine H1-receptor binding site. Alkylamines are considered to have relatively fewer sedative and gastrointestinal adverse effects, but relatively greater incidence of paradoxical CNS stimulation.

structurally-related to the ethylenediamines and the ethanolamines, and produce significant anticholinergic adverse effects.

an antihistamine considered to be an antiemetic. Meclizine is less anticholinergic than many other antihistamines and other agents used for their anti-emetic and anti-puritic effects, also shares the anxiolytic, analgesic-sparing (potentiating), sedative, and other effects of its chemical relatives cyclizine and hydroxyzine to varying extents. Due to its possible anticholinergic action, meclizine should be used carefully with patients who suffer from asthma, glaucoma, or an enlarged prostate gland.

These compounds differ from the phenothiazine antipsychotics in the ring-substitution and chain characteristics. (Nelson, 2002) They are also structurallyrelated to the tricyclic antidepressants (and tetracyclics), explaining the H1-antihistaminergic adverse effects of those three drug classes and also the poor tolerability profile of tricyclic H1-antihistamines. The second-generation H1-antihistamine loratadine was derived from compounds in this group.

an antihistaminic and antiserotonergic agent. It acts as a 5-HT2 receptor antagonist and also blocks calcium channels. Used in the treatment of allergies (specifically hay fever) and is also used to stimulate appetite in underweight people (e.g. anorexia nervosa). For nightmares including nightmares related to post traumatic stress disorder. In the management of moderate to severe cases of serotonin syndrome (a complex of symptoms associated with the use of serotonergic drugs, such as SSRIs or stimulants), and in the disease carcinoid in which serotonin is overproduced by tumor cells; a preventative measure against migraine in children and adolescents.Can relieve SSRI-induced sexual dysfunction and drug-induced hyperhydrosis (excess sweating). It can be used in anorexia nervosa, pruritus, and headache in children. Renal impairment.

2ed generation antihistamines: less sedative properties; Should avoid concurrent with Erythromycin, Ketoconazole, Clarithromycin, Propulsid (may inhibit the metabolism of these antihistamines and increase the risk of severe cardiac toxicity and tachycardia. used to treat allergies, and marketed for its non-sedating properties.

A major metabolite of hydroxyzine, and a racemic selective H1 receptor inverse agonist used in the treatment of allergies, pruritus, hay fever, angioedema, and urticaria. Effective agent in Kimura's disease, which mostly occurs in young Asian men, affecting the lymph nodes and soft tissue of the head and neck in the form of tumor-like lesions. causes less sedation and psychomotor impairment (because it penetrates the blood brain barrier only to a slight extent.) Most common side-effects: Drowsiness, headache, psychomotor impairment, and antimuscarinic effects such as urinary retention, dry mouth, blurred vision, and gastrointestinal disturbances are the most common side effects.

Antihistamines: First generation: diphenhydramine, clemastine, brompheniramine, chlorpheniramine, hyroxyzine, azatadine, cyproheptadine, promethazine, trimeprazine; Second generation: loratadine, fexofenadine, cetirizine, desloratadine, doxepin, ketotifen

a prodrug, generally completely metabolised to the active form fexofenadine by the intestinal cytochrome P450 CYP3A4 isoform. Due to this presystemic gut wall metabolism terfenadine normally is not measurable in the plasma. Terfenadine itself, however, has a cardiotoxic effect in higher doses while its metabolites have not such effect.

Metabolite of terfenadine; does not readily cross the blood-brain barrier, and so causes less drowsiness than first-generation histamine-receptor antagonists. Used in the treatment of allergic rhinitis, pruritus, hayfever and similar allergy symptoms.

Their action is attributed to their binding to serotonin 5-HT1B and 5-HT1D receptors in cranial blood vessels (causing their constriction) and subsequent inhibition of pro-inflammatory neuropeptide release. Evidence is accumulating that these drugs are effective because they act on serotonin receptors in nerve endings as well as the blood vessels. This leads to a decrease in the release of several peptides, including CGRP and substance P. 1. direct vasoconstriction, returning the blood vessel to its orignal diameter 2. by acting on neuronal receptors, it inhibits the release of additional vasodilating and pain-transmitting substances autacoid function) 3. direct antinociceptive action, preventing the firing of pain neurones directly

tablets, solution for injection, and nasal inhalers. Sumatriptan was the first triptan available (in 1991),

releasing of acetylcholine, increase GI motility and tone direct actions on the GI smooth muscle

block the ion-channel coupled 5-HT3-receptor, thus inhibiting the ability of serotonin to cause nause and or emesis both locally at the GI tract and centrally in the area postrema.

both agonistic and antagonistic actibity at adrenergic, dopaminergic, and serotonergic receptors

an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors and Parkinson's disease. Amenorrhea, female infertility, galactorrhea, hypogonadism, and acromegaly may all be caused by pituitary problems, such as hyperprolactinaemia, and therefore, these problems may be treated by this drug. Common side effects: associated with causing or worsening psychotic symptoms; breast engorgement ; syncope

The main medical use for pizotifen is for the prevention of vascular headache including migraine and cluster headache. Pizotifen is one of a range of medications used for this purpose, other options include propranolol, topiramate, valproic acid and amitryptyline.

Pizotifen is a serotonin antagonist acting mainly at the 5-HT1, 5-HT2A and 5HT2C receptors. It also has some activity as an antihistamine.

Antagonism of the 5-HT 3 receptor prevents stimulation of the chemoreceptor trigger zone and triggering of the vomiting center.

Few side effects. Very effective in combination with corticosteroids.

Slowing GI motility

The major antiemetics serotonin antagonists, dopamine antagonists, anticholinergics, and antihistamines target the specific neurotransmitters through receptor antagonism.

block serotonin receptors in the central nervous system and gastrointestinal tract. As such, they can be used to treat post-operative and cytotoxic drug nausea & vomiting.

Some of these drugs are limited in their usefullness by their extra-pyramidal and sedative side-effects.

(Reglan) by inhibiting stimulation of the chemoreceptor trigger zone; also enhances the rate of GI emptying and increases GI motility as a pro-kinetic, and is thus useful in gastrointestinal disease; however, it is poor in cytotoxic or post-op vomiting. So it can reduce the absorption of a number of drugs.

(H1 histamine receptor antagonists), effective in many conditions, including motion sickness and severe morning sickness in pregnancy.

(Gravol) (Pentazine, Phenergan, Promacot)

used in patients with cachexia, cytotoxic nausea, and vomiting, or who are unresponsive to other agents.

is (Marijuana). Most patients prefer smoked or vaporized cannabis over pharmaceutical versions because they do not contain all 66 cannabinoids that are in cannabis, many have medicinal applications. Medical marijuana is also much less expensive than related pharmaceuticals. CBD is a main cannabinoid not in Marinol or Cesamet.

inol (Marinol). Ninety percent of sales are for cancer and AIDS patients. The other 10% of its sales thought to be for pain, Multiple Sclerosis and also for Alzheimer's disease. ss, drowsiness, euphoria, ataxia and hallucination are reported side effects of the drug.

e (Cesamet). Put back on the market in late 2006. In the US, it is A Schedule II substance unlike Marinol which is Schedule III and cannabis which is Schedule I.

is an oral spray containing THC and CBD. It is currently legal in Canada and a few countries in Europe but not in the U.S.

am given at the onset of anesthesia has been shown in recent trials to be as effective as ondansetron, a 5HT3 antagonist in the prevention of post-operative nausea and . Further studies need to be undertaken.

am said to be very good as an adjunct treatment for nausea along with first line medications such as Compazine or Zofran.

(also known as scopolamine)

ethasone given in low dose at the onset of a general anaesthetic for surgery is an effective anti-emetic.
The specific mechanism of action is not fully understood.

ant Investigational NK1 receptor antagonist

thought to work on the CTZ (chemoreceptor trigger zones). It may mask symptoms and prolong the diagnosis of Reye's syndrome (nausea and vomiting) in children;

also claimed to be an effective antiemetic. given intravenously. It has been used in an acute care setting in hospital as a rescue therapy for emesis.

mint claimed to help nausea or stomach pain when added into a tea or peppermint candies.

ol purported as such [1] purported to be antiemetic. Also known as Bishop's weed, it is a popular spice in India, Ethiopia and Eritrea.

s: aluminum hydroxide/magnesium hydroxide combinations; amines: dimenhydrinate, diphenhydramine, meclizine inergics: scopolamine; ides: domperidone, metoclopramide (also dopamine antagonists); ne antagonists----Butyrophenones: haloperidol, droperidol iazines: chlorpromazine, perphenazine, prochlorperzaine, promethazine (--azines); n Antagonists: ondansetron;

a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. Antimuscarinic agents operate on the muscarinic acetylcholine receptors (The majority of anticholinergic drugs); Antinicotinic agents operate on the nicotinic acetylcholine receptors. An example of an anticholinergic is dicyclomine. Frequently, they reduce the effects mediated by acetylcholine on acetylcholine receptors in neurons through competitive inhibition. Therefore, their effects are reversible. Anticholinergics are classified according to the receptors that are affected:

uscular-blocking drug block neuromuscular transmission at the neuromuscular junction, causing paralysis of the affected skeletal muscles. This is accomplished either by resynaptically via the inhibition of acetylcholine (ACh) synthesis or release, or by acting postsynaptically at the acetylcholine receptor. While there are drugs that act ptically (such as botulin toxin and tetrodotoxin), the clinically-relevant drugs work postsynaptically.

ese agents act as competitive antagonists against acetylcholine at the site of postsynaptic acetylcholine receptors. _curium / curonium / curarine/ Gallamine
(Raplon) (Mivacron) (Tracrium) (Nuromax) (Nimbex) (Norcuron) (Zemuron) (Pavulon) (Jexin) (Flaxedil)

Suxamethonium chloride a medication widely used in emergency medicine and anesthesia to induce muscle relaxation, usually to make endotracheal intubation possible. Suxamethonium acts as a depolarizing neuromuscular blocker. It imitates the action of acetylcholine at the neuromuscular junction, acting on muscle type nicotinic receptors, but it is not degraded by acetylcholinesterase but by butyrylcholinesterase, a plasma cholinesterase. This hydrolysis by butyrylcholinesterase is much slower than that of acetylcholine by acetylcholinesterase.

May cause paralysis of the diaphragm, mechanical ventilation should be at hand to provide respiration; Cardiovascular effects; autonomic symptoms; may facilitate histamine release (hypotension, flushing, and tachycardia). Suxamethonium may trigger a transient release of large amounts of potassium from muscle fibers. (risk for life-threatening complications, such as hyperkalemia and cardiac arrhythmias).

a chemical that inhibits the cholinesterase enzyme from breaking down acetylcholine, so increasing both the level and duration of action of the neurotransmitter acetylcholine.

Are used medicinally: To treat myasthenia gravis. In myasthenia gravis, they are used to increase neuromuscular transmission. To treat Alzheimer's disease To treat Lewy Body Dementia As an antidote to anticholinergic poisoning Occur naturally as venoms and poisons ; Are used as weapons in the form of nerve agents

Physostigmine is used to treat myasthenia gravis, glaucoma and delayed gastric emptying. Because it is a tertiary amine, it can cross the blood-brain barrier and so it is also used to treat the CNS effects of atropine, scopolamine and other anticholinergic drug overdoses.

It is used to improve muscle tone in people with myasthenia gravis and routinely, in anesthesia at the end of an operation, to reverse the effects of non-depolarizing muscle relaxants such as rocuronium and vecuronium. It can also be used for urinary retention resulting from general anaesthesia and to treat curariform drug toxicity. Another indication for use is the Ogilvie syndrome which is a pseudoobstruction of the colon in critically ill patients. Neostigmine will cause slowing of the heart rate (bradycardia), for this reason it is usually given along with a parasympatholytic drug such as atropine or glycopyrrolate.

Cholinergic syndrome Cholinergic too much you will get a SLUDGE(Salivation, Lacrimation, Urination, Defecation , Gastrointestinal upset, Emesis) is a syndrome of pathological effects indicative of massive discharge of the parasympathetic nervous system.

Both used for treatment of dementia

roaminoacridine (THA')

Because its duration of action is only about 20 minutes, edrophonium (by the so-called Tensilon test) is used to differentiate myasthenic crisis from cholinergic crisis.

One common cause of SLUDGE is exposure to organophosphorus insecticides, including parathion, malathion, and diazinon. These agents irreversibly phosphorylate acetylcholinesterase, thereby raising acetylcholine levels and causing SLUDGE. SLUD may be treated with Atropine or other anticholinergics.

It has been proposed for use in treatment of Alzheimer's disease, but use for that purpose is not currently recommended.

Action on eye, GI tract, urinary bladder; contraction of ciliary m./ detrusor m. / sphincter m. of iris, increased peristalsis, sphincter relaxation; enhances the activity of the muscarinic acetylcholine receptor. The muscarinic receptor has different subtypes, labelled M1-M5, allowing for further differentiation.

M1-type muscarinic acetylcholine receptors play a role in cognitive processing. In Alzheimer disease (AD) amyloid formation may decrease the ability of these receptors to transmit their signals leading to decrease cholinergic activity. As these receptors themselves appear relatively unchanged in the disease process, they have become a potential therapeutic target when trying to improve cognitive function in patients with AD. In the form of pilocarpine muscarinic receptor agonists have been used medically for a long time. M3 agonists: Aceclidine, for glaucoma. Arecoline, an alkaloid present in the Betel nut. Pilocarpine is a drug that acts as a muscarinic receptor agonist that is used to treat glaucoma. Cevimeline (AF102B) (Evoxac) is a muscarinic agonist that is an Food and Drug Administration (FDA)-approved drug and used for the management of dry mouth in Sjgren's syndrome.

an agent that reduces the activity of the muscarinic acetylcholine receptor. Most of them are synthetic, but scopolamine and atropine are belladonna alkaloids, and are naturally extracted. contraindicated in:

non-selective antagonism, CNS stimulation; It causes tachycardia by blocking vagal effects on the sinoatrial;

ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, and possibly, notably in the elderly, extreme confusion, extreme dissociative hallucinations, and excitation. These latter effects are because atropine is able to cross the blood-brain barrier. In overdoses, atropine is poisonous. Atropine is sometimes added to other potentially addictive drugs, particularly anti-diarrhea opioid drugs such as diphenoxylate or difenoxin where the secretion-reducing effects of the atropine can also aid the anti-diarrhea effects.

es firing of SA node, conduction through AV node, opposes vagus nerve, blocks acetylcholine receptor sites, decreases bronchiole secretions.

ly, atropine lowers the parasympathetic activity of all muscles and glands regulated by the parasympathetic nervous system. Therefore, it may cause swallowing difficulties uced secretions.

smodic in gastrointestinal hypermotility; for organophosphate poisoning.

reactions to atropine include ventricular fibrillation, supraventricular or ventricular tachycardia, dizziness, nausea, blurred vision, loss of balance, dilated pupils, photophobia, sibly, notably in the elderly, extreme confusion, extreme dissociative hallucinations, and excitation.

h atropine treats bradycardia (slow heart rate) in emergency settings, it can cause paradoxical bradycardia when given at very low doses, presumably as a result of central the CNS.

lmic use: Topical atropine, used as a cycloplegic, to temporarily paralyze the accommodation reflex; and as a mydriatic to dilate the pupils. itation: Injections, used in the treatment of bradycardia, asystole and pulseless electrical activity (PEA) in cardiac arrest.

non-selective antagonism, without any mucociliary excretion inhibition.

long-acting, adm. once a day

increase bladder capacity and diminish frequency of uninhibited detrusor contractions;

First-line

M3-selective

non-selective antagonism, CNS depression

short acting non-selective antagonism, CNS depression

M1 receptor-selective antagonist inhibits gastric secretion used for extrapyramidal symptoms from typical antipsychotic medications

short acting non-selective antagonism, CNS depression non-selective antagonism, blocks transmission in ganglia

an antimuscarinic agent used for the treatment of excessive sweating (hyperhidrosis), cramps or spasms of the stomach, intestines (gut) or bladder, and involuntary urination (enuresis). It can also be used to control the symptoms of irritable bowel syndrome and similar conditions. Side effects include tachycardia, constipation, hypersensitivity to light, dry mouth, and urinary retention.

Reduces the effects of the relative central cholinergic excess that occurs as a result of dopamine deficiency.
Profenamine hydrochloride (INN, also known as ethopropazine) is a medication derived from phenothiazine. It is primarily used as an antidyskinetic to treat parkinsonism. It is sold under the trade names Parsidol in the United States, Parsidan in Canada Used for : Drug-induced parkinsonism, akathisia and acute dystonia; Parkinson disease; and Idiopathic or secondary dystonia.

synthesized from arachidonic acid by enzyme cyclooxygenase (COX) COX 1: daily synthesis prostaglandins COX 2: inflammatory response COX 3: thermoregulatory conrol and pain perception

a synthetic prostaglandin E1 (PGE1) analogue.

abortifacient effects to induce cerbical-ripening in pregnancy

abortifacient effects

used topically to lower intraocular pressure in glaucoma

emergent pulmonary hypertension

Leukotrienes are synthesized in the cell from arachidonic acid by 5-lipoxygenase. slow-reacting substance of anaphylaxis; powerful effect in bronchoconstriction, h vascular permeability and mucus secretion may be responsible for inflammatory response. Leukotrienes assist in the pathophysiology of asthma, causing or potentiating the following symptoms: airflow obstruction / increased secretion of mucus / mucosal accumulation / bronchoconstriction infiltration of inflammatory cells in the airway wall Platelet-activating factor(PAF), also known as an important mediator of bronchoconstriction. limited to treat ashma block 5-lipoxygenase, inhibiting the synthetic pathway of leukotriene metabolism,

used for the maintenance treatment of asthma and to relieve symptoms of seasonal allergies.[1] It is usually administered orally. Because of its method of operation, it is not useful for the treatment of acute asthma attacks. It does not interact with other allergy medications such as theophylline. Side effects include gastrointestinal disturbances, hypersensitivity reactions, sleep disorders and increased bleeding tendency, aside from many other generic adverse reactions.

block the actions of cysteinyl leukotrienes at the CysLT1 receptor on target cells such as bronchial smooth muscle. These modifiers have been shown to improve asthma symptoms, reduce asthma exacerbations and limit markers of inflammation such as eosinophil counts in the peripheral blood and bronchoalveolar lavage fluid. This demonstrates that they have anti-inflammatory properties.

Zafirlukast blocks the action of the cysteinyl leukotrienes on the CysLT1 receptors, thus reducing constriction of the airways, build-up of mucus in the lungs and inflammation of the breathing passages. It is used for the maintenance treatment of asthma, often used in conjunction with an inhaled steroid and/or long-acting bronchodilator. It is available as a tablet and is usually dosed twice daily. The reduction of the oral steroid dose, in some patients on ACCOLATE therapy, has been followed in rare cases by the occurrence of eosinophilia, vasculitic rash, worsening pulmonary symptoms, cardiac complications, and/or neuropathy sometimes presenting as Churg Strauss Syndrome, a systemic eosinophilic vasculitis.

Montelukast (Singulair), taken once daily, and Zyflo, taken four times per day.

weak acids, excretion influenced by urinary pH inhibit the enzyme cycloozygenase which is responsible for the formation of precursors of PGs and thromboxanes from arachidonic acid, and thus inhibit local prostaglandin synthesis. Low-intensity integumental pain, antipyretic, and anti-inflammatory

The action of aspirin results from both the acetyl and salicylate protions of the drug, The only irreversibly inhibits cyclooxygenase by covalent acetylation of the enzyme; It can also inhibits COX in platelets in low doses---prevents the formation of thromboxane A2 (aggregating agent) -----indicated for prophylaxis of myocardial infarction

A loading dose is usually used. Primarily used to treat symptoms of arthritis.

Mesalazine (INN, BAN), or 5-aminosalicylic acid (5-ASA); It is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects.

A sulfa drug, a derivative of Mesalazine (5-ASA), used primarily as an anti-inflammatory agent in the treatment of IBD (ulcerative colitis and Crohn's disease) as well as for rheumatoid arthritis. It may be abbeviated SSZ. It is not a pain killer. It does this via reducing the synthesis of inflammatory mediators (eicosanoids and inflammatory cytokines). However, unlike glucocorticoids, sulfasalazine has no immunosuppressant action.

Olsalazine sodium (Dipentum) is a salicylate compound that is converted to 5-ASA in the colon. This exerts an anti-inflammatory effect useful in treating ulcerative colitis.

5-aminosalicylic acid (5-ASA), is an anti-inflammatory drug used to treat inflammation of the digestive tract (Crohn's disease) and mild to moderate ulcerative colitis. Mesalazine is a bowel-specific aminosalicylate drug that is metabolized in the gut and has its predominant actions there, thereby having fewer systemic side effects. As a derivative of salicylic acid, 5-ASA is also an antioxidant that traps free radicals, which are potentially damaging by-products of metabolism. 5-ASA is considered the active moiety of sulfasalazine, which is metabolized to it. It is formulated for oral ingestion as tablets or granules, and for rectal administration as rectal suppository, suspension or enemas. Commonly side effects: Diarrhea / Nausea / Cramping / Flatulence

inhibit central prostaglandin synthesis through selectivity for COX 3 / little or without activity on COX 1 or 2; No anti-inflammatory activity; and do not affect platelet function.

inhibit prostaglandin synthesis and sabilzie lysosomal membranes

acute rheumatoid arthritic and acute gout when other therapeutic measures have failed.

control hyperuricemia in the treatment of intermitent and chronic gout

anti-inflammatory effects by inhibiting the cyclooxygenase enzyme system and thus reduce local prostaglandin synthesis; analgesic and antipyretic effects; mild uricosuric activity; weak inhibitory activity for lipoxygenase, COX 2, leukocyte proliferation and migration and to stablize lysosomal membranes

alicylic acid (Aspirin)

magnesium salicylate

_fenac, _metacin

The name is derived from its chemical name: 2-(2,6-dichloranilino) phenylacetic acid; Diclofenac is used for musculoskeletal complaints, especially arthritis (rheumatoid arthritis, osteoarthritis, spondylarthritis, ankylosing spondylitis), gout attacks, and pain management in case of kidney stones and gallstones. Also used for acute migraines, red eye;mild to moderate post-operative or post-traumatic pain, such as postoperative cataract (particularly when inflammation is also present) and menstrual pain (dysmenorrhea).

or indomethacin(USAN), Commonly used to reduce fever, pain, stiffness, and swelling. It works by inhibiting the production of prostaglandins, It can be used for arthiritis (RA, OA, juvenile-, psoriatic-); gout, dysmenorrhea, headache in adults, orthostatic hypotension, tendinitis, nephrogenic diabetes insipidus, delay premature labor, sunburn, Indometacin also reduces plasma renin activity and aldosterone levels, and increases sodium and potassium retention, and enhances the effects of vasopressin. Together these may lead to: edema, hyperkalemia, hypernatremia, hypertension. Also hserum creatinine and more serious renal damage such as acute renal failure, chronic nephritis and nephrotic syndrome.

useful in the treatment of acute or chronic inflammatory conditions. Sulindac is a prodrug, derived from sulfinylindene, that is converted in the body to the active NSAID. More specifically, the agent is converted by liver enzymes to a sulfide that is excreted in the bile and then reabsorbed from the intestine. This is thought to help maintain constant blood levels with reduced gastrointestinal side effects. Some studies have shown sulindac to be relatively less irritating to the stomach than other NSAID's except for drugs of the COX-2 inhibitor class.

Ibuprofen, Ketoprofen, and Naproxen are the only NASAIDs available in OTC

It is used for relief of symptoms of arthritis, primary dysmenorrhea, fever, and as an analgesic, especially where there is an inflammatory component. Ibuprofen is known to have an antiplatelet effect, though it is relatively mild and short-lived when compared with that of aspirin. Ibuprofen is a core medicine in the World Health Organization's "Essential Drugs List", which is a list of minimum medical needs for a basic health care system.

profen (withdrawn from the market)

(Actron, has been withdrawn from the market.)

in the family of heterocyclic acetic acid derivatives; used as an analgesic, antipyretic (fever reducer), and anti-inflammatory. Indicated for short-term management of pain. Can be given by IV, IM or oral route. It may reversibly inhibit the aggregation of platelets. Cefotetan, Ceforperazone, Moxalactam, Picamycin, Valproic acid may also inhibit the aggregation of platelets, concurrent use with ketorolac may increase the risk of bleeding; Gold-compound, methotrexate and Probenecid may increase the risk of nephrotoxicity. IV injection solution should avoid mixing with: morphine, meperidine, promethazine and hydroxyzine; precipitating may occur.

a non-narcotic, non-steroidal anti-inflammatory drug (NSAID), used to relieve the inflammation, swelling, stiffness, and joint pain associated with osteoarthritis and rheumatoid arthritis. Chemically, it is a propionic acid derivative. It is available in 600 mg tablets. Normal adult dosage is 1200 mg daily, not to exceed 1800 mg per day. Safety and efficacy has been established in children over 6 years with juvenile rheumatoid arthritis only, and there is an increased risk of adverse reactions in the elderly population.

_azone

used to relieve the symptoms of rheumatoid and osteoarthritis, primary dysmenorrhoea, postoperative pain; and act as an analgesic, especially where there is an inflammatory component. It is manufacturerd by Pfizer under the tradename Feldene

FDA alert

FDA withdrawn TGA cancelled registration FDA withdrawn withdrawn from market withdrawn from market

ide (banned by several countries for the potential risk of hepatotoxicity)

used to treat nausea, heartburn, indigestion, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract. Commonly known as pink bismuth, it is the active ingredient in popular medications such as Pepto-Bismol and (modern) Kaopectate. As a derivative of salicylic acid, bismuth salicylate displays anti-inflammatory action and also acts as an antacid.

Acute: NSAIDs, colchicine (first line) --phenylbutazone /oxyphybutazone (backup)

inhibits tubulin synthesis --- reducing the inflammatory response and reduces leukocyte lactic acid production

rescuces serum urate levels by blocking uric acid production. Comepetitively inhibits the enzyme xanthine oxidase; so it will affect the metabolism of 6-mercaptopurine (6-MP) from conversion to uric acid

inhibits the proximal tubular reabsorption of uric acid increasing uric acid excretion: The kidney's organic anion transporter (OAT) reclaims uric acid from the urine and returns it to the plasma. If probenecid (an organic acid) is administered to a patient, the OAT binds to probenecid instead of to uric acid, preventing the reabsorption of uric acid. As a result, more uric acid leaves the body in the urine, lowering the uric acid concentration in the plasma. This is an example of the way in which competition between substrates transported across cell membranes has been put to use in medicine.

acute rheumatoid arthritic and acute gout when other therapeutic measures have failed.

control hyperuricemia in the treatment of intermitent and chronic gout

Uricosuric medications (drugs) are substances that increase the excretion of uric acid in the urine, thus reducing the concentration of uric acid in blood plasma. Generally, this effect is achieved by action on the proximal tubule. Primarily uricosuric drugs include probenecid, benzbromarone and sulfinpyrazone. Secondary: Drugs with other primary uses, that have some uricosuric properties, include guaifenesin, losartan,and fenofibrate. However, by increasing urinary uric acid levels these drugs may contribute to stones (calculi) in the kidneys and urinary system (see Uric acid nephrolithiasis). Thus use of these drugs is contraindicated in persons who already have a high urine concentration of uric acid (hyperuricosuria).

Antiuricosuric drugs raise serum uric acid levels at the expense of urine uric acid levels. These drugs include all diuretics and aspirin. These drugs are useful for treatment of hypouricemia and perhaps also hyperuricosuria but are contraindicated in persons with conditions including hyperuricemia and gout.

has effects similar to, or the same as, epinephrine (adrenaline). Thus, they are a kind of sympathomimetic agents. The five categories of adrenergic receptors are: 1, 2, 1, 2, and 3, and agonists vary in specificity between these receptors, and may be classified respectively.

_zoline

stimulates phospholipase C activity. (vasoconstriction and mydriasis; used as vasopressors, nasal decongestants and eye exams). Selected examples are:

a selective alpha-1 agonist and partial alpha-2 agonist topical decongestant, used in the form of Oxymetazoline hydrochloride, Oxymetazoline is generally available as a nasal spray. It causes down-regulation of alpha-2 receptors, and therefore becomes less effective after a few doses. If overused it can cause a "rebound congestion" (rhinitis medicamentosa) where the mucosal surface of the sinuses are damaged due to ischemia, become swollen, and therefore become congested after the drug wears off.

inhibits adenylyl cyclase activity. (reduce brainstem vasomotor center-mediated SNS activation; used as antihypertensives, sedatives & treatment of opiate and alcohol withdrawal symptoms). Close-Guan- Men methyldopa

(mixed alpha2-adrenergic and imidazoline-I1 receptor agonist) Its antihypertension action works by stimulating 2 receptors in the brain which decreases cardiac output and peripheral vascular resistance, lowering blood pressure. Also used in some types of neuropathic pain, opioid detoxification, sleep hyperhidrosis, anaesthetic use, and off-label, to counter the side effects of stimulant medications such as methylphenidate or amphetamine. For insomnia, as well as for relief of menopausal symptoms. Used in conjunction with stimulants to treat attention-deficit hyperactivity disorder (ADHD), for which it is administered in late afternoon or evening for sleep, and because it sometimes helps moderate ADHD-associated impulsive and oppositional behavior, and may reduce tics. Clonidine can also be used in the treatment of Tourette syndrome.

It is metabolized in the intestines and liver; its metabolite alpha-methylnorepineprine acts in the brain to stimulate alpha-adrenergic receptors and leads to a decrease in total peripheral resistance (TPR) and cardiac output. It is excreted in urine. Side effects: many possible side-effects (usually fewer if the dose is less than 1 g per day): Gastro-intestinal disturbances, Dry mouth, Bradycardia, Worsening of angina, Postural hypotension,first dose syncope, palpitations, Sedation, headaches, dizziness, Myalgia (muscle pain), arthralgia (joint pain) or paraesthesia (numbness); Nightmares, mild psychosis, depression; Parkinsonism; Bell's palsy; Abnormal liver functions tests and hepatitis; Pancreatitis; Haemolytic anaemia; Bone marrow suppression leading to thrombocytopenia (low platelets) or leucopenia (low white blood cells); Hypersensitivity reactions: lupus erythematosus-like syndrome, myocarditis (heart muscle inflammation), pericarditis and rashes; Ejaculatory failure, Impotence, decreased libido, gynecomastia (breast enlargement in men), hyperprolactinaemia and amenorrhoea; Note that if used in pregnant women, it may cause a positive Coombs test

(preference for alpha2A-subtype of adrenoceptor); Do not confued with Guaifenesin

(most selective agonist for alpha2-adrenergic as opposed to imidazoline-I1) (metabolite of guanabenz) (periferal alpha2-receptor agonist)

It is a centrally acting -2 adrenergic agonist. It is used as a muscle relaxant and to treat the spasms (chronic spasticity) , cramping, and tightness of muscles caused by medical problems such as multiple sclerosis, spastic diplegia, back pain, or certain other injuries to the spine or central nervous system. It is also prescribed off-label as a sleep aid, seizure inhibitor, and for some symptoms of fibromyalgia; Tizanidine may cause hypotension so caution is advised when it is used in patients who have a history of orthostatic hypotension; Use caution with this drug as it can be very strong even at the 2mg dose. Also use caution when switching from gel cap to tablet form and vice versa.

Other side effects: drug induced liver injury, with hallucinations. Visual hallucinations and delusion, If therapy needs to be discontinued, especially in patients who have been receiving high doses for long periods, the dose should be decreased slowly to minimize the risk of withdrawal and rebound hypertension, tachycardia, and hypertonia. Concomitant use of tizanidine and moderate or potent CYP450 1A2 inhibitors is contraindicated. Concomitant use of tizanidine with fluvoxamine, a potent CYP450 1A2 inhibitor in man, resulted in a 33-fold increase in the tizanidine AUC by fluvoxamine

Its primary use is for bradycardia or heart block. By activating 1-receptors on the heart, it induces positive chronotropic, dromotropic, and inotropic effects. It can be used as an inhaled aerosol to treat asthma, although this is currently a rare treatment. Also available in IV and in sublingual pill form for treatment of asthma, chronic bronchitis and emphysema. Used with caution, it can also be used to treat torsades de pointes, in conjunction with overdrive pacing and magnesium. The adverse effects : can produce an elevated heart rate (tachycardia), which predisposes patients to cardiac dysrhythmias. Other side effects include: nervousness, insomnia, restlessness, and headaches Contrindecated in patients with myocardial ischaemia.

stimulates adenylyl cyclase activity; opening of calcium channel. (cardiac stimulants; used to treat cardiogenic shock, acute heart failure, bradyarrhythmias).

Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primarcy mechanism is direct stimulation of 1 receptors of the sympathetic nervous system. Primary side effects include those commonly seen for 1 active sympathomimetics: hypertension, angina, arrhythmia, and tachycardia.

stimulates adenylyl cyclase activity; closing of calcium channel (smooth muscle relaxants; used to treat asthma and COPD). salbutamol: Ipratropium/albuterol

terol------ ---Asthma/COPD

Orciprenaline (INN)

tive inotropes

positive inotropic effects: increase myocardial contratility and efficiency, improve systemic circulation, improve renal perfusion, reduce edema negative chronotropic effects: increase vagal tone of SA node, diminished CNS sympathetic outflow from increased carotid sinus baroreceptor sensitivity, systemic arteriolar and venous constriction

The occurrence of adverse drug reactions is common (narrow therapeutic index) and concentration-dependent ( rare when plasma digoxin concentration is <0.8 g/L). They are also more common in hypokalemia patients, since digoxin normally competes with K+ ions for the same binding site on the Na+/K+ ATPase pump. Common adverse effects: loss of appetite, nausea, vomiting, diarrhea, blurred vision, visual disturbances (yellow-green halos ----xanthopsia), confusion, drowsiness, dizziness, nightmares, agitation, and/or depression, as well as a higher acute sense of sensual activities. Less frequent adverse effects: acute psychosis, delirium, amnesia, shortened QRS complex, atrial or ventricular extrasystoles, paroxysmal atrial tachycardia with AV block, ventricular tachycardia or fibrillation, heart block but when systematically sought, the evidence for this is equivocal. Electrocardiogram (ECG) changes: ST depression or T wave inversion, which do not indicate toxicity. PR interval prolongation, however, may be a sign of digoxin toxicity. Additionally, increased intracellular Ca2+ may cause a type of arrhythmia called bigeminy (coupled beats), eventually ventricular tachycardia or fibrillation.

h digoxin levels: amidarone, quinidine, verapamil, propafenone, eryghromycin, clarithromycin, tetracycline, itraconazone, cyclosporine, ritonavir; h digoxin levels: antacids, cholestyramine, colestipol, sulfasalazine, neomycin, rifampin, St, John's wort; Beta-blockers, amiodarone, verapamil, diltiazem h risk of bradycardia g-strophanthin, a poisonous cardiac glycoside.

As type 3 pyridine phosphodiesterase inhibitor, acts by inhibiting the breakdown of both cAMP and cGMP; Classified as vasodilators; the positive inotropic action like Digoxin, known as inodilators positive inotropic effects:vasodilation and fall in vascular resistance, increased force of cardiac contraction, increased velocity of cardiac relaxtion,

As type 3 pyridine phosphodiesterase inhibitor, acts by inhibiting the breakdown of both cAMP and cGMP; Classified as vasodilators; the positive inotropic action like Digoxin, known as inodilators positive inotropic effects:vasodilation and fall in vascular resistance, increased force of cardiac contraction, increased velocity of cardiac relaxtion,

Angina pectoris, commonly known as angina, is severe chest pain due to ischemia (a lack of blood and hence oxygen supply) of the heart muscle, generally due to obstruction or spasm of the coronary arteries (the heart's blood vessels). Coronary artery disease, the main cause of angina, is due to atherosclerosis of the cardiac arteries

directly relax vascular smooth muscle (fast-acting nitrates dilate epicardial: coronary arteries, consequently decreasing coronary vasospasm.

long acting

decrease sympathetic-mediated myocardial stimulation. Negative inotropic and negative chronotropic effects reduce myocardial oxygen requirements

class I recomm. for HF

peripheral arteriles dilate and total peripheral resistance decrases, increase oxygen delivery

platelet aggregation inhibitor

block both Na channels and reduce K current; also prolong duration of action potential and increase effective refractory period. prolong repolarization; increase in the QRS interval and the QT interval

Used in: acute and chronic ventricular and supraventricular arrhythmias,esp. paroxysmal supraventricular tachycardias (PSVTs), PVC, premature atrial contraction (PAC) and ventricular tachycardia;

h serum levels of digoxin; severe orthostatic hypotension with vasodilators (e.g., nitroglycerin); phenytoin, rifampin, and barbiturates h its activity; Nifedipine reduce its plasma levels; Antacids, sodium bicarbonate, socium acetazolamide h its levels; Produce additive hypoprothrombinemic effects with coumarin anticoagulants

Procainamide is used more frequently than quinidine because it can be adm. IV and in sustained-release oral preparations.

contraindicated in pts with: hypersensitivity to procaine and related drugs, myasthenia gravis, second- or third-degree AV block with no pacemaker, a history of procainamide-induced SLE, prolonged QT syndrome (torsades de pointes)

Used in : alternative for ventricular arrhythmias: PVC, moderate ventricular tachycardia

Phenytoin may increase its metabolism and recue therapeutoc efficacy.

inhibit Na channels and decrease the action potential duration and effective refractory period. Shorten repolarization Decrease in the QT interval Have minimal effect on the rate of rise of phase 0

Phenytoin may increase cardiodepressant effects of lidocaine; b-blockers may reduce lidocaine metabolism and leading drug-toxicity.

Lidocaine is mostly cleared by hepatic metabolism, Any condition that impairs liver function or compromises liver blood flow may increase lidocaine levels.

Both mexiletine and tocainide are well absorbed orally. Reduce first-pass liver metabolism

contraindicated in pts with : sinus bradycardia or heart block; caustion in pts with HF, renal or hepatic impariment, myocardial insufficiency, respiratory depression, or hypotension

block Na channels; Strong depression depolarization Large increase in the QRS interval ; But no effect on repolarization or refractoriness

block Na channels; Strong depression depolarization Large increase in the QRS interval ; But no effect on repolarization or refractoriness

reduces fast inward sodium current, decreasing the action potential duration and effective refractory period, and increase the PR, QRS, QTe interval;

decrease in heart rate and a prolongation in the PR interval(artial depolarization)

-adrenergic blockers, block catecholamine-induced stimulation of cardiac -receptors and depress depolarization of phase 4; Decrease impulse conduction and lengthening the refractory period. Slow the sinus rhythm without significantly changing the QT or QRS intervals, reducing the heart rate and myocardial oxygen demand.

severe vasoconstriction may occur with epinephrine co-adm.; Digitalis can cause excessive bradycardia; Calcium-channel blockers( diltiazem, verapamil) and other negative inotropic and chronotropic drugs (disopyramide, quinidine) add to the myocardial depressant effects Morphine may h esmolol plasma levels.

inhibit outward K channels (prolongs action potential duration and repolarization) increase action potential duration by prolonging repolarization via blockade of the delayed rectifier K current; no effect on myocardial contractility or conduction time. increase in the QT interval

Also blocks Na and Ca channels; blocks beta-adrenergic receptors; impedes atrioventricular (AV) node conduction and slows heart rate Used in : Conversion maintenance of AF to NSR; ventricular arrhythmias (~ fibrillation and pulseless ~ tarchycardia) NSR (normal sinus rhythm ) Reduce arrhythmic deaths in pts after an MI;

D_D of amiodarone: May increase levels of digoxin (two-fold), procainamide, warfarin, quinidine, diltiazem, flecainide; May increase the pharmcological effcts of b-blockers, calcium-channel blockers, and warfarin

Sotalol has nonselective beta-blocking activity and also prolongs phase 3 potential, which makes it classified as a type III rather than type II. Great oral absorption (90% to 100%); PO only

cautiously in pts receiving agents with cardiac-depressant properties; avoid with other prolonged-QT interval drugs Contraindicated in patients with renal impairment (CrCI rate of < 40 ml/min) Or prolonged QT interval (> 450 msec). Checked for normal renal function before initiating therapy. Relies on activation of slow inward sodium current to prolong action potential and effective refractory period IV only Administer in setting of continuous ECG monitoring (to identify acute ventricular arrhythmias)

Great oral absorption (90% to 100%); PO only ; Used in Conversion of Af/AFI to NSR

Calcium-channel blockers (verapamil, diltiazem only, not the others)

The nondihydropyridine calcium channel blockers, block the slow inward current carried by calcium during phase 2, increase the effective refractory period and depress depolarization of phase 4; by depressing the SA and AV nodes, reduced heart rate and an increase in the PR interval.

Contraindicated in patients with: AV block, left ventricular dysfunction, severe hypotention, concomitant with IV b-blockers, atrial fibrillation with an accessory AV pathway; Cautiously in pts with CHF, sick sinus syndrome, MI, and hepatic or renal impairment; pts with slow heart rate or receiving digitalis glycosides

vagotonic response, increase AV nodel refractoriness Digoxin (cardiac glycoside) is a positive inotropic agent that inhibits the Na+/K+ ATPase pump. and causes an increase in intracellular sodium that allows the Na+/Ca 2+ exchanger to increase intracellular calcium to increase contractility of the heart. Renally cleared. May undergo enterohepatic recycling. Therapeutic plasma range: 0.5 to 2 g/L

acts at G-protein-coupled adenosine receptors to increase AV nodel refractoriness; slows the conduction and interrupts the re-entry pathways through the AV node, restoring dysrhythmia to NSR. Adenosine is only given IV and rapidly taken up by most types of cells and rapidly degraded by deamination or phosphorylation.

Treat hypertensive emergencies: arteriolar and venous casodilator: nitroprusside or bosentan; arteriolar casodilator: diazoxide or hydralazine; Dual / -receptor blockers: labetalol, carvedilol; -receptor blockers: propranolol ganglionic-blocking agent: trimetaphan

without the sulfonamide group exhibit no diuretic activity

K channel activators, produce membrane hyperpolarization; direct actions on arterious but little on venous capacity

Minoxidil is a potassium channel agonist. Relaxes arteriolar smooth muscle directly Decreaseing peripheral resistance; Decreases renal vascular resistance while preserving renal blood flow

serves as a source of nitric oxide, a potent peripheral vasodilator that affects both arterioles and venules (venules more than arterioles).

stimulate formation of EDRF(NO) to decrease arterial resistance, relax both arterioles and veins

() limiting the releasing of neurotransimitters from adrenergic neurons

depleting intraneuronal catecholamine storage sites

an indole alkaloid antipsychotic and antihypertensive drug that has been used for the control of high blood pressure and for the relief of psychotic behaviors; but it is rarely used today. Side effects: nasal congestion, nausea, vomiting, weight gain, gastric intolerance and ulceration, stomach cramps and diarrhea. Others: hypotension, bradycardia, worsen asthma, erectile dysfunction. Depression can occur at any dose and may be severe enough to lead to suicide.

by blocking ganglionic transmission, reduce sympathetic activity, resulting in a hypotensive effect, indicated for hypertensive crisis

It acts as a non-depolarizing competitive antagonist at the nicotinic acetylcholine receptor, is short-acting, and is given intravenously.

relieve vasospasm in Raynaud syndrome and for acute HPN emergencies resulting from pheochromocytoma or from intake of MAO inhibitors or sympathomimetics. Mostly used for the control of hypertensive emergencies; also effective in cocaine induced hypertension, where generally avoid beta blockers and where calcium channel blockers are not effective.

blocking postganglionic adrenergic receptors to relax both arterioles and veins; lower incidence of reflex tachycardia; No adverse effect on serum lipids and other cardiac risk factors

Sepcifically blocks the alpha 1 receptors in the prostate gland. It is indicated for treatment of BPH. The normal therapeutic dose of drug is 0.4 mg per day. It preferably should be taken after meals.

As a vasodilator it is used to treat spasms of peripheral blood vessels (as in acrocyanosis). Also as an antidote to reverse the severe peripheral vasoconstriction which can occur as a result of overdose with certain 5-HT2A agonist drugs

1 + 2 + 1

Beta-blockers competitively antagonize beta-receptors, leading to decreased calcium influx into myocardial cells, which in turn leads to both decreased heart rate (chronotropic effect) and cardiac contractility (inotropic effect) But relative cardioselectivity will lost as dosages are increased. No b-blocker is totally safe in pts with bronchospastic disease (asthma, chronic obstructive pulmonary disease COPD)

stoppage leads the risk for a withdrawal syndrome (exacerbated anginal attacks, myocardial infarction, BP rebound)

n pts with diabetes (mask hypoglycemic symptoms such as tachycardia), Raynaud phenomenon or peripheral vascular disease, nuerological disorders (esp. the lipid ones which can enter

blocking postganglionic adrenergic receptors. the most lipophilic agent which can penetrate the CNS, and is useful in treating migraines and anxiety,

The nonselective beta-blockers also have the disadvantage of masking hypoglycemic symptoms, especially in insulin-dependent diabetics. Contraindicated in patients with CHF, MI, DM congestive heart failure or myocardial infarct), bradycardia, diabetes mellitus.

At low doses, metoprolol and atenolol predominantly antagonize the receptors on cardiac tissues with less activity on 2-receptors. Therefore, they are less likely to cause bronchospasm in patients with COPD or asthma. Beta-blockers with 1-antagonist activity may produce more vasodilation activity and have a higher incidence of postural dizziness, lightheadedness, and fatigue. combind with nadolol, possessing intrinsic sympathomimetic activity; hypertension angina pectoris, including unstable angina ventricular and atrial cardiac arrhythmia acute myocardial infarction in high-risk patients

HTN, coronary heart disease, arrhythmias, angina (chest pain) and to treat and reduce the risk of heart complications following myocardial infarction (heart attack). also used to treat the symptoms of Graves Disease, until antithyroid medication can take effect.

once-daily dosing 5-20mg

once-daily dosing 2.5-10mg; no intrinsic sympathomimetic activity

ultrashot duration of action

It is used primarily in animal and tissue experiments to characterize beta-2 receptor involvement and identify beta-2 receptors.

The property of a drug (usually b-blockers) that produces partial agonist effect at the receptor similar to the cholinergic stimulation of the sympathetic nervous system. Beta-blockers with ISA are beta-blockers that exert a partial agonism at the adrenergic receptor while simultaneously blocking the endogenous catecholamines from binding to the receptor. Hence, they are less potent than catecholamines and other beta-agonists.

stimulating presynaptic 2-inhibitory receptors within CNS, resulting in a negative sympathetic outflow and lowered peripheral resistance

Effective in pts with renal impairment (reduced dose and longer dosing interval); initial paradoxical increase in pressure, abrupt withdrawal syptoms, sedation and dry mouth, depression common adverse effects: orthostatic hypotension, fluid accumulation (in the absence of a diuretic), rebound HPN on abrupt withdrawal. Sedation is common in initial therapy but usually decrease with continued therapy; Others: Fever and other flu-like symtoms (represents hepatic dysfuntion, monitoring liver funtion), positive Coombs test, dry mouth, subtly decreased mental activity, sleep disturbances, depression, impotence, and lactation in either gender.

cautiously with other sedating medications and in pts with severe coronary insufficiency, recent MI, cerebrovascular acident, and hepatic or renal disease. Common side effects: sedation, dry mouth, dizziness, reduced heart rate

bind to L-type channels in cardiac and smooth muscle, and inhibit influx of calcium into cardiac muscle, which decreases contractility and rate. blockade effects in arterioles are more sensitive than veins

AV node conduction hhh Myocardial contractility hh Peripheral vascular resistance hh Admistration: PO, IV Metabolism: liver(T1/2 3-7 hours) AV node conduction hh Myocardial contractility h Peripheral vascular resistance h Admistration: PO, IV Metabolism: liver(T1/2 3-7 hours)

AV node conduction 0 Myocardial contractility h Peripheral vascular resistance hhh Admistration: PO Metabolism: liver(T1/2 2-5 hours)

AV node conduction h Myocardial contractility h Peripheral vascular resistance h Admistration: PO Metabolism: liver(T1/2 24 hours) unique in blocking both fast sodium channels / calcium channels in heart.

Dihydropyridine calcium channel blockers are often used to reduce systemic vascular resistance and arterial pressure, but are not used to treat angina because the vasodilation and hypotension can lead to reflex tachycardia (with the exception of amlodipine, which carries an indication to treat chronic stable angina as well as vasospastic angina) . This CCB class is easily identified by the suffix "-dipine". Common side effects: Dizziness, headache, redness in the face; Fluid buildup in the legs; Rapid heart rate or Slow heart rate; Constipation; Gingival overgrowth Contraindications of amlodipine: cardiogenic shock; unstable angina; significant aortic stenosis; breast feeding

With a high lipid solubility it can be used for cerebral spasm following subarachnoid hemorrhage. Common side effects: hypotention, tachycardia, peripheral edema and GI hemorrhage. (Calan, Isoptin) (Procorum, D600) (Cardizem)

block the conversion of A I to A II (the potent casoconstrictor), also lower aldosterone concentration (limits sodium retention) promoting vasodilatation and decreasing sodium retention.

shortest-acting ACE inhibitor.

the only phosphonate-containing ACE inhibitor marketed. Both renal elimination and metabolism are important in the elimination of the drug and its active metabolites

Significant D_D: Antihypertensive effects may be deminished by NSAIDs (e.g., ibuprofen); Potassium-sparing diuretics increase serum potassium levels (need closely monitoring)

E inhibitors and ARBs are contraindicated in patients with bilateral renal stenosis. (decreased blood flow to the glomerulus). ibitors or ARBs, the effects of angiotensin II are reduced, which leads to vasodilatation of the efferent arterioles. This will result in a decrease in pressure and glomerular rate and a worsening of the renal function,

soconstriction and aldosterone-secreting effects similar to ACE-I. However, because ARBs do not block the metabolism or increase the levels of bradykinin, they are less be associated with nonrenin-angiotensin effects such as cough and angioedema.

nantly eliminated via hepatic metabolism

highly polar, low renal threshold, limit tubular reabsorption of water and thus promote diuresis, cause an alkaline in urinary pH

Can be used in the management of constipation when cognitively impaired or bedbound; Glycerin is also the same in this use. It is a synthetic disaccharide, is an analog of lactose. Unlike lactose, which is hydrolyzed enzymatically to its monosaccharide components, oral doses of lactulose pass to the colon virtually unchanged. In the colon, bacteria chemically convert the lactulose to low-molecularweight acids and carbon dioxide. The acids produce an osmotic effect that draws water into the colon and makes the stools more watery. They also permit ammonia in the body to be converted to ammonium ion in the acidic colon and allow it to be eliminated in the stool. It is also used in the treatment of hepatic encephalopathy, a complication of liver disease.

noncompetitively inhibit the enzyme carbonic anhydrase, result in sodium bicarbonate diuresis (block the formation of H+ and HCO3- from CO2 and H2O). ----bicarbonate is excreted in the urine. cause an alkaline urinary pH; Acts on proximal tubule

is also used to treat glaucoma, epileptic seizures, benign intracranial hypertension (pseudotumor cerebri), altitude sickness, cystinuria, and dural ectasia. Acetazolamide is available as a generic drug.

_thiazide; thazone, lazone

Thiazide diuretics: directly inhibit NaCl reabsorption, cause an alkaline urinary pH Inhibits reabsorption of NaCl in the ascending loop of Henle and the early distal convoluted tubules (DCT) (also as early distal tubules)

similar to benzothiadiazide diuretics

a thiazide-like diuretic because it acts similarly to the thiazides but does not contain the benzothiadiazine molecular structure; Compared with other medications of the thiazide class, chlorthalidone has the longest duration of action, but a similar diuretic effect at maximal therapeutic doses. It is often used in the management of hypertension and edema. Unlike loop diuretics, chlorthalidone efficacy is diminished in patients with certain renal diseaes (e.g. Chronic Renal Disease). Mild hypokalemia is often without symptoms, although it may cause a small elevation of blood pressure, and can occasionally provoke cardiac arrhythmias. Moderate hypokalemia may cause muscular weakness, myalgia, and muscle cramps (owing to disturbed function of the skeletal muscles), and constipation (from disturbed function of smooth muscles). Severe hypokalemia: flaccid paralysis, hyporeflexia, and tetany may result. There are reports of rhabdomyolysis occurring with profound hypokalemia. Respiratory depression from severe impairment of skeletal muscle function is not uncommon. Some electrocardiographic (ECG) findings associated with hypokalemia are flattened T waves, U waves, ST segment depression, and prolongation of the QT interval.

inhibit the cotransport of Na, K, Cl from the luminal filtrate, no change in urinary pH Inhibits reabsorption of NaCI in the thick ascending limb of the loop of Henle ; NSAIDs (e.g., ibuprofen) interact to diminish the antihypertensive effects

Contraindication Diuretics that act on the distal tubule (thiazides and potassium-sparing diuretics) lose their effectiveness when CrCl decreases to less than 30 to 50 mL/min. The loop diuretics are more potent and retain their effectiveness at low CrCl (> 5 mL/min)

acts by inhibiting the Na-K-2Cl symporter in the thick ascending limb of the loop of Henle. used in the treatment of hypertension, congestive heart failure and edema.

Bumetanide is 40 times more potent than furosemide (for patients with normal renal function). used in patients in whom high doses of furosemide are ineffective. The drug is often used for weight loss, but also to mask other drugs or steroids.

act on the late distal tubule and collecting duct,

They disrupt sodium exchange with K and H by blocking Na channels and decreasing the driving force for secretion of K and H cause an alkaline urinary pH and h K

They disrupt sodium exchange with K and H by blocking Na channels and decreasing the driving force for secretion of K and H cause an alkaline urinary pH and h K

Cometitive inhibitors of aldosterone, act on the late distal tubule and collecting duct, decreasing K secretion; Used primarily to treat acne; acute coronary syndromes; ascites; edema; heart failure; hypokalimia; renal impairment; hypertension (with HCTZ) systolic heart failure; hepatic cirrhosis and ascites, hypokalemia, and Conn's syndrome as well as high blood pressure, low-renin hypertension; Hirsutism, and a common component in hormone therapy for male-to-female transsexual and transgendered people; hair loss and acne in women and as a topical medication for treatment of male baldness.

Symptoms are fairly nonspecific and generally include malaise, palpitations and muscle weakness; mild hyperventilation may indicate a compensatory response to metabolic acidosis, which is one of the possible causes of hyperkalemia. other symptoms (paresthesias, bradycardia, fatigue, flaccid paralysis of the extremities, shock).

Pamabrom is a diuretic product included in retail drugs available in over-the-counter medications. The active diuretic ingredient is 8-bromotheophylline. It is also available in combination with acetaminophen (paracetamol) for menstrual relief. The acetaminophen helps reduce menstrual pains and the pamabrom reduces associated bloating. The acetaminophen/pamabrom combination is also marketed as a pain reliever for pain associated with back ache, headache, and muscle ache and can be used as a mild muscle relaxant.

--- Proximal tubule Osmotic / Carbonic anhydrase inhibitors loop + thiazide HCTZ 25 mg spironlactone and 25 mg HCTZ

--- Henle's Loop ---Loop

--- Distal Tubule ---Thiazdie

---Late DT & Collecting Duct ---K-sparing

5 mg amiloride plus 50 mg HCTZ 37.5 mg triamterene and 50 mg HCTZ 75 mg trizmeterene and 50 mg HCTZ 37.5 mg trizmeterene and 25 mg HCTZ

increase catabolism

bile acid sequestrants

increase the efficiency of lipoprotein removal

Niacin--- vitamin B3, Inhibit VLDL secretion

reduce lipoprotein production, h VLDL catabolism, PPAR agonist

Inhibit rate-limiting step in cholesterol synthesis Simvastatin causes the greatest percentage increase in HDL

(Lipitor, Pfizer), Common side effects: myalgia, mild transient GI symptoms (diarrhea, constipation, passing gas), elevated hepatic transaminase concentrations, headache, insomnia, joint pain, and/or dizziness. Rare: Myopathy and rhabdomyolysis. Risk is increased in patients with renal impairment, serious concurrent illness; and/or concomitant use of drugs which inhibit CYP3A4. The main clinical advantage of Lipitor over Simvastatin is that it is not metabolised by certain liver enzymes, and thus its blood concentration is not increased when combined with grapefruit juice which inhibits these enzymes. It was used to treat hypercholesterolemia and to prevent cardiovascular disease. It has also been shown to exhibit antiviral activity against Hepatitis

Common side effects: abdominal pain, diarrhea, indigestion, and a general feeling of weakness. Rare side effects: joint pain, memory loss, and muscle cramps. D_D: intake of grapefruit lows metabolization of simvastatin; when simvastatin is used with amiodarone can lead to kidney failure or death,

Used to lower cholesterol levels by decreasing cholesterol absorption in the intestine. It may be used alone when other cholesterol-lowering medications are not tolerated, or together with statins (e.g. ezetimibe/simvastatin, marketed as Vytorin and Inegy) when cholesterol levels are unable to be controlled on statins alone. Side effects: headache and/or diarrhea; Others: myalgia and/or raised liver function test (ALT/AST); hypersensitivity reactions (rash, angioedema) or myopathy.

Bind to bile acids in gut

Resins HMG-CoA-Is Niacin Fibrates Ezetimibe

LDL hh hhh hh h--hh hh hh

h h hh hh h

HDL TG (triglycerides) h (the only appropriate for children(>2) / pregnant / lactating women h---hh(Atorva-/Rosuva have the greast TG-lowering effect hh hhh Greatest in HDL increasing Greatest in TG lowering

inhibition of thrombin by antithrombin III preventing the conversion of fibrinogen to fibrin Differences from unfractionated heparin include: Average molecular weight: heparin is about 20000 Da and LMWH is about 3000 Da Once-daily dosing, rather than a continuous infusion of unfractionated heparin No need for monitoring of the APTT coagulation parameter Possibly a smaller risk of bleeding; Smaller risk of osteoporosis in long-term use Smaller risk of heparin-induced thrombocytopenia (HIT), a feared side-effect of heparin. The anticoagulant effects of heparin are typically reversible with protamine sulfate, while the effect on LMWH is limited Has less of an effect on thrombin compared to heparin, but maintains the same effect on Factor Xa. Carefully used in pts with hypersensitivity to heparin; It can also elevate AST, caution in pts with liver disease and pulmonary emlolism.

Hyperkalaemia: LMWH can cause hypoaldosteronism, which may result in hyperkalaemia. Potassium should be monitored before and during treatment, particularly in patients at risk of high potassium e.g. renal impairment, ACE inhibitors, Angiotension II receptor blockers, potassium sparing diuretics etc. Heparin induced thrombocytopenia (HIT): is a rare side effect of LMWH. HIT predisposes patients to an increased risk of VTE. Platelet count should be performed before treatment is started and during treatment. Danaparoid, Lepirudin and Argatroban are appoved for treatment of HIT in Canada.

Warfarin decrease blood coagulation by inhibiting vitamin K epoxide reductase, an enzyme that recycles oxidated vitamin K to its reduced form hydroquinone after it has participated in the carboxylation of several blood coagulation proteins, mainly prothrombin and factor VII. For this reason, drugs in this class are also referred to as vitamin K antagonists. Highly protein bound and extensively metabolized in the liver, susceptible to significant drug interactions; contraindicated in pregnancy;

teracts with many commonly-used drugs, and the metabolism of warfarin varies greatly between patients. rotein bound drugs can displace warfarin from albumin and cause an increase in INR; cs, such as metronidazole or the macrolides, will greatly increase the effect of warfarin by reducing the metabolism of warfarin; pectrum antibiotics can reduce the amount of the normal bacterial flora in the bowel, which make significant quantities of vitamin K, thus potentiating the effect of warfarin; roidism h the effects of warfarin; hyperthyroidism boosts the anticoagulant effect; ve use of alcohol h metabolism of warfarin and can elevate the INR;

Unlike Dicumarol, Warfarin and Aisindione (prothrombopenic, competitively inhibit Vitamin K and hepatic production of prothrombin), they act by other mechanisms. The citrate chelates with calcium ions and acts as an anticoagulant. It is used for anticoagulation and preparation of whole blood for transfusion.

The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage, and vitamin K status. The reference range for PT is usually around 1215 seconds; the normal range for the INR is 0.81.2. PT measures the extrinsic pathway including factors II, V, VII, X and fibrinogen. It is used in conjunction with the activated partial thromboplastin time (aPTT, 25-39 seconds) which measures both the intrinsic pathway (now referred to as the contact activation pathway) and the common coagulation pathways. aPTT is also used to monitor the treatment effects with heparin.

aspi- abci- efpti- tiroficilopy- dipy- trepro-

an inhibitor of platelet aggregation that is administered orally, with food, in doses of 250 mg twice daily. Patients using this drug should have a complete blood count (CBC) with differential performed every two weeks for three months to detect neutropenia (decreased number of white blood cells). The drug's antiplatelet effects are not maximal until at least 8 to 11 days of therapy have been completed. specific factor Xa inhibitors a platelet aggregation inhibitor mainly used during and after coronary artery procedures like angioplasty to prevent platelets from sticking together and causing thrombus (blood clot) formation within the coronary artery. Its mechanism of action is inhibition of glycoprotein IIb/IIIa; While Abciximab has a short plasma half life, due to its strong affinity for its receptor on the platelets, it may occupy some receptors for weeks. In practice, platelet aggregation gradually returns to normal about 24 to 48 hours after discontinuation of the drug.

anagre--not coagulate

Treprostinil is a synthetic analogue of prostacyclin, used to treat pulmonary hypertension. As an analogue of prostacyclin PGI2, treprostinil effects vasodilation, which in turn lowers the blood pressure. Treprostinil also inhibits platelet aggregation, though the role this phenomenon may play in relation to pulmonary hypertension has yet to be determined.

It inhibits the cellular reuptake of adenosine into platelets, red blood cells and endothelial cells leading to increased extracellular concentrations of adenosine. It also inhibits the enzyme adenosine deaminase which normally breaks down adenosine into inosine. This inhibition leads to further increased levels of extracellular adenosine. Dipyridamole also inhibits the phosphodiesterase enzymes

A thienopyridine compound; used in treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease. It works by blocking a receptor called P2Y12. Adverse effects include hemorrhage. Its combination with ASA was used in acute coronary syndromes, may also be used in acute ischemic stroke; stable angina; Used as secondary prevention for ischemic stroke, myocardial infarction, and pretreatment in percutaneous coronary intervention;

used in myocardial infarction (heart attack), ischemic strokes, deep vein thrombosis and pulmonary embolism to clear a blocked artery and avoid permanent damage to the perfused tissue (e.g. myocardium, brain, leg) and death. A less frequent use is to clear blocked catheters that are used in long-term medical therapy.

The tissue plasminogen activator produced by recombinant DNA technology. It is used in the management of acute myocardial infarction (AMI), acute ischemic stroke, and pulmonary embolism. Once injected into the circulation, alteplase binds to fibrin in a thrombus and converts the entrapped plasminogen to plasmin. This and assists in reopening a blocked blood vessel.

stimulates uterine contraction and plays an important roal in the induction of labor. vasopressor and antidiuretic hormone (ADH) activity, acts on the distal renal tubular epithelium, where it promotes the reabsorption of water.

FLAT PEG (FSH, LH, ACTH, TSH, Prolactin, Endorphin and GH) follicle stimulating hormone Luteinizing hormone adrenocorticotropic hormone ACTH, stimulating the adrenal cortex to produce and secrete adrenocorticosterioids thyroid-stimulating hormone TSH thyrotropin-releasing hormone associated with lactation

somatotropin, stimulate protein, carbohydrate, and lipid metabolism to promote increased cell, organ, connective tissue, and skeletal growth, causing a rapid increase in the overall rate of linear growth

human menopausal gonadotropin hMG, obtained from the urine of postmenopausal women, procuce ovarian follicular growth and induce ovulation by FSH-like / LH-like activity,

FSH-like, obtained from the urine of postmenopausal women

LH-like, obtained from the urine of pregnant women

an injectable gonadotropin releasing hormone super-agonist (GnRH agonist) also known as an LHRH agonist. It stops the production of sex hormones (testosterone and oestrogen). Goserelin Acetate is used to treat hormone-sensitive cancers of the prostate and breast (in pre-/perimenopausal women) and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, goserelin is used in assisted reproduction and in the treatment of precocious puberty.

bond to estrogen receptor, induce its comformational change which increases its affinity for DNA and alters the production of mRNA and ultimately leads to either an increase or decrease in enzyme or protein synthesis.

in equilibrium with estrone( converted to estriol before excretion)

l cypionate or calerate

The 3-methyl ether of ethinylestradiol. It was the estrogen used in many of the first oral contraceptives. It is a biologically inactive prodrug of ethinylestradiol to which it is demethylated in the liver with a conversion efficiency of 70%

Indicated to ovulatory dysfunction women to induce ovulation. It has estrogenic and antiestrogenic activity, It combines with estrogen receptors. Through negative feedback mechanism, the hypothalamus and pituitary are stimualted to increase secretion of FSH and LH and then stimulant ovulation; Recommended dose: 50 mg/day five days. Side effects: blurred vision, spots or flashes, posterior capsular cataract, spasm of retinal atteriole, and uterine bleeding.

competitively binding estrogen receptors in breast tissue, and then inhibit the action of estrogen

competitively binding estrogen receptors and preventing estrogen receptor dimerization in target tissue.

f medication that acts on the estrogen receptor. A characteristic that distinguishes these substances from pure receptor agonists and antagonists is that their action is different in various hereby granting the possibility to selectively inhibit or stimulate estrogen-like action in various tissues.

ms are scientificaly accepted SERMs from a botanical source.

an oral SERM that has oestrogenic actions on bone and antiestrogenic actions on the uterus and breast.

Raloxifene is contraindicated in lactating women or women who are or may become pregnant, in women with active or past history of venous thromboembolic events, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis and in women known to be hypersensitive to raloxifene. This may take hours which not only includer paramedic history, but also idiomatically.

ene (4-hydroxytamoxifen)

used for managing menopause symptoms and maintaining bone health

Selective nonsteroidal inhibitors of aromatase which is responsible for the conversion of androgens to estrogens

Anastrozole binds reversibly to the aromatase enzyme through competitive inhibition. Commonly indicated in the treatment of breast cancer in post-menopausal women; Combined with OC or a progestin is useful in reducing the risk of developing ovarian cysts; It is also used to relieve endometriosis pain; effective in the off-label use of reducing estrogens (in particular and more importantly, estradiol) in men; it is frequently used in the treatment of children with growth disorder to stop or slow the onset of puberty. Side effects: Bone weakness.

yprogesterone acetate Indicated for advance breast cancer and endometrium cancer. Weight gain is a common side effect. And it is also useful as an appetite stimulant agent in HIV pts (800 mg/day)

common adr: breakthrough bleeding

orally active prodrug( deacetylated and oxidized to norgestrel prodrug

An analog to spironolactone; it has anti-mineralocorticoid properties, counteracts the estrogen-stimulated activity of the renin-angiotensin-aldosterone system, and is not androgenic. With its activities similar to spironolactone it may lead to less water retention and breast tenderness while improving skin appearance (less acne).

91-day cycle extended oral contraception

inhibit the action of progestins by competitively binding progestin receptors

OCs decrease ovulation and sperm and egg transport and implantation. The estrogen component alters FSH (follicle stimulating hormone) and LH (Ieutinizing hormone) release, accelerates sport, and alters the endometrium so that it is unsuitable for implantation. Progestins alter FSH and LH release, thicken cervical mucous to reduce sperm and egg transport, inhibit enzymes y for fertilization, and also alter the endometrium so that it is unsuitable for implantation.

contain a constant dose of estrogen and progestin,

contain varying doses of progestin (generally increasing) every 7 days, and either a stable or a variable amount of estrogen every 7 days. No uniform

Patients who have contraindications to estrogen or who experience intolerable side effects

lower doses of hormones to be used and bypass first-pass metabolism, thereby limiting the production of factors produced by the liver (e,g., fibrinogen, Creactive protein)

depo-medroxyprogesterone acetate

Tesosterone is converted to DHT which bind to an androgen receptor in the nucleus, and thus increase the production of mRNA and ultimately leads to either an increase in enzyme or protein synthesis.

converted to DHT by 5-reductase

used to treat men with a testosterone deficiency. It is also used in women to treat breast cancer, breast pain, swelling due to pregnancy, and with the addition of estrogen it can treat symptoms of menopause.

Also called methyldihydrotestosterone, is the 17-methylated version of dihydrotestosterone (DHT). It is an orally bioavailable androgenic steroid that is highly androgenic while only slightly anabolic. It is incapable of aromatization and is not an agonist of the progesterone receptor. Indicated for the treatment of chronic wasting disease, negative nitrogen balance and osteoporosis. Liver toxicity and cholestatic jaundice are common side effects.

- Grow long ---anabolic

oxymetholone is the strongest androgenic steroid available. primary clinical applications include treatment of osteoporosis and anaemia, as well as stimulating muscle growth in undernourished or underdeveloped patients. Also used in treating HIV wasting syndrome. Schedule III drug oxymetholone is the strongest androgenic steroid available.

a derivative of the synthetic steroid ethisterone, a modified testosterone (17alpha-ethinyl testosterone). Danazol has been used - mostly off-label - for other indications, namely in the management of menorrhagia, fibrocystic breast disease, immune thrombocytopenic purpura and of hereditary angioedema. and occasionally used to treat endometriosis , usually when all other hormone therapies have not helped. Though danazol prevents pregnancy, it is not licenced for use as a contraceptive agent.

Nilutamide is an antiandrogen medication used in the treatment of advanced stage prostate cancer. Nilutamide blocks the androgen receptor, preventing its interaction with testosterone. A delay in adaption to the dark, ranging from seconds to a few minutes; tinted glasses will reduce this effect.

competitive inhibit 5 -reductase, reduce DHT

DHT, 5-Dihydrotestosterone, it is crucial to virilization and is necessary to mitigate estrogen's effects in men. It is responsible for the formation of male sexspecific characteristics and other characteristics generally attributed to males, including facial and body hair growth, and deepening of the voice. DHT may also play a crucial role in both sex drive and the growth of muscle tissue. DHT cannot be converted by the enzyme aromatase to estradiol. DHT is the primary contributing factor in male-pattern baldness; also participates in the development of acne.

The retinoids are related chemically to vitamin A and used in medicine, primarily due to the way they regulate epithelial cell growth. Its functions throughout the body includes roles in vision, regulation of cell proliferation and differentiation, growth of bone tissue, immune function, and activation of tumor suppressor genes. Research is also being done into their ability to treat skin cancers. Currently 9-cis retinoic acid may be used topically to help treat skin lesions from Kaposi's sarcoma. First generation retinoids: retinol, retinal, tretinoin (retinoic acid, Retin-A), isotretinoin and alitretinoin. Second generation retinoids: etretinate and its metabolite acitretin. Third generation retinoids: tazarotene , bexarotene and Adapalene.

It is a retinoid and derives from vitamin A and is found in small quantities naturally in the body. Used for the treatment of severe acne. It is sometimes used as a chemotherapy medication for prevention and treatment of certain skin cancers. In some cases, it is used to treat Harlequin type ichthyosis. pregnant X rating; administered orally;

A second generation retinoid. It is taken orally, and is typically used for psoriasis. It is a metabolite of etretinate, which was used prior to the introduction of acitretin. Etretinate was discontinued because it had a narrow therapeutic index as well as a long elimination half-life (t1/2=120 days), making dosing difficult. In contrast, acitretin's half-life is approximately 2 days. It is necessary to adjust the dosage in renal impairment patients. Teratogenicity: Because acitretin can be reverse metabolised into etretinate which has a long half life, women must avoid becoming pregnant for at least 2 years after discontinuing acitretin. Therefore, not recommended at for women of child bearing age with risk becoming pregnant. Acitretin is the least toxic systemic treatment for psoriasis. It is an oral retinoid of choice used in the treatment of severe resistant psoriasis.

A prescription topical retinoid sold as a cream or gel. This medication is approved for treatment of psoriasis, acne, and sun damaged skin (photodamage). It is commonly sold in two concentrations: 0.05% and 0.1%. Common side effects include worsening of acne, dry skin, itchiness, redness and in some cases extreme drying and cracking of skin. For most patients these side effects are uncomfortable but mild and decrease markedly after the first 24 weeks of use.

Indicated for the topical treatment of acne vulgaris. Adapalene has been shown to enhance the efficacy of topical clindamycin. Unlike Retin-A, adapalene has also been shown to retain its efficacy when applied at the same time as benzoyl peroxide due to its more stable chemical structure.

Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. 1. Topical steroids for use topically on the skin, eye, and mucous membranes. 2. Inhaled steroids for use to treat the nasal mucosa, sinuses, bronchii, and lungs. 3. Oral forms - such as prednisone and prednisolone. 4. Systemic forms - available in injectibles for use intravenously and parenteral routes.

: (short to medium acting glucocorticoids) Hydrocortisone, Hydrocortisone acetate, Cortisone acetate, Tixocortol pivalate, Prednisolone, Methyprednisolone, and Prednisone. Triamcinolone acetonide, Triamcinolone alcohol, Mometasone, Amcinonide, Budesonide, Desonide, Fluocinonide, Fluocinolone acetonide, and Halcinonide. Betamethasone, Betamethasone sodium phosphate, Dexamethasone, Dexamethasone sodium phosphate, and Fluocortolone.

C:

D: rtisone-17-butyrate, Hydrocortisone-17-valerate, Aclometasone dipropionate, Betamethasone valerate, Betamethasone dipropionate, Prednicarbate, Clobetasone-17, Clobetasol-17-propionate, Fluocortolone caproate, Fluocortolone pivalate, and Fluprednidene acetate.

Dexamethasone and Betamethasone are almost pure glucocorticoids, while prednisone and its derivatives have some mineralocorticoid action in addition to the glucocorticoid effect. Fludrocortisone (Florinef) is a synthetic mineralocorticoid. Hydrocortisone (cortisol) is available for replacement therapy, e.g. in adrenal insufficiency and congenital adrenal hyperplasia. used in the treatment of joint pain or inflammation (arthritis), temporal arteritis, dermatitis, allergic reactions, asthma, hepatitis, systemic lupus erythematosus, inflammatory bowel disease (ulcerative colitis and Crohn's disease), sarcoidosis and for glucocorticoid replacement in Addison's disease or other forms of adrenal insufficiency. Topical formulations for treatment of skin, eye diseases (uveitis) or inflammatory bowel disease are available. Corticosteroids are also used supportively to prevent nausea, often in combination with 5-HT3 antagonists (e.g. ondansetron).

Typical undesired effects of glucocorticoids present quite uniformly as drug-induced Cushing's syndrome. Typical mineralocorticoid side effects are hypertension, hypernatremia, hypokalemia, without causing peripheral edema, metabolic alkalosis and connective tissue weakness (Werner, 2005). Corticosteroids can cause permanent eye damage by inducing central serous retinopathy (CSR, also known as central serous chorioretinopathy, CSC).

, protein-catabolic, control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms.

formed in the middle(fasiccular) layer of the adrenal cortex

C-11- O essential for glucocorticoid activity

C-1 and C-2 double bond, increase gluco-act

C9 fluorination incrases mineralo- and gluco-act

C6 fluorination incrases gluco-act

17 -OH with 16 -OH or Me incrases gluco-act but abolish mineralo-act 17/ 16 isopropylidenedioxygroup or an acetate ester in C21 enhances topical absorption used after laser-based refractive surgery. Fluorometholone acetate ophthalmic suspension is indicated for use in the treatment of steroid responsive inflammatory conditions of the palpebral and bulbar conjunctiva, cornea, and anterior segment of the eye.

Budesonide is a glucocorticoid steroid for the treatment of asthma, non-infectious rhinitis (including hay fever and other allergies), and for treatment and prevention of nasal polyposis . Additionally, it is used for inflammatory bowel disease.

ects of glucocorticoids (review version):

osuppression ycemia due to increased gluconeogenesis, insulin resistance, and impaired glucose tolerance; caution in those with diabetes mellitus; ascular effects: edema and hepertension; fluid retention; ed skin fragility, easy bruising; bone density (osteoporosis, osteonecrosis , higher fracture risk, slower fracture repair); gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; insufficiency (if used for long time and stopped suddenly without a taper) breakdown (proteolysis), weakness; reduced muscle mass and repair; on of malar fat pads and dilation of small blood vessels in skin ation, irregularity of menstrual periods failure, pubertal delay ed plasma amino acids, increased urea formation; negative nitrogen balance ry effect on central nervous system (euphoria, psychosis) ma due to increased cranial pressure; ts

gain due to increased visceral and truncal fat deposition (central obesity) and appetite stimulation; insufficiency (if used for long time and stopped suddenly without a taper) breakdown (proteolysis), weakness; reduced muscle mass and repair; on of malar fat pads and dilation of small blood vessels in skin ation, irregularity of menstrual periods failure, pubertal delay ed plasma amino acids, increased urea formation; negative nitrogen balance ry effect on central nervous system (euphoria, psychosis) ma due to increased cranial pressure; ts

Comparative steroid potencies

Glucocorticoid potency 1 0.8 3.5-5 4 5-7.5 25-80 25-30 5 8 puffs 4 times a day equals 14 mg oral prednisone once a day 15 0 (Deoxy-corticosterone acetate) 0.3

Na retaining / K excreting: control electrolyte and water levels, mainly by promoting sodium retention in the kidney.

Aldosterone is a hormone that causes the tubules of the kidneys to retain sodium and water. It is formed in the outer (glomerular) layer of the adrenal cortex, the prototypical minralocorticoid. Aldosterone is part of the renin-angiotensin system. Spironolactone lower blood pressure by blocking the aldosterone receptor.

With moderate glucocorticoid potency and much greater mineralocorticoid potency. Used to treat Addison disease and the classic salt wasting (21hydroxylase deficiency) form of congenital adrenal hyperplasia. It has been used in the treatment of cerebral salt wasting and orthostatic intolerance.

diuretics similar to spironolactone, though it may be more specific for the mineralocorticoid receptor and is specifically marketed for reducing cardiovascular risk in patients following myocardial infarction

regualte growth and development , calorigenic and metabolic activity, through sensitization of beta-adrenergic receptors hance positive inotropic and chronotropic effects on the myocardium

TRH is secreted by the hypothalamus and stimulates the release of TSH from anterior pituitary. Thyrotropin(TSH) stimulates the thyroid gland to produce T4 and T3. These hormones regulate their own sysnthesis by binding to specific sites in the anterior pituitary and inhibiting the release TSH.

T4 / T3 in a ratio of 4:1; T4 less potent than T3 but longer duration of action (6-7 day versus 1-2 days); D_D: carefully with cholestyramine (acidic), carbamazepine, cimetidine

L-isomer of triiodothyronine (T3), a form of thyroid hormone used to treat hypothyroidism and myxedema coma. Liothyronine is the most potent form of thyroid hormone. In comparison to levothyroxine (T4), liothyronine has a faster onset of action as well as a shorter biological half-life, which may be due to less plasma protein binding to thyroxine-binding globulin and transthyretin.

4:1 mixture of levothroxine sodium to liothyronine sodium

an adjunct in the detection and treatment of thyroid cancer

used in hyperthyroidism Graves diease and toxic adenoma used before thyroid surgery to make the thyroid gland firmer and reduce its size High concentration of iodide

Used in older pts or with heart disease inhibit the enzyme iodoperoxidase

6-N-Propylthiouracil (PROP) is a thioamide drug used to treat hyperthyroidism by decreasing the amount of thyroid hormone produced by the thyroid gland. PTU inhibits the enzyme thyroperoxidase, to prevent adding iodide to the tyrosine residues on the hormone precursor thyroglobulin, thus forming thyroxine. PTU also acts by inhibiting the enzyme 5'-deiodinase prevent converting T4 to the active form T3.

Thioamides inhibit many steps in the synthesis of thyroid hormones, including the addition of iodide to thyroglobulin by the enzyme thyroperoxidase, a necessary step in the synthesis of thyroxine. Notably, they do not inhibit the action of the sodium-dependent iodide transporter located on follicular cells' basolateral membranes. Inhibition of this step requires competitive inhibitors such as perchlorate and thiocyanate. Side effects: agranulocytosis, thrombocytopenia, and agranulocytopenia, it is contraindicated in pregnancy

Type 1/2; Gestational diabetes mellitus (GDM), secondary DM

Type 1: beta cell destruction---absolute insulin deficiency; often immune mediated, but occasionally idioathic; prestents as acute metabolic symptoms of relative short duration in a child, adolescent or young adult; Ketoacidosis if untreated; the presentation may be more gradual in older individuals. In North America, 5-10 % of all patients with diabetes Type 2: insulin resistance combined with insulin deficiency, either can be predominant; presents as chorinic complications and increasingly frequent; prevalence in certain ethnic groups (aboriginal populaitons and obese children and adolesents) Gestational diabetes: glucose intolerance in pregnancy; insulin is the only choice for pregnant

Atypical antipsychotic agents: clozapine, olanzapine, quetiapine, risperidone, ziprasidone; beta-adrenergic agonists: atenolol, metoprolol, propranolol;...... Thiazide diuretics: hydrochlorothiazide, cyclothiazide, methyclothiazide, quinethazone, metolazone Protease inhibitors: _navir---- indinavir, ritonavir, tipranavir....... Glucocorticoids: Hydrocortisone, Betamethasone, Prednisone,Triamcinolone...... Others: Diazoxide; Interferon alfa; Nicotinic acid; Pentamidine; Phenytoin

secreted by -cells of the pancreas, a 51 amino acid protein composed of two polylpeptide chains; The purity of insulin can be measured by the content of proinsulin.

used in Type 1 DM; life-threatening hyperkalemia;

stress-induced hyperglycemia

A shorter 15-30 min onset, 3-4 hr duration; 15 min before or after the initiation of a meal; have a lower propensity to cause hypoglycemia, thus recuding the need for snacks between meals reversed in Lys29 and Pro28 of the B chain replaced the Pro28 with Asp of the B chain Asn3---Lysine Lys29---Glu the only type that can be given intravenously, soluble and prepared at neutral pH, it can be mixed with most other insulins (except glargine and detemir---longacting insulin)

Neutral Protamine Hagedorn insulin: the presence of protamine, along with low concentration of Zn, enhance the aggregation of insulin into dimers and hexamers after subcutaneous injection and prolongs its duration. neutral protamine lispro(NPL) / neutral protamine aspart(NPA) 30 / 70 U/ ml

a decreased solubility at physiological pH, precipitation and delayed absorption after subcutaneous injection and increased duration of action. Once dayly adm.

amide; ride; tide; formin; glitazone;glinide;

acidic diabetics: basic diabetics:

acidic compounds, block ATP sensitive K channels, which stimulates the release of insulin form pnacreatic cells ( K channel blcokers)

more lipid soluble and potent than first generation

basic compund, do not stimulate the release of insulin, no hypoglycemia increase in insulin action in peripheral tissues inhibition of gluconeogenesis; increase glucose transport across skeletal muscle cell membrances inhibit hepatic gluconeogenesis Can potentiate the hypoglycemic effects of insulin and sulfonylureas; The combination of use of metformin and iodinated contrast media are contraindicated as it increases the risk of lactic acidosis; also avoid in pts with hepatic impairment or renal impairment; previous lactic acidosis; not associated with Weight gain but annoying with lactic acidosis

basic compund Lowers postprandial blood glucose levels by delaying absorption of carbohydrates. Do not significantly inhibit intestinal lactase; inhibit the digestion of carbohydrates in the small intestine and therefore decrease the postprandial rise in glucose levels not available in Canada Do not cause hypoglycemia, but can potentiate the hypoglycemic effects of insulin and sulfonylureas; May elevate the serum transaminase enzyme level---monitoring AST level.

acidic compounds stimulate release of insulin, more rapid onset of action and a shorter duration of action

lowering postprandial glucose levels; Should be taken only with meals

acidic compounds bind to nuclear peroxisome proliferator-activated receptors(PPARs) involved in transcription of insulin-responsive genes and in regulation of adipocyte differentiation and lipid metabolism, enance the synthesis and translocation of glucose transporter proteins, enhance insulin sensitivity, and cause a favotable redistribution of fat. Active only when insulin is present; (no effect for type 1)

Do not cause hypoglycemia, but can potentiate the hypoglycemic effects of insulin and sulfonylureas;

withdrawn from market

treade name Xenical, OTC as alli, inhibitor of pancreatic lipases, an enzyme that breaks down triglycerides in the intestine. Should not be used as monotherapy for glycemic control. A drug designed to treat obesity. Its primary function is preventing the absorption of fats from the human diet, thereby reducing caloric intake. The primary side effects of the drug are gastrointestinal-related, and include steatorrheathat is, oily, loose stools; because orlistat blocks some of the dietary fat from being absorbed, the fat is excreted unchanged in the feces, fecal incontinence, frequent or urgent bowel movements, and flatulence.

an adjunt therapy in combination with insulin or oral antidiabetic agents binds and activates the human GLP-1 receptor, stimulate glucose-dependent insulin synthesis, enhances insulin secretion by the pancreatic cells, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying

slows gastric emptying, does not alter the overall absorption of nutrients; suppression of postprandial glucagon secretion and modulates central process, resulting in a decreased appetide and caloric intake

Glucagon is a polypeptide secreted by the pancreas. It acts to enhance gluconeogenesis and glycogenolysis, thereby causing higher levels of glucose in the blood. Glucagon is used to treat severe hypoglycemia. It is generally administered intramuscularly or intravenously.

-glucosidase inhibitors, biguanide and thiazolidinediones normally have lower chances of hypoglycemia because it is generally associtated with excessive secretion of insulin rather than a low intake of glucose. Those drugs do not stimulate the release insulin. Adrenergic manifestations: Shakiness, anxiety, nervousness, tremor; Palpitations, tachycardia; Sweating, feeling of warmth (diaphoresis); Pallor, coldness, clamminess; Dilated pupils (mydriasis); Feeling of numbness "pins and needles" (parasthaesia) in the fingers; Glucagon manifestations: Hunger, borborygmus; Nausea, vomiting, abdominal discomfort; Headache

Neuroglycopenic manifestations: Abnormal mentation, impaired judgement; Nonspecific dysphoria, anxiety, moodiness, depression, crying; Negativism, irritability, belligerence, combativeness, rage; Personality change, emotional lability; Fatigue, weakness, apathy, lethargy, daydreaming, sleep; Confusion, amnesia, dizziness, delirium; Staring, "glassy" look, blurred vision, double vision; Automatic behavior, also known as automatism; Difficulty speaking, slurred speech; Ataxia, incoordination, sometimes mistaken for "drunkenness"; Focal or general motor deficit, paralysis, hemiparesis; Paresthesia, headache; Stupor, coma, abnormal breathing; Generalized or focal seizures;

highly plasma protein bound, oxidatively metabolized by cytochrome P450 enzymes, may have interactions with: drugs capable of causing plasma protein displacement: fibrates, sulfonamides, phenylbutazone Potassium channel openers: minoxidil and diazoxide drugs capable of inducing or inhibiting cyctochrome P450 enzymes increased risk of lactic acidosis and acute renal failure can occur if metromin is co-administered with: cationic drugs: amiloride, cimetidine, dofetilide, midodrine,morphine, procainamide, quinidine, quinine, ranitidine, triamterene, cancomycin, may interfere with the renal tubular secretion of merformin; iodinated contrast materials corticosteroids

decrease the rate and extent of oral absorption of other drugs owing to their ability to slow gastric emptying. Avoid co-administration with drugs that significantly alter gastric motility:antimuscarinics pramlintide and insulin should not be mixed together but rather administered as separate injections

carbohydrate intolerence of varying severity during pregnancy; It is associated with increased risk of macrosomia (high birth weight), neonatal hypoglycemia, hyperbilirubinemia, hypocalcemia and polycythemia. May also increase the risk of childhood obesity and diabetes in the offspring and the mother. Usually detected towards the end of the second trimester based on the abnormal response to a 75 g oral glucose tolerance test. Should discontinue all oral antihyperglycemic agents, ACE inhibitors, and ARBs before conception; Optimize glycemic control with diet, if necessary insulin.

2-selective adrenergic agonists that induce broncodilation through activation of adenylate cyclase, causing an increase in cAMP levels and resulting in smooth muscle relaxation in the airways.

Block early and late reaction to allergen. Stabilize mast cell membranes and inhibit activation and release of inflammatory mediators from eosinophils and epithelial cells, inhibiting bronchoconstriction caused by exercise and cold dry air. Onset of action: 10-15 min Duration of action: 1-2 hr

Block late reaction to allergen and reduce airway hyperresponsive-ness, Inhibit production of cytokines responsible for initiation of inflammatory cascade,

Block late reaction to allergen and reduce airway hyperresponsive-ness, Inhibit production of cytokines responsible for initiation of inflammatory cascade,

_lukast

Bronchodilators are substances that dilate the bronchi and bronchioles, decreasing airway resistance and thereby facilitating airflow. most useful in obstructive lung diseases, of which asthma and chronic obstructive pulmonary disease are the most common conditions. they might be useful in bronchiolitis. They are often prescribed but of unproven significance in restrictive lung diseases.

Primatene (ephedrine) Proventil (salbutamol = albuterol)

used for smooth muscle relaxation;

Only available as an inhalant, ipratropium bromide relieves acute or new asthma symptoms. Because it has no effect on asthma symptoms when used alone, it is most often paired with a short-acting 2-agonist.

It acts by blocking muscarinic receptors in the lung, inhibiting bronchoconstriction and mucus secretion.

Ipratropium combined with albuterol (salbutamol) (trade names Combivent and Duoneb)

Ipratropium combined with fenoterol (trade names Duovent and Berodual N)

of alkaloids commonly used for their effects as mild stimulants and as bronchodilators, notably in treating the symptoms of asthma. They only inhibit the actions of sleepinessadenosine, making them somewhat less effective as stimulants than sympathomimetic amines. Due to widespread effects, the therapeutic range of xanthines is narrow, a second-line asthma treatment). apeutic level is 10-20 micrograms/mL blood; signs of toxicity include tremor, nausea, nervousness, and tachycardia/arrhythmia.

ted xanthine derivatives include caffeine, paraxanthine, theophylline, and theobromine which inhibit phosphodiesterase and antagonise adenosine. Xanthines are also ery rarely as constituents of nucleic acids.

The main actions: relaxing bronchial smooth muscle increasing heart muscle contractility and efficiency: positive inotropic increasing heart rate: positive chronotropic increasing blood pressure increasing renal blood flow some anti-inflammatory effects central nervous system stimulatory effect mainly on the medullary respiratory center.

Pentoxifylline is a PDE4 inhibitor increasing intracellular cAMP and stimulating PKA activity. It is also a known inhibitor of Tumor necrosis factor-alpha. It is used to treat intermittent claudication resulting from obstructed arteries in the limbs, and vascular dementia. It was also used in alcoholic heptatitis and renal impairment; Pentoxifylline improves blood flow through blood vessels and therefore helps with blood circulation in the arms and legs. For conservative treatment of Peyronie's disease and neuropathic injuries.

Additionally, as a PDE inhibitor, Pentoxifylline may be useful as a treatment for erectile dysfunction. It also helps prevent strokes, can be used in managing sickle cell disease and improves blood flow to the brain. Pentoxifylline has also been used to treat nausea and headaches in the mountains (altitude sickness), and has been shown to reduce mortality in acute alcoholic and non-alcoholic steatohepatitis, presumably through its ability to inhibit TNF-alpha.

The majority of chemotherapeutic drugs: alkylating agents, antimetabolites, anthracyclines, plant alkaloids, topoisomerase inhibitors, and other antitumour agents. All of these drugs affect cell division or DNA synthesis and function in some way. Some newer agents don't directly interfere with DNA. These include monoclonal antibodies and the new tyrosine kinase inhibitors e.g. imatinib mesylate (Gleevec or Glivec), which directly targets a molecular abnormality in certain types of cancer (chronic myelogenous leukemia, gastrointestinal stromal tumors).

Phase-specific agents: M (mitotic inhibitors: Vinca alkaloids; taxanes); G1 (Asparaginase; Prednisone) S (antimetabolites); G2 (Bleomycin; etoposide) Phase-nonspecific agents: (alkylating agents, antitumor antibiotics) Cell cycle-nonspecific agents: (carmustine, lomustine, radiation) Bone marrow suppression (myelosuppression, dose-limiting: neutropenia, febrile neutropenia; thromboctopenia, anemia) Dermatological toxicity (alopecia; ulceration or necrosis by vesicant chemotheraphy drugs(dactinomycin, daunorubicin, doxorubicin, idarubicin, mechlorethamine, mitomycin, vinblastine, vincristine, and vinorelbine), skin changes) GI toxicities ( nausea and vomiting which may be acute, delayed, or anticipatory; stomatitis)

Tumor lysis syndrome (TLS, the intracellular products from the lysis of cells may lead to renal failure and cardiac arrhythmias; including the uric acid, potassium, and phosphate. It can be prevented by alkalinizing the urine by allopurinol or rasburicase) Hypercalcemia / Chills and fever Pulmonary toxicity ( generally irreversible and may be fatal)---- bleomycin, busulfan, carmustine, mitomycin

Cardiac toxicity (daunorubicin, doxorubicin,epirubicin, mitoxantrone; Dexrazoxane as a cardioprotective agent may be used with doxorubicin); Hypersensitivity reactions (asparaginase, carboplatin, cisplatin, etoposide, paclitaxel, teniposide) Neurotoxicity (Cincristine, cisplatin, cytarabine, methotrexate) Hemorrhagic cystitis (cyclophosphamide, ifosfamide)

___mustin---paltin---sulfan---bazine---quone---amide---

also known as cytophosphane, from the oxazophorines group. It is used to treat various types of cancer and some autoimmune disorders as immunosuppressive agent. It is a "prodrug"; it is converted in the liver to active forms that have chemotherapeutic activity.

being investigated for use in the treatment of melanoma

Streptozocin is an alkylating agent with the capacity to cross-link DNA, thereby inhibiting its synthesis. It is a nitrosourea-like antibiotic that contains a glucosamine moiety that allows it to be selectively taken up by the cells of the islets of Langerhans. Consequently, it can be useful in treating metastatic islet cell carcinoma.

A platinum-based chemotherapy drug used to treat various types of cancers, including sarcomas, some carcinomas (e.g. small cell lung cancer, and ovarian cancer), lymphomas and germ cell tumors. Platinum complexes are formed in cells, which bind and cause Crosslinking of DNA-- ultimately triggering apoptosis.

Nephrotoxicity (kidney damage) is a major concern. The dose is reduced when the pts' creatinine clearance is reduced. Neurotoxicity (nerve damage); Nausea and vomiting: Cisplatin is one of the most emetogenic chemotherapy agents, but this is managed with prophylactic antiemetics (e.g. ondansetron, granisetron, etc.) in combination with corticosteroids. . Ototoxicity (hearing loss): Other ototoxicity drugs (such as the aminoglycoside antibiotic class) should be avoided co-admn. Alopecia (hair loss): this is generally not a major problem in patients treated with cisplatin. Electrolyte disturbance: hypomagnesaemia, hypokalaemia and hypocalcaemia.

used for the treatment of Grade IV astrocytoma -- an aggressive brain tumor, also known as glioblastoma multiforme.

Anthracyclines (Aclarubicin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Amrubicin, Pirarubicin, Valrubicin, Zorubicin) Anthracenediones (Mitoxantrone, Pixantrone) Streptomyces (Actinomycin, Bleomycin, Mitomycin, Plicamycin) Hydroxyurea

Intercalation into DNA, which leads to blockade of DNA and RNA synthesis; DNA strand breaks; free radical formation.

(Daunomycin) used to acute myeloid leukemia and acute lymphocytic leukemia, initially isolated from Streptomyces peucetius.

(liposomal) (Adriamycin) (liposomal)

used only to treat bladder cancer

al analogs of naturally occurring substrates for biochemical ractions----inhibit DNA synthesis by acting as false substitutions

d (Aminopterin, Methotrexate, Pemetrexed, Raltitrexed) Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Pentostatin, Thioguanine)----rabine, ribine ne (Cytarabine, Decitabine, Fluorouracil/Capecitabine, Floxuridine, Gemcitabine, Enocitabine, Sapacitabine) --tabine

MTX, is an antimetabolite and antifolate drug used in treatment of cancer and autoimmune diseases. It acts by inhibiting the metabolism of folic acid. Methotrexate replaced the more powerful and toxic antifolate aminopterin, and the two should not be confused with each other.

5-FU; Side effects: myelosuppression, mucositis, dermatitis, diarrhea and cardiac toxicity. Do not confused with HMG CoA reductase inhibitors (Stastins: -astatin ----lovastatin

s (Docetaxel, Larotaxel, Ortataxel, Paclitaxel, Tesetaxel) kaloids (Vinblastine, Vincristine, Vinflunine, Vindesine, Vinorelbine) Ixabepilone

xel stop mito

inhibition cell division by promoting microtubule assembly and stabilization,

Before initiating therapy, the pts need to be pretreated with corticosteroid, diphenhydramine, or H2-receptor antagonists to prevent the hypersensitivity reactions that are generally associated with the use of Taxels; Complete AV block, syncope, angioedema, and dyspnea are reported side effects of the drug.

arrest cell division by preventing microtubule formation Low incidence of nausea and vomiting. (10%)

Camptotheca (Camptothecin, Topotecan, Irinotecan, Rubitecan, Belotecan) Podophyllum (Etoposide, Teniposide)

a topoisomerase 1 inhibitor. It is used to treat ovarian cancer and lung cancer, as well as other cancer types.

an inhibitor of the enzyme topoisomerase II. Chemotherapy for malignancies such as Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs. It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.

Axitinib Bosutinib Cediranib Dasatinib Erlotinib Gefitinib Imatinib Lapatinib Lestaurtinib Nilotinib Semaxanib Sorafenib Sunitinib Vandetanib

evulinic acid/Methyl aminolevulinate Efaproxiral Porphyrin derivatives (Porfimer sodium, Talaporfin, Temoporfin, Verteporfin)

all-trans retinoic acid

proteosome inhibitor

as an angiogenesis inhibitor by interfering with the growth of new blood vessels needed for tumor growth and survial; inhibits the production of tumor necrosis factor alpha (TNF-a) production --- causes oxidative damage to DNA; stimulate human T cells. Used in multiple myeloma

soluble factors secreted or released by cells that affect the acitvity of other cells and/or the secreting cell itself. Generally act as regulatory or hematopoietic growth factors

identify cancer-specific antigens binding to the cancer cells, allowing immune system to eliminate those cells.

a monoclonal antibody made by Genentech / Novartis and used mainly in allergy-related asthma therapy, with the purpose of reducing allergic hypersensitivity. Xolair (Omalizumab) is a recombinant DNA-derived humanized IgG1k monoclonal antibody that selectively binds to human immunoglobulin E (IgE). IgE is commonly involved with allergies when present in high amounts in the body. Titanium dioxide is the most widely used white pigment because of its brightness and very high refractive index (n=2.7), in which it is surpassed only by a few other materials.

widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection in transplants of skin, heart, kidney, liver, lung, pancreas, bone marrow and small intestine. Also used in inflammatory bowel disease; psoriasis, renal impairment, rheumatoid arthritis;

Glucocorticoids suppress the cell-mediated immunity. They act by inhibiting genes that code for the cytokines IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-8 and IFN-, the most important of which is IL-2. Smaller cytokine production reduces the T cell proliferation. Glucocorticoids do however not only reduce T cell proliferation, another well known effect is glucocorticoid induced apoptosis. The effect is more prominent in immature T cells that still reside in the thymus, but also affect peripheral T cells.

Cytostatics inhibit cell division. In immunotherapy, they are used in smaller doses than in the treatment of malignant diseases. They affect the proliferation of both T cells and B cells. Due to their highest effectiveness, purine analogs are most frequently administered.

nitrogen mustards (cyclophosphamide), nitrosoureas, platinum compounds, and others. Cyclophosphamide is probably the most potent immunosuppressive compound. folic acid analogues, such as methotrexate purine analogues such as azathioprine and mercaptopurine pyrimidine analogues protein synthesis inhibitors.

As a folic acid analogue it act as an antagonist. It binds dihydrofolate reductase and prevents synthesis of tetrahydrofolate. It is used in the treatment of autoimmune diseases (for example rheumatoid arthritis) and in transplantations. It may raise the uric acid concentration, should be carefully used in pts with gout.

The main immunosuppressive cytotoxic substance. It is extensively used to control transplant rejection reactions. It is nonenzymatically cleaved to mercaptopurine, that acts as a purine analogue and an inhibitor of DNA synthesis. Mercaptopurine itself can also be administered directly. By preventing the clonal expansion of lymphocytes in the induction phase of the immune response, it affects both the cell and the humoral immunity. It is also efficient in the treatment of autoimmune diseases.

actinomycin is the most important. It is used in kidney transplantations. Other cytotoxic antibiotics are anthracyclines, mitomycin C, bleomycin, mithramycin.

used as a quick and potent immunosuppression method to prevent the acute rejection reaction.

nal antibodies

onal antibodies

ceptor directed antibodies

eptor directed antibodies

widely used in post-allogeneic organ transplant to reduce the activity of the patient's immune system and so the risk of organ rejection in transplants of skin, heart, kidney, liver, lung, pancreas, bone marrow and small intestine. Also used in inflammatory bowel disease; psoriasis, renal impairment, rheumatoid arthritis and many other autoimmune disorders.

D_D of cyclosporine: CYP inducers: Phenytoin, Phenobarbital, Caramazepine, Rifampin, Isoniazid, St. John's Wort CYP inhibitors: Ketocinazole, fluconazole, itraconazole, erythromycin, Josamycin, Verapamil, Diltiazem, Nicardipine, Grapefruit juice;

A fungal product (Streptomyces tsukubaensis). It is a macrolide lactone and acts by inhibiting calcineurin. Used particularly in the liver and kidney transplantations, also in heart, lung and heart/lung transplants. It binds to an immunophilin, followed by the binding of the complex to calcineurin and the inhibition of its phosphatase activity--- prevents the cell from transitioning from the G0 into G1 phase of the cell cycle. Tacrolimus is more potent than cyclosporin and has less-pronounced side-effects.

Muromonab-CD3

used to treat psoriasis. a recombinant humanized monoclonal antibody that binds to CD11a and acts as an immunosuppressant. It is administered once weekly by subcutaneous injection. Anti-thymocyte globulin Anti-lymphocyte globulin

Abatacept Aflibercept Alefacept Belatacept Rilonacept TNF inhibitor Etanercept

Mammalian target of rapamycin Sirolimus Deforolimus Everolimus Temsirolimus Zotarolimus

To block the action of histamine on parietal cells in the stomach, decreasing the production of acid by these cells. H2 antagonist are used in the treatment of dyspepsia, although they have largely been surpassed in popularity by the more effective proton pump inhibitors. In the United States, all four FDA-approved members of the groupcimetidine, ranitidine, famotidine, and nizatidineare available over the counter in relatively low doses. Like the H1-antihistamines, the H2 antagonists are inverse agonists rather than true receptor antagonists.

H2-antagonists are clinically used in the treatment of acid-related Gastrointestinal conditions: Peptic ulcer disease (PUD) Gastroesophageal reflux disease (GERD) Dyspepsia Prevention of stress ulcer (a specific indication of ranitidine)

Cimetidine is an inhibitor of the P450 enzymes CYP1A2, 2C9, 2C19, 2D6, 2E1, and 3A4. By reducing the metabolism of drugs through these enzymes, cimetidine may increase their serum concentrations to toxic levels. Many drugs are affected, including warfarin, theophylline, phenytoin, lidocaine, quinidine, propranolol, labetalol, metoprolol, tricyclic antidepressants, some benzodiazepines, dihydropyridine calcium channel blockers, sulfonylureas, metronidazole, and some recreational drugs such as ethanol and MDMA. Cimetidine should be used with caution in cases of hepatic impairment and cardiovascular disease Cimetidine may also cause gynecomastia in males, loss of libido, and impotence, which are reversible upon discontinuation.

longer-acting H2-receptor antagonists

also called Gastro-oesophageal reflux disease (GORD), defined as chronic symptoms or mucosal damage produced by the abnormal reflux in the esophagus. This is commonly due to transient or permanent changes in the barrier between the esophagus and the stomac. If the reflux reaches the throat, it is called laryngopharyngeal reflux disease. The most-common symptoms: heartburn, regurgitation, trouble swallowing (dysphagia), and chest pain; Pain with swallowing (odynophagia), excessive salivation, and nausea also may occur. GERD sometimes causes injury of the esophagus: Reflux esophagitis; Esophageal strictures; Barrett's esophagus; Esophageal adenocarcinomaa rare form of cancer.

Proton pump inhibitors act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (gastric proton pump) of the gastric parietal cell. Targeting the terminal-step in acid production, as well as the irreversible nature of the inhibition, result in a class of drugs that are significantly more effective than H2 antagonists and reduce gastric acid secretion by up to 99%. They are the most potent inhibitors of acid secretion available today. Structurally, the vast majority of these drugs are benzimidazole derivatives

These drugs are utilized in the treatment of many conditions such as: Dyspepsia Peptic ulcer disease (PUD) Gastroesophageal reflux disease (GORD/GERD) Laryngopharyngeal Reflux Disease Barrett's esophagus prevention of stress gastritis Gastrinomas and other conditions that cause hypersecretion of acid Zollinger-Ellison syndrome (brand names: Losec, Prilosec, Zegerid, ocid) Omeprazole is combined with the antibiotics clarithromycin and amoxicillin (or metronidazole in penicillin-hypersensitive patients) in the 7-14 day eradication triple therapy for Helicobacter pylori.

(brand names: Prevacid, Zoton, Inhibitol)

(brand names: Nexium)

(brand names: Protonix, Somac, Pantoloc, Pantozol, Zurcal, Pan)

(brand names: Rabecid, Aciphex, Pariet, Rabeloc)

an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers. Sulcrate in Canada. Sucralfate is also used for the treatment of GERD and stress ulcers. Unlike the other classes of medications used for treatment of peptic ulcers, sucralfate is a sucrose sulfate-aluminium complex that binds to the hydrochloric acid in the stomach and acts like an acid buffer with cytoprotective properties. The most common side effects: constipation and bezoar formation. Less commonly reported: flatulence, cephalalgia (headache), hypophosphatemia, and xerostomia (dry mouth).

Used on the digestive system. It includes all drugs whose primary effect is to augment the speed of intestinal transit, by increasing the frequency of contractions in the small intestine or making them stronger, but without disrupting their rhythm. They are mostly used to treat or prevent pathological gastroesophageal reflux, or to speed up absorption of certain other drugs. Some of them can also be used to help in the treatment of nausea or other symptoms associated with dyspepsia.

These drugs may increase acetylcholine concentrations by inhibiting dopamine D2 receptors and acetylcholinesterase. Higher acetylcholine would increase GI peristalsis and further increase the lower esophageal sphincter pressure, thereby stimulating gastric motility and accelerating gastric emptying and improve gastro-duodenal coordination. Some of these drugs may or may not have affinity for the 5-HT4 receptors depending on their class such as some benzamides like cisapride and mosapride which are 5-HT4 agonists. The affinity of cisapride for 5-HT4 receptors in the heart has been implicated as a potential cause of cardiac arrhythmias.

Dopamine antagonists; used orally, rectally or intravenously, generally to suppress nausea and vomiting. It has also been used to stimulate lactation. Parkinson's disease: does not cross the blood-brain barrier.

(Reglan) bind to dopamine D2 receptors where it is a receptor antagonist, Also a mixed 5-HT3 receptor antagonist / 5-HT4 receptor agonist.

(withdrawn for human use in the US)

used to treat nausea, heartburn, indigestion, diarrhea, and other temporary discomforts of the stomach and gastrointestinal tract. Commonly known as pink bismuth, it is the active ingredient in popular medications such as Pepto-Bismol and (modern) Kaopectate. As a derivative of salicylic acid, bismuth salicylate displays anti-inflammatory action and also acts as an antacid.

A drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), by the respective PDE subtype(s).

caffeine, a minor stimulant theophylline, a bronchodilator IBMX (3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research

EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine) used clinically for short-term treatment of cardiac failure(CHF). These drugs mimic sympathetic stimulation and increase cardiac output. PDE3 is sometimes referred to as cGMP-inhibited phosphodiesterase. PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells. PDE4 inhibitors have proven potential as anti-inflammatory drugs, especially in inflammatory pulmonary diseases such as asthma, COPD and rhinitis. They suppress the release of cytokines and other inflammatory signals and inhibit the production of reactive oxygen species. PDE4 inhibitors may have antidepressive effects[5] and have also recently been proposed for use as antipsychotics.

a neuroprotective and bronchodilator drug used mainly in the treatment of asthma and stroke. It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor depending on the dose.

Pentoxifylline is a xanthine derivative (see above); a drug that potentially enhances circulation and may have applicability in treatment of diabetes, fibrotic disorders, peripheral nerve damage, peripheral vascular and microvascular injuries; As a hemorrheologic agent, it can affect the blood viscosity.

A phosphodiesterase type 5 inhibitor is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. These drugs are used in the treatment of erectile dysfunction, and were the first effective oral treatment available for the condition. Because PDE5 is also present in the arterial wall smooth muscle within the lungs, PDE5 inhibitors have also been explored for the treatment of pulmonary hypertension, a disease in which blood vessels in the lungs become abnormally narrow.

The occurrence ADRs with PDE5 inhibitors appears to be dose related. Headache is a very common ADR, occurring in >10% of patients. Other common ADRs include: dizziness, flushing, dyspepsia, nasal congestion or rhinitis.[2] A warning about possible sudden hearing loss and anterior optic neuropathy would be added to drug labels of PDE5 inhibitors. Organic nitrates are contraindicated when used with sildenafil. PDE5 inhibitors are contraindicated in those taking nitrate medication. They are also contraindicated in men for whom sexual intercourse is inadvisable due to cardiovascular risk factors. PDE5 inhibitors are primarily metabolised by the cytochrome P450 enzyme CYP3A4. The potential exists for adverse drug interactions with other drugs which inhibit or induce CYP3A4, including HIV protease inhibitors, ketoconazole, itraconazole, and other anti-hypertensive drugs such as Nitro-spray (due to its capacity to diminish blood pressure).

the pharmaceutical name for prostaglandin E1. and normally relaxes teh smooth muscles of the ductus arteriosus and has vasodilatory properties. It is used as a drug in the treatment of erectile dysfunction. It is indicated to temporarily maintain the potency of ductus arteriosus until surgery can be performed (IV indomethacin is also an option); Side effects: apnea, cardia arrest, flushing, fever and sepsis;

drugs that block the action of proteasomes, cellular complexes that break down proteins, like the p53 protein. Proteasome inhibitors are being studied in the treatment of cancer. In 2003, bortezomib was the first proteasome inhibitor to be approved for use in the U.S.

The first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease. Bortezomib is associated with peripheral neuropathy in 30% of patients; occasionally, it can be painful. This can be worse in patients with pre-existing neuropathy. In addition, myelosuppression as neutropenia and thrombocytopenia can also occur and be dose limiting.

An aphrodisiac is a substance which is used in the belief that it increases sexual desire. [7AfrEu5diziAk]

Yohimbine Hydrochloride is a selective competitive alpha-2 adrenergic receptor antagonist. The alpha-2 receptor is responsible for sensing adrenaline and noradrenaline and telling the body to decrease its production as part of a negative feedback loop. It is a prescription medicine that has been used to treat erectile dysfunction.

Stimulants affecting the dopamine system such as cocaine and amphetamines (e.g. methamphetamine, aka crystal meth) are frequently associated with hyperarousal and hypersexuality, though both may impair sexual functioning, particularly with long term use. A newer dopamine reuptake inhibitor MDPV has also been noted to have characteristic hypersexual effects. Some directly acting dopamine agonists may also cause increased libido, although they can also cause various side effects. Pramipexole is the only dopamine agonist used in medicine as an aphrodisiac, and is sometimes prescribed to counteract the decrease in libido associated with SSRI antidepressant drugs.

Sibutramine (Meridia), mazindol (Sanorex, Mazanor), and benzphetamine (Didrex) are central nervous system stimulants used as anorexiants, ie, they are used to reduce appetite and used for obesity. mechanism: serotonin/NE reuptake inhibitor; phentermine: also dopamine release side effect: heart rate, blood pressue, constipation, dry mouth, headache, insomnia drug interaction: MAOI (selegiline and rasagiline) ; SSRI (fluoxetine); Serotonin agonist (sumatriptan-used for migraine); erythromycin, cimetidine)

CYP450 ( ketoconazole,

It is approved as an appetite suppressant to help reduce weight in obese patients when used short-term and combined with exercise, diet, and behavioral modification. It is typically prescribed for individuals who are at increased medical risk because of their weight and works by helping to release certain chemicals in the brain that control appetite.

Benzphetamine (brand name Didrex) is an anti-obesity drug marketed under this brand in the USA by Pharmacia. Benzphetamine is used as a short term adjunct in management of exogenous obesity. It is closely related to amphetamine. It works on the hypothalamus portion of the brain to release norepinephrine, a neurotransmitter that signals a fight-or-flight response, reducing hunger.It works outside the brain to release epinephrine or adrenaline causing fat cells to break down stored fat, but the principal basis of efficacy is hunger-reduction.

sympathomimetic drugs that have a mild appetite-suppressant effect and can be used for short-term induction of weight loss.

trade name Meridia in the U.S. and Canada, an orally administered agent for the treatment of obesity, as an appetite suppressant. It is a centrally-acting serotonin-norepinephrine reuptake inhibitor, It is classified as a Schedule IV controlled substance in the United States.

Act as lipase inhibitor which is responsible for breakdown fat into smaller moleculars. Also used as an adjunt therapy in diabetes. side effect: oil spotting; flatulence with discharge; fecal urgency; increased with defecation, b-carotene, carotenoid absorption contradiction: cholestasis patient

Mazindol is a central nervous system stimulant. It is used in short-term (i.e., a few weeks) treatment of exogenous obesity, in combination with a regimen of weight reduction based on caloric restriction, exercise, and behavior modification in patients with a BMI 30, or in patients with a BMI 27 in the presence of risk factors such as hypertension, diabetes, or hyperlipidemia.

Benzphetamine (brand name Didrex) is an anti-obesity drug marketed under this brand in the USA by Pharmacia. Benzphetamine is used as a short term adjunct in management of exogenous obesity. It is closely related to amphetamine.

DMARDs is a category of otherwise unrelated drugs defined by their use in rheumatoid arthritis to slow down disease progression. The term is often used in contrast to non-steroidal anti-inflammatory drug, which refers to agents that treat the inflammation but not the underlying cause. Although their use was first propagated in rheumatoid arthritis (hence their name) the term has come to include many other diseases, such as Crohn's disease, lupus erythematosus (SLE), idiopathic thrombocytopenic purpura (ITP), myasthenia gravis and various others. Many of these are autoimmune disorders, but others, such as ulcerative colitis, are not.

Hydroxychloroquine (HCQ) Methotrexate (MTX) TNF inhibitor; a fully human monoclonal antibody, Used for: rheumatoid or psoriatic arthritis, ankylosing spondylitis, Crohn's disease, moderate to severe chronic psoriasis and juvenile idiopathic arthritis. Side effects: serious and sometimes fatal blood disorders; serious infections including include TB (tuberculosis) and infections caused by viruses, fungi, or bacteria; Purine synthesis inhibitor (antimalarials) (Cyclosporin A) inhibit calcineurin

Reducing numbers of T-lymphocytes etc. TNF inhibitor (sodium aurothiomalate, auranofin) TNF inhibitor Pyrimidine synthesis inhibitor (MTX) Antifolate 5-LO inhibitor (SSZ)

an interleukin-1 receptor antagonist. It antagonizes the inflammation and pain associated with R. arthritis. The recommended dose of the drug is 100 mg SC daily. Erythema, pruritus, rash and pain are commonly reported side effects of the lung.

also called: diphosphonates) are a class of drugs that inhibit osteoclast action and the resorption of bone. Its uses include the prevention and treatment of osteoporosis, osteitis deformans ("Paget's disease of bone"), bone metastasis (with or without hypercalcaemia), multiple myeloma, osteogenesis imperfecta and other conditions that feature bone fragility. Bisphosphonates, when attached to bone tissue, are "ingested" by osteoclasts, the bone cell that breaks down bone tissue. Bisphosphonates are used clinically for the treatment of osteoporosis, osteitis deformans (Paget's disease of the bone), bone metastasis (with or without hypercalcaemia), multiple myeloma and other conditions that feature bone fragility. The non-nitrogenous bisphosphonates(disphosphonates) are metabolised in the cell to compounds that replace the terminal pyrophosphate moiety of ATP, forming a nonfunctional molecule that competes with adenosine triphosphate (ATP) in the cellular energy metabolism. The osteoclast initiates apoptosis and dies, leading to an overall decrease in the breakdown of bone. (Didronel) - 1 (potency relative to that of etidronate) (Bonefos, Loron) - 10 (Skelid) - 10

Nitrogenous bisphosphonates act on bone metabolism by binding and blocking the enzyme farnesyl diphosphate synthase (FPPS) in the HMG-CoA reductase pathway (also known as the mevalonate pathway.

nate (APD, Aredia) - 100

nate (Fosamax) - 500

nate (Bonviva) - 1000

nate (Actonel) - 2000

(Zometa, Aclasta) - 10000 Used to prevent skeletal fractures, hypercalcemia of malignancy; prevent recurring fractures; Paget's disease of bone; postmenopausal osteoporosis.

Lactase enzyme is effective in treating symptoms of lactose intolerance. These symptoms are most evident shortly after consuming a lactose-containing food and may include bloating and diarrhea. Lactase enzyme is available as a liquid (Lactaid), caplets (Lactaid), capsules (Lactrase), or as chewable tablets (Dairy Ease). It is also added to some commercial dairy products.

is a synthetic product of tachysterol, a substance similar to vitamin D. It is used in combination with calcium and parathyroid hormone in the treatment of hypoparathyroidism. It is activated in the liver that does not require renal hydroxylation like vitamin D2 (ergocalciferol) and vitamin D3 (cholecalciferol). DHT has a rapid onset of action (2 hours), a shorter half-life, and a greater effect on mineralization of bone salts than does vitamin D.

Desmopressin acetate (DDAVP) is the synthetic analog of naturally occurring human antidiuretic hormone (ADH) produced by the posterior pituitary gland. It is administered intranasally for the treatment of primary nocturnal enuresis. A single dose of the drug will produce an antidiuretic effect lasting from 8 to 20 hours. Desmopressin can be used to promote the release of von Willebrand factor and factor VIII in patients with coagulation disorders such as type I von Willebrand disease, mild hemophilia A, and thrombocytopenia. It is not effective in the treatment of hemophilia B or severe hemophilia A. Desmopressin is also used to reduce urine production in central diabetes insipidus patients.

Permethrin (Nix, Elimite) is a topical scabicide and pediculocide. It acts by disrupting the nerve cell membranes of parasites, resulting in their paralysis. Permethrin is widely used as an insect repellent. It belongs to the family of pyrethroids and functions as a neurotoxin, affecting neuron membranes by prolonging sodium channel activation. It is not known to harm most mammals or birds. It generally has a low mammalian toxicity and is poorly absorbed by skin.

Lypressin (Diapid) is a synthetic vasopressin analog possessing antidiuretic activity without producing a pressor or oxytocic effect. It is used clinically in the management of symptoms of diabetes insipidus. Lypressin is administered as a nasal spray.

Dyphylline is a theophylline derivative. These agents act by inhibiting the enzyme phosphodiesterase, thereby increasing cyclicAMP levels and producing bronchodilation.

Loperamide, a synthetic piperidine derivative, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor and Pepto Diarrhea Control. It was discovered at Janssen Pharmaceutica in 1969. Loperamide is an opioid receptor agonist and acts on the -opioid receptors in the myenteric plexus large intestines; it does not affect the CNS like other opioids. Treatment should be avoided in the presence of fever or if the stool is bloody. Treatment is not recommended for patients who could suffer detrimental effects from rebound constipation. If there is a suspicion of diarrhea associated with organisms that can penetrate the intestinal walls, such as E. coli O157:H7 or salmonella, loperamide is contraindicated.

Also glyceryl guaiacolate, is an expectorant drug sold OTC and usually taken by mouth to assist the bringing up ("expectoration") of phlegm from the airways in acute respiratory tract infections. The principal use of guaifenesin is in the treatment of coughing, but the drug has numerous other uses, including the thickened bronchial mucosa characteristic of asthma, gout (as a uricosuric, increasing excretion of uric acid from the blood serum into the urine), fibromyalgia; also widely used by women to facilitiate conception by thinning and increasing the amount of cervical mucus; Opera singers sometimes refer to guaifenesin as the "wonder drug" for its ability to promote secondary mucosal secretion in the respiratory system.

Phenazopyridine is a chemical which, when secreted into the urine, has a specifical local analgesic effect. It is often used to alleviate the pain, irritation, discomfort, or urgency caused by urinary tract infections, surgery, or injury to the urinary tract. Dangerous and prohibited for G6PD deficiency patients. A distinct color change in the urine, typically to a dark orange to reddish color. This effect is common and harmless, and indeed a key indicator of the presence of the drug in the body. Users of phenazopyridine are warned not to wear contact lenses, as phenazopyridine has been known to permanently discolor contact lenses and fabrics. Others: headaches, upset stomach (especially when not taken with food), or dizziness; a pigment change in the skin or eyes, to a noticeable yellowish color; fever, confusion, shortness of breath, skin rash, and swelling of the face, fingers, feet, or legs.

Clofazimine is a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy (MDT) for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients and Mycobacterium avium paratuberculosis infection in Crohn's disease patients May cause pink-to-brownish skin pitmentation within a few weeks of the initiation of therapy. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum (ENL).

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antibacterial agents

antibacterial agents

spectrum of activity

Therapeutic uses

Mechanism of action

gram stain

gram-positive: blue or purple----posi---purp

gram-negative: red or rose-pink----neg---red

aminoglycoside

G-, little activity on anaerobic and facultative organisms

streptomycin

G+, GPlague, tularemia ( rabbit fever, G+ gterptococci, bacterial endocarditis (comb. with penicillin) mycobaterium tuberculosis,

bactericidal, inhibit protein synthesis by binding to and impeding the function of the 30S(some are 50S) ribosomal subunit preventing the formation of the initiation complex and interfering with the accuracy of translation and translocation; Aminoglycosides initially diffuse passively across the bacterial plague, tularemia, acute outer membrane and are then actively brucellosis(combi. With transported into the cytoplasm, This tetracycline). Bacterial endocarditis active transport is inhibited in low pH or caused by Streptococcis viridans anaerobic conditions. (comb. with penicillin), tuberculosis(comb. with other post-antibiotic effect ; antitubercular agents)

Aminoglycosides are parenteral antibiotics most widely used in the treatment of infections due to enteric gramnegative bacteria, However, aminoglycosides are often used in combination with cell w lactams or vancomycin for treatment of endocarditis. Because aminoglycosides are inhibited in acidic or anaerobic conditions, aminoglycosides are not active against anaerobic bacteria or in low p necrotic tissue,

Aminoglycosides are most notably associated with ototoxicity and nephrotoxicity and have a narrow therapeutic window, Risk factors include prolonged therapy, preexisting renal dysfunction, elder other ototoxic or nephrotoxic agents. Ototoxicity typically presents as cochlear ( tinnitus, high-frequency hearing loss) and, not as commonly, vestibular toxicity (vertigo, ataxia), Nephrotoxic presents as an increase in serum creatinine or a decrease in creatinine clearance. Rarely, in high doses, aminoglycosides can cause neuromuscular paralysis due to a concentration-dependent inhibition of presynaptic release and postsynaptic binding of acetylcholine, This can lead to tingling, muscle paralysis, and apnea. There are two dosing regimens used for aminoglycosides: once daily and conventional (three times daily), Because aminoglycosides exhibit concentration-dependent killing, increasing concentrations kill an increasing proportion of bacteria. In addition, aminoglycosides exhibit a postantibiotic effect. Thus, antibacterial activity persists even when the drug falls below levels that are detectable in serum, By dosing aminoglycosides once daily, higher peak concentrations are achieved, leading to a more rapid bactericidal effect and longer postantibiotic effect. The less frequent dosing of once-daily aminoglycosides leads to lower or nondetectable trough concentrations and may lead to less nephrotoxicity.

Amikacin, gentamicin

G- broadest spect. serratia

serious G- bacillary infections, pneumonia (comb. With cephalosporin or penicillin), meningitis, complicated UTI, oesteomyelitis, bacteremia, peritonitis

tobramycin netilmicin

pseudomonas aeruginosa gentamicin-resistant organism, less ototoxic G-, G+(S. aureus) P. aeruginosa and most streptococci are now neomycin resistant

pneumonia (comb. With cephalosporin or penicillin), meningitis, complicated UTI, oesteomyelitis, bacteremia, peritonitis

neomycin

preoperative bowel sterilization, hepatic coma, topical form for skin and mucous infections

Kanamycin

ototoxicity: Strepto- = Kana- > Amika- = gentamicin = tobra- > netilmicin

carbapenem

broadest spect., most G+ cocci, Gcontain beita-lactam ring and a 5rods(including some P. aeruginosa strains), membered ring system anaerobes severe infections by drug-resistance prganisms; urinary tract and lower imipenem( cilastatin respiratory infections, intrainhibting bacterial cell wall synthesis meropenem abdominal and gynecological (cilastatin, a dipeptidase inhibitor) infections, skin, soft-tissue, bone, and joint infections ertapenem

Faropenem (not a carbapenem) Doripenem Panipenem/betamipron Biapenem 1: G+; 2: G+/ G3: G4: G- G+

cephalosporins

time-above-MIC-dependent bacterial killing

bactericidal, inhibting bacterial cell wall synthesis, reducing cell wall stability and thus causing membrane lysis

first geneation

most G+ cocci (except enterococci) and cefazolin, cephalexin, cephradine enteric aerobic G- bacilli(E. coli, K. cephadroxil, cephapirin pneumoniae, Proteus mirabilis

serious Klebsiella infetions other G+ infections; widely used in perioperative prophylaxis GI ( nausea, vomiting, diarrhea) superinfection, nephrotoxicity,

second geneation

cefaclor, cefmetazole, cefuroxime, covered 1st-generation, extended G-(bcefotetan, cefprozil, cefoxitin, lactamase-producing strains of loracarbef Haemophilus influenzae

UTI from E. coli, acute otitis media, Clostridium difficile-indeced colitis; sinusitis, gonococcal disease Except cefoperazone hapatic elimination, the others renally eliminated, need adjust for renal-impariment patients cross-sensityvity bleeding diatheses

false-positive glycosuria results on tests using the copper-reduction method; false-positive results in Coomb's test

Except cefoperazone hapatic elimination, the others renally eliminated, need adjust for renal-impariment patients cross-sensityvity cefdinir, cefoperazone. cefotaxime, ceftazidime, ceftriaxone, ceftibuten, cefixime, cefditoren cefpodoxime, bleeding diatheses most G- (Enterobacter, Citrobacter, Serratia, Providencia, Neisseria, Haemophilus organisms, including blactamase-producing strains meningitis mixed bacterial infections(e.g., sepsis)

third geneation

false-positive glycosuria results on tests using the copper-reduction method; false-positive results in Coomb's test

fourth geneation

cefepime cefpirome

more resistent to b-lactamases; greater activity in G- cocci, Enterobacteriaceae, and Pseudomonas than 3rd generation

Macrolides
erythromycin,

---thromycin

G+ (including S. aureus, streptococci; Corynebacterium), G- : Neisseria species, Legionella, and Bordetella; other strains: Mycoplasma, Treponema, azithromycin more active for H. influenzae and G- organisms

mycoplasma pneumoniae,

camphlobacter infections, legionnaries disease, chlamydial infection, diphtheria, pertussis

bactericidal or bacteriostatic; inhibit protein synthesis by binding to and impeding the function of the 50S ribosomal subunit

P450 system (CYP3A4) inhibitor: h simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor) levels (erythromycin and simvastatin: potential for rhab ergotamine and dihydroergotamine may be more pronounced if erythromycin is associated inhibiting the meatbolism of theophylline---toxic accumulation interferes with the metabolism of digoxin, corticosteroids, carbamazepine, cyclosporin, lovastatin; Co.-adm. of clarithromycin and cisapride may incresase risk of serious cardiac arrhythmias; Sudden death was reported with co-adm. pimozide therapy

erythromycin estolate; ethylsuccinate;sterate; gluceptate and lactobionate

erythromycin estolate has been associated with cholestasis. hepatotoxicity for other salts

azithromycin,

less active against G- cocci, but more active nongonococcal urethritis caused by chlamydia, lower respiratory tract in other G-; Concertrates within cells, and infections, MAC infection and prophylaxis, pharyngitis, pelvis inflammatory tissue levels are higher than serum levels disease, legionnaires' disease, also used for pediatric

Mycobacterium avium complex(MAC) infection, Otitis media, sinusitis, mycoplasmal pneumonia, and pharyngitis, also used with PPIs for Helicobacter pylori eradication; more active with staphylococci and streptococci; also active against MAI, Toxoplasma gondii, and Cryptosporidium spp. used to treat pharyngitis, tonsillitis, acute maxillary sinusitis, acute bacterial exacerbation of chronic bronchitis, pneumonia (especially atypical pneumonias associated with Chlamydia pneumoniae or TWAR), skin and skin structure infections, and, in HIV and AIDS patients to prevent, and to treat, disseminated Mycobacterium avium complex (MAC). In addition, it is sometimes used to treat Legionellosis.

clarithromycin

Contraindicated with pimozide; Rifampin can h macrolide concentrations; May h warfarin effects; h concentrations of benzodiazepines, buspirone, carbamazepine, cyclosporine, digoxin disopyramide, ergots, statins, theophylline dirithromycin

Penicillin
Natural penicillins G+ cocci & some G- cocci

bactericidal; inhibting bacterial cell wall synthesis,

Penicillin G Na / K Benzylpenicillin

PG 5-10 times active than PV against Gand some anaerobic. Ineffective against S. aureus and other resistance organism

sensitive organism( S. pneumoniae ) caused Pneumonia, arthritis, meningitis, peritonitis, pericarditis, osteomyelitis, mastoiditis

Given by a parenteral route (not orally) because it is unstable in the hydrochloric acid of the stomach. Higher tissue concentrations of penicillin G can be achieved via parenteral route to increased antibacterial activity.

PG prefered in gonococcal infections, syphilis, anthrax, actinomycosis, gas gangrene, and Listeria infections; PG procaine for syphilis and uncomplicated gonorrhea; Penicillin G procaine or benzathine (12-24hr action PG/V highly effective in streptococcal infections: pharyngitis, otitis media, sinusitis, and bacteremia, PG/V prophylactically to prevent streptococcal infection, rheumatic fever, neonatal gonorrhea ophthalmia

a repository form, IM, insoluble salts alow slow drug absorption from the injection site and have a long action

Penicillin V ( oral)
Phenoxymethylpenicillin

the first choice for odontogenic infections.

in skin, soft-tissue, and mild respiratory infections

orally active form

penicillinase-resistant penicillin

methi--naf---clo--oxa cloxa-naf-methy

not hydrolyzed by staphylococcal penicillinases

used solely in staphylococcal infections resulting from resistance organisms

methicillin nafcillin cloxacillin hepatic elimination

isoxazolyl penicillins dicloxacillin

oxacillin

aminopenicillin

broad-spectrum penicillin AM-broad-cast ampicillin combination with sulbactam combination with clavulanic acid more acid stable than ampicillin

gonococcal infections upper respiratory infections uncomplicatied UTI otitis media

amoxicillin

extended-spectrum penicillin

ticar-car-piper azlo-mezlo

widest spectrum, Klebsiella and serious infections by G- ( sepsis, enterobacter spp., some B. fragilis pneumonia, infections of abdomen, organisms, and indole-positive Proteus and bone and soft tissues) psedomonas organisms

carboxypenicillin ticarcillin ureidopenicillin mezlocillin, piperacillin

azlocillin carbenicillin mezlocillin piperacillin

combination with clavulanic acid

combination with tazobactam

nosocomial pneumonia

sulfonamides

G-: E. pyogenes, S. pneumoniae certain G+: H. influenzae, E. coli, P. mirabilis combination with pyrimethamine to treat toxoplasmosis

UTI caused by E. coli (acute and chronic cystitis, chronic urinary tract infections)

bacteriostatic: block folic acid synthesis

sulfadiazine

sulfamethoxazole

SMX, combination with trimethoprim in a 5:1 ratio

sulfisoxazole

combination with erythromycin ethylsuccinate

sulfamethizole

Sulfasalazine

Sulfasalazine is mainly used for treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is also effective in several types o arthritis.

Mafenide

Mafenide (INN; usually as mafenide acetate, trade name Sulfamylon) is a sulfonamide often used a bacteriostatic and is active against many gram-positive and gram-negative organisms. Topical products containing mafenide are applied to 2nd- and 3rd-degree burns in order to reduce the chance of infection and increase the speed of healing. (severe burns)

Trimethoprim-Sulfamethoxazole (TMP SMX) Sinomin Co-trimoxazole

Gram-positive organisms, particularly S. aureus; Gram-negative organisms: Haemophilus influenzae, E. coli, Listeria monocytogenes, Moraxella catarrhaJis, and Salmonella species Other organisms: Pneumocystis carinii, Toxoplasma gondii, Nocardia species, and Stenotrophomonas ma/tophilia

SMX interferes with bacterial folic acid syntheses via inhibition of dihydrofolic UTls acid formation from para-aminobenzoic Prostatitis acid. TMP inhibits dilhydrofolic acid Acute otitis media reduction to tetrahydrofolic acid, Exacerbations of chronic bronchitis resulting in sequential inhibition of Treatment and prophylaxis of enzymes of the folic acid pathway. Pneumocystis carinii infections TMP and SMX are synergistic when Traveler's diarrhea used together. toxoplasmosis. Renal elimination as metabolites and unchanged

The presence of food in GI will reduce the absorption of many antibiotics; exceptions: penicillin V K, amoxicillin, Doxycycline and Minocycline. G+, G-, spirochetes, Mycoplasma and Chlamydia organism, Rickettsial species, and certain protozoa bacteriostatic inhibit protein synthesis by binding to and impeding the function of the 30S ribosomal subunit

Tetracyclines

GI distress skin rash phototoxic reactions permanent tooth discoloration,

demeclocycline

adjunctive agent to treat syndrome tooth enamel defects and retarted bone growth in infants and children < 8y of inappropriate antidiuretic hormone(SIADH

doxycycline

Mainly excreted in the feces;

prophylaxis of "traveler's diarrhea" the safest tetracycline for extrarenal infections in pts with renal impairment

minocycline chlortetracycline

The highest incidence of vestibular toxicity among the tetracyclines.

Tigecycline

active to vancomycin-susceptible E. faecalis, methicillin-resistant strains of S. aureus and S. epidermidis

complicated intra-abdominal infections

Tetracyclines may be used in the treatment of infections of the respiratory tract, sinuses, middle ear, urinary tract, intestines, and also gonorrhoea, especially in patients allergic to -l their use for these indications is less popular than it once was due to widespread resistance development in the causative organisms. Their most common current use is in the treatment of moderately severe acne and rosacea (tetracycline, oxytetracycline, doxycycline or minocycline).

Doxycycline is also used as a prophylactic treatment for infection by Bacillus anthracis (anthrax) and is effective against Yersinia pestis, the infectious agent of bubonic plague. It is a prophylaxis, as well as treating elephantiasis.

Tetracyclines remain the treatment of choice for infections caused by chlamydia (trachoma, psittacosis, salpingitis, urethritis and L. venereum infection), Rickettsia (typhus, Rocky Mo and spirochetal infections (borreliosis, syphilis, and Lyme disease). In addition, they may be used to treat anthrax, plague, tularemia, and Legionnaires' disease. They may have a role in reducing the duration and severity of cholera, although drug-resistance is occurring and their effects on overall mortality is questioned. Demeclocycline has an additional use in the treatment of SIADH. Tetracycline derivatives are currently being investigated for the treatment of certain inflammatory disorders.

Fluoroquinolone

enteric G- bacilli, salmonella, shigella, campylobacter, Haemophilus, and Neisseria

concentration-dependant bacterial killing

inhibit DNA gyrase topoisomerase II and topoisomerase IV.

Inhibition of topoisomerases disrupts DNA replication and transcription resulting in bacterial cell death. First generation: UTls; Second and third generations: UTls, prostatitis, respiratory tract infections, sinusitis, infectious diarrhea, uncomplicated skin and skin structure infections, traveler's diarrhea Common side effects: seizure, bradycardia, CNS stimulation, QT interval prolongation and anaphylaxis

warning labels added to all of the Fluoroquinolones:

Wide distribution into body fluids and tissues including the prostate Well tolerated Peripheral Neuropathy (irreversible nerve damage), Tendon Damage, Heart Common adverse effects: CNS side effects (dizziness, headache, Problems (prolonged QT Interval / Torsades de pointes), Pseudomembranous insomnia), rash, nausea, vomiting, photosensitivity, elevated transaminases, colitis, Rhabdomyolysis (muscle wasting), Steven Johnson Syndrome, as well as and tremor. concurrent usage of NSAIDs contributing to the severity of these reactions. Rare side effects: cartilage toxicity, tendon rupture, and QTc prolongation. An increase in QTc prolongation and torsade de pointes has been Contraindicated in children and pregnant/ nursing women due to the risk of associated with the use of fluoroquinolones, particularly the newer cartilage erosin in growing bone tissue generations.

first generation

cinoxacin, enoxacin, norfloxacin

oral treatment of UTI, uncomplicated gonococcal infections,and prostatitis

second generation

ofloxacin, ciprofloxacin Lomefloxacin

ofloxacin greatest activity against Chlamydia; ciprofloxacin has activity against P. aeruginosa

Ciprofloxacin is available for oral, parenteral and topical use. Indications including lower respiratory tract infections (such as pneumonia and acute bronchitis), urinary tract infections, several STDs, skin and soft tissue infections, septicemia, legionellosis, and anthrax.

Ofloxacin is the racemic mixture of the chiral compound. The biologically active enantiomer is sold separately under the name of levofloxacin.

Ofloxacin is used as a treatment for gonorrhoea and is an alternative treatment to ciprofloxacin for anthrax. Syphilis: Ofloxacin is not effective in the treatment of syphilis. Antimicrobial agents used in high doses for short periods of time to treat gonorrhea may mask or delay the symptoms of incubating syphilis.

third generation

levofloxacin lebofloxacin, gatifloxacin moxifloxacin

UTI; Moxifloxacin used for complicated intra-abdominal infections but not for UTI

fourth generation

trovafloxacin

very broad spectrum(G+ and G- anaerobes, Chlamydia spp., and M. pneumoniae

Aminocoumarin

They are derived from Streptomyces species, whose most well-known representative Streptomyces coelicolor was completely sequenced in 2002.

act by an inhibition of the DNA Gyrase enzyme involved in the cell division in bacteria

Novobiocin, Albamycin (Pharmacia And Upjohn)

Novobiocin is effective antistaphylococcal agent used in the treatment of MRSA[22]. It is also active against Staphylococcus epidermidis and may be used to differentiate from the other coagulase-negative Staphylococcus saprophyticus, which is resistant to novobiocin, in culture.

Coumermycin Clorobiocin

Polypeptide antibiotics

used for eye, ear or bladder infections in addition to aminoglycosides. They are toxic, and are therefore not suitable for Their mechanism of action is protein systemic administration, but are administered topically on the skin.[1] They are usually applied directly to the eye or inhibition, but is largely unknown inhaled into the lungs; rarely given by injection.

actinomycin

bacitracin

Bacitracin inhibitis cell wall synthesis by interfering with the dephosphorylation of the C55-isoprenyl pyrophosphate, a molecule which carries the building blocks of the peptidoglycan bacterial cell wall outside of the inner membrane

colistin polymyxin B.

Urinary tract antiseptic

Also called Hexamine, it can be used as an antibiotic (commonly the hippurate salt, methenamine hippurate), and as a solid fuel tablet used for cooking while methenamine is more common in its medicinal uses and hexamine is more common in commercial uses. It is hydrolysed in the acidic pH of the urine to form formaldehyde which is an effective antiseptic against bacteria and fungi in vitro.

Methenamine

Nitrofurantoin

It is usually used in treating urinary tract infection. Like many other drugs, it is often used for killing E Coli. Nitrofuratoin can cause nausea and vomiting, fever, rash, hypersensitivity pneumonitis. When given for long periods of time, nitrofurantoin can cause progre All these side effects are much more common in the elderly. Patients should be informed that nitrofurantoin colours urine a dark orange-brown; this is completely harmless

Quinolones Fosfomycin tromethamine

Optic neuropathy related drugs: Chloramphenicol, isoniazid, streptomycin; V of this side effect.

the others:
aztreonam 1st monobactam G-, including enterobacter and P. aeruginosa UTI, septicemmia, skin infections , lower respiratory tract infection, intra-abdominal infections bactericidal inhibting bacterial cell wall synthesis

chloramphenicol [7klC : rAm5fenikEul]

rickettisia, H. influenzae, Salmonella typhi, Neisseria meningitidis, bordetella pertussis, Clostridium, B. fragilis, S. pyogenes, and S. pneumoniae typhoid fever and supress infections that cannot be treated effectively with other antibiotics. a second-line agent in the treatment of tetracycline-resistant cholera; bacteriostatic or bactericidal by inhibiting bacterial protein synthesis

Typhoid fever; Because of its excellent CSF penetration (far superior to any of the cephalosporins), chloramphenicol remains the first choice treatment for staphylococcal brain abscesses. It is also useful in the tre mixed organisms or when the causative organism is not known; used in the treatment of meningitis in patients with severe penicillin or cephalosporin allergy ; in the initial empirical treatment of chil when the differential diagnosis includes both Neisseria meningitidis septicaemia as well as Rocky Mountain spotted fever, pending the results of diagnostic investigations. also effective against Enterococcus faecium, which has led to it being considered for treatment of vancomycin-resistant enterococcus. Rickettsial infections in pregnant pts, tetracycline-allergic pts, and renally impaired pts Anerobic infections(e.g., pelvis or intestines), also including anaerobic or mixted infections of CNS; Serious H. influenzae infections, esp. in cephalosporin-allergic pts;

clindamycin

a lincosamide antibiotic. It is usually used to treat infections with anaerobic bacteria but can also be used to treat some protozoal diseases, such as malaria. It is a common topical treatment for acne, and can be useful against some methicillin-resistant Staphylococcus aureus (MRSA) infections.

Antibiotic-associated diarrhea due to C. difficile can occur with any antibio

With the administration of antibiotics, normal GI flora is inhibited, which allow Metronidazole is the treatment of choice for C. difficile infections. Although o against C. difficile, it is typically used as second-line treatment.

primary agent for leprosy ; but 40% may develop drug resistance; Dapsone Mycobacterium leprae, P. carinii, Plasmodium prophylaxis of P. carinii pneumonia in pts with AIDS; dermatitis hepeiformis

Maloprim

Dapsone+pyrimethamine

valuable in prophylaxis and treatment of malaria

infections caused by vancomycin-resistant E. faecium, nosocomial pneumonia caused by methicillin-susceptible and resistant strains of S. aureus; community-acquired pneumonia caused by penicillin-susceptible strains of S. pneumoniae, skin infections

linezolid

bacteriostatic or bactericidal inhibit protein synthesis

spectinomycin

active in G-; only to treat gonococccal infections in patients with penicillin allergy or for PPNG( penicillinase-producing gonococci)

trimethoprim

combined with sulfamethoxazole--co-trimoxazole , S. pneumoniae, N. meningitidis, Corynebacterium diphtheriae, Shigella, Serratia, E. coli, Staphylococcus epidermidis, Klebsiella. Spp.

uncomplicated UTI, acute gonococcal urethritis, acute exacerbation of chronic bronchitis, shigellosis, Salmonella infections

Most G+, including methicillin-resistant strains of S. aureus and Enterococci;

bactericidal inhibting bacterial cell wall synthesis Used in serious infections, esp. resistant strains; particulary useful inanephric (peptidoglycans) pts with G+ bacterial infection vancomycin

vancomycin-resistant enterococcus Faecium (VREF): susceptible to teicoplanin, linezolid, quinupristin/dalfopristin Therapy should be closely monitored for ototoxicity and nephrotoxicity. Parenteral administration for methicillin resistant types of infection; Oral administration is indicated for p colitis. Rapid infusion associated with anaphylactoid reactions, hypotension, wheezing dyspnea and urticaria. May also cause "red neck syndrome"

a glycopeptide antiobiotic extracted from Actinoplanes teichomyceticus, with a similar spectrum of activity to vancomycin. Its mechanism of action is to inhibit b Teicoplanin is marketed by Sanofi-Aventis under the trade name Targocid. teicoplanin

Teicoplanin is used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aur teicoplanin has been demonstrated to be effective in the treatment of pseudomembranous colitis and Clostridium difficile-associated diarrhoea, with comparab Its strength is considered to be due to the length of the hydrocarbon chain.

Telithromycin

aerobic and anaerobic G+ organisms, multidrug-resitant S. pneumoniae

Ketolides are derived from erythromycin by substituting the cladinose sugar with a keto-group and attaching a cy ring. These modifications give ketolides much broader spectrum than other macrolides. Moreover, ketolides are e bacteria, due to their ability to bind at two sites at the bacterial ribosome. Ketolides block protein synthesis by bind also inhibit the formation of newly forming ribosomes.

First of a new class antimicrobials called the ketolides, for community-acquired pneumonia, acute sinusitis, and ac bronchitis

A combination of two antibiotics used to treat infections by staphylococci and by vancomycin-resistant Enterococcus faecium (VREF). It is not effective against quinupristin/dalfopristin

Dalfopristin inhibits the early phase of protein synthesis in the bacterial ribosome and quinupristin inhibits the late phase of protein synthesis (translocation). Th acts synergistically and is more effective in vitro than each component alone.

clofazimine daptomycin

various mycobateria: M. leprae, M. tubersulosis and MAI resistant G+ organisms complicated skin infections and S. aureus bacteremia

Systemic Antifungal agents

amphotericin B

Aspergillus, Blastomyces, Candida spp. (Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae, which may acquire resistance during treatment), Cryptococcus, Coccidioides, Histoplasma, Paracoccidioides, Phycomycetes and Sporothrix. Some isolates of Scedosporium apiospermum, Fusarium spp. and Sporothrix schenckii also show primary resistance, whereas all strains of Scedosporium prolificans demonstrate resistance

systemic fungal infections esp. in immunocompromised patients: candidosis, cryptococcosis, histoplasmosis, blastomycosis, paracoccidioidomycosis, coccidioidomycosis, aspergillosis, extracutaneous sporotrichosis and mucormycosis, and some cases of hyalohyphomycosis and phaeohyphomycosis.

May cause many serious adverse effects and it should be adm in a hospital setting: Infusion reactions: occurred during the infusion, including fever, shaking chills, hypotension, anorexia, nausea, vomiting, headache, dyspnea, and tachypnea; Premedication with acetaminophen and diphenhydramine is helpful in prophylaxing against infusion reactions; Hydrocortisone, meperidine may also be added Nephrotoxicity, electrolyte abnormalities (hypo-K, Mg, Ca is common), normocytic anemia, elevated liver transaminases; Should be mixed only in dextrose 5% in water (D5W) and should be protected from light.

casposungin flucytosine given in combination with amphotericin B, primarily for Cryptococcus and Candida

acts by causing fungal cell wall lysis

Griseofulvin

CYP450 inducers; The drug binds to tubulin, interfering with microtubule function, thus inhibiting mitosis. It is an oral antifungal drug to treat ringworm infections of the skin and n Penicillium griseofulvum. Known side effects: Hives, Skin rashes, Confusion, Dizziness, Diarrhea, Fatigue, Headache, Impairment of performance of routine activities, Inability to fall or thrush (yeast infection of the mouth), Upper abdominal pain, Swelling, Itching, Tingling in the hands or feet, Loss of taste sensation, Sensitivity to prolonged su with a disulfiram-like reaction, Possibly a teratogen inducing mutations, Can reduce the effectiveness of oral contraceptives

Imidazole

A synthetic antifungal drug used to prevent and treat skin and fungal infections, especially in immunocompromised patients such as those with AIDS. ketoconazole Ketoconazole is very lipophilic, which leads to accumulation in fatty tissues- more toxic for systemic use. Usually prescribed for athlete's foot, ringworm, candidiasis and jock itch; eumycetoma; tinea versicolor (shampoo version); Also shown some beneficial in men suffering from androgenic alopecia.

miconazole fluconazole itraconazole voriconazole The less toxic and more effective triazole compounds fluconazole and itraconazole have largely replaced ketoconazole for internal use.

nystatin

A polyene antibiotic similar to amphotericin B; act by binding to sterols in the fungal cell membrane and permits leakage of intracellular contents; Primarily against candida spp. Side effects: GI distress; rarely hypersensitivity.

Terbinafine

A synthetic allylamine antifungal. It is highly lipophilic in nature and tends to accumulate in skin, nails, and fatty tissues. Terbinafine inhibits ergosterol synthesi by inhibiting squalene epoxidase, an enzyme that is part of the fungal cell membrane synthesis pathway. Terbinafine is mainly effective on the dermatophytes group of fungi.

As a 1% cream or powder: superficial skin infections such as jock itch (Tinea cruris), athlete's foot (Tinea pedis) and other types of ringworm (Tinea corporis).

Oral 250mg tablets: onychomycosis of the toenail or fingernail due to the dermatophyte Tinea unguium. Fungal nail infections are located deep under the na in the cuticle to which topically applied treatments are unable to penetrate in sufficient amounts.

The tablets may, rarely, cause hepatotoxicity, so patients are warned of this and may be monitored with liver function tests. May induce or exacerbate subacut cutaneous lupus erythematosus.

Topical antifungal agents

amphotericin B

Amphotericin B, is associated with multiple infusion-related reactions and adverse effects on the kidneys, Chills, rigors, fevers, and hypotension are common during amphotericin administration, Thus, patients are typically premedicated with diphenhydramine and acetaminophen or NSAIDs prior to infusion. Meperidine can be given in response to rigors, Renal toxicity is also commonly associated with amphotericin and can be irreversible. Renal toxicity may present as azotemia, renal tubular acidosis, or electrolyte wasting, Almost all patients receiving amphotericin will experience some degree of renal insufficiency.

ketoconazole Itraconazole Fluconazole miconazole Voriconazole butoconazole

clotrimazole econazole oxiconazole sulconazole terconazole tioconazole

ciclopirox

The ethanolamine contained in ciclopirox appears to enhance epidermal penetration It is used for superficial skin infections such as jock itch (Tinea cruris), athlete's foot (Tinea pedis) and other types of ringworm (Tinea corporis).

clioquinol

an antifungal drug and antiprotozoal drug. It is neurotoxic in large doses. It is a member of a family of drugs called hydroxyquinolines which inhibit certain enzymes related to DNA replication. The drugs have been found to have activity against both viral and protozoal infections. Used in the treatment and prevention of shigella infection and Entamoeba histolytica infection; Long-term high doses related to oculotoxic and neurotoxic effects.

gentian violet naftifine nystatin

allylamines

nafine

terbinafine

A synthetic allylamine antifungal. Like other allylamines, terbinafine inhibits ergosterol synthesis by inhibiting squalene epoxidase. It is highly lipophilic in natur nails, and fatty tissues.

Terbinafine is mainly effective on the dermatophytes group of fungi.As a 1% cream or powder it is used for superficial skin infections such as jock itch (Tinea c other types of ringworm (Tinea corporis).

Butenafine is indicated for the topical treatment of tinea (pityriasis) versicolor due to M. furfur, as well as athletes foot (Tinea pedis), ringworm (Tinea corporis) floccosum, T. mentagrophytes, T. rubrum, and T. tonsurans. It has superior fungicidal activity against this group of fungi when compared to that of terbinafine, butenafine

It also displays superior activity against Candida albicans when compared against terbinafine and naftifine. Butenafine demonstrates low minimum inhibitory c and aspergillus. Butenafine is typically available as a 1% topical cream.

Nafitifine tolnaftate

For Candidiasis

in the treatment of candidiasis are azoles and amphotericin B. Azole antifungals include systemic agents such as ketoconazole, fluconazole, itraconazole, and used for the treatment of vaginal candidiasis and thrush include miconazole and clotrimazole, Ketoconazole, the first oral azole developed, has poor bioavailab environment for enhanced absorption, Fluconazole, unlike itraconazole and ketoconazole, is hydrophillic and has increased penetration across the blood-brai azole that is renally eliminated.

Selenium sulfide (SeS2)

an antifungal agent often used in shampoos for the treatment of dandruff and seborrheic dermatitis associated in the scalp with Malassezia genus fungi. In the United States, a 1% strength is available over-the-counter, and a 2.5% strength is also available with a prescription. At the 2.5% strength, selenium(IV) sulfide is also used on the body to treat tinea versicolor, a type of fungal skin infection caused by a different species of Malassezia. It can be used for adults and children over the age of 5. It should be used twice a week for the first two weeks then once a week for the next two weeks.

Antifungals (D01 and J02)

Azoles Ketoconazole,

topical: imidazoles (Bifonazole, Clomidazole, Clotrimazole, Croconazole, Econazole, Fenticonazole, Isoconazole, Miconazole, Neticonazole, Oxiconazole, Sertaconazole, Sulconazole, Tioconazole) triazoles (Fluconazole, Fosfluconazole) benzimidazole (Thiabendazole)

(CYP51A1 inhibitors) systemic: Ergosterol inhibitors Polyene antimycotics (ergosterol binding)

triazoles (Itraconazole, Posaconazole, Voriconazole)

topical: (Natamycin, Nystatin)

Allylamines topical:

(Amorolfine, Butenafine, Naftifine, Terbinafine)

(squalene monooxygenase inhibitors

systemic: (Terbinafine)

1,3-beta-glucan synthase inhibitors

echinocandins (Anidulafungin, Caspofungin, Micafungin)

Pyrimidine analogues/
Intracellular Thymidylate synthase inhibitors

Flucytosine

Mitotic inhibitors

Griseofulvin

Ciclopirox Ethylparaben Salicylic acid Selenium sulfide Tolnaftate Undecylenic acid

Others

Tea tree oil citronella oil lemon grass orange oil patchouli lemon myrtle Whitfield's ointment

Anti-leprosy agents

Hansen's disease

most commonly used in combination with rifampicin and clofazimine as multidrug therapy (MDT) for the treatment of Mycobacterium leprae infections (leprosy). Dapsone can also be used to treat mucous membrane pemphigoid, an autoimmune blistering disaes of skin and mucous membranes, dermatitis herpetiformis and Linear immunoglobulin A dermatosis. It is also sometimes used to prevent Pneumocystis pneumonia (PCP) in people who are immunosuppressed and to treat idiopathic thrombocytopenic purpura.or for patients who are unable to tolerate trimethoprim with sulfamethoxazole. Dapsone is also used to treat Brown recluse spider bites.

Dapsone

Rifampicin

Rofact (in Canada.) There are various types of rifamycins from which this is derived, but this particular form, with a 4-methyl-1-piperazinaminyl group, is by far the most clinically effective. Rifampicin was used as a major addition to the cocktail-drug treatment of tuberculosis and inactive meningitis, along with isoniazid, ethambutol, and streptomycin.

clofazimine

a fat-soluble riminophenazine dye used in combination with rifampicin and dapsone as multidrug therapy (MDT) for the treatment of leprosy. It has been used investigationally in combination with other antimycobacterial drugs to treat Mycobacterium avium infections in AIDS patients. Clofazimine also has a marked anti-inflammatory effect and is given to control the leprosy reaction, erythema nodosum leprosum (ENL).

Antiprotozoal agents

antimalarial agents
chloroquine hydroxy-chloroquine

quinine halofantrine primaquine pyrimethamine mefloquine fansidar halofantrine malarone amebiasis, giardiasis and trichomoniases used in combination with a sulfonamide or fulfone for chloroquine-resistant strains of P. falciparum.

amebicides and trichomonacides

diloxanide

and

Antibiotic-associated diarrhea: treatment of choice for C. difficile infections. Although oral vancomycin also has activity against C. difficile, it is typically used as second-line treatment. metronidazole Prefered drug for amebic dysentery, giardiasis and trichomoniasis. It is also employed as an antibacterial in treating certain anaerobic bacterial infections. Patients using metronidazole should avoid alcoholic beverages to avoid disulfiram-like effects when the combination is used. nitazoxanide quinacrine lodoquinol paromomycin tinidazole

others

pentamidine isethionate

P. carinii; primarily given for prevention and treatment of Pneumocystis pneumonia (PCP) caused by Pneumocystis jirovecii, also formerly known as Pneumocystis carin pneumonia (PCP), a severe interstitial type of pneumonia often seen in patients with HIV infection. PCP is considered an 'opportunistic infection', endangering only immunodeficient patients such as those with HIV/AIDS.

atovaquone eflornithine HCl

Antitububercular agents

The standard "short" course treatment for tuberculosis (TB): isoniazid, rifampicin, pyrazinamide, and ethambutol (RIPE) for two months, then isoniazid and months. For latent TB, the standard treatment is six to nine months of isoniazid alone.

If the organism is known to be fully sensitive, then treatment is with isoniazid, rifampicin, and pyrazinamide for two months, followed by isoniazid and rifampicin not be used.

first line ethambutol

isoniazid (INH)

most widely used antitubercular drug, combination with others

requires pridoxine supplementation

blood dyscrasias----monitor complete blood count(CBC)

rifampin

Rifampicin inhibits DNA-dependent RNA polymerase in bacterial cells by binding its beta-subunit, thus preventing transcription to RNA and subsequent tran makes it a good candidate to treat the meningitis form of tuberculosis(penetration through the blood-brain barrier). Rifampicin is typically used to treat Mycoba leprosy); methicillin-resistant Staphylococcus aureus (MRSA) in combination with fusidic acid. It is used in prophylactic therapy against Neisseria meningitid

The most serious adverse effect is related to rifampicin's hepatotoxicity, and patients receiving rifampicin often undergo baseline and frequent liver function te can cause a reddish discoloration of the urine, sweat, sputum and tears. Side reactions Hepatotoxic - Hepatitis, jaundice, liver failure in severe cases. Respiratory - breathlessness Cutaneous - flushing, pruritus, rash, redness and watering of eyes. Abdominal - nausea, vomiting, abdominal cramps with or without diarrhea Flu-like symptoms - with chills, fever, headache, arthralgia and malaise

D_D

As a CYP 450 inducers, decrease the therapeutic effectiveness of: corticosteroids, warfarin, oral contraceptives, quinidine, digitoxin, protease inhibitors, nonnu inhibitors, ketoconazole, verapamil, methadone, oral antidiabetic agents, cyclosporine, dapsone, chloramphenicol, barbiturates. Probenecid may increase blood levels of rifampin. Aminosalicyclic acid may impair absorption of rifampin seconday to bentonite, an excipient used in preparation of ASA granules.

rifabutin rifapentine pyrazinamide

second line
aminosalicylic acid capreomycin

cycloserine

The terminal two amino acid residues of the murein precursor lipid II consist of D-alanine, which is produced by the enzyme alanine racemase; the two residue enzymes are competitively inhibited by cycloserine. (cell-wall synthesis inhibitor) Although in principle active against other bacteria as well, cycloserine is not commonly used in the treatment of infections other than tuberculosis.

ethionamide quinolones

Antiviral agents DNA viruses

acyclovir HSV 1. HSV 2, varicella zoster virus (VZV). Weak activity activity against Epstein-Barr virus (EBV). CMV.

valacyclovir adefovir dipivoxil entecavir

pro-drug of acyclovir only approved for chronic HBV HBV, not for HIV

amantadine famciclovir

Influenza A pro-drug of penciclovir; HSV-1, HSV-2, VZV, HSV-1, HSV-2, VZV, CMV. EBV. HHV-5.HHV-8. May be used for treatment of resistant HSV or VAV.

cidofovir foscarnet

ganciclovir

HSV-1, HSV-2, VZV, CMV. EBV. human herpes virus (HHV)-8. It was developed by Canadian scientist Kelvin K. Ogilvie.

an antiviral medication used to treat or prevent cytomegalovirus (CMV) infections: Sight-threatening CMV retinitis in severely immunocompromised people; CMV pneumonitis in bone marrow transplant recipients Prevention of CMV disease in bone marrow and solid organ transplant recipients; Confirmed CMV retinitis in people with AIDS (intravitreal implant) It is also used for acute CMV colitis in HIV/AIDS and CMV pneumonitis in immunosuppressed patients.

Side effects: granulocytopenia, neutropenia, anaemia, thrombocytopenia, fever, nausea, vomiting, dyspepsia, diarrhoea, abdominal pain, flatulence, anorexia, raised liver enzymes, headache, confusion, hallucination, seizures, pain and phlebitis at injection site (due to high pH), sweating, rash, itch, increased serum creatinine and blood urea concentrations.[1] Toxicity: Ganciclovir is considered a potential human carcinogen, teratogen, and mutagen. It is also considered likely to cause inhibition of spermatogenesis. Thus, it is used judiciously and handled as a cytotoxic drug in the clinical setting.

ribavirin

DNA and RNA viruses, Influenza A and B, RSV, Herpes simplex, and hepatitis C

rimantadine

Influenza A

Taking paracetamol (acetaminophen e.g. Tylenol) or acetylsalicylic acid (aspirin) while taking rimantadine is know rimantadine by approximately 12%. Cimetidine also affects the body's uptake of rimantadine. Rimantadine can produce gastrointestinal and central nervous system adverse effects: nausea, upset stomach, nervousness, tiredness, lightheadedness, trouble sleeping, difficulty concentrating

zanamivir oseltamivir valganciclovir

Influenza A and B, Influenza A and B,

For Herpes Viruses Acyclovir Acyclovir is an acyclic guanosine derivative that requires three phosphorylation steps for activation, Conversion to the monophosphate is carried out by the virus thymidine kinase, and conversion t Ganciclovir out by host kineases, The active nucleotide triphosphate inhibits viral replication by competing with the viral deoxy-GTP for the viral DNA polymerase, Thus, acyclovir triphosphate is inserted into th Foscarnet irreversible chain termination. Reduced susceptibility to acyclovir is due to altered viral thymidine kinase, Because the MOA of ganciclovir is similar to that of acyclovir, HSV that is resistant to acycl Cidofovir

famciclovir Peneciclovir

Although acyclovir is considered the drug of choice for the treatment of HSV infection, ganciclovir, foscarnet, and cidofovir also have in vitro activity against HSV, but these agents are most commo due to cytomegalovirus (CMV), Valacyclovir is the L-valyl ester of acyclovir and was developed to overcome the poor bioavailability of acyclovir. Famciclovir is the ester prod rug of penciclovir, an a to Valacyclorir serum H2 of penciclovir is similar H2 of peniclovir is extended, Penciclovir is not available as an oral agent, but only as a cream. that of acyclovir, the intracellular

Vidarabine

an anti-viral drug which is active against herpes simplex and varicella zoster viruses. Vidarabine works by interfering with the synthesis of viral DNA.[5] It is a nucleoside analog and therefore has to be phosphorylated to be active. It is administered by slow IV infusion for the treatment of herpes simplex encephalitis and is used ophthalmically for the treatment of herpes simplex infections of the eye.

Cytomegalovirus (CMV) is a DNA virus in the family Herpesviridae known for producing large cells with nuclear and cytoplasmic inclusions---- "owl's eye" effect.

Cytomegalovirus retinitis damage to the eye and the rest of the body. HIV positive persons are most at risk, especially when the CD4 cell count decreases. CMV is a common virus that infects those who are HIV positive.It
cases by causing damage to the retina. Symptoms can include blurred vision, eye pain, photophobia, redness, and blindness. It may affect just one eye at first, but then may spread to the other.

While CMV is found in almost everyone, and is usually fought off by the immune system, for people who are immunocompromised, by diseases, transplants, or chemotherapy the virus is not adequ

(CMV Retinitis)

Active Cytomegalovirus retinitis is treated by an uveitis and ocular immunology specialist. Because the virus is so threatening to vision, it is usually treated by a vitreo-retinal surgeon, by antivirals s which can be taken orally, IV, injected directly into the eye (intravitreal injection), or through an intravitreal implant. Fomivirsen is the first antisense drug approved by the FDA (brand name Vitravene) as an intraocular injection for the treatment of cytomegalovirus retinitis.

RNA viruses (HIV)

nucleoside reverse transcriptase inhibitors(NRTIs nucleotide .. NtRTI nonnucleoside NNRTIs

abacavir, didanosine, emtricitabine, lamivudine, stavudine, zalcitabine, zidovudine

dine/bine/sine on the side

lamivudine: HBV and HIV

tenofovir disoproxil fumarate delavirdine efavirenz nevirapine

tide---tenofovir

NN---Di-EN

Efavirenz: once-daily dosing

protease inhibitors PIs----navir

amprenavir, atazanavir, darunavir fosamprenavir, indinavir, lopinavir/ritonavir, nelfinavir, ritonavir, saquinavir, tipranavir

fusion inhibitor

enfuvirtide

reverse transcriptase inhibitor

Didanosine

It is a reverse transcriptase inhibitor, effective against HIV and used in combination with other antiretroviral drug therapy as part of highly active antiretroviral therapy (HAART). Within the cell, ddI is phosphorylated to the active metabolite of dideoxyadenosine triphosphate, ddATP, by cellular enzymes. Like other anti-HIV nucleoside analogs, it acts as a chain terminator by incorporation and inhibits viral reverse transcriptase by competing with natural dATP.

before initiating drug therapy, must obtain CD4+ cell count and plasma HIV RNA levels plus CBC, chemistry, lipid profile, and liver enzymes

For HIV-1-infected pts

NNRTI based: Efavirenz + (lamivudine or emtricitabine)+ (zidovudine or tenofovir) PI based: Lopinavir/ ritonavir + (lamivudine or emtricitabine)+ zidovudine

The preferred initial regimens (HAART): efavirenz (NNRTI) + zidovudine (NRTI) + lamivudine (NRTI) efavirenz + tenofovir (NtRTI) + emtricitabine (NRTI) lopinavir (PI) boosted with ritonavir (PI) + zidovudine + lamivudine lopinavir boosted with ritonavir + tenofovir + emtricitabine.

Antivirals, other than for HIV (primarily J05, also S01AD and D06BB) purine analogue (guanine) (Aciclovir, Famciclovir, Ganciclovir, Penciclovir, Valaciclovir, Valganciclovir) Vidarabine Anti-herpesvirus (DNA, I) pyrimidine analogue (uridine) (Idoxuridine, Trifluridine) Brivudine Cidofovir Docosanol Fomivirsen Foscarnet Tromantadine HPV/MC (DNA, I) Imiquimod Podophyllotoxin

Nucleoside analogues/NRTIs: Entecavir Lamivudine Telbivudine Clevudine Hepatitis B (DNA, VII) Nucleotide analogues/NtRTIs: Adefovir Tenofovir

Hepatitis C (RNA, IV) Picornavirus (RNA, IV) Anti-influenza agents (RNA, V)

protease inhibitor (Boceprevir, Telaprevir) Pleconaril Arbidol adamantane derivatives/M2 inhibitors (Amantadine, Rimantadine) neuraminidase inhibitors (Oseltamivir, Zanamivir, Peramivir)

HIV (Reverse, VI)

See HIV pharm

Inosine Multiple/general Interferon: Interferon alfa-2b Peginterferon alfa-2a Ribavirin/Taribavirin

anthelmintics

..dazole common hookworm, roundworm, philippine threadworm, pinworm, american hookworm, pin-, round-, hook-, whip-, philippine threadwhipworm liver flukes pork tapeworm, dog tapeworm thread-. round-, whip-, tape-, hook-

mebendazole

triclabendazole albendazole

diethylcarbamazine citrate

lymphatic filariasis caused by infection with Wuchereria bancrofti, Brugia malayi, or Brugia timori; tropical pulmonary Bancroft's filariasis, onchocerciasis, ascariasis, loiasis eosinophilia , and loiasis.

pyrantel pamoate thiabendazole ivermectin

most nematodes most intestinal nematodes most common intestinal worms except tapeworms

roundworm, pinworm, hookworm, hairworm thia----

praziquantel

trematode(flukes) nematodes

all types of schistosomiasis clonorchiasis and opisthorchiasis other types of infections of intestinal, liver, and lung flukes cestodiasis(tapeworm) infections

Niclosamide Levamisole Suramin octadepsipeptides emodepside

tapeworms

gastrointestinal helminths

Chlamydia infection is a common sexually transmitted infection (STI) in humans caused by the bacterium Chlamydia trachomatis (the most common bacterial STI ); C. trachomatis is naturally found living only inside human cells. Chlamydia can be transmitted during vaginal, anal, or oral sex, and can be passed from an infected mother to her baby during vagin or trachoma was once the most important cause of blindness worldwide, C. trachomatis infection can be effectively cured with antibiotics once it is detected. Current Centers for Disease Control guidelines provide for the following treatments: Azithromycin 1 gram oral as a single dose, or Doxycycline 100 milligrams twice daily for seven days. Tetracycline Erythromycin

Chlamydia infection

Untested Treatments Ciprofloxacin 500 milligrams twice daily for 3 days. (Although this is not an approved method of treatment.) -lactams are not suitable drugs for the treatment of chlamydia. While they have the ability to halt growth of the organism (i.e. are microbistatic), these antibiotics do not eliminate the bacteria. Once will begin to grow once more. (See below for Persistence.)

Sexually transmitted disease

A sexually transmitted disease (STD) or venereal disease (VD), is an illness that has a significant probability of transmission between humans or animals by means of sexual contact, including vag sex. Increasingly, the term sexually transmitted infection (STI) is used, as it has a broader range of meaning; a person may be infected, and may potentially infect others, without showing signs of d

Many STIs are (more easily) transmitted through the mucous membranes of the penis, vulva, rectum, and (less often)[citation needed] the mouth. The visible membrane covering the head of the pe produces no mucus (similar to the lips of the mouth). Mucous membranes differ from skin in that they allow certain pathogens into the body.

Chancroid (Haemophilus ducreyi) Donovanosis (Granuloma inguinale or Calymmatobacterium granulomatis) Gonorrhea (Neisseria gonorrhoeae) Bacterial Lymphogranuloma venereum (LGV) (Chlamydia trachomatis serotypes L1, L2, L3. See Chlamydia) Non-gonococcal urethritis (NGU) (Ureaplasma urealyticum or Mycoplasma hominis) Staphylococcus aureus, MRSA - Sexually transmissible.[6] Syphilis (Treponema pallidum)

Cytomegalovirus (CMV) through skin to skin contact, saliva, not only sexually. Hepatitis B. (Note: Hepatitis A and Hepatitis E are transmitted via the fcal-oral route; Hepatitis C is rarely sexually transmittable, and the route of transmission of Hepatitis D is uncertain, but may Herpes simplex / Herpes simplex virus implicated in Alzheimer's disease. Human Immunodeficiency Virus (HIV/AIDS) Viral Human papillomavirus (HPV) / Certain strains of HPV cause genital warts / Certain strains of HPV cause dysplasias and lead to cervical, penis, anal, oral, head and neck cancer. Molluscum (MC) Mononucleosis is spread through saliva, can occur during sex. Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) The cause of Kaposi's sarcoma

Parasites Pubic lice, colloquially known as "crabs" (Phthirius pubis) Scabies (Sarcoptes scabiei) Protozoal Trichomoniasis (Trichomonas vaginalis)

Sexually transmitted enteric infections Various bacterial (Shigella, Campylobacter, or Salmonella), viral (Hepatitis A), or parasitic (Giardia or amoeba) pathogens are transmitted by sexual practices that promote anal-oral contamination. multiple partnered barebacking can promote anal-anal contamination. Although the bacterial pathogens may coexist with or cause proctitis, they usually produce symptoms (diarrhea, fever, bloating suggesting disease more proximal in the GI tract. Sexually transmissible oral infections Common colds, influenza, Staphylococcus aureus, E. coli, Oral Herpes and the yeast Candida albicans can all be transmitted through the oral route.

Rheumatic fever

Rheumatic fever is an inflammatory disease which may develop two to three weeks after a Group A streptococcal infection (such as strep throat or scarlet fever). It is believed to be caused by antib the heart, joints, skin, and brain. Acute rheumatic fever commonly appears in children ages 5 through 15, with only 20% of first time attacks occurring in adults. The treatment: the reduction of inflammation with anti-inflammatory medications such as aspirin or corticosteroids. Individuals with positive cultures for strep throat should also be treated with antibi acting Penicillin must be given for a period of 5 years in patients having one attack of Rheumatic fever. Another important cornerstone in treating rheumatic fever includes the continual use of penicillin, sulfadiazine, or erythromycin) to prevent recurrence.

Tinea versicolor or pityriasis versicolor is a common skin infection caused by the yeast Malassezia furfur (formerly termed Pityrosporum ovale). This yeast is normally found on the human skin and certain circumstances, such as a warm and humid environment.

Tinea versicolor

Treatments for tinea versicolor include: Topical antifungal medications - containing either 2.5% selenium sulfide or 2% ketoconazole (Nizoral ointment and shampoo) applied to dry skin and washed off after 10 minutes, repeated daily fo olamine) is an alternative treatment to ketoconazole as it suppresses growth of the yeast Malassezia furfur. Initial results show similar efficacy to ketoconazole with a relative increase in subjective inflammatory properties. Other topical antifungal agents such as clotrimazole, miconazole or terbinafine are less widely recommended. Additionally, hydrogen peroxide has been known to lessen s remove the problem. Clotrimazole (1%) is also used combined with selenium sulfide (2.5%) (Candid-TV). Oral antifungal prescription-only medications include 400 mg of ketoconazole or fluconazole in a single dose, or ketoconazole 200 mg daily for 7 days, or itraconazole 400 mg daily for 3-7 days. The single-dose regimens can be made more effective by having the patient exercise 1-2 hours after the dose, to induce sweating. The sweat is allowed to evaporate, and showering is delayed for a day, leaving a film of the medication on the skin.[citation needed] Recurrence is common and may be reduced by intermittent application of topical agents (such as tea tree oil) or adding a small amount of anti-dandruff shampoo to water used for bathing.

Tuberculosis

Tuberculosis (TB, ) may be caused by one of three mycobacterial organisms: Mycobacterium tuberculosis (MTB), Mycobacterium bovis, or M. africanum, The vast majority of MTB cases thr tuberculosis. Mantoux test (tuberculin skin test or TST) for diagnosis of the infection;

Pyrazinamide MTB. When drug susceptibilities are known, the regimen should be tailored based on the results, Resistance develops rapidly with monotherapy; thus, multiple agents are used. Many of these dru Ethambutol interactions, so it is always important to take a complete medication history, Rifampin is a potent inducer of CYP450 and isoniazid is an inhibitor of CYP450,
RIPE

Rifampin Isoniazid The agents most commonly used for the treatment of active MTB are isoniazid, rifampin, pyrazinamide, and ethambutol. Usually a four-drug regimen consisting of these first-line agents is preferred

Side effects caused by isoniazid, rifampin, pyrazinamide, and ethambutol are common and can include hepatotoxicity, peripheral neuropathy, optic neuritis, and GI side effects. All four agents can p side effect is most frequently associated with isoniazid and rifampin, Peripheral neuropathy is most commonly associated with isoniazid, whereas optic neuritis is associated with ethambutol. The m predetermined. Patients of Scandinavian, European, and African descent metabolize isoniazid slower (slow acetylators) and are therefore more predisposed to hepatotoxicity and peripheral neurop include people of Asian or American Indian descent and are less predisposed to these adverse effects.

Rifampicin is a bactericidal antibiotic drug of the rifamycin group. It is a semisynthetic compound derived from Amycolatopsis rifamycinica. Rifampicin inhibits DNA-dependent RNA polymerase in b subunit, thus preventing transcription to RNA and subsequent translation to proteins. Adverse effects include: Hepatotoxic - Hepatitis, jaundice, liver failure in severe cases. / Respiratory - breathlessness / Cutaneous - flushing, pruritus, rash, redness and watering of eyes. / Abdom cramps with or without diarrhea / Flu-like symptoms - with chills, fever, headache, arthralgia and malaise

Isoniazid Adverse reactions include rash, abnormal liver function tests, hepatitis, sideroblastic anemia, peripheral neuropathy, mild central nervous system (CNS) effects, drug interactions resulting in increas (Antabuse) levels and intractable seizures (status epilepticus).

Peripheral neuropathy and CNS effects are associated with the use of isoniazid and are due to pyridoxine (vitamin B6) depletion, but are uncommon at doses of 5 mg/kg. Persons with conditions in diabetes, uremia, alcoholism, malnutrition, HIV-infection), as well as pregnant women and persons with a seizure disorder, may be given pyridoxine (vitamin B6) (10-50 mg/day) with isoniazid.

Pyrazinamide is a prodrug that stops the growth of Mycobacterium tuberculosis. M. tuberculosis has the enzyme pyrazinamidase which is only active in acidic conditions. Pyrazinamidase converts pyrazinoic acid. Pyrazinoic acid is thought to inhibit the enzyme fatty acid synthetase I, which is required by the bacterium to synthesise fatty acids although this has been disputed. Mutations of the responsible for pyrazinamide resistance in M. tuberculosis.

Ethambutol is a bacteriostatic antimycobacterial drug prescribed to treat tuberculosis (Mycobacterium tuberculosis. Bacteriostatic against actively growing TB bacilli, it works by obstructing the form Side Effects: Optic neuritis / Red-green color blindness / Peripheral neuropathy / Arthralgia

streptomycin levofloxacin moxifloxacin

Seconde-line agent in acitive TB; Useful in TB meningitis; Avoid in children, pregnanacy;

Seconde-line agent in acitive TB; Useful in pts with rifampin-resistant;

Onychomycosis

Onychomycosis means fungal infection of the nail. [7CnikEumai5kEusis] tinea [5tiniE] Onychomycosis caused by dermatophytes is also known as tinea unguium (tinea of the nails). The causative pathogens of onychomycosis include dermatophytes, Candida, and non-dermatophytic most commonly responsible for onychomycosis in the temperate western countries; meanwhile, Candida and non-dermatophytic moulds are more frequently involved in the tropics and subtropics w Most treatments are either systemic antifungal medications such as terbinafine and itraconazole, or topical such as nail paints containing ciclopirox or amorolfine. There is also evidence for com treatments.

Impetigo (sometimes impetaigo) is a superficial bacterial skin infection most common among children 2 to 6 years old. People who play close contact sports such as rugby, American football and w regardless of age. The name derives from the Latin impetere ("assail"). It is also known as school sores.It usually caused primarily by Staphylococcus aureus, and sometimes by Streptococcus py

Impetigo

Topical or oral antibiotics are usually prescribed. Neosporin works well in some cases, and is available over-the-counter. Treatment may involve washing with soap and water and letting the impet practitioners choose to treat impetigo with bactericidal ointment, such as fusidic acid or mupirocin, but in more severe cases oral antibiotics, such as flucloxacillin or erythromycin or Dicloxacillin Amoxicillin combined with clavulanate potassium or cephalosporins (1st generation) may also be used as an antibiotic treatment.

or borreliosis, is an emerging infectious disease caused by at least three species of bacteria belonging to the genus Borrelia. Borrelia burgdorferi is the predominant cause of Lyme disease in the afzelii and Borrelia garinii are implicated in most European cases. Lyme disease is the most common tick-borne disease in the Northern Hemisphere. Borrelia is transmitted to humans by the bite of infected hard ticks belonging to several species of the genus Ixod legged tick or deer tick (Ixodes scapularis) has been identified as the key to the disease's spread on the east coast.

Lyme disease

Antibiotics are the primary treatment for Lyme disease; the most appropriate antibiotic treatment depends upon the patient and the stage of the disease. The antibiotics of choice are doxycycline ( and ceftriaxone. Alternative choices are cefuroxime and cefotaxime. Macrolide antibiotics have limited efficacy when used alone.

In later stages, the bacteria disseminate throughout the body and may cross the blood-brain barrier, making the infection more difficult to treat. Late diagnosed Lyme is treated with oral or IV antibio minimum of four weeks. Minocycline is also indicated for neuroborreliosis for its ability to cross the blood-brain barrier.

Cellulitis

: [7selju5laitis] Group A Streptococcus Cellulitis is an infection of the deep subcutaneous tissue of the skin. Cellulitis can be caused by normal skin flora or by exogenous bacteria, and often occurs where the skin has previously been bro Staphylococcus burns, insect bites, surgical wounds, or sites of intravenous catheter insertion. Skin on the face or lower legs is most commonly affected by this infection, though cellulitis can occur on any part of th
remains treatment with appropriate antibiotics.

Flucloxacillin Cellulitis is caused by a type of bacteria entering by way of a break in the skin. This break need not be visible. Group A Streptococcus and Staphylococcus are the most common of these bacte oral Penicillin V of the skin but cause no actual infection until the skin is broken. Treatment with oral antibiotics, except in severe cases, which may require admission and intravenous (IV) therapy. Flucloxacillin m IV benzylpenicillin infection) is often sufficient in mild cellulitis, but in more moderate cases or where streptococcal infection is suspected then usually combined with oral phenoxymethylpenicillin or intravenous be ampicillin/amoxicillin ampicillin/amoxicillin

Normal skin flora:

Staphylococcus epidermidis and Staphylococcus aureus are normal flora of the skin. Streptococci, especially -hemolytic streptococci, are rarely seen on normal skin. Non-pathogenic members of the genus Corynebacterium are also normal skin flora in humans. Micrococcus luteus; Gram-negative bacteria make up a small proportion of the skin flora: Enterobacter, Klebsiella, Escherichia coli, and Proteus spp

Erysipelas streptococcus penicillins clindamycin erythromycin

Erysipelas ([7eri5sipilEs] red skin ) is an acute streptococcus bacterial infection of the dermis, resulting in inflammation and characteristically extending into underlying fat tissue. This disea elderly, infants, and children. People with immune deficiency, diabetes, alcoholism, skin ulceration, fungal infections and impaired lymphatic drainage (e.g., after mastectomy, pelvic surgery, bypass Depending on the severity, treatment involves either oral or intravenous antibiotics, using penicillins, clindamycin or erythromycin. While illness symptoms resolve in a day or two, the skin may Because of the risk of reinfection, prophylactic antibiotics are sometimes used after resolution of the initial condition. However, this approach does not always stop reinfection.

Folliculitis Staphylococcus aureus

[fE7likju5laitis], Folliculitis is the inflammation of one or more hair follicles. The condition may occur anywhere on the skin. Most carbuncles and furuncles and other cases of folliculitis develo fungus T. rubrum. malassezia yeast Pseudomonas aeruginosa can also cause this disease in different situations. Topical antiseptic treatment is adequate for most cases; Topical antibiotics such as mupirocin or neomycin containing ointment Some patients may benefit from systemic narrow-spectrum penicillinase-resistant penicillins (such as dicloxacillin in US, or flucloxacillin in UK)

[7menin5dVaitis] Meningitis is a medical condition that is caused by inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges.The inflam with viruses, bacteria, or other microorganisms but may also arise due to certain drugs, or other diseases. Meningitis is potentially life threatening due to the inflammation's proximity to the brain an emergency.

Meningitis N. meningitidis
Hemophilus influenza

The most common symptoms of meningitis are intense headache and neck stiffness associated with fever, confusion or altered consciousness, and an inability to tolerate bright light (photophobia) of muscle, convulsion and delirium.

Viruses that can cause meningitis include various enterovirus subtypes, herpes simplex virus 2 (and less commonly HSV-1), varicella zoster virus (known for causing chickenpox and shingles), mu

S. pneumoniae L. monocytogenes

The types of bacteria that cause bacterial meningitis vary by age group. In premature babies and newborn up to three months, common bacteria are group B streptococcus (subtype III)especially that normally inhabit the digestive tract such as Escherichia coli (carrying K1 antigen). Listeria monocytogenes (serotype IVb) may affect the newborn and occurs in epidemics. Older children are m meningitidis (meningococcus), Streptococcus pneumoniae (serotypes 6, 9, 14, 18 and 23) and those under five by Haemophilus influenzae type B (in areas without vaccination, see below). In adul pneumoniae together cause 80% of all cases of meningitis, with increased risk of L. monocytogenes in those over 50. Tuberculous meningitis, meningitis due to infection with Mycobacterium tuber from countries where tuberculosis is common, but is also encountered in those with immune problems, such as AIDS.

treatment for bacterial N. meningitidis: Penicillin G; cefotaxime or ceftriaxone; H. influenzae type b: Ampicillin; cefotaxime or ceftriaxone; meningitis Group B sterptococcus/ L. monocytogenes: penicillin + gentamicin for synergy
Enterobacteriaceae: cefotaxime or ceftriaxone +/- gentamicin;

S. pneumoniae: Penicillin G; cefotaxime or ceftriaxone; cefotaxime or ceftriaxone + vancomycin +/- rifampin;

H. pyroli infection

Adult dose: Omeprazole 20 mg; Clarithromycin 500 mg; Amoxicillin 1000 mg, each given twice per day for 10 days.

Peritonitis

inflammation and /or mucosal thickening of one or more of the paranasal sinus cabities, the cause of which may be allergic, viral, bacerial (S. pneumoniae, M. catarrhalis, H. influenzae, occasion anaerobes) or (rarely) fungal. Analgesics (acetaminophen, ibuprofen) for fever and pain;

Sinusitis

Antibiotics in childre: Penicillins: amoxicillin, amocixillin/clavulanate; Cephalosporins: cefuroxime axetil or sodium, cefprozil; Macrolides: Azithromycin and clarithromycin; Licosamides: clindamycin; SMX/TMP Antibiotics in adults: Penicillins: amoxicillin, amocixillin/clavulanate; Cephalosporins: cefuroxime axetil; Fluoroquinolones: levofloxacin, moxifloxacin; Tetracyclines: doxycycline Macrolides: Azithromycin and clarithromycin; Licosamides: clindamycin; SMX/TMP

Normally caused by viruses (RSV, parainfluenza, coronavirus, enterovirus); less than 10 % related to bacteria;

Acute Bronchitis

Analgesics: acetaminophen, ibuprofen; Antitussives: codeine, dextromethorphan, hydrocodone; Bronchodilators: inhaled salbutamol, terbutaline; Antibiotics: not recommended.

An acute viral illness of the respiratory tract caused by influenza A or B viruses. A typical influenza season in Canada runs from mid-Octomber to the end of April. Influenza Vaccine: annual influenza vaccination of individuals at high risk of influenza-related complications;

Influenza

Antiviral agents: Amantadine (for influenza A) Oseltamivir ( first-line agent during outbreaks of influenza A or B) Zanamivir (for both A and B)

Community-acquired Pneumonia

Streptococcus pneumoniae: penicillin nonresistant: penicillin G, amoxicillin; penicillin resistant (cefotaxime, cetriaxone, po or IV fluoroquinolone); Haemophilus influenzae: 2nd or 3rd cephalosporin or amoxicillin/clavulanate, fluoroquinolones; Staphylococcus aureus: methicillin-susceptible (cloxacillin, cefazolin, clindamycin); methicillin-resistant: vancomycin, linezolid, sulfamethoxazole/trimethoprim; Mycoplasma / Chlamydophila pneumoniae: macrolides or tetracyclines, fluoroquinolones (alternative) Aerobic G-- bacilli: 2nd or 3rd cephalosporin, carbapenem

aminoglycosides: gentamicin, tobramycin; Carbapenems: ertapenem, imipenem/cilastatin, meropenem; Cephalosporins: cefazolin; cefaclor, cefprozil, cfuroxime axitil or sodium; cefotaxime, ceftaz Penicillins: penicillin V K, penicillin G, amoxicillin, amoxicillin/clavulanate, ampicillin, cloxacillin, piperacillin, piperacillin/tazobactam, ticarcillin/ clavulanate; Rifamcins: rifampin; Tetracyclines: doxycycline; SMX/TMP; Fluoroquinolones: ciprofloxacin, lebofloxacin, moxifloxacin; Glycoperptides: vancomycin; Oxazolidinones: linezolid; Nitroimidazoles: metronidazole; Macrolides: erythromycin, azithromycin and clarithromycin; Ketolides: telithromycin; Licosamides: clindamycin.

Colitis

[mE5lZEriE] Insect repellents: diethyltoluamide (DEET); Chloroquine: only for resistance uncommon places ( 1-2 week before exposure; continue weekly for 4 week after leaving the edemic area; cetral america except Panama, Haiti, Middle East, Do Hydroxychoroquine (alternative), 2 week before exposure; continue weekly for 8 week after leaving the edemic area; Mefloquine: for areas reporting chloroquine-resistant P. falciparum.1 week prior to exposure; weekly during the stay and continue weekly for 4 week after leaving the edemic area;

Malaria Prevention

Doxycycline: for mefloquine intolerable pts or mefloquine-resistant areas; daily dosing, taken with food and liberal amounts of fluids while in the upright position; one day before exposure; daily du after leaving the edemic area; Primaquine: for teminal prophylaxis; not for pregnancy; 1 day prior to exposure; daily during the stay and continue 3 days after leaving the edemic area; Atovaquone/ Proguanil: better tolerated than mefloquine; taken daily with food; not for pregnancy or infants < 5 kg; 1 day prior to exposure; daily during the stay and continue 1 week after leaving the edemic area; Artemisinin (isolated from the plant Artemisia annua and used to treat multi-drug resistant strains of falciparum malaria), dicovered by Chinese Scientists.

Travel's diarrhea

"boil it, cook it, peel it or forget it" Intestinal absorbants: Bismuth subsalicylate (BSS): QID with food; Fluoroquinolones: (norfloxacin, ofloxacin, ciprofloxacin); Rifaximin: refamycin-derived, nonabsorbable antibiotic, with few or mild side effects; Not availabe in Canada; Macrolides: azithromycin; Antiperistaltics: loepramide ( not use in children < 3 y. SMX/TMP and doxycycline are no longer recommended due to significant bacterial resistance; only for resistence is uncommon; Vaccines: inactivated oral cholera vaccine;

scabies [5skeibii : z] a contagious ectoparasite skin infection characterized by superficial burrows, intense pruritus (itching) and secondary infection. It is caused by the mite Sarcoptes scabi from the Latin word for "scratch". The scabies mite usually is spread by direct, prolonged, skin-to-skin contact with a person who has scabies." Scabies is caused by the mite Sarcoptes scabiei, va

Scabies

Medications Topical: Permethrin: pesticide; Eurax (USP Crotamiton); Malathion; Lindane (Kwellada): when permethrin has failed or is contraindicated. Oral: Single dose of ivermectin

Epithelial keratitis

Epithelial keratitis is an ophthalmic disorder caused by the action of herpes simplex virus. Trifluridine (Viroptic) blocks herpes simplex virus reproduction and thereby helps to control this co

Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis are the primary bacterial phthogens;

Acute Otitis Meida in Childhood

Analgesics (acetaminophen, ibuprofen; codeine is an lternative); Antibiotics (amoxicillin or combind with clavulanate; cefuroxime axetil, cefprozil, ceftrizxone is most effective but need IV); Azithromycin and clarithromycin reserved for pts hypertensitive to b-lactam antibiotics.

Viruses, Neisseria gonorrhoeae, Mycoplasma/Chalmydophila pneumoniae, Chlamydia trachomatis are also the possible phthogens;

Streptococcal Sore Throat Pharyngitis

Analgesics (acetaminophen, ibuprofen) for fever and pain when necessary; Antibiotics: Penicillins: is the first choice; amoxicillin (liquid form useful for children); penecillin V K, amocixillin/clavulanate; Cephalosporins: cefuroxime axetil, cefprozil, cefixime, cephalexin, cefadroxil); Macrolides: Erythromycin, Azithromycin and clarithromycin; Ketolides: telithromycin, Licosamides: clindamycin,

[7CstiEu7maiE5laitis]

MRSA: methicillin-resistant S. aureus;

The blue part is used after the initial IV to complete the treatment course.

Acute Osteomyelitis

MSSA: Cloxacillin, cefazolin or clindamycin; Cloxacillin, cefalexin, amoxicillin/clavulanate, or clindamycin; Streptococcus group A: penicillin (initial); amoxicillin or clindamycin; Streptococcus group B: penicillin (in neonates, oral antibacterials are not appropriate); Enteric G-- : cefotaxime (in neonates, oral antibacterials are not appropriate); P. aeruginosa: ceftazidime + gentamicin; ciprofloxacin; MRSA: vancomycin Mixed aerobic/anaerobic: carbapenem, moxifloxacin, amoxicillin/clavulanate, or peperacillin/tazobactam; ciprofloxacin + clindamycin or amoxicillin/clavanate;

Sepsis and Septic Shock

Sepsis is a serious medical condition characterized by a whole-body inflammatory state (called a systemic inflammatory response syndrome or SIRS) caused by infection. The body may develop th in the blood. The related layman's term is blood poisoning. Severe sepsis occurs when sepsis leads to organ dysfunction, hypotension or insufficient blood flow (hypoperfusion) to one or more organs (causing lactic acidosis, decreased urine production or a to septic shock, multiple organ dysfunction syndrome and death.

3rd or 4th generation cephalosporin (cefotaxime, ceftazidime, ceftriaxone; cefepime); metronidazole, Extended-spectrum penicillin (peperacillin/tazobactam, ticarcillin/clavulanate); carbapenem (imipenem/cilastatin, meropenem), Extended-spectrum fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin); Macrolide (erhthromycin, azithromycin), Aminoglycosides (amikacin, gentamicin, tobramycin); Lincosamides (clindam Glycylcyclines (tigecycline); Vacomycin, Oxazolidinones (linezolid); Sterptogramins (quinupristin/dalfopristin; for most G-positive pathogens); Cyclic lipopeptides ( daptomycin, for MRSA and VRE)

Urinary Tract Infection

SMX/TMP: the choices for most UTIs; for sulfa allergy pts TMP alone may be used; Fluoroquinolones: norfloxacin, ciprofloxacin, ofloxacin, and levofloxacin, effective but expensive, second-line; Cephalosporins: cephalexin, cefazolin, cefaclor, cefuroxime, cefixime; ceftriaxone and cefotaxime (3rd generation for parenteral treatment of pyelonephritis ); Aminoglycosides: gentamicin, tobramycin, amikacin, the choice for acute pyelonephritis[7paiElEuni5fraitis]; Effective to most community-acquired G-negative organisms; Amoxicillin for known to be susceptible infections; Amoxicillin/clavulanate: expensive, for resistant organisms; Fosfomycin tromethamie: no cross resistance with other antimicrobials, most community-acquired organisms are susceptible, only for acute uncomplicated urinary infection; Nitrofurantoin: not for pelonephritis, and contraindicated in renal failure; Hepatic and pulmonary toxicity may occur.

Trichomoniasis: metronidazole; Not effective in intravaginal adm.; Bacterial Vaginosis: metronidazole (oral or vaginal gel, prefered choice, can be used in pregnanacy, nursing women); clindamycin oral or vaginal cream (alternative); Symptomatic Vulvovaginal Candidiasis: nystatin; fluconazole (oral); Topical: clotrimazole, econazole, miconazole, butoconazole, terconazole; Uncomplicated Chalmydia infection: zaithromycin; doxycycline (prefered); erythromycin; levofloxacin, ofloxacin; amoxicillin;

Sexually transmitted infections

Uncomplicated Gonorrhea infection: cefixime, cetriaxone; ciprofloxacin ofloxacin (prefered); spectinomycin;

Sexually transmitted infections

Syphilis: penicillin G benzathine (prefered), penicillin G; docycycline; Lymphogranuloma Venereum: doxycycline (prefered); azithromycin, erhthromycin (alternative); External Anogenital Warts: topical; podofilox; podophyllum resin; dichloracetic acid (DCA); trichloroacetic acid (TCA); Immune Response Modifiers (imiquimod Aldara); Vaccines;

Pelvic inflammatory Disease (PID): Outpatient: levofloxacin+/-metronidazole; ofloxacin+/-metronidazole; ceftriaxone+doxycycline +/-metronidazole; cefotaxime+doxycycline +/-metronidazole; cefo metronidazole; Intpatient: cefoxitin+doxycycline; clindamycin+gentamicin; levofloxacin+/-metronidazole;

Orolabial and Mouth HSV infections: acyclovir; famciclovir; penciclovir; valacyclovir;

Herpes Virus infection

Skin, Genital and Anal HSV infections: acyclovir; famciclovir; valacyclovir; HSV Encephalitis: acyclovir; HSV Keratoconjunctivitis: acyclovir;

Cytomegalovirus infection

Guanine Nucleoside Analogue Antiviral Agents: Ganciclovir, calganciclovir; Cytidine Nucleoside Analogue Antiviral Agents: Cidofovir; Inorganic Pyrophosphate Analogue Antiviral Agents: Forscarnet

Acute Otitis Media in children Otitis externa Swimmer's ear Jarish Herxheimer reaction

Generally caused by H. influenza and S. pneumonia, and Moraxella catarrhalis; Treatment: Amoxicillin +/- clavulanate; Cefuroxime axetil, cefprozil, Ceftriaxone; Azithromycin and Clarithromycin reserved for pts with hypersensitivity to beta-lactam antibiotics. An pseudomonad infection (P. aeruginosa); Centamicin and carbenicillin can be used for the treatment.

Defined as an exacerbation of the symptoms of syphilis that may occur upon starting Penicillin therapy. The effect is transient and require no treatment.

Pyelonephritis is an ascending urinary tract infection that has reached the pyelum (pelvis) of the kidney (nephros in Greek). If the infection is severe, the term "urosepsis" is used interchangeably (s response syndrome due to infection). It requires antibiotics as therapy, and treatment of any underlying causes to prevent recurrence. It is a form of nephritis. It can also be called pyelitis.

Pyelonephritis

It presents with dysuria (painful voiding of urine), abdominal pain and tenderness of the bladder area and the side of the involved kidney ("renal angle tenderness"). In many cases there are system rigors (violent shivering while the temperature rises), headache and vomiting. In severe cases, delirium may be present.

Antibiotic depends on local practice, and may include fluoroquinolones (e.g. ciprofloxacin), beta-lactam antibiotics (e.g. amoxicillin or a cephalosporin), trimethoprim (or co-trimoxazole) or nitrofu due to their toxicity, but may be added for a short duration

MAC

Mycobacterium avium complex (MAC), is a group of genetically related bacteria belonging to the genus Mycobacterium. It includes Mycobacterium avium subspecies avium (MAA), Mycobacteriu and Mycobacterium avium subspecies paratuberculosis (MAP). MAC bacteria are common in the environment and cause infection when inhaled or swallowed. Symptoms of MAC diseases are rem fever, fatigue, and weight loss. Many patients will have anemia and neutropenia if bone marrow is involved. Pulmonary involvement is similar to TB, while diarrhea and abdominal pain are associat MAC should always be considered in a person with HIV infection presenting with diarrhea.

Clarithromycin and Azithromycin are the first line agent for the treatment. Ventricular arrhythmia, leukopenia, thrombocytopenia and Steven Johnson syndrome are reported side effects of these

Bacterial endocarditis

Penicillin/ Streptomycin or Gentamicin are the choice in patients not allergic to penicillin in the treatment of bacterial endocarditis. Vancomycin and cefazolin are the alternatives when allergic

stomatitis

stomatitis [7stEumE5taitis] Inflammation of the mucous tissue of the mouth.

Syphilis infection

Aortitis is defined as an inflammation of the aorta, most common in a late complication of syphilis. Aortitis principally affects the ascending thoracic aorta. It may result in the formation of an aneurys blood flow. Chest pain is normally reported due to pressure on the surrounding structure, or from the reduced supply of blodd. The syphilis is treated by Penicillin G.

Important Human Pathogens and their diseases: Gram + cocci Staphylococcus aureus Streptococcus pyogenes Streptococcus pneumoniae Acid-fast rods Mycobacterium tuberculosis Mycobacterium leprae Nocardia Abscess, skin infections, toxic shock Strep throat, erysipolas, rheumatic fever pneumonia Tuberculosis Leprosy Nocardiosis

Gram + rods

Bacillus Clostridium Corynebacterium

Anthrax

Baci-An

Tetanus , Gas gangrene Clos-Gas-Te Diphtheria Gonorrhea Meningitis Cory-Diph

Gram cocci

Neisseria gonorrhoeae Neisseria meningitidis

Gram rods

Bodetella Salmonella Pseudomonas Shigella Vibrio cholerae Yersinia pestis

Pertussis Bod-Pert Typhoid fever Salm-Typh

Opportunistic lung and burn infection Dysentery Shig-Dysen Cholera plague Lyme disease Syphilis Pneumonia, urinary infections Rocky mountain spotted fever Urethritis, vaginitis

Spirochetes

Borrelia Treponema pallidum

Mycoplasma Rickettsia Chlamydia Fungi Systemic mycoses Candiada albicans Coccidioides immitis Protozoa Entamoeba histolytica Plasmodium Trichomonas vaginalis Helminths Schistosoma DNA viruses Variola and vaccinia Herpes simpex 1 virus HSV-2 Varicella zoster virus (VZV) Human cytomegalovirus (CMV) Human papillomavirus (HPV)

Candidiasis Valley fever Amoebiasis Malaria Trichomoniasis

schistosomiasis

Smallpox, cowpox Vario ----small Fever blister, cold sores Genital herpes Chickenpox, shingles Chicken CMV infections Warts VZV--

Hepatitis B virus (HBV) RNA virus Poliovirus Coxsackievirus Human rhinovirus Rubella virus Human rotavirus Influenza virus A Mumps virus Measles virus Respiratory syncytial virus (RSV) Rabies virus HIV (1 and 2) Infectious bronchitis virus (IBV)

Serum heptitis

Poliomyelitis Hand-foot-mouth disease Common cold, bronchitis Rubella, German measles Rotavirus gastroenteritis ( infant diarrhea) stomach flu Influenza, flu Mumps Measles(red) Common cold syndrome Rabies(hydrophobia) AIDS bronchitis

precautions and monitoring effects

significant interactions

ototoxicity, nephrotoxicity, neuromuscular blockade hypersensitivity

IV loop diuretics can result in increased ototoxity;

TDM, therapeutic drug monitoring, is Other aminoglycosides, necessary to obtain the correct dose. cephlosporin, cisplatin, amphotericin B, and methoxyflurane can cause May cause neuromuscular blockage increased nephrotoxicity when with severe respiratory muscle given concurrently with streptomycin paralysis. Contraindicated to use in pts with M. gravis due to impaired neuromuscular transmission.

cosides are often used in combination with cell wall-active agents such as betanot active against anaerobic bacteria or in low pH conditions such as abscesses or

ged therapy, preexisting renal dysfunction, elderly patients, and concurrent use of , vestibular toxicity (vertigo, ataxia), Nephrotoxicity due to aminoglycosides typically

lease and postsynaptic

ntration-dependent killing, ctivity persists , leading to a more rapid ncentrations

most nephrotoxic aminoglycoside

- > Amika- = gentamicin = tobra- > netilmicin

GI ( nausea, vomiting, diarrhea) seizure, dizziness hypotension( pts allerigic to penicillin or cephalosporins may suffer crosscensitivity)

al cell wall synthesis, reducing cell wall stability lysis

ea)

y,

Probenecid impair the excretion(except Ceftazidime)

disulfiram-type ed colitis; c elimination, the others renally eliminated, need reaction for alcohol consuption; patients iron supplements reduce absorption of cefdinir;

antacids may reduce the plasma ults on tests using the copper-reduction method; conc. of cefaclor extended-release tablet, cefdinir, and cefpodoxime; mb's test H2-antagonists may reduce plasma levels of cefpodoxime and cefuroxime

heses

c elimination, the others renally eliminated, need consuption; patients iron supplements reduce absorption of cefdinir;

antacids may reduce the plasma ults on tests using the copper-reduction method; conc. of cefaclor extended-release tablet, cefdinir, and cefpodoxime; mb's test H2-antagonists may reduce plasma levels of cefpodoxime and cefuroxime

heses

GI distress, cholestatic hepatitis, transient hearing impairment

erythromycin and simvastatin: potential for rhabdomyolysis. Adverse effects of

een associated with cholestasis.

sitis, mycoplasmal pneumonia, and pharyngitis, caution if the patient has liver or kidney disease, certain heart problems (e.g., QT prolongation or bradycardia), or an electrolyte imbalance (e.g., low K or Mg levels).

e bacterial exacerbation of chronic bronchitis, mydia pneumoniae or TWAR), skin and skin d to treat, disseminated Mycobacterium avium llosis.

Many other drugs can interact with trations; clarithromycin:. uspirone, carbamazepine, cyclosporine, digoxin,

hypersensitivity reactions, 10%, mild rash( urticarial, cesicular, bullous, scarlatiniform, maculopapular) to anaphylaxis ( severe hypotention, bronchoconstriction, nausea, vominting,abdominal pain and extreme weakness)

Probenecid increases blood levels of natural penicillins if given concurrently antibiotic antagonism occurs when erythromycins, tetracyclines or chloramphenicol is given within 1 hr.

other adverse effects: GI distress, bone marrow suppression, superinfection. High dose therapy,seizures may occur in patients with renal impairment

nephrotoxicity and interstitial nephritis probenecid increases blood levels

hepatotoxic

erythematous maculopapular rash

inhibit platelet aggregation---result in bleeding

high Na content---risk for pts with HF(hart failure); hypokalemia

cross-sensitivity drug interaction with celecoxib

blood dyscrasias: hemolytic anemia potentiate the effects of phenytoin, hypersensitivity reactions oral anticoagulants, crystalluria and hematuria and sulfonylureas

n's disease. It is also effective in several types of arthritis, particularly rheumatoid

atic are applied to 2nd- and 3rd-degree burns in

Well tolerated Common adverse effects: rash, nausea, vomiting, and photosensitivity, Rare: hepatotoxicity (increased transaminases), anemia, leukopenia, and Stevens-Johnson syndrome. TMP-SMX should be used with caution in patients with G6PD deficiency since this can cause hemolytic anemia

TMP-SMX is a known inhibitor of CYP450 and can substantially increase warfarin plasma concentrations and hypoprothrombinemic response.

cline.

n,

dairy products and iron preparations and antacids and laxatives ( Al, Ca Mg) reduce its absorption. (but etarted bone growth in infants and children < not for doxycycline) methoxyflurane exacerbate the nephrotoxic effect barbiturates and phenytoin decrease the antibiotic effectiveness Demeclocycline antagonizes the action of antidiuretic hormone(ADH)

GI distress, phototoxic reactions

norrhoea, especially in patients allergic to -lactams and macrolides; however,

minocycline).

he infectious agent of bubonic plague. It is also used for malaria treatment and

reum infection), Rickettsia (typhus, Rocky Mountain spotted fever), brucellosis,

mortality is questioned.

(esp Al and Mg containing) antacids and sucralfate and divalent or trivalent cations such as iron significantly decrease the absorption of fluoroquinolones

nd skin structure infections, traveler's diarrhea

increase prothrombin time in patients receiving warfarin

Cytochrome interactions: CYP450 inhibitors Norfloxacin > ciprofloxacin > moxifloxacin > levofloxacin = gatifloxacin. Warfarin: The exact warfarin-quinolone drug interaction is unknown. Reduction of intestinal flora responsible for vitamin K production by antibiotics is probable, as are decreased metabolism and clearance of warfarin due to CYP450 inhibition by the quinolones. Multivalent cations such as aluminum, magnesium, calcium, iron, zinc, and multivitamins with minerals may chelate with fluoroquinolones and decrease the oral absorption if administered concurrently.

concurent use with NSAIDs may increase the risk of CNS stimulation (seizures)

produce prolonged QT interval if administered with cisapride and antiarrhythmic agents;

ciprofloxacin increase theophylline levels

tive treatment to ciprofloxacin for anthrax.

timicrobial agents used in high doses for short ms of incubating syphilis.

gatifloxacin is contraindicated in diabetic patients

Didanosine should be adm.at least 4 hours after gatifloxacin

a black box warning: serious liver injury

The clinical use of these antibiotic class has been restricted due to their low water solubility, low activity against gram-negative bacteria and toxiciy in vivo.

Adverse effects are kidney and nerve damage when given by injection.

and as a solid fuel tablet used for cooking while camping or hiking. The name

ria and fungi in vitro.

g periods of time, nitrofurantoin can cause progressive pulmonary interstitial fibrosis.

gs: Chloramphenicol, isoniazid, streptomycin; Vitamin B12 can be used for treatment

inhibits the metabolism of phenytoin, tolbutamide, chlorpropamide, dicumarol; Phenobarbital shortens its half-life; acetaminophem elevates its levels bone marrow suppresion: pancytopenia, rarely aplastic anemia; and may cause toxicity; gray baby syndrome in neonates; Penicillin can cause antibiotic antagonism

coccal brain abscesses. It is also useful in the treatment of brain abscesses due to n allergy ; in the initial empirical treatment of children with fever and a petechial rash, gnostic investigations.

hea due to C. difficile can occur with any antibiotic, but particularly with clindamycin.

tibiotics, normal GI flora is inhibited, which allows C. difficile to overgrow, ent of choice for C. difficile infections. Although oral vancomycin also has activity ally used as second-line treatment.

hemolytic anemia in high dose, GI distress, CNS effects

Probenecid elevates blood levels

concomitant with adrenergic or serotonergic agents or consuming more than 100g of tyramine a day may enhance it's effect or serotonin syndrome

ototoxicity, nephrotoxicity with high dose, hypersensitivity red man's syndrome irritating to vein when injection

n/dalfopristin

so cause "red neck syndrome"

ancomycin. Its mechanism of action is to inhibit bacterial cell wall synthesis.

cluding methicillin-resistant Staphylococcus aureus and Enterococcus faecalis.Oral um difficile-associated diarrhoea, with comparable efficacy to vancomycin.

nose sugar with a keto-group and attaching a cyclic carbamate group in the lactone han other macrolides. Moreover, ketolides are effective against macrolide-resistant osome. Ketolides block protein synthesis by binding to ribosomal subunits and may

nity-acquired pneumonia, acute sinusitis, and acute exacerbations of chronic

occus faecium (VREF). It is not effective against Enterococcus faecalis infections.

ate phase of protein synthesis (translocation). The combination of the two components

p. in immunocompromised patients: candidosis, sis, blastomycosis, paracoccidioidomycosis, losis, extracutaneous sporotrichosis and ses of hyalohyphomycosis and

vomiting, headache, dyspnea, and tachypnea; Hydrocortisone, meperidine may also be added;

aminases;

all lysis

ug to treat ringworm infections of the skin and nails. It is derived from the mold

rformance of routine activities, Inability to fall or stay asleep, Nausea/ Vomiting, Oral ss of taste sensation, Sensitivity to prolonged sun exposure, Sensitivity to alcohol, al contraceptives

D_D: raise the serum level of astemizole, terfenadine, loratadine, cisapride; increase the risk of cardiac arrhythmia and cardiac toxicity.

s leakage of intracellular contents;

y tissues. Terbinafine inhibits ergosterol synthesis

s) and other types of ringworm (Tinea corporis).

gal nail infections are located deep under the nail

unction tests. May induce or exacerbate subacute

renal dysfunction is common, electrolyte wasting: hypokalemia, hypomagnemesia, Infusion-related toxicities (fever, chills, and rigons and hypotension)

increased renal toxicity used in combination with other nephrotoxic agents such as cyclosporine, tacrolimus, or aminoglycosides)

kin infections such as jock itch (Tinea cruris),

lled hydroxyquinolines which inhibit certain al infections.

qualene epoxidase. It is highly lipophilic in nature and tends to accumulate in skin,

perficial skin infections such as jock itch (Tinea cruris), athlete's foot (Tinea pedis) and

es foot (Tinea pedis), ringworm (Tinea corporis) and jock itch (Tinea cruris) due to E. p of fungi when compared to that of terbinafine, naftifine, clotrimazole, and tolnaftate.

tenafine demonstrates low minimum inhibitory concentrations against cryptococcus

as ketoconazole, fluconazole, itraconazole, and voriconazole and Topical agents he first oral azole developed, has poor bioavailability and requires an acidic has increased penetration across the blood-brain barrier. Fluconazole is also the only

in the scalp with Malassezia genus fungi. In the ption. At the 2.5% strength, selenium(IV) sulfide f Malassezia. then once a week for the next two weeks.

conazole, dazole, nazole, mazole;

Nazole---antifungal Dazole---antihelmintics metronidazole--trichomoniasis

_fungin

tment of Mycobacterium leprae infections and mucous membranes, dermatitis

nd to treat idiopathic thrombocytopenic

th a 4-methyl-1-piperazinaminyl group, is by far along with isoniazid, ethambutol, and

T) for the treatment of leprosy. It has been used AIDS patients. Clofazimine also has a marked

cautious in pts with hepatic disease

contraindicated in G6DP deficiency, tinnitus and optic neuritis patients

activity against C. difficile, it is typically used as ating certain anaerobic bacterial infections.

nation is used.

ecii, also formerly known as Pneumocystis carinii sidered an 'opportunistic infection', endangering

butol (RIPE) for two months, then isoniazid and rifampicin alone for a further four

two months, followed by isoniazid and rifampicin for four months. Ethambutol need

phenytoin can increase both drugs' blood levels Al- cotaining antacids may reduce isoniazid absorption carbamazepine may increase the risk of hepatitis

enting transcription to RNA and subsequent translation to proteins. Its lipophilic nature er). Rifampicin is typically used to treat Mycobacterium infections (tuberculosis and ophylactic therapy against Neisseria meningitidis (meningococcal) infection.

n undergo baseline and frequent liver function tests to detect liver damage. Rifampin

s, quinidine, digitoxin, protease inhibitors, nonnucleoside reverse transcriptase icol, barbiturates. of ASA granules.

y the enzyme alanine racemase; the two residues are joined by D-alanine ligase. Both

f infections other than tuberculosis.

Thrombophlebitis from IV adm., Headache, crystal nephropathy, concentration-dependant neurotoxicity (lethargy, coma, seizure, tremor, hallucinations)

Nephrotoxicity, teratogenic, carcinogenic, with intraocular adm.: hypotony, iritis, vitritis Renal impairment; Frequent monitoring of creatine clearance is required.

Thrombophlebitis from IV adm.,nephrotoxicity (acute tubular necrosis, crystalluria, interstitial nephritis), anema, elcetrolyte disturbances(Ca, Mg, / PO4), neurotoxicity.

diarrhoea, abdominal pain, flatulence, anorexia, igh pH), sweating, rash, itch, increased serum

d likely to cause inhibition of spermatogenesis.

c acid (aspirin) while taking rimantadine is known to reduce the body's uptake of dy's uptake of rimantadine. stem adverse effects: nausea, upset stomach, lty concentrating

by the virus thymidine kinase, and conversion to the di- and triphosphate is carried e, Thus, acyclovir triphosphate is inserted into the growing viral DNA, leading to o that of acyclovir, HSV that is resistant to acyclovir is also resistant to ganciclovir.

against HSV, but these agents are most commonly used for the treatment of infections mciclovir is the ester prod rug of penciclovir, an acyclovir analogue. Although the

eye" effect.

nsplants, or chemotherapy the virus is not adequately destroyed and can cause n virus that infects those who are HIV positive.It affects the eye in about 30% of the eye at first, but then may spread to the other.

reated by a vitreo-retinal surgeon, by antivirals such as ganciclovir or foscarnet,

retinitis.

Kidney stones Metabolic abnormalities including hyperlipidemia (cholesterol or triglyceride elevations) Bizarre alterations in body shape known as lipodystrophy

g therapy as part of highly active antiretroviral hate, ddATP, by cellular enzymes. Like other se by competing with natural dATP.

es

Nazole---antifungal Dazole---antihelmintics

bacterial STI ); from an infected mother to her baby during vaginal childbirth. Chlamydia conjunctivitis

llowing treatments:

se antibiotics do not eliminate the bacteria. Once treatment is stopped, the bacteria

mals by means of sexual contact, including vaginal intercourse, oral sex, and anal entially infect others, without showing signs of disease.

he visible membrane covering the head of the penis is a mucous membrane, though it

Fungal Jock Itch - Sexually transmissible. Yeast Infection

ransmission of Hepatitis D is uncertain, but may include sexual transmission. )

l, oral, head and neck cancer.

practices that promote anal-oral contamination. Sharing sex toys without washing or ally produce symptoms (diarrhea, fever, bloating, nausea, and abdominal pain)

carlet fever). It is believed to be caused by antibody cross-reactivity and can involve g in adults. or strep throat should also be treated with antibiotics. Monthly injections of Longng rheumatic fever includes the continual use of low dose antibiotics (such as

yeast is normally found on the human skin and only becomes troublesome under

d washed off after 10 minutes, repeated daily for 2 weeks[1]. Ciclopirox (Ciclopirox oconazole with a relative increase in subjective symptom relief due to its inherent antihydrogen peroxide has been known to lessen symptoms, and on certain occasions,

ys, or itraconazole 400 mg daily sweat is allowed to evaporate,

ruff shampoo to water used for

M. africanum, The vast majority of MTB cases throughout the world are due to M.

n consisting of these first-line agents is preferred for the initial empiric treatment of hus, multiple agents are used. Many of these drugs have significant drug-drug CYP450,

neuritis, and GI side effects. All four agents can potentially be hepatotoxic, but this tic neuritis is associated with ethambutol. The metabolism of isoniazid is genetically disposed to hepatotoxicity and peripheral neuropathy due to isoniazid. Fast acetylators

in inhibits DNA-dependent RNA polymerase in bacterial cells by binding its beta-

us, rash, redness and watering of eyes. / Abdominal - nausea, vomiting, abdominal

NS) effects, drug interactions resulting in increased phenytoin (Dilantin) or disulfiram

n at doses of 5 mg/kg. Persons with conditions in which neuropathy is common (e.g., (vitamin B6) (10-50 mg/day) with isoniazid.

e in acidic conditions. Pyrazinamidase converts pyrazinamide to the active form, lthough this has been disputed. Mutations of the pyrazinamidase gene (pncA) are

rowing TB bacilli, it works by obstructing the formation of cell wall.

ermatophytes, Candida, and non-dermatophytic moulds. Dermatophytes are the fungi equently involved in the tropics and subtropics with a hot and humid climate. ox or amorolfine. There is also evidence for combining systemic and topical

ct sports such as rugby, American football and wrestling are also susceptible, cus aureus, and sometimes by Streptococcus pyogenes.

ashing with soap and water and letting the impetigo dry in the air. Many general flucloxacillin or erythromycin or Dicloxacillin are necessary.

s the predominant cause of Lyme disease in the United States, whereas Borrelia

s belonging to several species of the genus Ixodes.In North America, the black-

ase. The antibiotics of choice are doxycycline (in adults), amoxicillin (in children),

diagnosed Lyme is treated with oral or IV antibiotics, frequently ceftriaxone for a

n occurs where the skin has previously been broken: cracks in the skin, cuts, blisters, tion, though cellulitis can occur on any part of the body. The mainstay of therapy

ylococcus are the most common of these bacteria, which are part of the normal flora n and intravenous (IV) therapy. Flucloxacillin monotherapy (to cover staphylococcal al phenoxymethylpenicillin or intravenous benzylpenicillin, or

y extending into underlying fat tissue. This disease is most common among the e (e.g., after mastectomy, pelvic surgery, bypass grafting) are also at increased risk.

symptoms resolve in a day or two, the skin may take weeks to return to normal. ot always stop reinfection.

nd furuncles and other cases of folliculitis develop from Staphylococcus aureus.

, known collectively as the meninges.The inflammation is usually caused by infection ue to the inflammation's proximity to the brain and spinal cord; it is therefore a medical an inability to tolerate bright light (photophobia) or loud noises (phonophobia). Rigidity

nown for causing chickenpox and shingles), mumps virus and HIV.

group B streptococcus (subtype III)especially in the first week of lifeand bacteria n and occurs in epidemics. Older children are more commonly affected by Neisseria n areas without vaccination, see below). In adults, N. meningitidis and S. ingitis due to infection with Mycobacterium tuberculosis, is more common in those

moniae, M. catarrhalis, H. influenzae, occasionally S. aureus, S. pyogenes,

ycycline

he end of April.

methoprim;

zil, cfuroxime axitil or sodium; cefotaxime, ceftazidime, ceftriaxone; Cefepime; lanate;

l america except Panama, Haiti, Middle East, Dominican); safe to use in pregnancy;

k after leaving the edemic area;

ight position; one day before exposure; daily during the stay and continue 4 weeks

area;

during the stay

entists.

fection. It is caused by the mite Sarcoptes scabiei. The word scabies itself is derived bies is caused by the mite Sarcoptes scabiei, variety hominis.

reproduction and thereby helps to control this condition.

rse.

avanate;

S) caused by infection. The body may develop this inflammatory response to microbes

g lactic acidosis, decreased urine production or altered mental status). Sepsis can lead

gentamicin, tobramycin); Lincosamides (clindamycin, to cover anaeroes);

onephritis ); quired G-negative organisms;

mplicated urinary infection;

ream (alternative);

miquimod Aldara); Vaccines;

; cefotaxime+doxycycline +/-metronidazole; cefoxitin+probenecid+doxycycline +/-

nt.

the term "urosepsis" is used interchangeably (sepsis being a systemic inflammatory nephritis. It can also be called pyelitis.

gle tenderness"). In many cases there are systemic symptoms in the form of fever,

orin), trimethoprim (or co-trimoxazole) or nitrofurantoin. Aminoglycosides are avoided

m avium subspecies avium (MAA), Mycobacterium avium subspecies hominis (MAH), swallowed. Symptoms of MAC diseases are reminiscent of tuberculosis. They include while diarrhea and abdominal pain are associated with gastrointestinal involvement.

son syndrome are reported side effects of these drugs.

nd cefazolin are the alternatives when allergic occurs.

orta. It may result in the formation of an aneurysm and obstruction to the coronary by Penicillin G.

page 1-50

Pathogenesis

Therapy

Arthritis

Osteoarthritis Rheumatoid arthritis Septic arthritis Gout ( Metabolic arthritis) Juvenile idiopathic arthritis Ankylosing spondylitis monosodium urate crystals form in articular tissues--set off an inflammatory reaction, Trauma, exposure to cold trigger the attack; Tophi may presented immobilize the affected joint/ anti-inflammatory drug should be used immediately / Urate-lowering drugs should not be used until the acute attack if controlled ---or prolong the attack by causing a change in uric acid equibrium. The presence of negatively birefringent crystals in the affected synovial joint fluid---Diagnosis

Gouty arthritis

Primary: defect in purine metabolism or uric acid excretion; uric acid over production; Secondary: Hematological causes (lymphoproliferative or myeloproliferative disorders, certain hemolytic anemias, hemoglobinopathies); Causes Chronic renal failure; Drugs-induced: aspirin and other salicylate; cytotoxid drugs; diuretics (except spironolactone); ethambutol and nicotinic acid; cyclosporine; ethanol; Other states: diabetic ketoacidosis, psoriasis, and chronic lead poisoning; NSAIDs: indomethacin--taken with food/milk GI effects naproxen/sulindac Colchicine: impairs leukocyte migration, disrupts urate deposition

Acute gouty arthritis Symptoms of Gout Periods of acute attacks with intense pain that completely resolve after a few days;

The attacks typically occur suddenly in the middle of the night; cortcosteroids: intra-articular injections of triamcinolone hexacetonide Most commonly affects the first metatarsophalangeal System: oral prednisone joint of the big toe and in an asymmetrical pattern. IV glucocorticoids or subcutaneous ACTH ( adrenocorticotropic hormone) if oral is not OK

intercritical gout

avoid urate production factors: high-purine diet, obesity, alcohol consumption prophylaxis: low-dose colchicine or NSAIDs after acute attack Urate-reducing drug: uricosurics: probenecid / sulfinpyrazone xanthine oxidase inhibitor: allopurinal losartan fenofibrate febuxostat

chronic tophaceous gout

allopurinal and probenecid in combination

Agents for osteoarthritis (OA)

Osteoarthritis is the most common form of arthritis in the United States, This disease affects men and women equally, but symptoms occur earlier and are more severe in women, Risk factors associated with the development of OA include age greater than 50 years, obesity (weight-bearing joints), injury to joints, joint overuse due to prolonged occupational or sports stress, and family history. There are cellular, mechanical, and biochemical processes that continually remodel and repair healthy joint cartilage, When these processes are altered, as in OA, the disruption leads to degenerative changes of the joint and abnormal repair responses, Inflammation may be present in OA but it is usually mild, Unlike rheumatoid arthritis, OA only involves the joints,

Improved function and quality of life are the primary goals of treatment. Nonpharmacologic therapy options for patients with OA are the mainstay of treatment. These measures, in addition to the pharmacologic options, are needed to provide patients with sufficient symptom relief and adequate function, The nonpharmacologic measures include patient NSAIDs education, exercise programs, weight loss if overweight, assistive devices if needed, and support group programs, Indomethacin Ibuprofen Naproxen Pharmacologic options include acetaminophen and NSAIDs. Acetaminophen has long been considered the drug of first choice in patients with OA. It provides effective pain COX-2 inhibitors relief for a number of patients and is safe to use in a wide range of patients, For patients in whom acetaminophen is not providing adequate pain control, an NSAID should be Celecoxib used, There are many NSAIDs that can be used, and the choice should be based on dosing regimen, cost, tolerance, comorbid diseases, concurrent medications, and patient preferences, The treatment of OA with COX-2 inhibitors is still being explored, These agents can be considered as an alternative for patients at risk for adverse GI effects from NSAIDs,

Rheumatoid arthritis (RA)

RA symptoms: Rheumatoid arthritis (RA) The early morning attack at least 30 min, usually 1 hr before maximal improvement; Most commonly, small joints of the hands (metacarpophalangeal and proximal interphalangeal), feet and cervical spine are affected. The joints are often affected in a fairly symmetrical fashion although at the beginning it is asymmetrical. The rheumatoid nodule, which is often subcutaneous, is the feature most characteristic of rheumatoid arthritis. Lab test Diagosis: presence of rheumatoid factor and antinuclear antibody; low hematocrit; eleated ESR; Inflammation of synovial fluid with an increased number of polymeorphonuclear leukoctes; Rheumatoid arthritis is a chronic, inflammatory, autoimmune disease of unknown etiology that if left untreated results in progressive joint destruction, deformity, disability, and premature death, Theories of possible etiologies include genetic, hormonal, viral, autoimmune, and environmental factors. The disease peaks between the fourth through sixth decades of life and is two to three times more common in women than in men, Differences in prevalence rates between ethnic groups are small, The pathogenesis of RA is a combination of cellular (e.g" macrophages, lymphocytes), biochemical (e,g., prostaglandins, cytotoxins) and mechanical factors that promote the inflammatory condition of the synovial lining. The normal anatomy of joints is altered in RA by immunologically mediated changes in bone, cartilage, supporting tissues, and synovial tissue and fluid,

Agents for Rheumatoid Arthritis (RA)

Indomethacin Piroxicam Ibuprofen Ketoprofen Naproxen Aspirin

The primary goals of therapy are to improve or maintain the patient's ability to function and carry out daily living activities, minimize symptoms, and diminish the progression of joint disease, Patient education, rest, exercise, proper diet, and NSAIDs are the foundation of RA therapy. NSAIDs are used to reduce joint swelling and pain, Onset effect is within a few days to a week, with peak effects in 1 to 4 weeks, The analgesic and anti-inflammatory effects of these agents do not alter the course of the disease, All NSAIDs are equally efficacious, Factors to be considered when choosing an anti-inflammatory agent are ease of dosing administration, tolerance, cost, patient's age, presence of comorbid diseases, concurrent drugs, and patient preferences.

DMARDs Disease-modifying antirheumatic drugs are second-line therapy when despite maximum doses of NSAIDs, a patient has ongoing joint pain, significant morning stiffness or Hydroxychloroquine (HCQ) fatigue, active synovitis, or persistent elevation of the erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) level. Methotrexate (MTX) Azathioprine (AZA) DMARDs have the potential to reduce or prevent joint damage and preserve joint integrity and function, The exact mechanism for these drugs is not known, The drugs in this Sulfasalazine (SSZ) class are relatively slow acting, with a delay of 1 to 6 months before a clinical response is evident.

Penicillamine is a pharmaceutical of the chelator class. The pharmaceutical form is D-penicillamine, as L-penicillamine is toxic (it inhibits the action of pyridoxine). It is a metabolite of penicillin, although it has no antibiotic properties. Penicillamine is used as a form of immunosuppression to treat RA. It works by reducing numbers of T-lymphocytes, inhibiting macrophage function, decreasing IL-1, decreasing rheumatoid factor, and preventing collagen from cross-linking. Penicillamine is also used for treatment of scleroderma. [7skliErEu5dE : mE] In Wilson's disease, a rare genetic disorder of copper metabolism, penicillamine treatment relies on its binding to accumulated copper and elimination through urine. In cystinuria, a hereditary disorder featuring formation of cystine stones, penicillamine binds with cysteine to to yield a mixed disulfide which is more soluble than cystine. Penicillamine has been used to treat mercury poisoning.

Penicillamine

Asthma

In asthma, constriction of the airways occurs due to bronchoconstriction and bronchial inflammation. Bronchoconstriction is the narrowing of the airways in the lungs due to the tightening of surrounding smooth muscle. Bronchial inflammation also causes narrowing due to edema and swelling caused by an immune response to allergens.

Quick-relief (rescue) medications are used to provide rapid relief of asthma symptoms (wheezing, cough, and SOB) and include short-acting inhaled 2-agonists and systemic corticosteroids. Long-term control (maintenance) medications are taken on a daily basis to achieve and maintain control of persistent asthma and include anti-inflammatory agents (inhaled corticosteroids, mast cell stabilizers), long-acting 2-agonists, methylxanthines, and leukotriene modifiers. Normal Concurrent Diseases : allergic rhinitis, sinusitis, GERD;

exercise-induced bronchospasm (EIB)

The goal of EIB treatment is to allow patients to exercise (including vigorous activities) without experiencing symptoms of bronchospasm.

albuterol Recommended treatments consist of medications taken as needed just prior to exercise to prevent symptoms or those taken long term on a daily basis to decrease inflammation bitolterol and airway hyperresponsiveness. Medications taken immediately before exercise include 2 -agonists and mast cell stabilizing agents. Inhaled 2-agonists are the mainstay of pirbuterol treatment and are more than 80% effective in preventing EIB if administered prophylactically.

salmeterol formoterol

Short-acting inhaled 2-agonists (albuterol, bitolterol, pirbuterol) administered 5-15 minutes before exercise are generally effective for 2 to 3 hours. (others: Salbutamol, terbutaline, fenoterol) Long-acting agents (salmeterol, formoterol) offer protection for up to 12 hours. The mast cell stabilizing agents (cromolyn, nedocromil) when taken 10 to 15 minutes before exercise are also effective alternatives.

COPD

Chronic Obstructive Pulmonary Disease is a respiratory condition characterized by irreversible airway obstruction caused by chronic bronchitis or emphysema, The major symptoms: chronic cough, increased sputum production, dyspnea.

The vast majority of patients with COPD are those who are current or former heavy smokers, Other risk factors: occupational exposure to (dusts, chemicals) and rare genetic disorders (1-antitrypsin deficiency),

Emphysema (emf-fi-see-maa ) is a chronic obstructive pulmonary disease (COPD, as it is otherwise known, formerly termed a chronic obstructive lung disease). It is often caused by exposure to toxic chemicals, including long-term exposure to tobacco smoke. Emphysema is characterized by loss of elasticity (increased Pulmonary compliance) of the lung tissue, from destruction of structures supporting the alveoli, and destruction of capillaries feeding the alveoli, owing to the action of alpha 1 antitrypsin deficiency. Thus the small airways collapse during exhalation, as alveolar collapsibility has increased. This impedes airflow and traps air in the lungs, as with other obstructive lung diseases. Symptoms include shortness of breath on exertion and later at rest, hyperventilation, and an expanded chest. Bronchodilators; Anticholinergics (ipratropium, tiotropium); 2 agonists(SABA salbutamol, terbutaline, fenoterol; LABA: salmeterol, formoterol); Therapeutic choices for Corticosteroids (inhaled beclomethasone, budesonide, fluticasone); Theophylline (aminophylline, oxtriphylline, theophylline); Oxygen Therapy (for pts with Stable COPD significant hypoxemia, PaO2 <55 mm Hg or SaO2 < 88%) Vaccines (vaccinate---penumonococal vaccination annually against influenza early in the fall)

Combination short-acting beta2-agonist (SABA: salbutamol, terbutaline, fenoterol) and ipratropium; Systemic Corticosteroids (two-week course of oral prednisone); Therapeutic choices for Antibiotics (extended macrolides: azithromycin, clarithromycin; cephalosporins: cefprozil, cefuroxime axetil; Fluoroquinolones: ciprofloxacin, gemifloxacin, Acute exacerbations COPD levofloxacin, moxifloxacin; Ketolides: telithromycin; Penicillins:amoxicilin+/- clavulanate; Tetracyclines: doxycycline; Sulfonamide combinations:TMP/SMX); Oxygen Therapy

Other informations Beta-adrenergic blockers Decrease aqueous inflow Betaxolol Carteolol levobunolol Metipranolol

Timolol Sympathomimetics Increase aqueous outflow Alpha/beta agonist Epinephrine Dipivefrin 2-agonists Decrease aqueous inflow Apraclonidine Brimonidine

2-agonists

Short-actin inhaled 2-agonists (Salbutamol, terbutaline, fenoterol, albuterol.) ; SABA Long-acting agents (salmeterol, formoterol) offer protection for up to 12 hours. LABA

Parasympathomimetics

(direct acting) Increase aqueous outflow Pilocarpine Carbachol Carbonic anhydrase Decrease aqueous inflow inhibitors Dorzolamide Brinzolamide Prostaglandin analogues Increase aqueous outflow latanoprost Bimatoprost Unoprostone Travoprost

POAG primary open-angle glaucoma

Usually asymptomatic upon initial presentation, Elevated IOP is frequently unaccompanied by pain or loss of vision, As the disease progresses, gradual nerve damage leads to cupping of the optic disc (an increase in cup-disc ratio) and subsequent visual field defects. This eventually results in loss of peripheral vision and even blindness, An lOP > 21 mm Hg without changes in visual fields and optic discs is defined as ocular hypertension. Intraocular pressure (IOP) (normal 10-20 mm Hg)

Topical beta-blockers: favored as a class due to their minimal local adverse effects but caution in patients with a history of reactive airway disease or cardiovascular diseases, Prostaglandin analogues: gained popularity by their convenient dosing frequency and minimal local and systemic side effects. Topical carbonic anhydrase inhibitors: effective IOP-reducing agents; but caution in patients with sulfa allergy, Topical miotic and mydriatic agents: bothersome local and systemic adverse effects; Oral carbonic anhydrase inhibitors and oral cholinergic agents: last-line therapies due to their serious side effect profiles,

Ophthalmics: Topical beta-blockers: timolol, betaxolol, levobunolol (caution in patients with a history of reactive airway disease or syncope or bradycardia); Carbonic Anhydrase inhibitors: dorzolamide, brinzolamide ( with caution in patients with sulfa allergy); Therapeutic choices of 2 -adrenergic agonists: apraclonidine, brimonidine; Canada Cholinergic agonists: pilocarpine, carbachol; Combinations: dorzolamide/timolol, lantanoprost/timolo, travoprost/timolol; brimonidine/timolol; Oral Carbonic Anhydrase inhibitors: acetazolamide, methazolamide

The definitive treatment for acute angle-closure glaucoma is a surgical or laser iridectomy.

Angle-closure Glaucoma
Acute narrow angle glaucoma narrow angle glaucoma

Angle-closure Glaucoma
Acute narrow angle glaucoma narrow angle glaucoma

Dilation of the pupil in the preexisting narrow anterior chamber may cause the iris to block aqueous humor Management includes combination therapy with PO/IV outflow via the anterior chamber. This leads to an acetazolamide, topical beta-blockers, PO/IV hyperosmotic abrupt increase in lOP, resulting in an acute attack of agents, and pilocarpine. angle-closure glaucoma, When the IOP reduced to levels fit for surgery, laser peripheral iridotomy is used to create a hole in the peripheral iris to relieve pupillary block.

Medical management is used initially to rapidly reduce the lOP, although surgical intervention is necessary for a permanent cure,

Symptoms: blurred vision (often with colored halos Hyperosmotic agents lower the IOP by creating an osmotic around the light), severe ocular pain, red conjunctiva, gradient between the plasma and aqueous humor from the diaphoresis, and nausea/vomiting, The cornea may anterior chamber of the eye, Available agents include glycerin, appear cloudy due to edema. Upon presentation, the urea, mannitol, isosorbide, and ethyl alcohol. lOP is frequently above 50 mm Hg.

1) muscarinic cholinomimetics: direct-acting ( pilocarpine, carbachol); indirect-acting (physostigmine) 2) adrenoceptor agonists: epinphrine 3) adrenoceptor blockers: timolol Glycerin 50% PO Mannitol 20% IV Hyperosmotic agents Urea 30% IV Isosorbide 45% PO Ethyl alcohol 50% PO Drug of choice among oral agents; use with caution in diabetic patients Drug of choice among intravascular agents; more effective for glaucoma with inflammation than urea or glycerol Contraindicated in patients with renal disease; caution in hepatic impairment Safe to use in diabetic patients (not metabolized to provide calories) Effective in emergency situations when other ag,ents are unava.i'able

BPH

Benign prostatic hyperplasia; the increase in size of the prostate in middle-aged and elderly men. the process is one of hyperplasia rather than hypertrophy ( prostatic stromal and epithelial cells), resulting in the formation of large, fairly discrete nodules in the periurethral region of the prostate. It leads to symptoms of urinary hesitancy, frequent urination, increased risk of urinary tract infections and urinary retention. Patients should decrease fluid intake before bedtime, moderate the consumption of alcohol and caffeine-containing products, and follow timed voiding schedules.

Alpha blockers (1-adrenergic receptor antagonists) provide symptomatic relief of BPH symptoms. Alpha-blockers relax smooth muscle in the prostate and the bladder neck, Alpha blockers and decrease the degree of blockage of urine flow. doxazosin, terazosin, Available drugs include doxazosin, terazosin, alfuzosin and tamsulosin. alfuzosin Older drugs, phenoxybenzamine and prazosin are not recommended for treatment of BPH. tamsulosin. Alpha-blockers may cause ejaculation back into the bladder (retrograde ejaculation).

5-reductase inhibitors The 5-reductase inhibitors (finasteride dutasteride) are another treatment option. This medication inhibits 5a-reductase, which in turn inhibits production of DHT, a hormone responsible for enlarging the prostate. finasteride dutasteride When used together with alpha blockers a reduction of BPH progression to acute urinary retention and surgery has been noted in patients with larger prostates.

Antihistamines, nasal decongestants and parasympatholytic drugs (such as dephenhydramien, phenylephrine, atropine) can precipitate urinary retention, and should be avoided by pts suffering from BPH

Alzheimer's disease AD

also called Alzheimer disease, Senile Dementia of the Alzheimer Type (SDAT) or simply Alzheimer's, is the most common form of dementia. This incurable, degenerative, and terminal disease was first described by German psychiatrist Alois Alzheimer in 1906. Generally it is diagnosed in people over 65 years of age, although the less-prevalent earlyonset Alzheimer's can occur much earlier. the early stages, the most commonly recognised symptom is memory loss; as the disease advances, symptoms include confusion, irritability and aggression, mood swings, language breakdown, long-term memory loss, and the general withdrawal of the sufferer as their senses decline. Gradually, bodily functions are lost, ultimately leading to death.

Reduction in the activity of the cholinergic cholinesterase inhibitors : neurons is a well-known feature of Alzheimer's donepezil disease. galantamine rivastigmine Neuropathology Alzheimer's disease is characterised by loss of neurons and synapses in the cerebral cortex and NMDA receptor antagonist : certain subcortical regions. This loss results in gross Memantine atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus

As of 2008, the cholinesterase inhibitors approved for the management of AD symptoms are donepezil (brand name Aricept), galantamine (Razadyne),and rivastigmine (branded as Exelonand Exelon Patch). There is evidence for the efficacy of these medications in mild to moderate Alzheimers disease. Only donepezil is approved for treatment of advanced AD dementia. Memantine (brand names Akatinol, Axura, Ebixa/Abixa, Memox and Namenda), is a noncompetitive NMDA (N-methyl Daspartate) receptor antagonist first used as an anti-influenza agent. Memantine has been shown to be moderately efficacious in the treatment of moderate to severe Alzheimers disease.

Acetylcholinesterase inhibitors are employed to The combination of memantine and donepezil has been shown reduce the rate at which acetylcholine (ACh) is to be "of statistically significant but Acetylcholinesterase broken down, thereby increasing the concentration of clinically marginal effectiveness". inhibitors ACh in the brain and combating the loss of ACh caused by the death of cholinergic neurons

noncompetitive NMDA It acts on the glutamatergic system by blocking NMDA receptors and inhibiting their overstimulation by glutamate. receptor antagonist

Glutamate

Glutamate is a useful excitatory neurotransmitter of the nervous system. Excitotoxicity is useful in other neurological diseases such as Parkinson's disease and multiple sclerosis. (but excessive amounts in the brain can lead to cell death through excitotoxicity which consists of the overstimulation of glutamate receptors. )

Tacrine is a parasympathomimetic and a centrally acting cholinesterase inhibitor (anticholinesterase). It was the first centrally-acting cholinesterase inhibitor approved for the Tacrine treatment of Alzheimer's disease, Limited by poor oral bioavailability, the necessity for four-times daily dosing, and considerable adverse drug reactions (including nausea, diarrhea, urinary incontinence and hepatotoxicity), tacrine is not preferred as other newer cholinesterase inhibitors, such as donepezil.

Parkinson's disease PD

PD is a degenerative disorder of the CNS that often impairs the sufferer's motor skills, speech, and other functions. It belongs movement disorders and characterized by muscle rigidity, tremor, a slowing of physical movement (bradykinesia) and, in extreme cases, a loss of physical movement (akinesia). Motor symptoms / cardinal symptoms (mnemonic "TRAP"): Tremor, Rigidity; bradykinesia/Akinesia; Postural instability (failure of postural reflexes, which leads to impaired balance and falls) The primary symptoms are the results of decreased stimulation of the motor cortex by the basal ganglia, normally caused by the insufficient formation and action of dopamine, which is produced in the dopaminergic neurons of the brain. Secondary symptoms may include high level cognitive dysfunction and subtle language problems. PD is both chronic and progressive that requires broad-based management including patient and family education, support group services, general wellness maintenance, physiotherapy, exercise, and nutrition.

Levodopa preparations: levodopa/carbidopa; Dopamine Agonists: bromocriptine, pergolide, pramipexole, ropinirole; ( Bromo- Pergo- Prami- Ropini) Therpeutic choices MAO-B inhibitors: rasagiline, selegiline in Canada COMT inhibitors: entacapone; Anticholinergic Agents: benztropine, ethopropazine, procyclidine, triexyphendidyl; (Benz- Etho- Procyc- Triexy) NMDA Receptor Antagonisits: amantadine

The symptoms of Parkinson's disease result from the loss of pigmented dopamine-secreting (dopaminergic) cells in the pars compacta region of the substantia nigra (literally Pathogenesis "black substance"). These neurons project to the striatum and their loss leads to alterations in the activity of the neural circuits within the basal ganglia that regulate movement, in essence an inhibition of the direct pathway and excitation of the indirect pathway.

Carbidopa/levodopa (co-careldopa); benserazide/levodopa L-dopa is transformed into dopamine in the dopaminergic neurons by L-aromatic amino acid decarboxylase. However, only 1-5% of L-DOPA enters the dopaminergic neurons. Levodopa The remaining L-DOPA is often metabolised to dopamine elsewhere, causing a wide variety of side effects. Due to feedback inhibition, L-dopa results in a reduction in the endogenous formation of L-dopa, and so eventually becomes counterproductive. Carbidopa and benserazide are dopa decarboxylase inhibitors.They help to prevent the metabolism of L-dopa before it reaches the dopaminergic neurons

Tolcapone inhibits the COMT enzyme, thereby prolonging the effects of L-dopa, and so has been used to complement L-dopa. However, due to its possible side effects such as COMT Inhibitors liver failure, it's limited in its availability. A similar drug, entacapone has not been shown to cause significant alterations of liver function and maintains adequate inhibition of COMT over time.

The dopamine agonists bromocriptine, pergolide, pramipexole, ropinirole , cabergoline, apomorphine, and lisuride are moderately effective. These have their own side effects including those listed above in addition to somnolence , hallucinations and/or insomnia. Several forms of dopamine agonism have been linked with a markedly Dopamine agonists increased risk of problem gambling. Dopamine agonists initially act by stimulating some of the dopamine receptors. However, they cause the dopamine receptors to become progressively less sensitive, thereby eventually increasing the symptoms.

Selegiline and rasagiline reduce the symptoms by inhibiting monoamine oxidase-B (MAO-B), which inhibits the breakdown of dopamine secreted by the dopaminergic neurons. Metabolites of selegiline include L-amphetamine and L-methamphetamine (dextrorotary isomers: more notorious and potent ). This might result in side effects such as insomnia. MAO-B inhibitors Unlike other non selective monoamine oxidase inhibitors, tyramine-containing foods do not cause a hypertensive crisis. Use of L-dopa in conjunction with selegiline has increased mortality rates that have not been effectively explained. Another side effect of the combination can be stomatitis.

It is an N-methyl-D-aspartate (NMDA) receptor antagonist. As an antiparkinsonian it can be used as monotherapy; or together with L-DOPA to treat L-DOPA-related motor Amantadine fluctuations (i.e., shortening of L-DOPA duration of clinical effect, probably related to progressive neuronal loss) and L-DOPA-related dyskinesias (choreiform movements associated with long-term L-DOPA use, probably related to chronic pulsatile stimulation of dopamine receptors).

Anticholinergics

Their major putative effect is on tremor, but not on bradykinesia; including benztropine, biperiden, ethopropazine, procyclidine, trihexyphenidyl; The side effects (dry mouth, urinary retention, constipation) limit their use, especially in the elderly.

Seizures and Epilepsy

Seneralized Tonic-clonic: carbamazepine, lamotrigine, phenytoin, valproic acid; clobazam, levetrizcetam, topiramate; Partial: carbamazepine, lamotrigine, phenytoin; clobazam, gabapentin, levetrizcetam, oxcarbazepine, phenobaral, primidone, topiramate, valproic acid, vigabatrin; Absence: ethosuximide, valproic acid; clobazam, lamotrigine, levetrizcetam, topiramate; Myoclonic and Atonic: valproic acid; clobazam, lamotrigine, levetrizcetam, topiramate; Status: diazepam (IV), lorazepam, phentoin, phenobarbital; Psycomoter: phentoin

Bipolar Disorder BD

It is a complex, recurrent mood disorder that affects 1-2% of the population. The pts have either a manic, hypomanic or mixed episode, and usually includes episodes of clinical depression. Acute Mania in BD: First line: lithium, divalproes, olanzapine, risperidone, quetiapine, lithium or divalproex plus risperidone, or quetiapine, or olanzapine; Second line: carbamazepine, oxcarbazepine, ECT (electroconvulsive therapy), lithium plus divalproex; Third line: haloperidol, chlorpromazine, lithium or divalproex plus haloperidol, lithium + carbamazepine; clozapine;

First line: lithium, lamotrigine, quetiapine, lithium or divalproex plus SSRI, or bupropion; olanzapine+fluoxetine; Second line: quetiapine plus SSRI; lithium or divalproex plus lamotrigine; Acute depression in BD: Third line: Carbamazepine, divalproex, olanzapine, lithium plus carbamazepine, or pramipexole, or MAOI, or venlafaxine; divalproex plus venlafaxine; atypical antipsychotic +/TCA; First line: lithium, lamotrigine, olanzapine, divalproes; Maintenance treatment of Second line: carbamazepine, oxcarbazepine, ECT (electroconvulsive therapy), lithium plus divalproex, or carbamazepine; lithium or divalproex plus olanzapine; resiperidone, BD: quetiapine, olanzapine plus fluoxetine; Third line: adjunctive therapy with phenytoin, clozapine, ECT, topiramate, omega-3 fatty acid, oxcarbazepine, gabapentin;

Second generation: clozapine, olanzapine, quetiapine, risperidone oral or IM; ---- Improving in negative symptoms; First line. Less sedation, cardiovascular and anticholinergic side effects. First generation: low potency (chlopramazine, methotrimeprazine); medium (loxapine, perphnazine, zuclopenthixol); high (flupenthixol, fluphenazine, haloperidol, pimozide, thiothixene, trifluperazine) Psychoses Weight gain: greatest in low potency FGAs; Higher in SGA than FGAs. Clo>Olan>Queti>Risperidone Glucose abnormalities:hyperglycemia, insulin resistance, new onset type 2 diabetes, exacerbation of type 1 diabetes and ketoacidosis; SGAs are higher risk than FGAs; hyperlipidimias is also common; Cardiovascular S/N: orthostatic hypotension, prolongation of QTc interval (chlorpromazine, pimozide, haloperidol; olan, queti, risperidone), torsades de pointes Endocrine and sexual S/N:

Secondary hypertension

Cushing syndrome: Weight gain, moon face, osteroporosis, hypokalemia, diabetes, hirsutism.; Pheochromocytoma: weight loss, episodic flushing, diaphoresis, tremors, h urinary catecholamines, headache, palpitations; Drugs induced: Oral contraceptives, NSAIDs, nasal decongestants, TCAs, MAOIs, appetite suppressants, cyclosporine, erythropoietin; Renal Diseases: repeated urinary tract infections, elevated serum creatinine levels, nocturia, hematuria ---chronic kidney disease; renal artery stenosis, renovascular disease..... Primary aldosteronism: muscle cramps, weakness, excess urination, isolated hypokalemia; Others conditions: Sleep apnea, Aortic Coarctation, Thyroid disease, and Parathyroid disease

the formation of a blood clot ("thrombus") in a deep vein. It is a form of thrombophlebitis (inflammation of a vein with clot formation). The classical symptoms of DVT include pain, swelling and redness of the leg and dilation of the surface veins. In up to 25% of all hospitalized patients, there may be some form of DVT, which often remains clinically inapparent (unless pulmonary embolism develops).
Deep vein thrombosis

DVT

Anticoagulation is the usual treatment for DVT. In general, patients are initiated on a brief course (i.e., less than a week) of heparin treatment while they start on a 3- to 6-month course of warfarin. LMWH is preferred, though unfractionated heparin is given in patients who have a contraindication to LMWH (e.g., renal failure or imminent need for invasive procedure). Thrombolysis is generally reserved for extensive clot, e.g. an iliofemoral thrombosis. Elastic compression stockings should be routinely applied "beginning within 1 month of diagnosis of proximal DVT and continuing for a minimum of 1 year after diagnosis". Inferior vena cava filter reduces pulmonary embolism and is an option for patients with an absolute contraindiciation to anticoagulant treatment.

what kind of drug can be used to treat the thrombolysis of a pregnant woman? treat the thrombolysis of a UFH or LMWH is the anticoagulant choice during pregnancy; SC injections of UFH twice dayily achievetherapeutic levels; and should be stopped at the first sign of labour; pregnant woman Warfarin or SC UFH may be used for about six weeks after delivery for secondary prevention. Women can breastfeed while being treated with warfarin. Urokinase (pregnancy category B); Heparin (hospital); LMWH (hospital: iv + outpatient: iv & sc)

Heart failure

Heart failure is a cardiac condition, that occurs when a problem with the structure or function of the heart impairs its ability to supply sufficient blood flow to meet the body's needs. Heart failure is a global term for the physiological state in which cardiac output is insufficient for the body's needs. This may occur when the cardiac output is low (often termed "congestive heart failure").In contrast, it may also occur when the body's requirements are increased, and demand outstrips what the heart can provide, (termed "high output cardiac failure") . This can occur in the context of severe anemia, beriberi (vitamin B1/thiamine deficiency), thyrotoxicosis, Paget's disease, arteriovenous fistulae or arteriovenous malformations.

Age> 65 y occurs most common; but it may occur at any age; Causes CAD (cornary artery disease): the cause of HF in about 2/3 of patients with left ventricular systolic dysfunction; Nonischemic causes: trauma, disease, or other abnormal states ( pulmonary emlolism, infection, anemia, pregnancy, drug use, or abuse, fluid overload, arrhythmia, valvular heart disease, cardiomyopathies, congenital heart disease) Cardiac arrest, and asystole: there is no cardiac output at all. Without urgent treatment, these result in sudden death. Heart attack refers to a blockage in a coronary (heart) artery resulting in heart muscle damage. Related terms and Cardiomyopathy refers specifically to problems within the heart muscle, and these problems usually result in heart failure. presences Ischemic cardiomyopathy implies that the cause of muscle damage is coronary artery disease. Dilated cardiomyopathy implies that the muscle damage has resulted in enlargement of the heart. Hypertrophic cardiomyopathy involves enlargement and thickening of the heart muscle.

Left-sided HF Left to Lung

Backward failure of the left ventricle causes congestion of the pulmonary vasculature, and so the symptoms are predominantly respiratory. The patient will have dyspnea (shortness of breath) on exertion (dyspne d'effort) and in severe cases, dyspnea at rest. Increasing breathlessness on reclining, called orthopnea, occurs. It is often measured in the number of pillows required to lie comfortably, and in severe cases, the patient may resort to sleeping while sitting up. Another symptom of heart failure is paroxysmal nocturnal dyspnea, a sudden nighttime attack of severe breathlessness, usually several hours after going to sleep. Easy fatigueability and exercise intolerance are also common complaints related to respiratory compromise. Compromise of left ventricular forward function may result in symptoms of poor systemic circulation such as dizziness, confusion and cool extremities at rest.

Common respiratory signs are tachypnea (increased rate of breathing) and increased work of breathing (non-specific signs of respiratory distress). Rales or crackles, heard initially in the lung bases, and when severe, throughout the lung fields suggest the development of pulmonary edema (fluid in the alveoli). Dullness of the lung fields to finger percussion and reduced breath sounds at the bases of the lung may suggest the development of a pleural effusion (fluid collection in the between the lung and the chest wall). Cyanosis which suggests severe hypoxemia, is a late sign of extremely severe pulonary edema. Additional signs indicating left ventricular failure include a laterally displaced apex beat (which occurs if the heart is enlarged) and a gallop rhythm (additional heart sounds) may be heard as a marker of increased blood flow, or increased intra-cardiac pressure. Heart murmurs may indicate the presence of valvular heart disease, either as a cause (e.g. aortic stenosis) or as a result (e.g. mitral regurgitation) of the heart failure.

Right-sided failure

Backward failure of the right ventricle leads to congestion of systemic capillaries. This helps to generate excess fluid accumulation in the body. This causes swelling under the skin (termed peripheral edema or anasarca) and usually affects the dependent parts of the body first (causing foot and ankle swelling in people who are standing up, and sacral edema in people who are predominantly lying down). Nocturia (frequent nighttime urination) may occur when fluid from the legs is returned to the bloodstream while lying down at night. In progressively severe cases, ascites (fluid accumulation in the abdominal cavity causing swelling) and hepatomegaly (painful enlargement of the liver) may develop. Significant liver congestion may result in impaired liver function, and jaundice and even coagulopathy (problems of decreased blood clotting) may occur.

Physical examination can reveal pitting peripheral edema, ascites, and hepatomegaly. Jugular venous pressure is frequently assessed as a marker of fluid status, which can be accentuated by the hepatojugular reflex. If the right ventriclar pressure is increased, a parasternal heave may be present, signifying the compensatory increase in contraction strength.

Long-term treatment with ACEIs (captopril, enalapril, lisinopril, ramipril, trandolapril) with the combination of beta-blockers (Carvedilol, Bisoprolol, Metoprolol tartrate); ARBs (Candesartan, Valsartan, alternative to ACEIs in pts intolerance of cough or angioedema) Diuretics for congestion (Loop: Furosemide, bumetanide, ethacrynic acid in most pts, Thiazide diuretics (Chlorthalidone, HCTZ, Metolazone, for pts with minimal fluid retention); Therapy choices Aldosterone Antagonists (Spironolactone for severe HF or post-MI pts with LVEF<40% and either HF symptoms or DM, Eplerenone (NA in CA)) Inotropic agents ( Digoxin, milrinone, dobutamine, for pts in hospitalization; or for ventricular rate with atrial fibrillation that not ok with b-blockers) Vasodilators (Nitrates/Hydralazine combination: in black pts with NYHA class III-IV HF Ca-channel blockers ( Amlodipine, Felodipine, for pts with persistent angina or with uncontrolled Hypertension ) Antiarrhythmics (in pts with atrial fibrillation, only amiodarone, avoid others)

ACE inhibitor Angiotensin-modulating agents ARBs ACE inhibitor (ACE) therapy is recommended for all patients with systolic heart failure, irrespective of symptomatic severity or blood pressure. ACE inhibitors improve symptoms, decrease mortality and reduce ventricular hypertrophy. Angiotensin II receptor antagonist therapy (also referred to as AT1-antagonists or angiotensin receptor blockers), particularly using candesartan, is an acceptable alternative if the patient is unable to tolerate ACEI therapy. ACEIs and ARBs decrease afterload by antagonizing the vasopressor effect of angiotensin, thereby decreasing the amount of work the heart must perform. It is also believed that angiotensin directly affects cardiac remodeling, and blocking its activity can thereby slow the deterioration of cardiac function.

Until recently (within the last 20 years), -blockers were contraindicated in CHF, owing to their negative inotropic effect and ability to produce bradycardia effects which worsen heart failure. However, current guidelines recommend -blocker therapy for patients with systolic heart failure due to left ventricular systolic dysfunction after stabilization with diuretic and ACEI therapy, irrespective of symptomatic severity or blood pressure. As with ACEI therapy, the addition of a -blocker can decrease mortality and improve left Beta blockers ventricular function. Several -blockers are specifically indicated for CHF including: bisoprolol, carvedilol, and extended-release metoprolol. The antagonism of 1 inotropic and chronotropic effects decreases the amount of work the heart must perform. It is also thought that catecholamines and other sympathomimetics have an effect on cardiac remodeling, and blocking their activity can slow the deterioration of cardiac function.

Diuretic therapy is indicated for relief of congestive symptoms. Several classes are used, with combinations Loop diuretics (e.g. furosemide, bumetanide) most commonly used class in CHF, usually for moderate CHF. Thiazide diuretics (e.g. hydrochlorothiazide, chlorthalidone, chlorthiazide) may be useful for mild CHF, but typically used in severe CHF in combination with loop diuretics, resulting in a synergistic effect. Potassium-sparing diuretics (e.g. amiloride) used first-line use to correct hypokalaemia. Diuretics Spironolactone is used as add-on therapy to ACEI plus loop diuretic in severe CHF. Eplerenone is specifically indicated for post-MI reduction of cardiovascular risk. If a heart failure patient exhibits a resistance to or poor response to diuretic therapy, ultrafiltration or aquapheresis may be needed to achieve adequate control of fluid retention and congestion. The use of such mechanical methods of fluid removal can produce meaningful clinical benefits in patients with diuretic-resistant heart failure and may restore responsiveness to conventional doses of diuretics.

Nesiritide is the recombinant form of the 32 amino acid human B-type natriuretic peptide, and works to facilitate cardiovascular fluid homeostasis through counterregulation of the renin-angiotensin-aldoesterone system, stimulating cyclic guanosine monophosphate, leading to smooth muscle cell relaxation. In simpler terms, it promotes vasodilation, Nesiritide natriuresis, and diuresis. Used to treat acutely decompensated congestive heart failure with dyspnea at rest or with minimal exertion (such as talk, eating or bathing).

Stable Angina

Antiplatelet agents: ASA (80-325 mg daily); clopidogrel, ticlopidine: ACE inhibitors: ramipril, decreasing adrenergic transmission, reducing afterload and blood pressure and improving coronary flow reserve; prevent major cardiovascular events in pts with stable angina. HMG CoA (Statins): simvastatin; Nitrates: nitroglycerin, isosorbide dinitrate; effective for acute and chronic angina; Sit when taking sublingul nitrates to reduce syncope; beta-blockers: nadolol, propranolol, timolol; atenolol, bisoprolol, metoprolol; pindolol, acebutolol, labetalol; lower heart rate, blood pressure and free fatty acid levels, and prevent angina by decreasing myocardial oxygen demand. It can reduce the risk of MI and mortality in pts with a prior MI. Avoid in pts with coronary arterial spasm (Prinzmetal's angina); Ca-channel blockers: Verapamil and diltiazem lower heart rate and reduce blood pressure; whereas the dihydropyridines (nifedipine, felodipine, amlodipine) exert their effects by arteriolar dilatation. The choice in pts with coronary arterial spasm. Short-acting nifedipine associated with higher mortality rates when used in pts with acute ischemic syndromes and hypertension, should be avoided.

Pindolol (Visken ), Oxprenolol (Trasicor ), Labetalol and Acebutolol have intrinsic sympathomimetic activity (ISA). These agents act as partial agonists and cause intrinsic sympathomimetic smaller reductions in heart rate and cardiac output. The clinical significance of these effects has yet to be clearly demonstrated. Agents with ISA should be avoided in patients activity (ISA) post-MI, or with CHF. Some people think they should be contraindicated in Angina, but some do not think so (Therapeutic choices P441)

It results from altered sodium homeostasis that leads to increased extracellular fluid volume (ECFV): peripheral edema, and anasarca ; Common conditions associated with edema: CHF, cirrhosis, renal failure, nephrotic syndrome, pregnancy. Edema Therapy choices for peripheral edema: Thiazides (Chlorthalidone, HCTZ, Indapamide, Metolazone, first-line agents if the creatinine clearance > 50 mL/min) Loop diuretics: (Furosemide, bumetanide, ethacrynic acid, first-line agents if the creatinine clearance < 50 mL/min) Potassium-sparing diuretics (Amiloride, Spironolactone, first-line agent in hepatic disease; or edema in CHF)

Renal Failure

or kidney failure, is the kidneys fail to function adequately and divided in acute and chronic forms; either form may be due to a large number of other medical problems. it is typically detected by an elevated serum creatinine and result a decrease in the glomerular filtration rate (GFR). Problems frequently encountered: abnormal fluid levels in the body, deranged acid levels, abnormal levels of potassium, calcium, phosphate, hematuria (blood in the urine) and (in the longer term) anemia. Long-term kidney problems have significant repercussions on other diseases, such as cardiovascular disease.

a rapid loss of renal function due to damage to the kidneys, resulting in retention of nitrogenous (urea and creatinine) and non-nitrogenous waste products. Generally characterized by oliguria ( less than 400 mL per day in adults, 0.5 mL/kg/h in children or 1 mL/kg/h in infants); body water and body fluids disturbances; and electrolyte Acute renal disease derangement. Accompanied by metabolic disturbances: metabolic acidosis and hyperkalaemia, changes in body fluid balance, and effects on many other organ systems. It can be characterised by oliguria or anuria. It is a serious disease and treated as a medical emergency.

Pre-renal (causes in the blood supply): hypovolemia; hepatorenal syndrome in which renal perfusion is compromised in liver failure; vascular problems (atheroembolic disease and renal vein thrombosis); infection usually sepsis, systemic inflammation due to infection; Renal (damage to the kidney itself): Acute tubular necrosis (ATN), the leading cause of ARF, may be associated with toxins or medication (e.g. some NSAIDs, aminoglycoside antibiotics, iodinated contrast, Causes lithium); phosphate nephropathy due to bowel preparation for colonoscopy with sodium phosphates) Ischemic injusry (e.g., surgery, circulatory collapse, severe hypotension); Pigment (e.g., hemolysis, myoglobinuria) Others: acute glomerulonephritis; rhabdomyolysis [can be caused by injury (crush injury and extensive blunt trauma), statins, stimulants and some other drugs] hemolysis; multiple myeloma;

 Post-renal (obstructive causes in the urinary tract) due to: ureteral, bladder, ureathral, extrinstic obstruction. o medication interfering with normal bladder emptying. o benign prostatic hypertrophy or prostate cancer. o kidney stones. o due to abdominal malignancy (e.g. ovarian cancer, colorectal cancer). o obstructed urinary catheter. Urine output: 20-500 ml/day; Uremia (excesive nitrogenous waste rention, leads to nausea, vomiting, diarrhea, edema, confusion, fatigue, neuromuscular irritability, and coma); Metabolic acidosis; Hyperkalemia; Hyperphosphatemia; Hyponatremia; Intravascular volume depletion (prerenal failure) --------------High H+, N-waste, K, PO43-, Low Na, intra-volune a progressive loss of renal function over a period of months or years through five stages.
Chronic kidney disease All individuals with a Glomerular filtration rate (GFR) < 60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence

of kidney damage. Stage 1 CKD: Slightly diminished function; Kidney damage with normal or increased GFR (>90 mL/min/1.73 m2). Stage 3 CKD: Moderate reduction in GFR (30-59 mL/min/1.73 m2) ----- "3---30" Stage 5 CKD: Established kidney failure (GFR <15 mL/min/1.73 m2, or permanent renal replacement therapy (RRT)

Influenza Amantadine rimantadine Zanamivir oseltamivir

Influenza is characterized by the abrupt onset of constitutional and respiratory signs and symptoms such as fever, myalgia, headache, severe malaise, nonproductive cough, sore throat, and rhinitis. In the United States, influenza is responsible for approximately 20,000 deaths annually, Immunoprophylaxis with inactivated vaccine remains the principal means for reducing influenza-related morbidity and death. Although the vaccine provides the best protection against influenza, there are four antiviral agents that are used to prevent or treat influenza: amantadine, rimantadine, zanamivir, and oseltamivir. To shorten the duration of influenza symptoms, all agents should be initiated within 2 days of onset of symptoms. Amantadine and rimantadine are chemically related antiviral drugs active against influenza A but not influenza B viruses. Amantadine differs from rimantadine because it is primarily renally eliminated and is associated with more CNS side effects and can potentially lower the seizure threshold, Zanamivir and oseltamivir are neuraminidase inhibitors that are active against influenza A and B viruses.

Antianaerobic Agents Metronidazole Clindamycin

Metronidazole and clindamycin are protein synthesis inhibitors that inhibit bacteria by interacting with the DNA to cause a loss of helical DNA structure and strand breakage, Metronidazole and clindamycin are commonly used in the treatment of intra-abdominal infections. Metronidazole has excellent activity against gram-negative anaerobes, whereas clindamycin has activity against both gram-positive and gram-negative anaerobes, The expression, "clindamycin for above the belt and metronidazole for below the belt" highlights the fact that metronidazole does not have good activity against gram-positive anaerobes found in the mouth, whereas clindamycin does. Metronidazole is also an antiprotozoan drug, and is the treatment of choice for amebiasis, giardiasis, and trichomoniasis.

The most troublesome side effect associated with metronidazole is GI intolerance. Metronidazole can cause a disulfiram-like reaction in patients who consume ethanol, due to inhibition of aldehyde dehydrogenase. The most notable adverse effect associated with clindamycin is antibiotic-associated colitis secondary to toxigenic Clostridium difficile. This organism usually overgrows in the GI tract in the presence of antibiotics due to the inhibition of normal GI flora. Ironically, the drug of choice for the treatment of antibiotic-associated colitis is metronidazole. Clindamycin also can cause diarrhea that is not related to C. difficile.

Tuberculosis

Tuberculosis (TB) may be caused by one of three mycobacterial organisms: Mycobacterium tuberculosis (MTB), Mycobacterium bovis, or M. africanum, The vast majority of MTB cases throughout the world are due to M. tuberculosis.

Pyrazinamide rapidly with monotherapy; thus, multiple agents are used. Many of these drugs have significant drug-drug interactions, so it is always important to take a complete medication Ethambutol history, Rifampin is a potent inducer of CYP450 and isoniazid is an inhibitor of CYP450,
RIPE

Rifampin Isoniazid The agents most commonly used for the treatment of active MTB are isoniazid, rifampin, pyrazinamide, and ethambutol. Usually a four-drug regimen consisting of these first-line
agents is preferred for the initial empiric treatment of MTB. When drug susceptibilities are known, the regimen should be tailored based on the results, Resistance develops

Side effects caused by isoniazid, rifampin, pyrazinamide, and ethambutol are common and can include hepatotoxicity, peripheral neuropathy, optic neuritis, and GI side effects. All four agents can potentially be hepatotoxic, but this side effect is most frequently associated with isoniazid and rifampin, Peripheral neuropathy is most commonly associated with isoniazid, whereas optic neuritis is associated with ethambutol. The metabolism of isoniazid is genetically predetermined. Patients of Scandinavian, European, and African descent metabolize isoniazid slower (slow acetylators) and are therefore more predisposed to hepatotoxicity and peripheral neuropathy due to isoniazid. Fast acetylators include people of Asian or American Indian descent and are less predisposed to these adverse effects.

Hepatitis C virus infection is a leading cause of chronic liver disease in the United States.

Interferon-a and the combination of interferon-a plus oral ribavirin are the only FDA-approved drugs for the treatment of chronic HCV infection. The combination of interferon and ribavirin has a significant benefit on sustained virologic response (the absence of detectable HCV RNA more than 6 months after treatment), biochemical response (normalization of transaminases), and liver histology in patients with hepatitis C compared with interferon by itself. Ribavirin is ineffective by itself and should not be used as monotherapy.

Hepatitis

It is the leading cause of cirrhosis, and is the most common reason for liver transplantation.

Side effects

Interferon therapy: Fatigue, fever, headache, chills, myalgia, dizziness, anorexia, nausea, alopecia, myelosuppression, and depression (common side effects). Interferon therapy is contraindicated in patients with a history of autoimmune disorders, and should be used with extreme caution in organ transplant recipients, and those with a history of neuropsychiatric disorders. Common side effects of ribavirin therapy include dose-dependent hemolytic anemia, pruritis, and anemia. Because ribavirin is highly teratogenic (pregnancy category X), ribavirin is contraindicated in women who are pregnant or in men whose female partners are pregnant.

ADHD hyperkinesis disorders

Attention-Deficit Hyperactivity Disorder (ADHD) is a neurobehavioral developmental disorder affecting about 3-5% of the world's population. It typically presents during childhood, and is characterized by a persistent pattern of impulsiveness and inattention, with or without a component of hyperactivity. The most common symptoms of ADHD are: Impulsiveness: a person who acts quickly without thinking things through. / Hyperactivity: a person who is unable to sit still. / Inattention: a person who daydreams or seems to be in another world.

First line treatments: stimulants (Methylphenidate, Dextroamphetamine, mixed salts Amphetamine)-- ADHD need AMD-atom-Bup-TCA Norepinephrine Reuptake inhibitors (atomoxetine); Therapeutic Choices in Antidepreessants (bupropion), TCAs (desipramine, imipramine); 2ed or 3rd line options; Canada 2-adrenergic agonists (clonidine), 2ed or 3rd line options; Atypical antipsychotics (risperidone) ; Natural Health Products: chamomile, valerian, melatonin, used in children who are restless, anxious, or sleep-dificult situations.

Methods of treatment usually involve some combination of medications, behavior modifications, life style changes, and counseling. The American Academy of Pediatrics states that stimulant medications and/or behavior therapy are appropriate and generally safe treatments for ADHD. Long term safety of stimulants however has not been determined beyond three years and drug treatment of pre-school children is not recommended.

Stimulants include different formulations of methylphenidate: short acting, such as Methylphenidate (Ritalin) and Dexmethylphenidate (Focalin), with a duration of 3-5 hours intermediate acting, such as Ritalin SR (sustained-release), Metadate ER (methylphenidate hydrochloride extended-release) , and Methylin ER, with a duration of 3-8 hours long acting, such as Concerta, Rilatin LA and Metadate CD, with a duration of 8-12 hours and which can be used just once a day (Canadian guidelines recommend the longMethylphenidate acting agents as the first-line treatment of ADHD) Amphetamine The other type of stimulant includes different formulations of amphetamine: short acting, such as Dexedrine and Dextrostat, with a duration of 4-6 hours intermediate acting, such as Adderall and Dexedrine spansule, with a duration of 6-8 hours; long acting, such as Adderall-XR

Similar to Methylphenidate, the mechanism of action of Pemoline is to inhibit the reuptake of Dopamine and to increase the release of Dopamine and Norepinephrine in the central nervous system. Pemoline Used to treat attention-deficit hyperactivity disorder (ADHD) and narcolepsy. Under the Convention on Psychotropic Substances, it is a Schedule IV drug. Pemoline has some advantages over other stimulants in that it does not reduce the appetite or cause dry mouth.

Atomoxetine

a norepinephrine reuptake inhibitor not classified as a stimulant, indicated in children >6 years of age, adolescents and adults with ADHD; appropriate for those who have either not responded to or not toletated an adequate trial of stimulant medicaitons.

Bupropion, TCAs (Dedipramine, Imipramine, Nortriptyline) RNRIs (Venlafaxine) second or third-line options or as adjunctive therapy for the treatment ADHD in both children and Antidepressants adults; Less effective than stimulants in the management of ADHD in children; but may be benefit pts with comobid conditions such as depression, anxiety, enuresis or tic disorders; 2-adrenergic agonists clonidine; used as second or third-line options or as adjunctive therapy for the treatment ADHD; reducing symptoms of aggression, impulsibity, overarousal and hyperactivity, but have minimal effect on symptoms of inatention or poor concentration.

Antipsychotics low doses of atypical antipsychotics (e.g., risperidone) may be moderately effective for the behavioural symptoms seen in hyperactive and impulsive children. Natural products chamomile, valerian, melatonin for recuding restless, anxious or sleep difficulties; The other antioxidants: Blue-green algae, Vitamin B, ginkgo biloba, pycnogenol, and evening primrose oil;

Dyspepsia is a chronic or recurrent discomfort/pain in the upper abdomen, The causes for dyspepsia involve gastroduodenal ulcer, atypical gastroesophageal reflux, and gastric cancer. Classic symptoms related to gastroduodenal ulcers, such as postprandial epigastric pain or pain relieved by eating, are common. More importantly, dyspepsia may be associated with certain alarm features such as recurrent vomiting, weight loss, dysphagia, bleeding, or anemia. Peptic Ulcer Disease Helicobacter pylori is a gram-negative spiral bacterium that has been implicated in the pathogenesis of gastroduodenal ulcers, H, pylori has been found in nearly 90% of patients with duodenal ulcers and nearly 70% of patients with gastric ulcers. Eradication of H, pylori has been shown to decrease the recurrence rate and accelerate the ulcer healing process, In cases of H, pylori-positive dyspepsia, treatment is aimed at eradicating bacteria as well as alleviating symptoms, In cases of H. pylori-negative dyspepsia, empiric antisecretory drugs or prokinetic agents are often initiated, If treatment with these agents fails, the patient should be referred for endoscopy to rule out chronic ulceration or other causes,

Cimetidine Ranitidine Nizatidine Famotidine

Patients with documented H. pylori cultures and active ulceration should be treated with antisecretory agents(H2 -Receptor Antagonists ) and combination antibiotics, Treatment regimens are individualized and may include one, two, or three of the following antimicrobials: amoxicillin, clarithromycin. metronidazole, tetracycline, and bismuth subsalicylate. Treatment regimens for H. pylori can be taken together at the same time, without regard to meals or drug interactions among the regimens. This is because systemic blood levels are not necessary; rather, the goal of therapy is local gastrointestinal antimicrobial activity.

Herpes simplex

Herpes simplex is a viral disease caused by Herpes simplex viruses; both herpes simplex virus 1 (HSV-1) and herpes simplex virus 2 (HSV-2) cause herpes simplex. Infection with the herpes virus is categorized into one of several distinct disorders based on the site of infection. Oral herpes, the visible symptoms of which are colloquially called cold sores, infects the face and mouth. Oral herpes is the most common form of infection. Infection of the genitals, commonly known as herpes, is the second most common form of herpes. Other disorders such as herpetic whitlow, herpes gladiatorum, ocular herpes (keratitis), cerebral herpes infection encephalitis, Mollaret's meningitis, neonatal herpes, and possibly Bell's palsy are all caused by herpes simplex viruses.

Orofacial herpes affects the face and mouth. Infection occurs when the virus comes into contact with oral mucosa or abraded skin. Infection by the type 1 strain of herpes simplex virus (HSV-1) is the most common cause of orofacial herpes, though cases of oral infection by the type 2 strain are increasing. (Mouth is on the top, so is related to the first HSV---HSV-1; Genital infections is related to HSV-2)

Viral meningitis

HSV-2 is the most common cause of Mollaret's meningitis, a type of recurrent viral meningitis. This condition was first described in 1944 by French neurologist Pierre Mollaret. Recurrences usually last a few days or a few weeks, and resolve without treatment. They may recur weekly or monthly for approximately 5 years following primary infection

Following active infection herpes viruses establish a latent infection in sensory and autonomic ganglia of the nervous system. The double-stranded DNA of the virus is incorporated into the cell physiology by infection of the nucleus of a nerve's cell body. HSV latency is staticno virus is producedand is controlled by a number of viral genes, including Latency Associated Transcript (LAT). Recurrence Many HSV infected people experience recurrence within the first year of infection. Prodrome precedes development of lesions. Prodromal symptoms include tingling (paresthesia), itching, and pain where lumbosacral nerves innervate the skin. Prodrome may occur as long as several days or as short as a few hours before lesions develop. Beginning antiviral treatment when prodrome is experienced can reduce the appearance and duration of lesions in some individuals. During recurrence fewer lesions are likely to develop, lesions are less painful, and lesions heal faster (within 510 days without antiviral treatment), than those occurring during the primary infection. Subsequent outbreaks tend to be periodic or episodic, occurring on average four to five times a year when not using antiviral therapy.

There are several prescription antiviral medications for controlling herpes simplex outbreaks, including aciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), and Antiviral medication penciclovir. Aciclovir was the original, and prototypical, member of this drug class; it is now available in generic brands at a greatly reduced cost. Valaciclovir and famciclovir prodrugs of aciclovir and penciclovir, respectivelyhave improved solubility in water and better bioavailability when taken orally. Aciclovir is the recommended antiviral for suppressive therapy for use during the last months of pregnancy to prevent transmission of herpes simplex to the neonate in cases of maternal recurrent herpes.

Docosanol, also known as behenyl alcohol, is a saturated fatty alcohol used mainly as an antiviral agent, specifically for treatment of "cold sores" caused by the herpes simplex Docosanol virus. It is normally administered topically in a cream containing a base and a 10% mix of the active ingredient. It probably functions by inhibiting the fusion of the human host cell with the viral envelope of the herpes virus, thus preventing its replication.

Herpes zoster shingles

Herpes zoster (or simply zoster), commonly known as shingles, is a viral disease characterised by a painful skin rash with blisters in a limited area on one side of the body, often in a stripe. The initial infection with varicella zoster virus (VZV) causes the acute (short-lived) illness chickenpox, and generally occurs in children and young people. Once an episode of chickenpox has resolved, the virus is not eliminated from the body but can go on to cause shinglesan illness with very different symptomsoften many years after the initial infection.

The earliest symptoms of herpes zoster, which include headache, fever, and malaise, are nonspecific, and may result in an incorrect diagnosis. These symptoms are commonly followed by sensations of burning pain, itching, hyperesthesia, or paresthesia (sensitivity to heat, cold, light or touch). The pain may be extreme in the affected dermatome, with sensations that are often described as stinging, tingling, aching, numbing or throbbing, and can be interspersed with quick stabs of agonizing pain. In most cases, after 12 days (but sometimes as long as 3 weeks) the initial phase is followed by the appearance of the characteristic skin rash. The pain and rash most commonly occurs on the torso, but can appear on the face, eyes or other parts of the body. At first, the rash appears similar to the first appearance of hives; however, unlike hives, herpes zoster causes skin changes limited to a dermatome, normally resulting in a stripe or belt-like pattern that is limited to one side of the body and does not cross the midline. Zoster sine herpete describes a patient who has all of the symptoms of herpes zoster except this characteristic rash.

Lipodystrophy

(=lipodystrophia), Lipodystrophy is a medical condition characterized by abnormal or degenerative conditions of the body's adipose tissue.

A lipodystrophy can be a lump or small dent in the skin that forms when a person keeps performing injections in the same spot. These types of lipodystrophies are harmless. People who want to avoid them can do so by changing (rotating) the places where they perform injections. For people with diabetes, using purified insulins may also help. Insulin injections One of the side-effects of lipodystrophy is the rejection of the injected medication, the slowing down of the absorption of the medication, or trauma that can cause bleeding that, in turn, will reject the medication. In either scenarios, the dosage of the medication, such as insulin for diabetics, becomes impossible to gauge correctly and the treatment of the disease for which the medication is administered is impaired thereby allowing the medical condition to worsen. In some cases, rotation of the injection sites may not be enough to prevent lipodystrophy.

Antiretroviral drugs

Lipodystrophies can be a possible side effect of antiretroviral drugs. Other lipodystrophies manifest as lipid redistribution; with excess, or lack of, fat in various regions of the body. These include, but are not limited to, having sunken cheeks and/or "humps" on the back or back of the neck (also referred to as buffalo hump).

Hereditary forms Lipodystrophy can be caused by metabolic abnormalities due to genetic issues. These are often characterized by insulin resistance and are associated with Syndrome X.

Travelers' Diarrhea

Infectious agents are the primary cause of TD. Bacterial enteropathogens cause approximately 80% TD usually is a self-limited disorder and often resolves without specific treatment; however, oral rehydration is often of TD cases. The most common causative agent beneficial to replace lost fluids and electrolytes. Clear liquids are routinely recommended for adults. Travelers who develop isolated in countries surveyed has been three or more loose stools in an 8-hour period---especially if associated with nausea, vomiting, abdominal cramps, fever, or enterotoxigenic Escherichia coli (ETEC). ETEC blood in stools---may benefit from antimicrobial therapy. Antibiotics usually are given for 3-5 days. Currently, produce watery diarrhea with associated cramps and fluoroquinolones are the drugs of choice. Commonly prescribed regimens are 500 mg of ciprofloxacin twice a day or 400 low-grade or no fever. Besides ETEC and other mg of norfloxacin twice a day for 3-5 days. Trimethoprim-sulfamethoxazole and doxycycline are no longer recommended bacterial pathogens, a variety of viral and parasitic because of the high level of resistance to these agents. Bismuth subsalicylate also may be used as treatment: 1 fluid enteric pathogens also are potential causative ounce or 2 262 mg tablets every 30 minutes for up to eight doses in a 24-hour period, which can be agents. repeated on a second day. If diarrhea persists despite therapy, travelers should be evaluated by a doctor and treated for possible parasitic infection.

CDC does not recommend antimicrobial drugs to prevent TD. Studies show a decrease in the incidence of TD with use of bismuth subsalicylate and with use of antimicrobial chemoprophylaxis;

Acute Diarrhea

Oral Rehydration therapy: ORT; Opioids: loperamide (less side effects and abuse potential), diphenoxylate with atropine sulfate; codeine; Bismuth: Bismuth subsalicylate; Hydrophillic Bulking Agents: psyllium hydrophillic mucilloid, chloestyamine resin; 2 -adrenergic agonists: clonidine ( effecitve for opioid-withdrawal diarrhea and diarrhea associated with diabetic autonomic neuropathy) Somatostatin: Octreotide, octreotide acetate, lanreotide acetate (to control diarrhea caused by neuroendocrine tumors); Not recommended Empiric Antibiotics for acute diarrhea because of the self-limiting nature of most illnesses, the cost of treatment, the potential for promoting antimicrobial resistance and the possibility of adverse drug reactions.

Diabetes insipidus Desmopressin CT or HCTZ indomethacin amiloride

Diabetes insipidus (DI) is a condition characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the kidney to concentrate urine.

Excessive urination and extreme thirst (especially for cold water and sometimes ice or ice water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine is not sweet as it does not contain glucose and there is no hyperglycemia. Blurred vision is a rarity. Signs of dehydration may also appear in some individuals since the body cannot conserve much (if any) of the water it takes in.The extreme urination continues throughout the day and the night. In children,

DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is drunk to offset the urinary losses. DI is caused by a deficiency of antidiuretic hormone However, there is a continuous risk of dehydration. (ADH), also known as vasopressin, due to the destruction of the posterior pituitary gland where Central DI and gestational DI respond to desmopressin. Also gestational DI tends to abate on its own 4 to 6 weeks vasopressin is normally released from, or by an following labour, though some women may develop it again in subsequent pregnancies. In dipsogenic DI, desmopressin is insensitivity of the kidneys to vasopressin. It can also not usually an option. be induced iatrogenically by various drugs. Desmopressin will be ineffective in nephrogenic DI. Instead, the diuretic hydrochlorothiazide (HCT HCTZ hydrochlorothiazide) or indomethacin, amiloride can improve nephrogenic diabetes insipidus; HCTZ is sometimes combined with amiloride to prevent hypokalemia. Again, adequate hydration is important for patients with DI, as they may become dehydrated easily.

Anemia

defined as a qualitative or quantitative deficiency of hemoglobin, a molecule found inside red blood cells (RBCs). Since hemoglobin normally carries oxygen from the lungs to the tissues, anemia leads to hypoxia (lack of oxygen) in organs. Since all human cells depend on oxygen for survival, varying degrees of anemia can have a wide range of clinical consequences. Anemia is caused by the lack of iron in the body as well. The three main classes of anemia include excessive blood loss (acutely such as a hemorrhage or chronically through low-volume loss), excessive blood cell destruction (hemolysis) or deficient red blood cell production (ineffective hematopoiesis).

Megaloblastic anemia

Megaloblastic anemia, the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid (or both). Deficiency in folate and/or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does. Causes: Hypothyroidism; Alcoholism commonly causes a macrocytosis, although not specifically anemia. Other types of Liver Disease can also cause macrocytosis. Methotrexate, zidovudine, and other drugs that inhibit DNA replication.

(MCV>100)

Microcytic anemia is primarily a result of hemoglobin Heme synthesis defect: Iron deficiency anemia / Anemia of chronic disease (more commonly presenting as normocytic synthesis failure/insufficiency. anemia) Microcytic anemia (MCV<80) Iron deficiency anemia is the most common type of anemia overall and it has many causes. RBCs often appear hypochromic (paler than usual) and microcytic (smaller than usual) when viewed with a microscope. Globin synthesis defect: -, and -thalassemia / HbE syndrome / HbC syndrome / and various other unstable hemoglobin diseases Sideroblastic defect: Hereditary sideroblastic anemia / Acquired sideroblastic anemia, including lead toxicity / Reversible sideroblastic anemia

Normocytic anaemia occurs when the overall hemoglobin levels are always decreased, but the red blood cell size (Mean corpuscular volume) remains normal. Causes include: Normocytic anemia (80<MCV<100) Acute blood loss Anemia of chronic disease Aplastic anemia (bone marrow failure) Hemolytic anemia

Migraine
[5mi : ^rein , 5mai - ]

Migraine is a neurological syndrome characterized by altered bodily experiences, painful headaches, and nausea. It is a common condition which affects women more frequently than men. The typical migraine headache is one-sided and pulsating, lasting 4 to 72 hours. Accompanying complaints are nausea and vomiting, and a heightened sensitivity to bright lights (photophobia) and noise (hyperacusis). Approximately one third of people who experience migraines get a preceding aura, in which a patient may sense a strange light or unpleasant smell. The treatment of migraine begins with simple painkillers for headache and anti-emetics for nausea, and avoidance of triggers if present.

Migraine attacks may be triggered by: Allergic reactions / Bright lights, loud noises, and certain odors or perfumes / Physical or emotional stress / Changes in sleep patterns Smoking or exposure to smoke / Skipping meals / Alcohol / Menstrual cycle fluctuations, birth control pills, hormone fluctuations during the menopause transition / Tension headaches Foods containing tyramine (red wine, aged cheese, smoked fish, chicken livers, figs, and some beans), monosodium glutamate (MSG) or nitrates (like bacon, hot dogs, and salami) / Other foods such as chocolate, nuts, peanut butter, avocado, banana, citrus, onions, dairy products, and fermented or pickled foods.

beta blockers such as propranolol and atenolol. anticonvulsants such as valproic acid and topiramate. antidepressants include tricyclic antidepressants (TCAs) such as amitriptyline and the newer selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine. Treatment Other drugs: Sansert was withdrawn from the US market by Novartis, but is available in Canadian pharmacies. Although highly effective, it has rare but serious side effects, including retroperitoneal fibrosis. Namenda, memantine HCI tablets, which is used in the treatment of Alzheimer's Disease, is beginning to be used off label for the treatment of migraines. It has not yet been approved by the FDA for the treatment of migraines. ASA or Aspirin can be taken daily in low doses such as 80 mg, the blood thinners in ASA have been shown to help some migrainures, especially those who have an aura.

Migraine and cardiovascular risks The risk of stroke may be increased two- to threefold in migraine sufferers. Young adult sufferers and women using hormonal contraception appear to be at particular risk. The mechanism of any association is unclear, but chronic abnormalities of cerebral blood vessel tone may be involved. Women who experience auras have been found to have twice the risk of strokes and heart attacks over non-aura migraine sufferers and women who do not have migraines. Migraine sufferers seem to be at risk for both thrombotic and hemorrhagic stroke as well as transient ischemic attacks. Death from cardiovascular causes was higher in people with migraine with aura in a Women's Health Initiative study, but more research is needed to confirm this.

Symptomatic treatment: Analgesics: Ibuprofen, naproxen, and ASA or acetaminophen +/- codeine and/or butalbital; Should used < 15 days per month; < 10 days if opioids added; Therapeutic choices Ergot Derivatives: Ergotamine (rebound headaches when used >10 days/month), Dihydroergotamine mesylate (DHE); for headache in adult Serotonin agonists (Triptans): almotriptan, eletriptan, naratriptan (slowest onset with maximal efficacy at 4 hours, less headache recurrence, best for moderately severe in Canada migraine or pts with low tolerance for other treatment), rizatriptan, sumatriptan (fasted onset, most efficacious for severe migraine attack); and zolmitriptan; Others: Corticosteroids; Phenothiazines (prochlorperazine, chlorpromazine); Ketorolac; Meperidine, Indomethacin; Antinauseants (dimenhydrinate); Antiemetic/prokinetic agents (metoclopramide, domperidone) are also choices based on situations.

Prophylactic Therapy

beta-blockers (metoprolol, propranolol, nadolol, atenolol); Ca-channel blockers (verapamil, flunarizine); TCAs (amitriptyline, nortriptyline, doxepin); Antiepileptic drugs (valproic acid, divalproex sodium, topiramate, gabapentin); Serotonin antagonists ( methysergide, pizotifen) others (riboflavin, lithium, botulinum toxin)

Therapeutic choices for headache in Children in Canada

Prophylactic Therapy

delirium tremens

An acute, sometimes fatal episode of delirium usually caused by withdrawal or abstinence from alcohol following habitual, excessive drinking. It also may occur during an episode of heavy alcohol consumption.

osteoporosis

Osteoporosis is a disease of bone that leads to an increased risk of fracture. In osteoporosis the bone mineral density (BMD) is reduced (in women as a BMD 2.5 standard deviations below peak bone mass), bone microarchitecture is disrupted, and the amount and variety of non-collagenous proteins in bone is altered. Osteoporosis can be prevented with lifestyle changes and sometimes medication; in people with osteoporosis, treatment may involve both. Lifestyle change includes preventing falls and exercise; medication includes calcium, vitamin D, bisphosphonates and several others.

Risk factors

Osteoporosis is most common in women after menopause, when it is called postmenopausal osteoporosis, but may also develop in men, and may occur in anyone in the presence of particular hormonal disorders and other chronic diseases or as a result of medications, specifically glucocorticoids, when the disease is called steroid- or glucocorticoid-induced osteoporosis (SIOP or GIOP).

Nonmodifiable

The most important risk factors for osteoporosis are advanced age (in both men and women) and female sex; estrogen deficiency following menopause is correlated with a rapid reduction in BMD, while in men a decrease in testosterone levels has a comparable (but less pronounced) effect.

Potentially modifiable

Excess alcohol; Vitamin D deficiency; Tobacco smoking; High body mass index - being overweight protects against osteoporosis; Malnutrition; Physical inactivity lead to significant bone loss. Excess physical activity; Heavy metals - cadmium, lead; Soft drinks;

Immobilization; Hypogonadal states: Turner syndrome, Klinefelter syndrome, Kallmann syndrome, anorexia nervosa, andropause, hypothalamic amenorrhea or hyperprolactinemia. In females, the effect of hypogonadism is mediated by estrogen deficiency. Endocrine disorders: Cushing's syndrome, hyperparathyroidism, thyrotoxicosis, hypothyroidism, diabetes mellitus type 1 and 2, acromegaly and adrenal insufficiency. In pregnancy and lactation, there can be a reversible bone loss. Nutritional and gastrointestinal disorders: coeliac disease, Crohn's disease, lactose intolerance, surgery (after gastrectomy, intestinal bypass surgery or bowel resection) and severe liver disease (especially primary biliary cirrhosis). Patients with bulimia ; or inability to absorb calcium and/or vitamin D; and other micro-nutrients such as vitamin K or vitamin B12 deficiency may also contribute. diseases / disorders associated with osteoporosis: Rheumatologic disorders: rheumatoid arthritis, ankylosing spondylitis, systemic lupus erythematosus and polyarticular juvenile idiopathic arthritis; Renal insufficiency can lead to osteodystrophy. Hematologic disorders: multiple myeloma and other monoclonal gammopathies, lymphoma and leukemia, mastocytosis, hemophilia, sickle-cell disease and thalassemia. Several inherited disorders: osteogenesis imperfecta, Marfan syndrome, hemochromatosis, hypophosphatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos syndrome, porphyria, Menkes' syndrome, epidermolysis bullosa and Gaucher's disease. People with scoliosis of unknown cause; a feature of complex regional pain syndrome; more frequent in people with Parkinson's disease and chronic obstructive pulmonary disease.

Steroid-induced osteoporosis (SIOP) : prednisone ; or prophylaxis in patients who take the equivalent of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially when this is in excess of three months. Alternate day use may not prevent this complication. Barbiturates, phenytoin and some other enzyme-inducing antiepileptics: accelerate the metabolism of vitamin D. L-Thyroxine over-replacement : subclinical hypothyroidism. Several drugs induce hypogonadism: aromatase inhibitors used in breast cancer, methotrexate and other anti-metabolite drugs, depot progesterone and gonadotropin-releasing Medications associated with hormone agonists. osteoporosis: Anticoagulants - long-term use of heparin and warfarin (and related coumarins) Proton pump inhibitors - these drugs inhibit the production of stomach acid then interferes with calcium absorption. Chronic phosphate binding may also occur with aluminiumcontaining antacids. Thiazolidinediones (used for diabetes) - rosiglitazone and possibly pioglitazone, inhibitors of PPAR Chronic lithium therapy has been associated with osteoporosis.[16]

Bisphosphonates

Bisphosphonate drugs are the first-line treatment in women. The most often prescribed bisphosphonates are presently sodium alendronate (Fosamax) 10 mg a day or 70 mg once a week, risedronate (Actonel) 5 mg a day or 35 mg once a week and or ibandronate (Boniva) once a month.

risedronate sodium

Alendronic acid (INN) is a bisphosphonate drug used for osteoporosis and several other bone diseases. It is marketed alone as well as in combination with vitamin D; Unlike most drugs, the strong negative charge on the two phosphate moieties limits oral bioavailability, and in turn, the exposure to tissues other than bone is very low. After absorption in the bone, alendronate has an estimated terminal half-life of 10 years. Risedronate is taken orally, usually 5 mg daily or 35 mg weekly. Notably, if risedronate lodges in the esophagus, it can lead to esophageal ulcers. Therefore, it is recommended that risedronate be taken with the body upright, and followed by a glass of water. Moreover, risedronate is poorly absorbed when taken with food, so it is recommended that no food or drink other than water be taken for 2 hours before and 30 minutes after taking risedronate.

Teriparatide

(Forteo, recombinant parathyroid hormone residues 134) acts like parathyroid hormone and stimulates osteoblasts, thus increasing their activity. It is used mostly for patients with established osteoporosis (who have already fractured), have particularly low BMD or several risk factors for fracture or cannot tolerate the oral bisphosphonates.

In laboratory experiments, strontium ranelate was noted to stimulate the proliferation of osteoblasts, as well as inhibiting the proliferation of osteoclasts. Strontium ranelate Strontium ranelate is taken as a 2 g oral suspension daily, and is licenced for the treatment of osteoporosis to prevent vertebral and hip fracture. It has side effect benefits over the bisphosphonates, as it does not cause any form of upper GI side effect, which is the most common cause for medication withdrawal in osteoporosis.

Hormone remains a good treatment for prevention of osteoporosis but, at this time, is not recommended unless there are other indications for its use as well. replacement

Selective estrogen receptor Act on the estrogen receptors throughout the body in a selective manner. Normally, bone mineral density (BMD) is tightly regulated by a balance between osteoblast and modulator (SERM) osteoclast activity in the trabecular bone. Estrogen has a major role in regulation of the bone formation-resorption equilibrium, as it stimulates osteoblast activity. Some SERMs such as raloxifene (Evista), act on the bone by slowing bone resorption by the osteoclasts. SERMs have been proved as effective in clinical trials.

a nervous system ailment caused by thiamine (vitamin B1) deficiency. Thiamine is involved in the breakdown of energy molecules such as glucose. It is also found on the membranes of neurons. Beriberi Thiamine found in unrefined cereals and fresh foods, particularly whole grain bread, fresh meat, legumes, green vegetables, fruit, and milk. Beriberi is therefore common in people whose diet excludes these particular types of nutrition. Also in chronic alcoholics with an inadequate diet (Wernicke-Korsakoff syndrome), as well as being a rare side effect of gastric bypass surgery. The baby mainly fed on the milk of a mother with thiamine deficiency; Treatment for beriberi is with thiamine hydrochloride, either in tablet form or injection. A rapid and dramatic recovery within hours can be made when this is administered to patients, and their health can be improved within an hour of starting treatment.

Symptoms of Beriberi include severe lethargy and fatigue, together with complications affecting the cardiovascular, nervous, muscular, and gastrointestinal systems; weight loss, emotional disturbances, impaired sensory perception (Wernicke's encephalopathy), weakness and pain in the limbs, and periods of irregular heart rate. Edema (swelling of bodily tissues) is common. Wet beriberi affects the heart; it is sometimes fatal, as it causes a combination of heart failure and weakening of the capillary walls, which causes the peripheral tissues to become edematous. Dry beriberi causes wasting and partial paralysis resulting from damaged peripheral nerves. It is also referred to as endemic neuritis.

B1 Beriberi1901 1925B1

Athlete's foot
;

Athlete's foot, also called Tinea pedis, is a parasitic fungal (dermatophytes) infection of the epidermis of the human foot. Moreover, a fungus species that causes athlete's foot can also cause, for example, jock itch (tinea cruris). It is typically caused by a mold (but in some cases a yeast) that grows on the surface of the skin and then into the living skin tissue itself, causing the infection. It usually occurs between the toes, but in severely lasting cases may appear as an extensive "moccasin" pattern on the bottom and sides of the foot. The malady more commonly affects males than females. Tinea pedis is estimated to be the second most common skin disease in the United States, after acne. Up to 15% of the U.S. population may have tinea pedis.

The most common ingredients in over-the-counter products are miconazole nitrate (2% typical concentration in the United States) and tolnaftate (1% typ. in the U.S.). Terbinafine, marketed as Lamisil is another over-the-counter drug. There exists a large number of prescription antifungal drugs, from several different drug families. These include ketaconazole, itraconazole, naftifine, nystatin, caspofungin. Undecylenic acid (a castor oil derivative) is a known fungicide;

Pellagra

Pellagra is a vitamin deficiency disease caused by dietary lack of niacin (B3) and protein, especially proteins containing the essential amino acid tryptophan. Because tryptophan can be converted into niacin, foods with tryptophan but without niacin, such as milk, prevent pellagra. However, if dietary tryptophan is diverted into protein production, niacin deficiency may still result. Pellagra is an endemic disease in Africa, Mexico, Indonesia and China. In affluent societies, a majority of patients with clinical pellagra are poor, homeless, alcohol dependent, or psychiatric patients who refuse food. Tryptophan is an essential amino acid found in soybeans, meat, poultry, fish, and eggs. If one's diet contains these foods, one's need for niacin from other sources will be reduced. The main results of pellagra can easily be remembered as "the four D's": diarrhea, dermatitis, dementia, and death.

Erectile dysfunction ED

Erectile dysfunction (ED or (male) impotence) is a sexual dysfunction characterized by the inability to develop or maintain an erection of the penis sufficient for satisfactory sexual performance. An erection occurs due to hydraulic effects due to blood entering and being retained in sponge-like bodies inside the penis. The most important organic causes are cardiovascular disease and diabetes, neurological problems (for example, trauma from prostatectomy surgery), hormonal insufficiencies (hypogonadism) and drug side effects. It is important to realise that erectile dysfunction can signal underlying risk for cardiovascular disease. the first line treatment of erectile dysfunction consists of a trial of PDE5 inhibitor drugs (the first of which was sildenafil or Viagra; tadalafil vardenafil ).

Causes Neurogenic Disorders (spinal cord and brain injuries, nerve disorders such as Parkinson's disease, Alzheimer's disease, multiple sclerosis, and stroke. Hormonal Disorders (pituitary gland tumor; low level of the hormone testosterone). Arterial Disorders (peripheral vascular disease, hypertension; reduced blood flow to the penis). Cavernosal Disorders (Peyronie's disease. ) Nonphysical causes: Mental disorders (clinical depression, schizophrenia, substance abuse, panic disorder, generalized anxiety disorder, personality disorders or traits), psychological problems, negative feelings. Surgery (radiation therapy, surgery of the colon, prostate, bladder, or rectum may damage the nerves and blood vessels involved in erection. Prostate and bladder cancer surgery often require removing tissue and nerves surrounding a tumor, which increases the risk for impotence.[8]) Aging.

Lifestyle: alcohol and drugs, obesity, cigarette smoking (Incidence of impotence is approximately 85 percent higher in male smokers compared to non-smokers. Smoking is a key cause of erectile dysfunction because it promotes arterial narrowing. ) Other disorders. A few causes of impotence may be iatrogenic (medically caused). Various antihypertensivesand some drugs that modify central nervous system response may inhibit erection by denying blood supply or by altering nerve activity.

cystic fibrosis (CF)

It is an autosomal recessive disorder, caused by a genetic defect [CF transmembrane Conductance Regulator (CFTR)] that affects the transport of sodium and chloride ions across the membrane of epitheliallined cells and thus thickened epithelial secretions and mucus, CF is most damaging to epithelial surfaces, such as those of the lungs and pancreas, and lead to pulmonary, gastrointestinal, pancreatic and hepatic manifestitaions. Approximately 90% of patients with CF require supplementation with pancreatic enzyme products to treat pancreatic insufficiency. Due to pancreatic insufficiency, streatorrhea and foul-smelling stools, diarrhea and malnutrition are common. This can occur even if supplementation is adequate. The dosing must be individualized for the needs of the specific patient. Dornase alfa acts as a mucolytic agent can be used to reduce sputum viscoelasticity and infections.

Multiple sclerosis [skliE5rEusis] MS, also known as disseminated sclerosis or encephalomyelitis disseminata

A chronic degenerative disease of the central nervous system in which gradual destruction of myelin occurs in patches throughout the brain or spinal cord or both, interfering with the nerve pathways and causing muscular weakness, loss of coordination, and speech and visual disturbances. It occurs chiefly in young adults and is thought to be caused by a defect in the immune system that may be of genetic or viral origin.

An autoimmune condition in which the immune system attacks the central nervous system (CNS), leading to demyelination. It may cause numerous physical and mental symptoms, and often progresses to physical and cognitive disability. Disease onset usually occurs in young adults, is more common in women, More specifically, MS destroys oligodendrocytes which are the cells responsible for creating and maintaining a fatty layer, known as the myelin sheath, which helps the neurons carry electrical signals. MS results in a thinning or complete loss of myelin and, less frequently, the cutting (transection) of the neuron's extensions or axons. When the myelin is lost, the neurons can no longer effectively conduct their electrical signals. The name multiple sclerosis refers to the scars (scleroses - better known as plaques or lesions) in the white matter. Loss of myelin in these lesions causes some of the symptoms, which vary widely depending upon which signals are interrupted. However, more advanced forms of imaging are now showing that much of the damage happens outside these regions. Almost any neurological symptom can accompany the disease.

Symptoms of MS usually appear in episodic acute periods of worsening (relapses, exacerbations, bouts or attacks), in a gradually-progressive deterioration of neurologic function, or in a combination of both. The most common presentation of MS is the clinically isolated syndrome (CIS). In CIS, a patient has an attack suggestive of demyelination, The person with MS can suffer almost any neurological symptom or sign, including changes in sensation (hypoesthesias and paraesthesias), muscle weakness, muscle spasms, Symptoms of MS or difficulty in moving; difficulties with coordination and balance (ataxia); problems in speech (dysarthria) or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, or diplopia), fatigue and acute or chronic pain, and bladder and bowel difficulties. Cognitive impairment of varying degrees and emotional symptomatology in the form of depression or labile affect are also common. The main clinical measure of disability progression and symptom severity is the Expanded Disability Status Scale or EDSS.

Multiple sclerosis is a disease in which the myelin (a fatty substance which covers the axons of nerve cells) degenerates. According to the view of most researchers, T cells plays a key role in the development of MS. T cells gain entry into the brain via blood-brain According to a strictly immunological explanation of MS, the inflammatory process is triggered by the T cells. T cells gain entry into the brain via the blood-brain barrier (a barrier and trapped inside capillary system that should prevent entrance of T-cells into the nervous system). The blood brain barrier is normally not permeable to these types of cells, unless triggered by the brain which triggered either infection or a virus, where the integrity of the tight junctions forming the blood-brain barrier is decreased. When the blood brain barrier regains its integrity (usually after inflammatory processes to infection or virus has cleared) the T cells are trapped inside the brain. These lymphocytes recognize myelin as foreign and attack it as if it were an invading virus. That triggers destroy myelin inflammatory processes, stimulating other immune cells and soluble factors like cytokines and antibodies. Leaks form in the blood-brain barrier. These leaks, in turn, cause a ( demyelination) number of other damaging effects such as swelling, activation of macrophages, and more activation of cytokines and other destructive proteins such as matrix metalloproteinases. A deficiency of uric acid has been implicated in this process.

Management of acute attacks

During symptomatic attacks administration of high doses of intravenous corticosteroids, such as methylprednisolone, is the routine therapy for acute relapses. The aim of this kind of treatment is to end the attack sooner and leave fewer lasting deficits in the patient. Although generally effective in the short term for relieving symptoms, corticosteroid treatments do not appear to have a significant impact on long-term recovery. Potential side effects include osteoporosis and impaired memory, the latter being reversible. Dantrolene acts directly on the skeletal muscles and interferes with intracellular calcium movement. This will reduce the contractions and excitation of muscles. Baclofen is another choice to treat spasticity associated with MD.

The earliest clinical presentation of relapsing-remitting MS (RRMS) is the clinically isolated syndrome (CIS). Several studies have shown that treatment with interferons during an initial attack can decrease the chance that a patient will develop clinical MS. Disease-modifying As of 2007, six disease-modifying treatments have been approved by regulatory agencies of different countries for RRMS. Three are interferons: two formulations of interferon treatments beta-1a and one of interferon beta-1b. A fourth medication is glatiramer acetate (Copaxone). The fifth medication, mitoxantrone, is an immunosuppressant also used in cancer chemotherapy, approved only in the USA and largely for secondary progressive MS. The sixth is natalizumab (marketed as Tysabri). All six medications are modestly effective at decreasing the number of attacks and slowing progression to disability, ACTH (adrenocorticotropic hormone)

Corticotropin can relieve symptoms during multiple sclerosis (MS) attacks by stimulating the body to produce and release corticosteroids that naturally reduce inflammation. This medication is injected into the muscle or beneath the skin. ACTH may be used to treat sudden, severe (acute) MS attacks. ACTH is rarely used today because of the severe ACTH allergic reactions it can cause. Synthetic corticosteroids, such as methylprednisolone, are considered the medications of choice for treating acute attacks since they rarely & cause allergic reactions. Synthetic corticosteroids Side effects of ACTH may include: Retention of fluids. Muscle weakness. High blood pressure. Menstrual irregularities. Lowered resistance to infections. Allergic reactions. Agitation. Impaired sleep. Delirium (confusion). Long-term use of ACTH can result in more serious side effects that may not go away.

Myasthenia gravis

The disease myasthenia gravis, characterized by muscle weakness and fatigue, occurs when the body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits proper acetylcholine signal transmission. Over time, the motor end plate is destroyed. Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine, physostigmine, or primarily mestinon) are effective in treating this disorder. They allow endogenously-released acetylcholine more time to interact with its respective receptor before being inactivated by acetylcholinesterase in the gap junction.

Mnire's disease

A disorder of the inner ear that can affect hearing and balance. It is characterized by episodes of dizziness and tinnitus and progressive hearing loss, usually in one ear. It is caused by an increase in volume and pressure of the endolymph of the inner ear. The exact cause of Mnire's disease is not known, but it is believed to be related to endolymphatic hydrops or excess fluid in the inner ear. The symptoms of Mnire's are variable; not all sufferers the same. However, so-called "classic Mnire's" is considered to comprise the following four symptoms: Periodic episodes of rotary vertigo or dizziness. Fluctuating, progressive, unilateral (in one ear) or bilateral (in both ears) hearing loss. Unilateral or bilateral tinnitus. A sensation of fullness or pressure in one or both ears.

Some doctors recommend Lipoflavonoids. Outside of the United States, Betahistine is used to manage symptoms. Treatments aimed at lowering the pressure within the inner ear include antihistamines, anticholinergics, steroids, and diuretics.

Insomnia

Benzodiazepines: four were officially indicated for insomnia in Canada (flurazepam, nitrazepam, temazepam and triazolam), lorazepam and oxazepam are also widely used. Triazolam (fast onset and short duration, suitable for initial insomnia); Temazepam is a good all-purpose hypnotic. It cause less rebound insomnia than more potent BDZs such as lorazepam, but may associated with falls in elderly); BDZ receptor agonists: zopiclone and its (S+)-isomer Eszopiclone; Serotonin precursors: L-tryptophan

Nausea in adults

Antacids: aluminum hydroxide/magnesium hydroxide combinations; Antihistamines: dimenhydrinate, diphenhydramine, meclizine Anticholinergics: scopolamine; Benzamides: domperidone, metoclopramide; Dopamine antagonists----Butyrophenones: haloperidol, droperidol Phenothiazines: chlorpromazine, perphenazine, prochlorperzaine, promethazine (--azines); Serotonin Antagonists: ondansetron;

Motion Sickness

Antihistamine: Meclizine, Dimenhydrinate, Cyclizine; Anti-psychotic drugs: Haldol, Thorazine; Promethazine (one of the most effective available for MS, One dose lasts up to 8 hours, Like the other drugs, it can cause drowsiness). BDZs: Diazepam, lorazepam, klonazepam.(not traditionally used for MS, still useful in small amounts). Scopolamine patches -- these patches are sometimes very helpful. Serotonin-family antinausea drugs: Zofran and other -- these are powerful anti-nausea/emesis but do not prevent MS. Other medications. Verapamil, phenytoin and carbamazepine (sodium channel blocker); Buspirone, Beta-histine.

Vertigo

A specific type of dizziness, a major symptom of a balance disorder. It is the sensation of spinning or swaying while the body is actually stationary with respect to the surroundings. Vertigo is usually associated with a problem in the inner ear balance mechanisms (vestibular system), in the syndrome and Meniere's disease. Treatment: anticholinergics (scopolamine), antihistamines (meclizine, dimenhydrinate), benzodiazepines(lorazepam, diazepam), calcium channel antagonists (Verapamil and Nimodipine); GABA modulators (gabapentin, baclofen); neurotransmitter reuptake inhibitors: SSRI's, SNRI's and tricyclics (amitriptyline)

Fibromyalgia

Fibromyalgia, chronic widespread pain (muscle and connective tissue pain) and a heightened and painful response to gentle touch (tactile allodynia, tender points). Other core features include debilitating fatigue, sleep disturbance, and joint stiffness. Tricyclic Agents (amitriptyline, cyclobenzapine, low dose before bedtime); SSRIs (fluoxetine); SNRIs (venlafaxine); Hypnotics (zopiclone); Analgesics (acetaminophen, tramadol, ibuprofen); Natural Health Products (S-adenosyl-L-methionine)

Alcohol withdraw syndrome

Treatment of alcohol withdrawal syndrome can be managed with various pharmaceutical medications including: Barbiturates: phenobarbital; benzodiazepines: diazepam, lorazepam, chlordiazepoxide; antipsychotics: haloperidol; antiepileptics: phenytoin Others: Baclofen, clonidine, carbamazepine, trazodone, low dose ethanol, Vitamin deficiency is common in alcoholic: most import B1 and B9 (thiamine and folic acid) Excessive salivation, sweating, perspiration, nausea, vomiting, diarrhea, restlessness, anxiety, GI cramps, fever, muscle spasm, jerking movements and lacrimation are normal symtoms in opioid withdrawal patients. Treatment include:

Opioid withdraw syndrome Opioid agonists: methadone, for acute wirhdrawal symptoms in new patient; Partial opioid agonists: buprenorphine; for long-term maintenance; Opioid Antagonists: naltrexone; Alpha 2-adrenergic agonists: clonidine;

Skin disorders Antihistamines: First generation: diphenhydramine, clemastine, brompheniramine, chlorpheniramine, hyroxyzine, azatadine, cyproheptadine, promethazine, trimeprazine; Second generation: loratadine, fexofenadine, cetirizine, desloratadine, doxepin, ketotifen

Pruritus

Atopic Eczema

Allergic Rhinitis

Oral drugs: Antihistamines: chlorpheniramine (take with food), diphenhydramine, azatadine, cetirizine, fexofenadine, loratadine (empty stomach, food delays absorbtion), desloratadine; Decongestants: pseudoephedrine, phenylephrine; Combinations: azatadine, triprolidine, cetirizine, loratadine, fexofenadine ---- combinded with /pseudoephedrine; Intranazal: Antihistamines: levocabastine, Anticolinergics: ipratropium, Mast cell stabilizers: sodium ceomoglycate, Corticosteroids: beclomethasone, buesonide, flunisolide, fluticasone, memetasone, triamcinolone.

It is an involuntary velocity-dependent increase in muscle tone resulting from injury to the motor pathways in the brain or spinal cord. It is common in spinal cord injury, multiple sclerosis, stroke and cerebral palsy. Spasticity can impair feeding, dressing, bowel/bladder function, hygiene and gait; Chronic spasticity GABA derivatives: baclofen (standard initial medication for spasticity) -2 adrenergic agonist: tizanidine (a good first-line choice, can also be combined with baclofen; side effects: dry mouth and drowsiness); Direct-acting skeletal muscle relaxants: dantrolene (effective in control of spasticity, but with liver toxicity and muscle weaknes, less use) Benzodiazepines: diazepam, clonazepam (especially good for treating spasm at night; sedation is common side effects); Others: Gabapentin useful if there is concurrent neuropathic pain; Cannabinoids (dronabinol, nabilone, satives) may be another option.

Cancer related Acute nausea / vomiting: Dexamethasone + Serotonin antagonist; Delayed nausea / vomiting: Dexamethasone + metoclopramide; Chemotherapy-induced Nausea and Vomiting Benzamides: Metoclopramide; Benzodiazapines: Lorazepam, Alprazolam; Buryrophenones: Haloperidol; Cannabinoids: Nabilone, Dronabinol; Corticosteroids: Dexamethasone, Methylprednisolone; Phenothiazines: prochlorperazine; Serotonin antagonists: Dolasetron, Granisetron, Ondansetron; Acute Side effects: Extravasation (cancer cells exiting the capillaries and entering organs; related to Vesicant drugs, Alkylating agents, Antibiotics), treatment: topical DMSO, or S.C. saline, steroids, hyaluronidase or NaHCO3; Hyersensitivity:(related to etoposide and taxanes; rituximab, trastuzumab and other biologics), Antihistamines, steroids, vasoconstrictors; Tumor lysis Syndrome (not specific, can be reduced by alkalinizing the urine by allopurinol or rasburicase)

Chemotherapy Toxicity Management

Alopecia; Anemia; Cardiotoxicity: 5-FU, Capecitabine (coronary vasospasms, mimicking MI); Trastuzumab (cardiac dysfunction, severe HF); Anthracyclines (acute inflammation, congestive myopathy); Taxanes (bradycardia); Chemotherapy Toxicity Diarrhea: irinotecan, 5-FU, antimetabolities; Management Hepatotoxicity: methotrexate, azathioprine, cytarabine, nitrosiureas, etoposide; (Azath- Meth- Cytara- Etopo- Nitro-) Nephrotoxicity:

Neutotoxicity: vinca alkaloids, platinum-based chemotherapy, taxanes; Ocular: 5-FU, taxanes; Ototoxicity: platinum compounds; Pulmonary: Interstitial pneumonitis (methotrexate, bleomycin, anthracyclines, vinca alkaloids, alkylating agents); Acute respiratory distress syndrome (gemcitabine) (Anthra- Alkylating- Bleo- Gem- Metho- Vinca-)

Bone marrow suppression (myelosuppression, dose-limiting: neutropenia, febrile neutropenia; thromboctopenia, anemia) Dermatological toxicity (alopecia ; ulceration or necrosis by vesicant chemotheraphy drugs (dactinomycin, daunorubicin, doxorubicin, idarubicin, mechlorethamine, mitomycin, vinblastine, vincristine, and vinorelbine), skin changes)

Inflammatory bowel disease

Corticosteroids: Systemic (Hydrocortisone, methylprednisolone, predinisone, budesonide); Topical (enema---hydrocortisone, betamethasone, budesonide); Aminosalicylates: sulfasalazine, olsalazine, 5-ASA; Immunosuppressives: azathioprine, 6-mercaptopurine, methotrexate, cyclosporine; Biologic response modifiers: infliximab;

Comparisons of various factors in Crohn's disease and ulcerative colitis Crohn's disease Terminal ileum involvement Colon involvement Rectum involvement Involvement around the anus Bile duct involvement Distribution of Disease Endoscopy Depth of inflammation Fistulae Stenosis Autoimmune disease Cytokine response Granulomas on biopsy Surgical cure Smoking Treatment of Crohn's disease Commonly Usually Seldom Common No increase in rate of primary sclerosing cholangitis Patchy areas of inflammation (Skip lesions) Deep geographic and serpiginous (snake-like) ulcers May be transmural, deep into tissues Common Common Widely regarded as an autoimmune disease Associated with Th1 Can have granulomas Often returns following removal of affected part Higher risk for smokers

Currently there is no cure for Crohn's disease and remission may not be possible or prolonged if achieved; in cases where remission is possible, relapse can be prevented and symptoms controlled with medication, lifestyle changes and in some cases, surgery. Adequately controlled, Crohn's disease may not significantly restrict daily living. Treatment for Crohn's disease is only when symptoms are active and involve first treating the acute problem, then maintaining remission.

Acute treatment uses medications to treat any infection (normally antibiotics) and to reduce inflammation (normally aminosalicylate anti-inflammatory drugs and corticosteroids). When symptoms are in remission, treatment enters maintenance with a goal of avoiding the recurrence of symptoms. Prolonged use of corticosteroids has significant sideeffects; as a result they are generally not used for long-term treatment. Alternatives include aminosalicylates alone, though only a minority are able to maintain the treatment, and many require immunosuppressive drugs. Medications used to treat the symptoms of Crohn's disease include 5-aminosalicylic acid (5-ASA) formulations, prednisone, immunomodulators such as azathioprine, mercaptopurine, methotrexate, infliximab, adalimumab[14] and natalizumab.[72][73] Hydrocortisone should be used in severe attacks of Crohn's disease.

Certain lifestyle changes can reduce symptoms, including dietary adjustments, proper hydration and smoking cessation.

1 Aminosalicylate antiinflammatory drugs

5-aminosalicylates (5-ASA) include the following: Mesalazine or mesalamine, which is marketed in the forms Asacol, Pentasa, Salofalk, Dipentum and Rowasa. Sulfasalazine, which is converted to 5-ASA and sulfapyridine by intestinal bacteria. The sulfapyridine may have some therapeutic effect in rheumatoid arthritis. However, the sulfapyridine component is often the limiting factor in treatment of Crohn's disease because of high side-effect profile. 5-ASA compounds have been shown to be useful in the treatment of mild-to-moderate Crohn's disease.[2] They are usually considered to be first line therapy for disease in the ileum and right side of the colon particularly due to their lower side effect profile compared to corticosteroids

2 Corticosteroid anti-inflammatory drugs

Corticosteroids are used primarily for treatment of moderate to severe flares of Crohn's disease. They are used more sparingly due to the availability of effective treatments with less side-effects.[4] The side effects of corticosteroids include Cushing's syndrome, mania, insomnia, hypertension, high blood glucose, osteoporosis, and avascular necrosis of long bones. These should not be confused with the anabolic steroids used to enhance athletic performance. The most commonly prescribed oral steroid is prednisone, which is typically dosed at 0.5 mg/kg for induction of remission.[5] Intravenous steroids are used for cases refractory to oral steroids, or where oral steroids cannot be taken.[4] These are administered in the hospital setting. Budesonide is an oral corticosteroid with limited absorption and high level of first-pass metabolism, meaning that less quantities of steroid enter into the bloodstream. It has been shown to be useful in the treatment of mild-to-moderate Crohn's disease[6] and for maintenance of remission in Crohn's disease.[7] Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.[6] Budesonide is also useful when used in combination with antibiotics for active Crohn's disease.[8] Steroid enemas can also be used for disease of the lower colon and rectum, in order to treat symptoms. Hydrocortisone and budesonide liquid and foam enemas are being marketed for these reasons. Corticosteroids however have a host of side effects, some very serious, and it is desirable to curtail their use whenever possible.

Corticosteroids are used primarily for treatment of moderate to severe flares of Crohn's disease. They are used more sparingly due to the availability of effective treatments with less side-effects.[4] The side effects of corticosteroids include Cushing's syndrome, mania, insomnia, hypertension, high blood glucose, osteoporosis, and avascular necrosis of long bones. These should not be confused with the anabolic steroids used to enhance athletic performance. The most commonly prescribed oral steroid is prednisone, which is typically dosed at 0.5 mg/kg for induction of remission.[5] Intravenous steroids are used for cases refractory to oral steroids, or where oral steroids cannot be taken.[4] These are administered in the hospital setting. Budesonide is an oral corticosteroid with limited absorption and high level of first-pass metabolism, meaning that less quantities of steroid enter into the bloodstream. It has been shown to be useful in the treatment of mild-to-moderate Crohn's disease[6] and for maintenance of remission in Crohn's disease.[7] Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.[6] Budesonide is also useful when used in combination with antibiotics for active Crohn's disease.[8] Steroid enemas can also be used for disease of the lower colon and rectum, in order to treat symptoms. Hydrocortisone and budesonide liquid and foam enemas are being marketed for these reasons. Corticosteroids however have a host of side effects, some very serious, and it is desirable to curtail their use whenever possible.

3 Mercaptopurine immunosuppressing drugs

Azathioprine and 6-mercaptopurine (6-MP) are the most used immunosuppressants for maintenance therapy of Crohn's disease. They are purine anti-metabolites, meaning that they interfere with the synthesis of purines required for inflammatory cells. They have a duration of action of months, making it unwieldy to use them for induction of remission. Both drugs are dosed at 1.5 to 2.5 mg/kg, with literature supporting the use of higher doses. Azathioprine and 6-MP have been found to be useful for the following indications: For maintenance therapy for people who are dependent on steroids. / Fistulizing disease. / Induction of remission in steroid refractory disease. / Maintenance of remission after surgery for Crohn's disease. / Azathioprine is however a particularily dangerous drug, with great potential for inviting a host of potentially fatal infections, and is also listed by the FDA as a human carcinogen.

Infliximab, marketed as Remicade, is a mouse-human chimeric antibody that targets tumour necrosis factor, a cytokine in the inflammatory response. It is administered intravenously and dosed per weight. 4 Infliximab Infliximab has found utility as follows: Maintenance of remission for people with Crohn's disease. / Induction of remission for people with Crohn's disease. / Maintenance for fistulizing Crohn's disease. Side effects of infliximab, like other immunosuppressants of the TNF class, can be serious and potentially fatal, and infliximab carries an FDA black-box warning on the label. Listed side effects include hypersensitivity and allergic reactions, risk of re-activation of tuberculosis, serum sickness, and risk of multiple sclerosis.[16] Serious side effect also include lymphoma and severe infections, inclduing progressive multifocal leukoencephalopathy (PML) an opportunistic viral infection of the brain that can cause death

Adalimumab, marketed as Humira, like infliximab is an antibody that targets tumour necrosis factor.[17] Adalimumab has been shown to reduce the signs and symptoms of, and is approved for treatment of, moderate to severe Crohns disease (CD) in adults who have not responded well to conventional treatments and who have lost response to, or are unable to tolerate infliximab.[18] 5 Adalimumab Adalimumab also has a number of serious safety concerns, potentially fatal, typical of the TNF class, and it is also has black-box warning on its FDA label. Listed potential side effects include serious and sometimes fatal blood disorders; serious infections including include TB (tuberculosis) and infections caused by viruses, fungi, or bacteria; rare reports of lymphoma and solid tissue cancers; rare reports of serious liver injury; and rare reports of demyelinating central nervous system disorders); and rare reports of cardiac failure

Natalizumab, marketed as Tysabri, is an anti-integrin monoclonal antibody that has shown utility as induction and maintenance treatment for moderate to severe Crohn's disease. Natalizumab may be appropriate in patients who do not respond to medications that block tumor necrosis factor-alpha such as infliximab. In January 2008, the FDA approved natalizumab for both induction of remission and maintenance of remission for moderate to severe Crohn's disease. 6 Natalizumab A total of 3 large randomized controlled trials have demonstrated that natalizumab is effective in increasing rates of remission[22] and maintaining symptom-free status[23] in patients with Crohn's disease. Like infliximab, natalizumab has also been linked to PML (though only when used in combination with interferon beta-1a).[24][25] The label also recommends monitoring of liver enzymes due to conerns over possible damage or failure.

Aminosalicylates Sulfasalazine has been a major agent in the therapy of mild to moderate UC for over 50 years. 5-aminosalicylic acid (5-ASA and mesalazine) was the therapeutically active compound in sulfasalazine. Mesalazine, also known as 5-aminosalicylic acid, mesalamine, or 5-ASA. Brand name formulations include Asacol, Pentasa, Mezavant, Lialda, and Salofalk. Sulfasalazine, also known as Azulfidine. Balsalazide - Disodium, also known as Colazal. Olsalazine, also known as Dipentum.

Corticosteroids: Cortisone / Prednisone / Prednisolone / Cortifoam / Hydrocortisone / Methylprednisolone / Beclometasone / Budesonide - under the brand name of Entocort Immunosuppressive drugs Mercaptopurine, also known as 6-Mercaptopurine, 6-MP and Purinethol. Azathioprine, also known as Imuran, Azasan or Azamun, which metabolises to 6-MP. Methotrexate, which inhibits folic acid Tacrolimus Biological treatment Infliximab Visilizumab Low Molecular Weight Heparin (LMWH) e.g clexane is used in acute management of the flare of UC.

Treatment of ulcers

H2-antagonists, PPIs, misoprostol, sucralfate

an oral gastrointestinal medication primarily indicated for the treatment of active duodenal ulcers not related to NSAID use. Brand names Sulcrate in Canada; Sucralfate is a locally acting substance that in an acidic environment (pH < 4), reacts with hydrochloric acid in the stomach to form a cross-linking, viscous, paste-like material capable of acting as an acid buffer for as long as 6 to 8 hours after a single dose. It also attaches to proteins on the surface of ulcers, such as albumin and fibrinogen, to form Sucralfate stable insoluble complexes as protective barriers at the ulcer surface. In addition, it prevents back diffusion of hydrogen ions, and adsorbs both pepsin and bile acids. Recently, it has been indicated that sucralfate also stimulates the increase of prostaglandin E2, epidermal growth factors (EGF), bFGF), and gastric mucus. The most common side effects : constipation and bezoar formation. Less reported: flatulence, headache, hypophosphatemia, and dry mouth (xerostomia);

Misoprostol used for NSAIDs-induced ulceration

Bulimia nervosa is an eating disorder characterized by recurrent binge eating, followed by compensatory behaviors, referred to as "purging". The most common formpracticed more than 75% of people with bulimia nervosais self-induced vomiting; fasting, the use of laxatives, enemas, diuretics, and overexercising are also common Recurrent episodes of binge eating. An episode of binge eating is characterized by both of the following: Bulimia nervosa Eating, in a fixed period of time, an amount of food that is definitely larger than most people would eat under similar circumstances. A lack of control over eating during the episode: a feeling that one cannot stop eating or control what or how much one is eating. Recurrent inappropriate compensatory behavior to prevent weight gain, such as: self-induced vomiting; misuse of laxatives, diuretics, or other medications; fasting; excessive exercise. Self-evaluation is unduly influenced by body shape and weight. These symptoms occur at least twice a week on average and persist for at least 3 months. The disturbance does not occur exclusively during episodes of Anorexia Nervosa.

Anorexia Nervosa

A psychiatric diagnosis that describes an eating disorder, characterized by low body weight and body image distortion, with an obsessive fear of gaining weight. Individuals with anorexia are known to control body weight commonly through the means of voluntary starvation, purging, vomiting, excessive exercise or other weight control measures, such as diet pills or diuretic drugs. While the condition primarily affects adolescent females, approximately 10% of people with the diagnosis are male. Anorexia nervosa, involving neurobiological, psychological, and sociological components, is a complex condition that can lead to death in severe cases. Treatment: antipsychotic drugs (chorpromazine); antidepressants (TCAs: clomipramine and amitriptyline); antihistimine and seratonin antagonist (e.g., cyproheptadine; Flouxetine)

Prevention of Stroke Secondary

Anticoagulants: warfarin, nicoumalone; Antiplatelet agents: ASA, clopidogrel, ticlopidine, dipyridamole / ASA

Superventricular Tachycarida

Heart rate control: digoxin; b-blockers (atenolol, metoprolol, nadolol, propranolol); Ca-channel blockers (verapamil, diltiazem); Heart rhythm control: class IC (flecainide, propafenone); Class III ( sotalol, amiodarone, dofetilide)

Ventricular Tachyarrhythmias

Ventricular tachycardia and Ventricular fibrillation (VT and VF); Immediate therapy for sustained VT or VF: amiodarone, procainamide, magnesium, b-blockers ( metoprolol, propranolol, esmolol), lidocaine; Chronic therapy: b-blockers (first choice); Amiodarone and sotalol; Class I (mexiletine, quinidine, procainamide) may be added when the first choices are ineffective or not tolerated by pts;

Atrial arrhythmia

Atrial Flutter: First choices (Propranolol, verapamil); digoxin; Atrial Fibrillation: most common, 100-150 beats/min; First choices (Propranolol, amidarone, anticoagulant); Dofitilide (hospital use) ;

Fainting, a sudden, usually temporary, loss of consciousness generally caused by insufficient oxygen in the brain either through cerebral hypoxia or hypotension but possibly for other reasons. Vasovagal Syncope; Orthostatic Hypotension; Syncope NaCl; Mineralocirticoids (fludrocortisone); alpha1-adrenergic agonist ( midorine); alpha2-adrenergic agonist ( yohimbine); beta1-adrenergic agonist ( metoprolol)--- not recommend for vasovagal syncope; [7vAsEu5vei^l , 5veiz - ]

claudication [7klC : di5keiFEn] --- a clinical diagnosis given for muscle pain (ache, cramp, numbness or sense of fatigue), classically calf muscle, which occurs during exercise and is relieved by a short period of rest. Most commonly it is due to vascular intermittent claudication caused by peripheral arterial disease. Neurogenic intermittent claudication is caused by spinal canal stenosis. Intermittent claudication in and of itself is often a symptom of severe atherosclerotic disease of the peripheral Intermittent claudication vascular system. It often indicates severe atherosclerosis as it is the most common cause. Antiplatelet: ASA; Clopidogrel; Rheologic modifiers: pentoxifylline;

Raynaud's phenomenon is a vasospastic disorder causing discoloration of the fingers, toes, and occasionally other extremities (). This condition can also cause nails to become brittle with longitudinal ridges. It comprises both Raynaud's disease (primary Raynaud's), where the phenomenon is idiopathic, and Raynaud's syndrome Raynaud's phenomenon (secondary Raynaud's), where it is caused by some other instigating factor. Primary Raynaud phenomenon, stemming from Raynaud disease, is an exaggeration of vasomotor responses to cold or emotional stress. More specifically, it is a hyperactivation of the sympathetic system causing extreme vasoconstriction of the peripheral blood vessels, leading to tissue hypoxia. Chronic, recurrent cases of Raynaud phenomenon can result in atrophy of the skin, subcutaneous tissues, and muscle. It can also rarely cause ulceration and ischemic gangrene. Drugs: Beta-blockers; cytotoxic drugs - particularly chemotherapeutics and most especially bleomycin; cyclosporin; ergotamine; sulfasalazine may cause this disease. Treatment: Ca-channel blockers ( dihydropyridines: nifedipine, felodipine, amlodipine; non-dihydropyridines: diltiazem); Alpha1-adrenergic antagonists (prazosin); PGI2 analogue (Iloprost) and Serotonin receptor antagonist (Ketanserin) also useful, but not available in Canada; PDE5 inhibitors (sildenafil, vardenafil) were tested to show some benefits;

Risk factors: nonmodifiable ( age, sex, family history); modifiable (hypertention, dyslipidemia, smoking, diabetes mellitus, carotid disease) Prevention of Ischemic stroke Antiplatelet agents: Acetylsalicyclic acid (ASA, 50-325 mg/day); Thienopyridines (clopidogrel, 75 mg/day; ticloidine, 250 mg/2day); Dipridamole/ASA, Anticoagulants (warfarin, nicoumalone)

Acute Ischemic Stroke

The sudden onset of a focal diturbance of CNS function, may be caused by cerebral infarction (ischemic stroke, for 85% of all strokes), intracerebral hemorrhage or subarachnoid hemorrhage. Treatment: Alteplase: IV within 3 hours of stroke, to restore perfusion and minimize teh brain damage; Prevent complications: aspiration and malnutrition; venous thromboembolism (ASA 75-325 mg daily) Reduce the risk of recurrence stroke: ASA; Clopidogrel, or a combination of ASA and sustained-release dipyridamole; Anticoagulant therapy: for pts with HF, warfarin or ASA (maintain the INR in the range 2.0-3.0) Post-acute treatment of primary intracerebral hemogghage is similar to that of ischemic stroke except that antithrombotic drugs are avoided.

Fever in Children

Defined as > 38 (rectal or rectal equivalent); Fever itself is not harmful, which is the host defense mechanims to infection. Acetaminophen first line; Ibuprofen, second line. ASA should be avoid in children < 15 y, due to the high risk of Reye's syndrome;

Hyperthermia: a symptomatic increase in core body temperature above 38.2 ; Unlike fever it is not mediated by the hypothalamus; Extreme of age, chronic diseases, some drugs ( anticholinergics, tricyclic antidepressants, sympathomimetics, slicylates, beta-lactams, succinylcholine, halothane, isoflurane, antipsychotics) may cause hyperthermia. Thermoregulatory disorders in Adults Hyperpyrexia: a fever of > 41.5 , most often a sign of an overwhelming infection; Dantrolene was used for Malignant Hyperthermia; Bromocriptine can be used for neuroleptic maglignant syndrome. Hypothermia: core body temperature < 35 ; If it lower to 32 , normally related to ventricular fibrillation; Thiamine can be used for alcohol intoxication related symptom; If opioid overdose is suspected, glucose and naloxone should be administered.

Phenylketonuria

Phenylketonuria (PKU) is an autosomal recessive genetic disorder characterized by a deficiency in the autozome phenylalanine hydroxylase (PAH). This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and is converted into phenylpyruvate (also known as phenylketone), which is detected in the urine. , . Left untreated, this condition can cause problems with brain development, leading to progressive mental retardation and seizures. However, PKU is one of the few genetic diseases that can be controlled by diet. A diet low in phenylalanine and high in tyrosine can be a very effective treatment. There is no cure. Damage done is irreversible so early detection is crucial.

hypercapnia

also known as hypercarbia, is a condition where there is too much carbon dioxide (CO2) in the blood. Carbon dioxide is a gaseous product of the body's metabolism and is normally expelled through the lungs. Hypercapnia is generally caused by hypoventilation, lung disease, or diminished consciousness. It may also be caused by exposure to environments containing abnormally high concentrations of carbon dioxide, or by rebreathing exhaled carbon dioxide. It can also be an initial effect of administering supplemental oxygen on a patient with sleep apnea. In this situation the hypercapnia can also be accompanied by respiratory acidosis. Doxapram is indicated as the respiratory stimulant agent in postanesthesia and in chronic obstructive pulmonary diseae associated with acute hypercapnia.

Hypocalcemia

Calcitriol and dihydrotachysterol

Hemophilia

Any of several hereditary blood-coagulation disorders in which the blood fails to clot normally because of a deficiency or an abnormality of one of the clotting factors. Hemophilia, a recessive trait associated with the X-chromosome, is manifested almost exclusively in males. Antihemophilic factors are used for hemophilia.

side effects

g should be used immediately / Urate-lowering drugs should not be used attack by causing a change in uric acid equibrium.

the affected synovial joint fluid---Diagnosis

hemoglobinopathies);

hepertension / CHF /peptic ulcer disease /renal failure patients should be caution GI distress for oral adm. Local extracasation for IV cone marrow depression

esity, alcohol consumption acute attack

omen equally, but symptoms occur earlier and are more severe in (weight-bearing joints), injury to joints, joint overuse due to prolonged

oint cartilage, When these processes are altered, as in OA, the disruption t in OA but it is usually mild, Unlike rheumatoid arthritis, OA only involves

ns for patients with OA are the mainstay of treatment. These measures, nd adequate function, The nonpharmacologic measures include patient programs,

d the drug of first choice in patients with OA. It provides effective pain minophen is not providing adequate pain control, an NSAID should be ost, tolerance, comorbid diseases, concurrent medications, and patient sidered as an alternative for patients at risk for adverse GI effects from

and cervical spine are affected. The joints are often affected in a fairly

toid arthritis.

; Inflammation of synovial fluid with an increased number of

eated results in progressive joint destruction, deformity, disability, and ronmental factors. The disease peaks between the fourth through sixth e rates between ethnic groups are small,

., prostaglandins, cytotoxins) and mechanical factors that promote the gically mediated changes in bone, cartilage, supporting tissues, and

y living activities, minimize symptoms, and diminish the progression of erapy.

k effects in 1 to 4 weeks, The analgesic and anti-inflammatory effects of nsidered when choosing an anti-inflammatory agent are ease of dosing ient preferences.

Ds, a patient has ongoing joint pain, significant morning stiffness or e protein (CRP) level.

The exact mechanism for these drugs is not known, The drugs in this

s L-penicillamine is toxic (it inhibits the action of pyridoxine). It is a

-lymphocytes, inhibiting macrophage function, decreasing IL-1,

binding to accumulated copper and elimination through urine. ne to to yield a mixed disulfide which is more soluble than cystine.

vide rapid relief of asthma symptoms (wheezing, cough, and SOB) and stemic corticosteroids.

re taken on a daily basis to achieve and maintain control of persistent aled corticosteroids, mast cell stabilizers), long-acting 2-agonists,

nusitis, GERD;

ercise (including vigorous activities) without experiencing symptoms of

ptoms or those taken long term on a daily basis to decrease inflammation nd mast cell stabilizing agents. Inhaled 2-agonists are the mainstay of

xercise are generally effective for 2 to 3 hours. (others: Salbutamol,

g agents (cromolyn, nedocromil) when taken 10 to 15 minutes before

The medical management of COPD includes pharmacotherapy (bronchodilators, corticosteroids, and antibiotics) in combination with interventions to reduce risk factors for disease progression (e,g" smoking cessation). Some patients require long-term administration of supplemental oxygen,

wise known, formerly termed a chronic obstructive lung disease). It is

rom destruction of structures supporting the alveoli, and destruction of ys collapse during exhalation, as alveolar collapsibility has increased. de shortness of breath on exertion and later at rest, hyperventilation, and

ne, oxtriphylline, theophylline); Oxygen Therapy (for pts with

me axetil; Fluoroquinolones: ciprofloxacin, gemifloxacin, ines: doxycycline; Sulfonamide combinations:TMP/SMX);

Stinging, dry eyes, blurred vision, blepharitis

Tearing, burning, conjunctival hyperemia, mydriasis, blurred vision, pigment deposition in conjunctiva and cornea, precipitation of narrowangle glaucoma

Allergic reactions (edema, foreign object sensation, hyperemia, itching, eyelid discomfort)

Miosis, accommodative spasm, constriction of visual field, retinal tears, cataracts, periorbital pain, precipitation of angle-closure glaucoma (at high doses) Ocular burning and stinging, transient blurry vision, itching, conjunctivitis, superficial punctate keratitis, tearing, photophobia

Blurry vision, conjunctival hyperemia, iris pigmentation, increase in eyelash length and coarseness

Risk factors associated with POAG include advanced age, family history, race (Caucasian and African American), myopia, HTN, diabetes mellitus, and vascular diseases, Drugs associated with increasing IOP include topical and systemic corticosteroids, anticholinergic agents, amphetamines, and tricyclic antidepressants,

y disease or syncope or bradycardia);

Any agents with anticholinergic effects, which may dilate the pupil, should be used with caution in patients predisposed to angle-closure glaucoma, Strong miotic agents also should be voided because they may lead to pupillary block. Other agents associated with inducing angle-closure glaucoma in rare cases include adrenergics, tricyclic antidepressants, MOA inhibitors, acetazolamide, and amphetamines,

Common side effects of hyperosmotic agents are headache, nausea, vomiting, diuresis, and dehydration, However, patients should not be given fluids, which antagonize the effect of the hyperosmotic agent.

n in diabetic patients

effective for glaucoma with inflammation than urea or glycerol

tion in hepatic impairment

o provide calories)

nts are unava.i'able

ocess is one of hyperplasia rather than hypertrophy eriurethral region of the prostate. It leads to symptoms of urinary

-containing products, and follow timed voiding schedules.

a-blockers relax smooth muscle in the prostate and the bladder neck,

ts 5a-reductase, which in turn inhibits production of DHT, a hormone

surgery has been noted in patients with larger prostates.

enylephrine, atropine) can precipitate urinary retention, and should be

the most common form of dementia. This incurable, degenerative, and nosed in people over 65 years of age, although the less-prevalent earlymemory loss; as the disease advances, symptoms include confusion, withdrawal of the sufferer as their senses decline. Gradually, bodily

The most common side effects are nausea and vomiting, both of which are linked to cholinergic excess. (10-20% of users and mild to moderate in severity). Less common secondary effects include muscle cramps, decreased heart rate (bradycardia), decreased appetite and weight, and increased gastric acid production.

Reported adverse events with memantine are infrequent and mild, including hallucinations, confusion, dizziness, headache and fatigue.

er neurological diseases such as Parkinson's disease and multiple s of the overstimulation of glutamate receptors. )

was the first centrally-acting cholinesterase inhibitor approved for the dosing, and considerable adverse drug reactions (including nausea, e inhibitors, such as donepezil.

r functions. It belongs movement disorders and characterized by muscle movement (akinesia). Motor symptoms / cardinal symptoms (mnemonic eads to impaired balance and falls)

normally caused by the insufficient formation and action of ude high level cognitive dysfunction and subtle language problems. education, support group services, general wellness maintenance,

opini)

ocyc- Triexy)

gic) cells in the pars compacta region of the substantia nigra (literally ty of the neural circuits within the basal ganglia that regulate movement,

lase. However, only 1-5% of L-DOPA enters the dopaminergic neurons. cts. Due to feedback inhibition, L-dopa results in a reduction in the azide are dopa decarboxylase inhibitors.They help to prevent the

to complement L-dopa. However, due to its possible side effects such as cant alterations of liver function and maintains adequate inhibition of

e, and lisuride are moderately effective. These have their own side eral forms of dopamine agonism have been linked with a markedly e receptors. However, they cause the dopamine receptors to become

hibits the breakdown of dopamine secreted by the dopaminergic neurons. notorious and potent ). This might result in side effects such as insomnia. ertensive crisis. explained. Another side effect of the combination can be stomatitis.

notherapy; or together with L-DOPA to treat L-DOPA-related motor nal loss) and L-DOPA-related dyskinesias (choreiform movements ceptors).

ropazine, procyclidine, trihexyphenidyl; The side effects (dry mouth,

etam, topiramate; e, phenobaral,

, hypomanic or mixed episode, and usually includes episodes of clinical

or quetiapine, or olanzapine;

clozapine;

xetine;

OI, or venlafaxine; divalproex plus venlafaxine; atypical antipsychotic +/-

r carbamazepine; lithium or divalproex plus olanzapine; resiperidone,

epine, gabapentin;

symptoms; First line. c side effects. openthixol); high (flupenthixol, fluphenazine, haloperidol, pimozide,

pe 1 diabetes and ketoacidosis; SGAs are higher risk than FGAs;

loperidol; olan, queti, risperidone), torsades de pointes

adache, palpitations;

a vein with clot formation). The classical symptoms of DVT include pain, , there may be some form of DVT, which often remains clinically

less than a week) of heparin treatment while they start on a 3- to 6-month ontraindication to LMWH (e.g., renal failure or imminent need for invasive

n stockings should be routinely after diagnosis". Inferior vena cava ticoagulant treatment.

herapeutic levels; and should be stopped at the first sign of labour; an breastfeed while being treated with warfarin.

t impairs its ability to supply sufficient blood flow to meet the body's he body's needs. This may occur when the cardiac output is low (often ased, and demand outstrips what the heart can provide, (termed "high eficiency), thyrotoxicosis, Paget's disease, arteriovenous fistulae or

unction;

a, pregnancy, drug use, or abuse, omyopathies, congenital heart disease)

sudden death.

ult in heart failure.

oms are predominantly respiratory. The patient will have dyspnea athlessness on reclining, called orthopnea, occurs. It is often measured ng while sitting up. Another symptom of heart failure is paroxysmal g to sleep. Easy fatigueability and exercise intolerance are also common

h as dizziness, confusion and cool extremities at rest.

(non-specific signs of respiratory distress). Rales or crackles, heard onary edema (fluid in the alveoli). Dullness of the lung fields to finger ral effusion (fluid collection in the between the lung and the chest wall). ema.

he heart is enlarged) and a gallop rhythm (additional heart sounds) may ndicate the presence of valvular heart disease, either as a cause (e.g.

ate excess fluid accumulation in the body. This causes swelling under the ausing foot and ankle swelling in people who are standing up, and sacral cur when fluid from the legs is returned to the bloodstream while lying g swelling) and hepatomegaly (painful enlargement of the liver) may opathy (problems of decreased blood clotting) may occur.

ressure is frequently assessed as a marker of fluid status, which can be e may be present, signifying the compensatory increase in contraction

bination of

uid retention); toms or DM, Eplerenone (NA in CA)) ial fibrillation that not ok with b-blockers)

rtension )

mptomatic severity or blood pressure. ACE inhibitors improve symptoms, referred to as AT1-antagonists or angiotensin receptor blockers), apy. ACEIs and ARBs decrease afterload by antagonizing the lso believed that angiotensin directly affects cardiac remodeling, and

inotropic effect and ability to produce bradycardia effects which worsen ailure due to left ventricular systolic dysfunction after stabilization with , the addition of a -blocker can decrease mortality and improve left lol, and extended-release metoprolol. The antagonism of 1 inotropic techolamines and other sympathomimetics have an effect on cardiac

ons te CHF. but typically used in severe CHF in combination with loop diuretics,

apheresis may be needed to achieve adequate control of fluid retention benefits in patients with diuretic-resistant heart failure and may restore

acilitate cardiovascular fluid homeostasis through counterregulation of ooth muscle cell relaxation. In simpler terms, it promotes vasodilation,

tion (such as talk, eating or bathing).

d improving coronary flow reserve; prevent major cardiovascular events

blingul nitrates to reduce syncope; labetalol; lower heart rate, blood pressure and free fatty acid levels, and ts with a prior MI. Avoid in pts with coronary arterial spasm

e dihydropyridines (nifedipine, felodipine, amlodipine) exert their

n, should be avoided.

tic activity (ISA). These agents act as partial agonists and cause e clearly demonstrated. Agents with ISA should be avoided in patients

ices P441)

ipheral edema, and anasarca ; Common conditions associated

e > 50 mL/min) < 50 mL/min) n CHF)

form may be due to a large number of other medical problems. it is ate (GFR). Problems frequently encountered: abnormal fluid levels in the urine) and (in the longer term) anemia. sease.

nd creatinine) and non-nitrogenous waste products. Generally fants); body water and body fluids disturbances; and electrolyte

d balance, and effects on many other organ systems. It can be

s compromised in liver failure; vascular problems (atheroembolic disease

(e.g. some NSAIDs, aminoglycoside antibiotics, iodinated contrast,

globinuria)

blunt trauma), statins, stimulants and some other drugs] hemolysis;

uction. r. o kidney stones.

iarrhea, edema, confusion, fatigue, neuromuscular irritability, and coma); pletion (prerenal failure) --------------High H+, N-waste, K, PO43-, Low

s having chronic kidney disease, irrespective of the presence or absence

1.73 m2).

erapy (RRT)

h as fever, myalgia, headache, severe malaise, nonproductive cough, nnually, Immunoprophylaxis with inactivated vaccine remains the est protection against influenza, there are four antiviral agents that are he duration of influenza symptoms, all agents should be initiated within 2

uenza B viruses. Amantadine differs from rimantadine because it is eizure threshold, Zanamivir and oseltamivir are neuraminidase

e DNA to cause a loss of helical DNA structure and strand breakage, tronidazole has excellent activity against gram-negative anaerobes, sion, "clindamycin for above the belt and metronidazole for below the found in the mouth, whereas clindamycin does. Metronidazole is also an

use a disulfiram-like reaction in patients who consume ethanol, due to ntibiotic-associated colitis secondary to toxigenic Clostridium difficile.

otic-associated colitis is

and ethambutol. Usually a four-drug regimen consisting of these first-line gimen should be tailored based on the results, Resistance develops g interactions, so it is always important to take a complete medication

hepatotoxicity, peripheral neuropathy, optic neuritis, and GI side effects. iazid and rifampin, Peripheral neuropathy is most commonly associated tically predetermined. Patients of Scandinavian, European, and African xicity and peripheral neuropathy due to isoniazid. Fast acetylators include

lus oral ribavirin are the only FDA-approved drugs for the treatment of

ignificant benefit on sustained virologic response (the absence of atment), biochemical response (normalization of transaminases), and d with interferon by itself.

used as monotherapy.

losuppression, and depression (common side effects). Interferon therapy caution in organ transplant recipients, and those with a history of anemia, pruritis, and anemia. Because ribavirin is highly teratogenic e partners are pregnant.

about 3-5% of the world's population. It typically presents during a component of hyperactivity. hings through. / Hyperactivity: a person who is unable to sit still. /

- ADHD need AMD-atom-Bup-TCA

sleep-dificult situations.

e changes, and counseling. The American Academy of Pediatrics states DHD. Long term safety of stimulants however has not been determined

hours de extended-release) , and Methylin ER, with a duration of 3-8 hours n be used just once a day (Canadian guidelines recommend the long-

s Adderall and Dexedrine spansule, with a duration of 6-8 hours; long

and to increase the release of Dopamine and Norepinephrine in the

Psychotropic Substances, it is a Schedule IV drug.

y mouth.

dolescents and adults with ADHD; appropriate for those who have either

ons or as adjunctive therapy for the treatment ADHD in both children and th comobid conditions such as depression, anxiety, enuresis or tic

g symptoms of aggression, impulsibity, overarousal and hyperactivity, but

ymptoms seen in hyperactive and impulsive children.

oil;

volve gastroduodenal ulcer, atypical gastroesophageal reflux, and gastric relieved by eating, are common. More importantly, dyspepsia may be anemia.

f gastroduodenal ulcers, H, pylori has been found in nearly 90% of been shown to decrease the recurrence rate and accelerate the ulcer well as alleviating symptoms, In cases of H. pylori-negative dyspepsia, he patient should be referred for endoscopy to rule out chronic ulceration

gents(H2 -Receptor Antagonists ) and combination antibiotics, Treatment n, clarithromycin. metronidazole, tetracycline, and bismuth subsalicylate. g interactions among the regimens. This is because systemic blood

-1) and herpes simplex virus 2 (HSV-2) cause herpes simplex. Infection Oral herpes, the visible symptoms of which are colloquially called cold nitals, commonly known as herpes, is the second most common form of herpes infection encephalitis, Mollaret's meningitis, neonatal herpes,

ral mucosa or abraded skin. Infection by the type 1 strain of herpes he type 2 strain are increasing. (Mouth is on the top, so is related to

ition was first described in 1944 by French neurologist Pierre Mollaret. ekly or monthly for approximately 5 years following primary infection

the nervous system. The double-stranded DNA of the virus is aticno virus is producedand is controlled by a number of viral genes,

development of lesions. Prodromal symptoms include tingling ng as several days or as short as a few hours before lesions develop. f lesions in some individuals. During recurrence fewer lesions are likely to han those occurring during the primary infection. Subsequent outbreaks erapy.

ciclovir (Zovirax), valaciclovir (Valtrex), famciclovir (Famvir), and generic brands at a greatly reduced cost. Valaciclovir and famciclovir ability when taken orally. Aciclovir is the recommended antiviral for lex to the neonate in cases of maternal recurrent herpes.

, specifically for treatment of "cold sores" caused by the herpes simplex edient. It probably functions by inhibiting the fusion of the human host cell

ainful skin rash with blisters in a limited area on one side of the body, s chickenpox, and generally occurs in children and young people. Once shinglesan illness with very different symptomsoften many years

nd may result in an incorrect diagnosis. These symptoms are commonly ght or touch). The pain may be extreme in the affected dermatome, with spersed with quick stabs of agonizing pain. In most cases, after 12 days skin rash. The pain and rash most commonly occurs on the torso, but earance of hives; however, unlike hives, herpes zoster causes skin de of the body and does not cross the midline. Zoster sine herpete

normal or degenerative conditions of the body's adipose tissue.

ctions in the same spot. These types of lipodystrophies are harmless. ns. For people with diabetes, using purified insulins may also help.

he absorption of the medication, or trauma that can cause bleeding that, abetics, becomes impossible to gauge correctly and the treatment of the orsen.

pid redistribution; with excess, or lack of, fat in various regions of the f the neck (also referred to as buffalo hump).

erized by insulin resistance and are associated with Syndrome X.

prevent TD. Studies show a decrease in the incidence of TD with use of l chemoprophylaxis;

lves without specific treatment; however, oral rehydration is often ear liquids are routinely recommended for adults. Travelers who develop pecially if associated with nausea, vomiting, abdominal cramps, fever, or erapy. Antibiotics usually are given for 3-5 days. Currently, only prescribed regimens are 500 mg of ciprofloxacin twice a day or 400 hoprim-sulfamethoxazole and doxycycline are no longer recommended ents. Bismuth subsalicylate also may be used as treatment: 1 fluid to eight doses in a 24-hour period, which can be pite therapy, travelers should be evaluated ction.

eine;

h diabetic autonomic neuropathy) endocrine tumors);

esses, the cost of treatment, the potential for promoting antimicrobial

for cold water and sometimes ice or ice water) are typical for DI. o those of untreated diabetes mellitus, with the distinction that the urine is is no hyperglycemia. Blurred vision is a rarity. Signs of dehydration may nnot conserve much (if any) of the water it takes in.The extreme urination dren,

and growth as well. They may present with fever, vomiting, or diarrhea. ecades as long as enough water is drunk to offset the urinary losses. .

ressin. Also gestational DI tends to abate on its own 4 to 6 weeks p it again in subsequent pregnancies. In dipsogenic DI, desmopressin is

I. Instead, the diuretic hydrochlorothiazide (HCT ride can improve nephrogenic diabetes insipidus; revent hypokalemia. s with DI, as they may become dehydrated easily.

Four parameters (RBC count, hemoglobin concentration, MCV and RDW) are measured, allowing others (hematocrit, MCH and MCHC) to be calculated, and compared to values adjusted for age and sex. For adult men, a hemoglobin level < 13.0 g/dl (grams per deciliter) is diagnostic of anemia, and for adult women, the diagnostic threshold is below 12.0 g/dl.

vitamin B12, folic acid (or both). Deficiency in folate and/or vitamin B12 oduce neurological symptoms, while B12 deficiency does.

emia. Other types of Liver Disease can also cause macrocytosis.

nemia of chronic disease (more commonly presenting as normocytic

HbE syndrome / HbC syndrome / and various other unstable hemoglobin

mia / Acquired sideroblastic anemia, including lead toxicity / Reversible

d cell size (Mean corpuscular volume) remains normal. Causes include:

d nausea. It is a common condition which affects women more frequently ng complaints are nausea and vomiting, and a heightened sensitivity to migraines get a preceding aura, in which a patient may sense a strange -emetics for nausea, and avoidance of triggers if present.

ss / Changes in sleep patterns lls, hormone fluctuations during the menopause transition / Tension

monosodium glutamate (MSG) or nitrates (like bacon, hot dogs, and ducts, and fermented or pickled foods.

serotonin reuptake inhibitors (SSRIs) such as fluoxetine.

ugh highly effective, it has rare but serious side effects, including

o be used off label for the treatment of migraines. It has not yet been

own to help some migrainures, especially those who have an aura.

omen using hormonal contraception appear to be at particular risk. The e involved. Women who experience auras have been found to have twice aines. Migraine sufferers seem to be at risk for both thrombotic and in people with migraine with aura in a Women's Health Initiative study,

mesylate (DHE); y at 4 hours, less headache recurrence, best for moderately severe cacious for severe migraine attack); and zolmitriptan; omethacin; Antinauseants (dimenhydrinate); Antiemetic/prokinetic agents

ne); TCAs (amitriptyline, nortriptyline, doxepin); Antiepileptic drugs pizotifen) others (riboflavin, lithium, botulinum toxin)

ollowing habitual, excessive drinking. It also may occur during an

mineral density (BMD) is reduced (in women as a BMD 2.5 standard non-collagenous proteins in bone is altered.

orosis, treatment may involve both. Lifestyle change includes preventing

sis, but may also develop in men, and may occur in anyone in the cifically glucocorticoids, when the disease is called steroid- or

e sex; estrogen deficiency following menopause is correlated with a rapid d) effect.

ects against osteoporosis; Malnutrition; Physical inactivity lead to

andropause, hypothalamic amenorrhea or hyperprolactinemia. In

tes mellitus type 1 and 2, acromegaly and adrenal insufficiency. In

(after gastrectomy, intestinal bypass surgery or bowel resection) and ty to absorb calcium and/or vitamin D; and other micro-nutrients such as

and polyarticular juvenile idiopathic arthritis;

mia, mastocytosis, hemophilia, sickle-cell disease and thalassemia. hatasia, glycogen storage diseases, homocystinuria, Ehlers-Danlos

n people with Parkinson's disease

of more than 30 mg hydrocortisone (7.5 mg of prednisolone), especially

itamin D.

er anti-metabolite drugs, depot progesterone and gonadotropin-releasing

absorption. Chronic phosphate binding may also occur with aluminium-

es are presently sodium alendronate (Fosamax) 10 mg a day or 70 mg ce a month.

It is marketed alone as well as in combination with vitamin D; and in turn, the exposure to tissues other than bone is very low. After

phagus, it can lead to esophageal ulcers. Therefore, it is recommended is poorly absorbed when taken with food, so it is recommended that no

s osteoblasts, thus increasing their activity. It is used mostly for patients ctors for fracture or cannot tolerate the oral bisphosphonates.

well as inhibiting the proliferation of osteoclasts.

sis to prevent vertebral and hip fracture. It has side effect benefits over cause for medication withdrawal in osteoporosis.

ere are other indications for its use as well.

y (BMD) is tightly regulated by a balance between osteoblast and esorption equilibrium, as it stimulates osteoblast activity. Some SERMs ve been proved as effective in clinical trials.

down of energy molecules such as glucose. It is also found on the

s, green vegetables, fruit, and milk. Beriberi is therefore common in uate diet (Wernicke-Korsakoff syndrome), as well as being a rare side

atic recovery within hours can be made when this is administered to

iovascular, nervous, muscular, and gastrointestinal systems; weight loss, in the limbs, and periods of irregular heart rate. Edema (swelling of

kening of the capillary walls, which causes the peripheral tissues to

eferred to as endemic neuritis.

1901

the human foot. Moreover, a fungus species that causes athlete's foot yeast) that grows on the surface of the skin and then into the living skin appear as an extensive "moccasin" pattern on the bottom and sides of ond most common skin disease in the United States, after acne. Up to

ration in the United States) and tolnaftate (1% typ. in the U.S.). cription antifungal drugs, from several different drug families. These ative) is a known fungicide;

eins containing the essential amino acid tryptophan. Because tryptophan owever, if dietary tryptophan is diverted into protein production, niacin

of patients with clinical pellagra are poor, homeless, alcohol dependent, poultry, fish, and eggs. If one's diet contains these foods, one's need for

a, and death.

velop or maintain an erection of the penis sufficient for satisfactory

es inside the penis. The most important organic causes are urgery), hormonal insufficiencies (hypogonadism) and drug side effects. It was sildenafil or Viagra; tadalafil

eimer's disease, multiple sclerosis, and stroke.

der, generalized anxiety disorder, personality disorders or traits),

nd blood vessels involved in erection. Prostate and bladder cancer otence.[8])

cent higher in male smokers compared to non-smokers. Smoking is a

rugs that modify central nervous system response may inhibit erection

gulator (CFTR)] that affects the transport of sodium and chloride ions most damaging to epithelial surfaces, such as those of the lungs and

eat pancreatic insufficiency. Due to pancreatic insufficiency, plementation is adequate. The dosing must be individualized for the

curs in patches throughout the brain or spinal cord or both, interfering isturbances. It occurs chiefly in young adults and is thought to be caused

ng to demyelination. It may cause numerous physical and mental ung adults, is more common in women, More specifically, MS destroys myelin sheath, which helps the neurons carry electrical signals. MS n's extensions or axons. When the myelin is lost, the neurons can no ses - better known as plaques or lesions) in the white matter. Loss of are interrupted. However, more advanced forms of imaging are now

or attacks), in a gradually-progressive deterioration of neurologic ndrome (CIS). In CIS, a patient has an attack suggestive of

n (hypoesthesias and paraesthesias), muscle weakness, muscle spasms, or swallowing (dysphagia), visual problems (nystagmus, optic neuritis, of varying degrees and emotional symptomatology in the form of and symptom severity is the Expanded Disability Status Scale or

lls) degenerates. According to the view of most researchers, T cells

cells. T cells gain entry into the brain via the blood-brain barrier (a r is normally not permeable to these types of cells, unless triggered by eased. When the blood brain barrier regains its integrity (usually after elin as foreign and attack it as if it were an invading virus. That triggers s. Leaks form in the blood-brain barrier. These leaks, in turn, cause a been implicated in this process.

prednisolone, is the routine therapy for acute relapses. The aim of this erally effective in the short term for relieving symptoms, corticosteroid de osteoporosis and impaired memory, the latter being reversible. s will reduce the contractions and excitation of muscles. Baclofen is

IS). Several studies have shown that treatment with interferons during an

untries for RRMS. Three are interferons: two formulations of interferon medication, mitoxantrone, is an immunosuppressant also used in natalizumab (marketed as Tysabri). All six medications are modestly

duce and release corticosteroids that naturally reduce inflammation. This acute) MS attacks. ACTH is rarely used today because of the severe he medications of choice for treating acute attacks since they rarely

al irregularities. Lowered resistance to infections. Allergic reactions. effects that may not go away.

y inappropriately produces antibodies against acetylcholine nicotinic e is destroyed.

mestinon) are effective in treating this disorder. They allow tivated by acetylcholinesterase in the gap junction.

ness and tinnitus and progressive hearing loss, usually in one ear. It is nire's disease is not known, but it is believed to be related to sufferers the same. However, so-called "classic Mnire's" is considered

cs, steroids, and diuretics.

zepam and triazolam), lorazepam and oxazepam are also widely used. e hypnotic. It cause less rebound insomnia than more potent BDZs such

r drugs, it can cause drowsiness). ).

not prevent MS. , Beta-histine.

aying while the body is actually stationary with respect to the ular system), in the syndrome and Meniere's disease.

epam, diazepam),

nful response to gentle touch (tactile allodynia, tender points). Other

(venlafaxine); -adenosyl-L-methionine)

cluding: ide;

ps, fever, muscle spasm, jerking movements and lacrimation are normal

atadine;

doephedrine;

ys in the brain or spinal cord. It is common in spinal cord injury, multiple iene and gait;

ects: dry mouth and drowsiness); y and muscle weaknes, less use) mon side effects); , satives) may be another option.

idol; hiazines: prochlorperazine;

ing agents, Antibiotics), onidase or NaHCO3; amines, steroids, vasoconstrictors; ase)

unction, severe HF); Anthracyclines (acute inflammation, congestive

tara- Etopo- Nitro-)

ating agents); - Metho- Vinca-)

topenia, anemia) ctinomycin, daunorubicin, doxorubicin, idarubicin,

Ulcerative colitis Seldom Always Usually cured by removal of colon Seldom Higher rate Continuous area of inflammation Continuous ulcer Shallow, mucosal Seldom Seldom No consensus Vaguely associated with Th2 Granulomas uncommon Usually cured by removal of colon Lower risk for smokers

ed; in cases where remission is possible, relapse can be prevented and ed, Crohn's disease may not significantly restrict daily living. Treatment maintaining remission.

n (normally aminosalicylate anti-inflammatory drugs and corticosteroids). of symptoms. Prolonged use of corticosteroids has significant sideates alone, though only a minority are able to maintain the treatment, and

ations, prednisone, immunomodulators such as azathioprine, uld be used in severe attacks of Crohn's disease.

oking cessation.

wasa. ay have some therapeutic effect in rheumatoid arthritis. However, the -effect profile. [2] They are usually considered to be first line therapy for disease in the oids

re used more sparingly due to the availability of effective treatments with pertension, high blood glucose, osteoporosis, and avascular necrosis of nce.

uction of remission.[5] Intravenous steroids are used for cases refractory .

ning that less quantities of steroid enter into the bloodstream. It has been ssion in Crohn's disease.[7] Formulated as Entocort, budesonide is ] Budesonide is also useful when used in combination with antibiotics for

Hydrocortisone and budesonide liquid ffects, some very serious, and it is

erapy of Crohn's disease. They are purine anti-metabolites, meaning that n of months, making it unwieldy to use them for induction of remission.

remission in steroid refractory disease. / Maintenance of remission after al for inviting a host of potentially fatal infections, and is also listed by the

ctor, a cytokine in the inflammatory response. It is administered

n's disease. / Maintenance for fistulizing Crohn's disease. y fatal, and infliximab carries an FDA black-box warning on the label. um sickness, and risk of multiple sclerosis.[16] Serious side effect also n opportunistic viral infection of the brain that can cause death

Adalimumab has been shown to reduce the signs and symptoms of, and d well to conventional treatments and who have lost response to, or are

d it is also has black-box warning on its FDA label. Listed potential side erculosis) and infections caused by viruses, fungi, or bacteria; rare myelinating central nervous system disorders); and rare reports of cardiac

ction and maintenance treatment for moderate to severe Crohn's or necrosis factor-alpha such as infliximab. mission for moderate to severe Crohn's disease.

ing rates of remission[22] and maintaining symptom-free status[23] in hen used in combination with interferon beta-1a).[24][25] The label also

salicylic acid (5-ASA and mesalazine) was the therapeutically active

ude Asacol, Pentasa, Mezavant, Lialda, and Salofalk.

sone / Budesonide - under the brand name of Entocort

ated to NSAID use. Brand names Sulcrate in Canada;

cid in the stomach to form a cross-linking, viscous, paste-like material eins on the surface of ulcers, such as albumin and fibrinogen, to form on of hydrogen ions, and adsorbs both pepsin and bile acids. Recently, it ctors (EGF), bFGF), and gastric mucus.

y behaviors, referred to as "purging". The most common formpracticed nemas, diuretics, and overexercising are also common

nder similar circumstances. how much one is eating. misuse of laxatives, diuretics, or other medications; fasting; excessive

week on average and persist for at least 3 months. The disturbance does

age distortion, with an obsessive fear of gaining weight. Individuals with g, vomiting, excessive exercise or other weight control measures, such as of people with the diagnosis are male. Anorexia nervosa, involving ath in severe cases.

yline); antihistimine and seratonin antagonist (e.g., cyproheptadine;

kers (verapamil, diltiazem);

prolol, propranolol, esmolol), lidocaine; ainamide) may be added es are ineffective or not tolerated by pts;

gulant); Dofitilide (hospital use) ;

the brain either through cerebral hypoxia or hypotension but possibly for

gonist ( yohimbine); beta1-adrenergic agonist ( metoprolol)--- not

ramp, numbness or sense of fatigue), classically calf muscle, which rmittent claudication caused by peripheral arterial disease. Neurogenic en a symptom of severe atherosclerotic disease of the peripheral

nd occasionally other extremities (). This condition can also naud's), where the phenomenon is idiopathic, and Raynaud's syndrome

ponses to cold or emotional stress. More specifically, it is a vessels, leading to tissue hypoxia. Chronic, recurrent cases of arely cause ulceration and ischemic gangrene.

yclosporin; ergotamine;

idines: diltiazem); Canada;

stroke, for 85% of all strokes), intracerebral hemorrhage or

dipyridamole;

at antithrombotic drugs are avoided.

hanims to infection.

diated by the hypothalamus; Extreme of age, chronic diseases, some holine, halothane, isoflurane, antipsychotics) may cause hyperthermia.

ed for Malignant Hyperthermia; r neuroleptic maglignant syndrome.

tion; Thiamine can be used for alcohol intoxication related symptom; If

autozome phenylalanine hydroxylase (PAH). This enzyme is necessary to ne accumulates and is converted into phenylpyruvate (also known as

retardation and seizures. However, PKU is one of the few genetic fective treatment. There is no cure. Damage done is irreversible so early

arbon dioxide is a gaseous product of the body's metabolism and is or diminished consciousness. It may also be caused by exposure to arbon dioxide. It can also be an initial effect of administering panied by respiratory acidosis. ulmonary diseae associated with acute hypercapnia.

f a deficiency or an abnormality of one of the clotting factors. Hemophilia,

Evaluating Examination Blueprint Subject Areas

Drug metabolism inactive metabolites

retain similar activity

with altered activity

bioactivated metabolites

Biotransformation pathway Phase I reactions:

oxidation

reduction

Enzymatic hydrolysis

Phase II reactions:

conjugation

Factors influencing drug metabolism

Chemical structure species differences

physiological/disease state genetic variations

drug dosage

nutrional status

Age

Gender

circadian rhythms

drug administration route

councurrent drug therapy

Extrahepatic metabolism

plasma

Intestinal mucosa

intestinal bacterial flora

stomach

nasal musoca

lung

Placental and fetal metabolism Placenta

fetus

Strategies to manage drug metabolism

pharmaceutical: sublingual tablets transdermal patches ointment formulaiton IM depot injections enteric-coated formulation nasal administration

pharmacological:

chemical:

Prodrugs

Pharmacogenetic

isotonic solution Isotonicity

How many mg of sodium chloride are needed to adjust 30 mL of a 4% cocaine HCl solution to isotonicity. The freezing point depression of a 1% solution of cocaine HCl is 0.09 degrees.

Allopathy

Insulin preparations are usually administered by subcutaneous injection

fluorouracil

venoclysis

piggyback

isotonic solution

intravenous push (bolus) administration

vastus lateralis

ascorbic acid

Gentamicin sulfate (Garamycin)

toxoids

Active immunizations Passive immunizations

activated charcoal

topical formulas as sunscreens

Colostomy pouches

targeted drug delivery systems

surfactants

HLB system

polycarbophil Bulk-forming agents

Phenylpropanolamine (PPA)

internal analgesic

Emetrol

Calcium carbonate

antacids

magaldrate Ayerst's Riopan

Masking the bitter taste of drugs

diluent

lubricant in tablet formulation

Aspartame

Mannitol

Benzyl alcohol

suspension

Inhalation aerosol products

ileostomy

heroin

burn

Benzocaine

basal thermometer

French system

Emergency insect sting and bite kits

Melatonin

Allantoin

gelatin capsule prochlorperazine Lanoxicaps cyclosporine ethchlorvynol ethosuximide ranitidine

rectal drug administration

PEGs

Lactose

Starch

Carbomers

Disintegration tests

colligative properties

osmotic pressure

methylcellulose

Papain and subtilisin

membrane filtration

Henderson-Hasselbalch equation

the half-neutralization point

Decay rate first-order process

osmotic tablets

sustained-release dosage forms

liposome

antacid

(A) bevel (B) cannula (C) hub (D) heel of bevel (E) lumen

Alcohol

(A) 4.0-4.5 (B) 5.5 (C) 6.4 (D) 7.0 (E) 7.4 Blood 7.36 to 7.40 Eye 7.4 Skin 4.0 to 6.5 Vagina 3.5 to 4.2

Herbs

NEWBORNS: Undeveloped Pharmacokinetic Profile

Hypersensitivity reactions
Type I IgE-mediated

Anaphylaxis

Urticaria [7E : tE5kZEriE]

Type II Cytotoxic/antibodydependent Erythroblastosis fetalis Goodpasture's syndrome Autoimmune hemolytic anemia Hashimoto thyroiditis

Type III immune complex Serum sickness Arthus reaction SLE Rheumatoid arthritis Farmers lung Humidifier lung

Type IV cell mediated or delayed type hypersensitivity Contact dermatitis Tuberculin skin test Chronic transplant rejection

Type V Graves disease Myasthenia gravis

Tb 5 al e

- Cm r o opi as

c a cesi s hr tr t a i c
parathroid hormone (PTH), or parathormone bones kidney

intestine via kidney

at i oy n bd atgn ne i

hyper- or hypoparathyroidism

r s os tm epnei e

Calcitonin

Neuromuscular junction (NMJ)

Acetylcholine

open Na channels, stimu. Muscle contraction but decrease cardiac muscle fibers contraction

Muscle---Curare Neuronal---Hexamethonium

Muscarinic blocked by atropine

Gamma-aminobutyric acid (GABA)

chief inhibitory neurotransmitter regulation of muscle tone

Drugs that affect GABA receptors

Drugs that affect GABA in other ways

Peripheral nervous system (PNS)

Somatic nervous system

Autonomic nervous system (ANS) or visceral nervous system

Proprioceptor

Complement system

complement control proteins

Immunocompetence

White blood cell leukocytes

granulocytes

agranulocytes

Lymphocyte Large---NK cells small--T cells small-- B cells

B cells

T cells

Helper T cells

Cytotoxic T cells

Memory T cells

Regulatory T cells

Natural killer T cells

 T cells

T cells

B cells

Memory T cells

Memory B cells

Phagocytic cells and phagocytosis

MHC proteins

APCs

Complement fixation test

Natural killer cell

Perforin

hematocrit [5hemEtEkrit]

packed cell volume (PCV)

Polycythemia vera (PV)

Lowered hematocrit

Oxygen Transport

Animal tissues

Epithelium

Connective tissue

Muscle tissue

Neural tissue

Sebum

blood-thymus barrier

Thyrotropin-releasing hormone

Thyroid-stimulating hormone

Somatostatin

Follicle-stimulating hormone FSH

Luteinizing hormone LH

Endorphin

ACTH

Anterior pituitary FLAT PEG

Hypothalamus

Name Corticotropin-releasing hormone Dopamine Gonadotropin-releasing hormone Growth hormone-releasing hormone Somatostatin

Thyrotropin-releasing hormone Vasopressin

posterior pituitary vasopressin Oxytocin

Hormone Oxytocin Vasopressin

parathyroid gland PTH calcitonin

Region

bones

kidney

intestine via kidney

Adrenal medulla

fight-or-flight response

Human chorionic gonadotropin hCG

cholestasis [7kCli5steisis]

Spirometry

picnometer [pik5nCmitE]

Hydrometer

diabetes mellitus

Diabetes insipidus

Autacoids

Testosterone

Prostaglandin

Langerhans cell

DNA Deoxyribonucleic acid

Ribonucleic acid RNA

Regulatory RNAs

Transcription

DNA replication

reverse transcription

Translation

nucleoside

nucleotide

The structure of the common nucleotides

Viral Replication

Operon

Coumarin

Complex Homeostasis

Prostate specific antigen PSA

Adipose tissue

Renal function

Estimated creatinine clearance rate (eCcr)

Cockcroft-Gault formula

Estimated GFR for Children using Schwartz formula

chronic kidney disease (CKD)

Prothrombin time

cretinism [`kretInIzEm]

Cell death

Apoptosis

Necrosis

Gastritis

Atrophic gastritis

AMAG

Eosinophilic gastritis

erosive gastritis

Cancer

neurodegenerative disease

Hepatic encephalopathy

cholestasis

Antiemetics

Gold compounds

schizophrenia [7skizEu5fri : niE]

Neurotransmitters

Off-label use

ENDOTOXINS

Lipopolysaccharides LPS

LPS and virulence of Gram-negative bacteria

Cytochrome P450 http://www.medicine.iupui.ed u/Flockhart/table.htm

disulfiram-like reaction

Glycogen

Glucagon anti-insulin

Glycogenesis

Glycogenolysis

Glycolysis

Gluconeogenesis

clathrate compound or cage compound

Rheumatic fever

undulant fever Malta fever

Mean corpuscular volume MCV

Mean corpuscular hemoglobin MCH

Liver function tests

Hypercalcemia CHIMPANZEES.

hypermetropic

presbyopia [7prezbi5EupiE]

Myopia

Miosis constriction of the pupil of the eye. Miotic

Mydriasis

Conjunctivitis

Tropinin I

methemoglobinemia

Cyanosis

D-xylose test

Acquired porphyria

Anion gap

Multidrug resistance Aldosterone

CBC

hematologic testing

ALP alkaline phosphatase

Monitoring drugs level

Carcinoembryonic antigen (CEA)

Serum eosinophils

P-glycoprotein P-gp

Sympathomimetic drug

Platelet-activating factor (PAF)

Eicosanoid

Macrosomia

hematopoiesis

Bradykinin

Phosphodiesterase inhibitor

PDE1 selective inhibitors

PDE2 selective inhibitors

PDE3 selective inhibitors

PDE4 selective inhibitors

PDE5 selective inhibitors

Coombs test

Drug-induced immunemediated hemolysis

Drug-induced hemolytic anemia

Protein strutures

Amino Acids strutures:

Amino acids:

Codon

restriction enzyme

DNA ligase

Protein biosynthesis

RNA interference

Complementary DNA cDNA

Regulation of gene expression

Post-transcriptional regulation

Up-regulation Down-regulation

Plasmid

Proteomics

Side Effects of Steroid

Cytokines

Hypertrophy

Hyperplasia

amphiprotic

Tuberculin Sensitivity Test

expectorant action

Penicillamine

Hypovolemia

Transcription

Reverse transcription

Translation

Burn

N en om clatu re

T it rad n en om cl

S uperficial

F irst -deg

hernia

Examples include:

Toxicity of Cynide

Cyanocobalamin vitamin B12

Aldehyde dehydrogenase inhibitors

Causes of Erectile Dysfunction

haploid

Anemia

Microcytic anemia

Macrocytic anemia

Iron deficiency anemia

Sickle cell anemia

G6PD-hemolytic anemia

Aplastic Anemia Granulocytopenia

Agranulocytosis Leukopenia thrombocytopenia

duodenum

Metabolic acidosis

Respiratory acidosis Respiratory alkalosis Metabolic alkalosis

Mantoux test

Hymenoptera

Achlorhydria

Adrenal virilism

Vasculitis

Mitral stenosis

Cystic fibrosis

Kernicterus

Oocyte

Spermatogenesis

SCID

Acapnia

Thyroid function test

Melenoma neonatorum

Malnutrition

Marasmus

Kwashiorkor

Cachexia

testicond

Bronze diabetes

Islets of Langerhans

Aaerobic Oxidation

Lecithin Sphingomyelin ratio

Myxedema

Trigeminal neuragia

Keratolytic therapy

Hyperammonia

Hyperammonemia

Organ-Specific autoimmune disorders Non-Organ-Specific autoimmune disorders

page 1-39 (take note 50-60)

300 -----180---------------------------200 right and 100 wrong BIOMEDICAL SCIENCES (25%)----74 PHARMACEUTICAL SCIENCES (35%) ----106 PHARMACY PRACTICE (30%)----90 BEHAVIOURAL, SOCIAL AND ADMINISTRATIVE PHARMACY SCIENCES (10%)---30

hydrolysis procaine to p-aminobenzoic acid oxidation of 6-mercaptopurine to 6-mercapturic acid

imipranmine demethylated to desipramine acetohexamide reduced to l-hydroxyhexamide codeine demethylated to morphine

irponiazid(antidepressant) dealkylated to isoniazid(antitubercular retinoic acid(Vitamin A) isomerized to the anti-acne agent, isoretinoic acid

prodrugs enalapril hydrolyzed to enalaprilat, a potent antihypertensive sulindac, a sulfoxide, reduced to the active sulfide levodopa decarboxylated in the neuron to active dopamine

hway

The most common phase I: Hydroxylation, Oxidative deamination, N, O, S-Dealkylation, N,S-Oxidation, Desulfuration, Dehalogenation, Oxidation of -OH or CHO; primarily occur in liver,the other sites: intestinalmucosa, lungs, and kidney catalyed by cytochrome P450 ( unlike most enzymes, CYP450 uses a variety of oxidative biotransformations to metabolize a diverse group of substrates,) 6 Mammalian families involed in steroid and bile acid metabolism: CYP7/11/17/19/21/27 4 Mammalian families involed in xenobiotic, or drug, metabolism: CYP1/2/3/4 the oxidized products increase polarity and enhance water solubility and reduce reabsorption, under further biotranformation by phase II pathways

less commonly than oxidation, overall goal is the same: create polar functional groups that can be eliminated in urine, CYP450 might be involved in some reductions Bacteria resident in GI involve in azo and nitro reductions Carbonyl reduction, Azoreduction, Nitroreduction Esterase: usually in plasma, nonspecific and for de-esterification to an alcohol and an acid.( conveting prodrugs) Amidase: hydrolyze amides into amines and acids (deamination), primarily in the liver Ester drugs usually shorter acting than similar amide drug Lactones and lactams are cyclic esters and amides, also susceptible to hydrolytic metabolism

functional groups of the original drug or the metabolite are marked by a conjugation reaction

combine the parent drug with certain natural endogenous constituents(glucuronic acid, glycine, glutamine, sulfate, glutathione, 2-carbon acetyl fragment, or 1-carbon methyl group, require: high-energy molecule, enzyme conjugates are highly polar and unable to cross cell membranes, almost phrmacologically inactive and of little or no toxicity acetylated and methylated conjugate are exceptions: no increasing in polarity but usually inactive 6 conjugation pathways: glucuronidation: most common, glucuronic acid is easy available and a large of functional groups; (OH, NR2, COOH, SH, Acidic Carbon) sulfate conjugation: high energy form, can react with phenols, alcohols, arylamines, NH-OH) amino acid conjugation: involves glycine or glutamine with aliphatic or aromatic acids to form amides glutathione conjugation: important to remove harmful electrophilic agents (halides, epoxides, or other electrophilic Miachael acceptors) methylation: SAM as the methyltransferase (OH,NH2, SH) acetylation: primary amine, hydrazides, sulfonamides and occasionally amides, lead to N-acetylated products which less polar and can retain phmaco-acitivity. The N-acetylated metabolites of certain antibacterial sulfonamide can accumulate in tissue or in the kidneys and induce crystalluria and subsequent tissue damage. Acetylation is conducted by Acetyl-CoA / N-acetyltransferase

ug metabolism

qualitative differences: primarily in phase II, result from a genetic deficiency of a enzyme or endogenous substrate quantitative: primarily in phase I, result from the different levels of enzyme, endogenous inhibitor or inducer... Alter liver function can affect the drug's clearance Congestive heart failure decrease hepatic blood flow which alters the extent of drug metabolism Alteration in albumin production can alter the fraction of bound to unbound drug.

increase in drug dosage results in saturation certain metabolic enzymes When the metabolic pathway is saturated, an alternative pathway may be pursued conjugateing agents/endogenous substrate: a low protein diet can lead to a deficiency of certain amino acids and decrease oxidative drug metabolism capacity deficient in essential fatty acids reduce the metabolism of ethyl-morphine and hexobarbital deficiency of certain dietary mineral: Ca, Mg, Zn, Cu Deficiency of vitamin: particularly A,C,E and B groups e.g. less Vc decrease oxidative pathways; less Ve, retard dealkylation and hydroxylation

infants and young children:metabolizing systems not fully developed, smaller doses,esp for drugs requiring glucuronide conjugation Older children: some drugs less active than in adults, liver develops faster than genral body weitht. Elderly: body fat increasing; metabolizing system decline, liver function decrased (reduced hepatic blood flow and less enzymes available; high first-pass effect drugs will increase the concentration of unmetabolized drugs in the general circulation); slowing the process of elimination and causing higher plasma drug level; Phase I metabolism reduced; Phase II metabolism is not affected by age. metabolism of diazepam, prednisolone, caffeine and acetaminophen is slightly faster in women (Di ac ca pre) oxidative metabolism of propranolol, chlordiazepoxide, lidocain, and some steroids occures faster in men (Pro chlo lido stero)

nocturnal plasma levels of drugs( theophylline and diazepam) are lower than the diurnal plasma levels oral adm.: First-pass effect or presystemic eliminaiton: loss of drug activity via hepatic metabolism before it reaches its site of action. (GI tract---mesenteric vein---hepatic protal vein---liver---system circulation) IM/IV,sublingual and rectal administration bypass first-pass effect Nasal administration? can effect the activity of specific CYP450 and thus alter the metabolism

sm

contains esterases for hydrolysis of esters cotains metabolism enzymes---microsomal oxidation, glucuronide conjugation, and sulfate conjugation As a lipid-solubal drug can be metabolized into polar or inactive metabolites in intestinal muscosa before entering the blood, the result is comparable to a first-pass effect.

factors modify the intestinal flora may modify drug activity: age, diet, disease state, exposure to chemicals or drugs. Certain diseases ( ulcerative colitis promotes bacterial growth while diarrhea reduces, antibiotics decrese) enterohepatic circulation : bacterial flora secrete glucuronidase which hydrolyzes the conjugates of bile Certain bacterial flora convert vitamin precursors to their active forms: vitamin K bacterial flora produce azoreductase, reduce the prodrug sulfasalazine to active aminosalicylic acid and sulfapyridine.( sulfasalazine is one of the few agents effective in the treatment of ulcerative colitis) acidic enviroment produces nonenzymatic degradation of a number of drugs: penicillin G, carbenicillin, erythromycin, tetracycline. Assists in the degradation of proteins and peptides( insulin) provides a high level of CPY450 activity which can significantly alter the amount of drug that reaches the system circulaiton: nasal decongestants, anesthetics, nicotine, cocaine, ets responsible for first-pass metabolism of drugs adminitered IV/IM, transdermally, or subcutaneously total amount of metabolizing enzymes in lungs is less than that in liver the lung provides second-pass metabolism for drugs leaving the liver

etabolism if lipid soluble enough, the drug/xenobiotic will likely pass through the placenta--not a physical or metabolic barrier Presence of a small amount of aryl aromatic hydroxylase in placenta induced in pregnant women who smoke cigarettes Major deficiency is that of glucuronic acid conjugating activity both in fetus and the neonate Resullting in gray baby syndrome (decreased chloramphenical glucuronidation) and neonatal hyperbilirubinemia (decrease in bilirubin glucuronide formation)

drug metabolism

bypassing hepatic first-pass effects and directly enter into systemic circulation, nitroglycerin, continuous supple of drug over an extended period of time, usful for rapidly metabolized compounds: nitroglycerin for prophylactic concentrations useful for highly lipid soluble esters of estradiol and testosterone (estradiol benzoate, testosteron enanthate) (intramuscular) protect acid-sensitive drugs: methenamien, erythromycin, omeprazole useful for peptides: calcitonin salmon, which have very low oral bioavailability

L-dopa, concurrent administration of carbidopa to ensure adequate concentration of L-dopa reach CNS

Clavulanic acid / sulbactam / tazobactam as lactamase inhibitor useful for -lactam antibiotics Ifosfamide is coadministered with mesna to prevent its toxicity.( neutralize the acrolein produced in kidney the metabolite of ifosfamide Combines a low dose of ritonavir with a therapeutic dose of lopinavir, to inhibit the activity of CYP3A which can extensively metabolize lopinavir.

testosterone----methyltestosterone: not subject to rapid first-pass metabolism tolbutamide---chlorpropamide: much longer duration isoproterenol---metaproterenol: not susceptible to COMT, orally active and longer dutation somatostatine---octreotide: increase half-life and can be administered as a subcutaneous injection

increase in water solubility: sodium succinate esters and sodium phosphate esters increase in lipid solubility: duration / oral absorption /topical abosorption /palatability decrease GI irritation site specificity: Methyldopa: a significant amount of -methyldopamine to reach the CNS and bind to 2-adenergic receptor Omeprazole: selectively activate at the acidic pH(less than 1) seen in gastric parietal cells Methenamine: a prodrug of formaldehyde, to avoid its toxicity in oral administration Olsalazine: only effective when reaching the large intestine via metablizing by bacteria cleave the azo bond Diethylstilbestroldophosphate: ester prodrug, avoid the side effects of diethylstilbestrol.

The freezing point depression method for determining isotonicity calculations is more accurate than the sodium chloride equivalent method. It is based upon the premise that isotonic solutions have a reduction in freezing points of 0.52 degrees Celsius. This problem now becomes Step 1: What is the change in the freezing point of a 4% cocaine HCl solution if a 1% solution has a depression of .09 degrees?

Step 2: Determine the amount of sodium chloride needed for a total freezing point depression of 0.52 degrees. Remember that a 0.9% concentration of sodium chloride is isotonic and must have a freezing point depression of 0.52 degrees and that 4% cocaine HCl gave a depression of 0.36 degrees. Thus, the further reduction needed will be 0.52 - 0.36 = 0.16. Step 3: Since 30 mL of solution is required,30 mL x 0.277% = 0.083 g or 83 mg of sodium chloride.

A method of treating disease with remedies that produce effects different from those caused by the disease itself.

Insulin is usually administered by subcutaneous injection into the arm or thigh. Absorption of the insulin is good, and this route is both convenient and safe for selfadministration of the drug. Some studies indicate that the absorption rate from the arm is 50% faster than from the thigh.

Which of the following statements concerning fluorouracil is NOT true? (A) Its chemical structure is a modified pyrimidine similar to uracil and idoxuridine. (B) It is effective only when administered by injection. (C) Anorexia and nausea and vomiting are very common side effects. (D) The drug interferes with the synthesis of ribonucleic acid. (E) Leukopenia is a major clinical toxic effect. Fluorouracil (5-FU or f5U) is a pyrimidine analog, which is used as a drug in the treatment of cancer. It belongs to the family of drugs called antimetabolites. It is typically administered with leucovorin. The term "venoclysis" is synonymous with intravenous infusion. Intermittent therapy refers to administration of parenteral drugs at spaced intervals. One of the most convenient methods for administration is for the pharmacist to prepare a minibottle containing active drug solution such as an antibiotic added to a diluent. This unit is attached to the tubing of a largevolume parenteral (LVP) bottle already hanging on the patient. This "piggyback" concept saves the patient from multiple injections and assures high blood levels of the additive drug because the minibottle solution is infused in a short period of time.

TPN (total parenteral nutrition) and TNA (total nutritional admixture) refer to solutions administered parenterally to provide calories, amino acids, and other nutrients by parenteral infusion. PMN is an abbreviation sometimes used for phenylmercuric nitrate, an antimicrobial preservative.

What is the approximate maximum volume of fluid that should be administered daily by intravenous infusion to a stabilized patient?

(B) 4L

A subcutaneous injection will come into contact with a large number of nerve endings and may remain at the injection site for a long period of time. Pain will be experienced if the solution is not isotonic.

The abbreviation of IVP represents intravenous push (bolus) administration indicating fast injection (usually < 1 minute) of the parenteral solution. IVPB requests a minibottIe or minibag setup known as the piggyback arrangement. These bottles are usually infused over a time span of 20 minutes to 1 hour. KVO means to "keep the vein open" by setting up a large volume parenteral (LVP) of 5% dextrose or 0.9% sodium chloride injection for very slow infusion. The intent is to allow the quick hookup of additional drug solutions without having to enter the vein several times.

A suspension is NOT a suitable dosage form for: intravenous injections It is ok for (A) intra-articular injections (B) intradermal injections (C) intramuscular injections (E) subcutaneous injections The usual expiration date that should be placed on a parenteral admixture prepared in a hospital pharmacy is 24 hours Which of the following types of injection routes should be limited to volumes of 1 mL or less? Subcutaneous Osmolarity, expressed as mOsm/L, is included on the labels of large-volume parenteral (LVPs). Those injections with a value of approximately 300 mOsm/L will be isoosmotic and presumably isotonic with the blood. For example, 5% dextrose injection has a value of 280 mOsm/L, whereas 0.9% sodium chloride injection has a value of 308 mOsm/L. One calculates the osmolarity of a solution by first determining the millimoles of chemical present, then multiplying by the number of ions formed from one molecule. One liter of 0.9% sodium chloride solution contains 9 g of sodium chloride (MW = 58.4). The milliosmole (mOsm) concentration willbe : 154 mM x 2 (ions present in NaCl) =308 mOsm.

56. (E) should be 1 mL.

Although vitamin C's main attribute is in the prevention and cure of scurvy, it has been advocated for the prevention and alleviation of symptoms of the "common cold," to facilitate absorption of iron by maintaining iron in the ferrous state, and as an antioxidant in both pharmaceuticals and foods. The fat-soluble vitamin E also possesses antioxidant properties, especially within the body. Vitamin D2 prevents or treats rickets and is used in the management of hypoparathyroidism and hypocalcemia. Pantothenic acid is biologically important as a component in coenzyme A (CoA). is stable for 2 years at room temperature. Of the five antibiotics listed, it is the only one marketed as an aqueous solution, ready for injection. The others are packaged as powders for reconstitution. Potassium chloride concentrate solutions are potentially very dangerous if infused undiluted. Because of numerous fatalities in hospitals, the FDA specifies that it is the only product that must be packaged in vials with black flip-off buttons. There is no color code for other parenteral solutions that are packaged in vials.

Attenuvax against measles. Protection against measles is recommended for persons 15 months and older. Usually the vaccine is administered as part of the measles, mumps, and rubella virus mixture. However, all individuals born after 1956 are considered susceptible to natural measles and should be revaccinated if they are unable to show immunity to measles. Fluogen protects against influenza; Havrix against hepatitis A; Recombivax HB against hepatitis B; and Sabin against poliomyelitis

The immune gamma globulin is used via intramuscular to prevent or modify several diseases, including measles, infectious hepatitis, German measles, and chickenpox. The immunity is passive, lasting for 1 to 2 months. There are also special forms for individuals exposed to mumps, pertussis, tetanus , vaccinia, and rabies.

The labeling on biologicals is required to specify the recommended storage temperature. With few exceptions, biologicals are stored in a refrigerator at 2 to 8C.

(A) detoxified toxins (B) antigens (D) are often available in a precipitated or adsorbed form (E) produce artificial active immunity but not (C) produce permanent immunity. Booster doses of the common toxoids are required to sustain immunity. For example, a 0.5-mL dose of tetanus toxoid should be administered as a routine booster about every 10 years or, as a booster in the management of minor clean wounds, not more frequently than every 6 years.

Diphtheria & Tetanus Toxoid and Pertussis Vaccine (DTP) is administered as a series of four injections starting when the baby is 6 weeks to 2 months of age. Two additional injections are given at 6-week intervals, with a final dose given 1 year later. If needed, a booster injection can be given when the child is 4 to 6 years old. DTP must never be given to children older than 6 years because of serious reactions that may occur.

Passive immunizations are usually accomplished by the administration of purified and concentrated antibody solutions (antitoxins) derived from humans or animals that have been actively immunized against a live antigen; normally long-lasting. TIG (passive) vs Td (active) Active immunizations are usually accomplished by the administration of one of the following: (1) toxoids, (2) inactivated (or killed) vaccines, (3) live attenuated vaccines.

Both ipecac syrup and activated charcoal have proved effective in the treatment of many types of drug poisoning. Chemicals that are not significantly adsorbed by activated charcoal include boric acid, cyanides, DDT, and ferrous sulfate. The benzophenones are effective in screening out the harmful (skin burning) UVB wavelengths as well as some of the UVA spectra. The cinnamates will screen the UVB wavelengths and a combination of the two categories of sunscreens are often incorporated into commercial formulas. Methyl salicylate (oil of wintergreen) is included in topical products mainly for its pleasant odor. It does not possess sunscreening properties. However, homomenthyl salicylate (homosalate) is a sunscreen.

Colostomy pouches are available in several sizes based on the opening that will surround the stoma on the body. These sizes are designated in inches of diameter. Pouches are designed as either open end, in which the effluent may be drained while the pouch is on the patient, or closed end, for which the pouch must be removed to be either emptied or discarded. There is no difference between pouches worn by males or females but there are pediatric pouches with a smaller capacity.

Liposomes consist of phospholipids that when dispersed in water form multilamellar vesicles. These liposomes can be utilized as drug carriers delivering drugs to specific body sites. Nanoparticles refer to dispersed drug consisting of colloidal size particles with diameters between 200 and 500 nm. After IV injection, the nanoparticles will be taken up by the reticuloendothelial system and localized in the liver. Transdermal delivery systems allow diffusion of drug through the skin into the general circulation. They do not "target" specific sites for drug delivery.

The increased sensitivity of both types of tests is due to the use of monoclonal antibodies (MAb), which allow earlier determination of the specific hormones involved. Ovulation prediction tests detect surges in luteinizing hormone (LH), which indicate that ovulation is about to occur. Pregnancy determination tests detect an increased level of human chorionic gonadotropin (HCG) hormone that occurs when the egg is fertilized. The fecal occult blood tests are based on the colorimetric detection of hemoglobin. Various chemicals, such as guaiac, tramethylbenzidine, etc., are used to elicit a characteristic color.The occult blood tests are not very selective or sensitive.

97. (E) The inclusion of surfactants in topical preparations appears to enhance the penetration of active drugs through the skin. Contact lens solutions may contain surfactants for the cleansing of the lenses before storage or insertion. Nontoxic and nonirritating surfactants such as docusate (dioctyl sodium sulfosuccinate) are used as emollient laxatives because they soften stools.

98. (0) The hydrophilic-lipophilic balance (HLB) system was originally designed by using combinations of nonionic surfactants in the preparation of a standard emulsion. Although some anionic and cationic emulsifiers have been assigned HLB values, the system's primary use is to classify the hundreds of nonionics that are commercially available. In the HLB system, emulsifiers are given numeric designations between 1 and 20, depending on the relative strength of the hydrophilic and hydrophobic portions of the molecule. Emulsifiers with low HLB values are hydrophobic (lipophilic), whereas emulsifiers with high HLB values are hydrophilic. By mixing two emulsifiers with different HLB values, one may determine the best HLB value in a certain emulsion formula. Generally, an emulsifier with an HLB of less than 9 will produce water in oil (W/0) emulsions, whereas those with values of greater than 11 will produce oil in water (O/W) emulsions. Emulsion systems between 9 and 11 will form either W/O or O/W, depending on other formulation factors. 0-3 (antifoaming agent); 4-6 (W/O emulsifying); 7-9 (wetting agent); 8-18 (O/W emulsifying); 13-15 (detergents); 10-18 (solubilizing agent)

Which one of the following chemicals is an effective and safe drug in the treatment of either diarrhea or constipation? polycarbophil also Calcium Polycarbophil, is used as stool stabilizer to treat constipation, diarrhea and abdominal discomfort. Bulk laxatives absorb liquid in the intestines and swell to form a soft bulky stool. The bulky mass stimulates the intestinal muscles, speeding stool transit time through the colon. Results usually occur within 12 to 72 hours. Calcium Polycarbophil will not work without increased fluid intake. Phenylpropanolamine (PPA) in combination with behavioral modification and mild caloric restriction and exercise appears to result in weight loss. Although phenylpropanolamine appears to have anorexigenic properties, the dose present in most OTC products (25 mg) is too low. The FDA permits doses of 37.5 mg in immediaterelease products and not more than 75 mg in sustainedrelease products. Higher doses increase the incidence of side effects, such as nervousness, insomnia, hypertension, nausea, and tachycardia. Another OTC drug that is considered effective for weight control is benzocaine.

Actron contains 12.5 mg of ketoprofen. Aleve contains 225 mg naproxyn sodium and Nuprin has 200 mg ibuprofen.

Emetrol is a phosphorated carbohydrate solution containing levulose, dextrose, and orthophosphoric acid with a pH adjusted to 1.5. Take 15 to 30 mL every 15 minutes for not more than five doses. Its effectiveness in preventing or treating motion sickness has not been proved but is considered effective for nausea associated with pregnancy. The Emetrol label states that the oral solution should not be diluted with or accompanied by other fluids.

Calcium carbonate is a rapid, prolonged, potent neutralizer of gastric acid. Some scientists and consumer groups have advocated its use because of its high effectiveness and low cost. However, the listed side effects should warrant curtailment of its use, particularly for chronic therapy. Some of the insoluble calcium carbonate is converted to soluble calcium chloride, which is absorbed. Significant amounts of calcium may be absorbed after a few days of antacid therapy. Gastric hypersecretion is believed to be caused by the local effect of calcium on the gastrin-producing cells.

Calcium carbonate appears to be the antacid of choice when formulating chewable tablets. Although both the Titralac and Rolaid products contain calcium carbonate, Rolaids chewable tablets also contain magnesium hydroxide. Basaljel capsules contain only aluminum hydroxide. Other antacids containing only aluminum hydroxide include Amphojel and ALternaGEL.

The generic name for Ayerst's Riopan is magaldrate. The product is a chemical rather than a physical combination of aluminum and magnesium hydroxides. Although this chemical form has a lower neutralizing capacity, it is still considered to be an effective antacid with a low sodium level and does not cause electrolyte imbalance in the body.

Both film and sugar coats are water soluble and most will readily disintegrate in the stomach. However, the smooth tablet surface makes the tablet easier to dissolve with less chance of bitter drug powder remaining in the mouth or throat. Enteric coats are intended to slow the disintegration of the tablet until the unit reaches the small intestine. Advantages to the manufacturer for tablet film coating when compared to sugar coating include I. shorter production times II. less gross weight III. lower incidence in coat chipping Which of the following is NOT used primarily as a diluent in tablet formulations? (A) Magnesium stearate (as well as other stearates) is included in tablet formulations as a lubricant. (B) phosphate (C) lactose (D) mannitol (E) starch

Tablet lubricants are characterized by lubricity, as they are usually water-insoluble and difficult to wet. The waterproofing property might retard disintegration and dissolution.

Aspartame is a dipeptide that is approximately 200 times sweeter than sucrose. Because it provides less than 1 calorie per dose and does not impart the bitter aftertaste experienced by some people after consuming saccharin, it is a popular sweetening agent in drug products and foods. Its tendency to disintegrate on heating limits potential uses. Patients with phenylketonuria should avoid aspartame because one breakdown ingredient is phenylalanine.

Mannitol possesses characteristics that make it an almost ideal sweetener for chewable tablets. Although not as sweet as sucrose, it has "good body," leaves a cool taste in the mouth, and is not hygroscopic. Mannitol is also easily compressed by wet granulation.

Benzyl alcohol is used in many parenterals, especially in Bacteriostatic Sterile Water for Injection, as an antimicrobial agent. Although its relative toxicity is low, there are a few reports of hypersensitivity. Also, it is contraindicated for use in premature infants because of incidences of fetal toxic syndrome.

Thickening a suspension will slow its sedimentation, but it is still necessary to get the product out of the bottle. A pseudoplastic flow is desirable because it is characterized by a greater flow rate after the system has been agitated. Thixotropy refers to a reversible sol-gel system; it is characterized by a gel that forms a flowable sol when shaken. On standing, the reformation of the gel will slow particle settling. Caking is undesirable because settling particles form a dense pack in the bottom of the container. It is very difficult to break this cake and to reconstitute the original suspension.

Inhalation aerosol products may be intended for either localized activity (bronchodilators for asthma) or systemic action(ergotamine for migraine). In either situation, the onset of action will be rapid. When the drug is absorbed through the alveolar-capillary membrane, the first-pass metabolism in the liver is avoided. Because of the limited capacity of aerosol units, especially in the small-chamber metered valves, only a limited amount of drug can be administered.

An ileostomy differs from a colostomy in which of the following characteristics? I. The discharge from an ileostomy is more viscous. II. The stoma is significantly larger. III. The discharge is more irritating to the skin. An ileostomy results when the entire colon (large intestine) and a portion of the small intestine is removed and the remaining end of the small intestine is attached to the abdominal wall. Because of the narrow diameter of the small intestine, the wall opening (stoma) is not as large when compared to colostomy stomas. The fecal discharge is watery because there has been limited opportunity for water reabsorption. Also, there are higher concentrations of enzymes present that may irritate the skin.

Diacetylmorphine is commonly known as heroin. It is a Class I controlled substance; this means that it may be used only for experimental work by special permit. (A) diacetylmorphine but (B) ethylmorphine (C) dihydrocodeinone (D) methylmorphine can be used for medicinal purposes

The first-degree burn is the mildest injury because only the epidermis is affected. Blisters and pain are characteristics of a second-degree burn, which affects the epidermis and portions of the dermis. The skin will regenerate. A third-degree burn penetrates through the entire skin. Damage may be permanent. Blackened skin is characteristic of a fourth-degree or char burn. Both the skin and underlying tissues are affected. There is a danger of deep infection.

Benzocaine is widely used for surface anesthesia of the skin and mucous membranes. It remains on the skin for a long period of time because of its poor water solubility and because it is poorly absorbed. Systemic toxicity is rare. Although the possibility of local sensitization should be considered, the incidence is low considering the frequent use of benzocaine. A topical preparation should contain a minimum of 5% benzocaine. Benzocaine may be present in some OTC products as (A) an appetite suppressant Benzocaine is included in some dietary aid products at levels of 3 to 15 mg. The products are formulated as lozenges, gum, or candies. The benzocaine is believed to decrease the person's ability to detect sweetness, thus reducing appetite.

A basal thermometer is used to estimate time of ovulation Because fertilization can occur within only a few hours (perhaps 24) after ovulation, accurate knowledge of this event could permit timing of intercourse to either increase or decrease the possibility of conception. Basal temperature (the lowest temperature of the body during waking hours) typically passes through a biphasic cycle over the course of the menstrual cycle. From an initially low temperature, a midcycle thermal shift occurs to a high level, where it remains until it again becomes low premenstrually. The temperature rise roughly corresponds with the time of ovulation. The thermometer is used orally or rectally once daily, immediately on awakening in the morning and before getting out of bed. The scale may be either Fahrenheit or Celsius. The temperature rise is only about 0.5 F, which would be difficult to measure on the usual clinical thermometer. The basal thermometer scale ranges only from 96 to 100 F and is graduated to 0.1.

The French system is used for designating sizes of both urinary catheters and tubing used for enteral feedings. One French unit equals 1 mm on the outside circumference. Thus, a catheter with an outside circumference of 20 mm is identified as a 20F or 20Fr size. Syringe needles are sized by another system-the Stubbs numbers and which is based on the external diameter of the cannula. Persons who experience severe anaphylactic reactions to insect sting or bites should carry emergency kits. These kits usually contain antiseptic pads (to clean and disinfect the area), both an antihistamine and epinephrine injection (to counteract the anaphylactic reaction), and tweezers (to remove the stingers). A tourniquet would be of little value because the amount of venom is very small. Self-injectable units of epinephrine, such as EpiPen, are also available for individuals known to be susceptible to stings.

Melatonin is an endogenous hormone produced by the human pineal gland. It appears to shift the circadian rhythm and serves as a sleep aid when taken 1 to 2 hours before bedtime.

Allantoin is included in many topical formulations as a vulnerary (healing agent ), which is a substance that stimulates tissue repair.

Which one of the following drug products is NOT formulated into a soft gelatin capsule? (A) cyclosporine (B) ethchlorvynol (C) ethosuximide (D) prochlorperazine (F) ranitidine (0) Compazine is available in hard gelatin spansules for sustained release of the drug. It is used to treat anxiety and as an antiemetic. All of the other drugs are formulated into soft gelatin capsules which allow formulation of water insoluble drugs in other solvents such as corn oil, coconut oil, and propylene glycol. Because of the liquid nature of the drug or its formula, the solid dosage form has faster disintegration/dissolution rates. All of the other choices consist of drug in soft gelatin capsules. Cyclosporine (Sandimmune) is an immunosuppressive agent. Ethchlorvynol (Placidyl) is used as an hypnotic. Ethosuximide (Zerontin) is an anticonvulsant, and ranitidine (Zantac GELdose) helps prevent peptic ulcers. Another example of a soft gelatin capsule is Lanoxicaps which is a form of digoxin. Less drug is required for the same activity as the solid tablet dosage form.

The extent of drug release and absorption will vary depending upon the properties of the drug, the suppository base, and the condition of the colon. Oil-soluble drugs will be poorly released from a cocoa-butter base because of their high lipid/water solubility. The rectal fluid pH is essentially neutral and has a low buffer capacity. Therefore, drugs that can be destroyed by the acidity of the stomach may be successfully administered rectally. Drugs that are absorbed through the colon pass into the lower hemorrhoidal veins and into the general systematic circulation. Avoidance of first-pass exposure to the liver may enhance the effect of those drugs inactivated by the liver. Drugs that are absorbed from the upper intestinal tract pass directly through the portal vein into the liver, where metabolism may occur. The lesser dose frequency and lower propensity for irritation are the reasons certain drugs can be administered rectally but not orally.

Most commercial vaginal suppositories use a base of (E) polyethylene glycols Selected combinations of the polyethylene glycols (PEGs) can be formulated into water-miscible suppositories with a range of consistency. They are easy to insert and do not require refrigeration. Which one of the following diluents is usually used for compressed vaginal tablet formulation? (A) Lactose is a readily compressible and water-soluble inert ingredient. It also encourages the growth of Doderlein's bacilli, a microorganism present in the healthy vagina. Starch may be included in tablet formulations as a I. binder II. Disintegrant Carbomers may be included in a topical product as (E) thickening agents Disintegration tests are required for which of the following types of tablets? I. sugar coated II. enteric coated III. Buccal

(A) Properties of a solution that depend on the number of particles of the solute and are independent of the chemical nature of the solute are termed colligative properties. The magnitude of vapor pressure, freezing-point reduction, boiling-point elevation, and osmotic pressure are all related to the number of particles in solution.

Solutions with the same osmotic pressure as blood are usually isotonic with blood. Solutions that have a higher osmotic pressure (ie, hypertonic) will cause water to pass out of the red blood cells.Because of the loss of volume, the cell will shrink and take on a wrinkled appearance (crenation). Solutions that have a lower osmotic pressure (ie, hypotonic) will allow water to pass into the cells. This causes them to swell and rupture with a release of hemoglobin (hemolysis).

Aqueous solutions that freeze at the same temperature as blood have the same osmotic pressure as blood (ie, are isoosmotic with blood and each other). However, to be isotonic a solution must maintain a certain pressure, or "tone," with the red blood cells. If the chemical in a solution passes freely through the red blood cell membrane, equalized pressure on both sides of the membrane is not possible without changes in the cell volume. Tone will not be maintained, and the solution will not be isotonic, though it might be isoosmotic with blood.

The main reason why methylcellulose and similar agents are included in ophthalmic solutions is to increase ocular contact time

The combination of benzalkonium chloride and edetate (0.01% of each) is effective against those microorganisms likely to contaminate ophthalmic solutions. These include some strains of Pseudomonas aeruginosa that are resistant to benzalkonium chloride alone.

Papain and subtilisin are proteolytic enzymes that aid in the removal of proteinaceous residues that slowly build up on soft lenses during wear.

Because membrane filtration does not involve heat, it is suitable for drug solutions that either are sensitive to heat or have not been studied sufficiently concerning their heat stability. The pharmacist may purchase presterilized filter units such as Millipore's Millex through which 15 to 100 mL of solution can be filtered. However, autoclaving is still considered the most reliable sterilization procedure.

The Henderson-Hasselbalch equation, or buffer equation, for a weak acid and its corresponding salt, is represented by

According to the Henderson-Hasselbalch equation, pH will equal pKa when the expression log [salt]/[acid] is equal to zero. This can occur only when the salt/acid ratio equals 1. The point at which the salt concentration equals the acid concentration is the half-neutralization point. It is also the pH at which a buffer system, based upon the weak acid's pKa, has the best buffering capacity.

For many years, the curie (Ci) has been the basic unit for expressing radioisotope decay. Now the becquerel is recognized as the "official" unit. One becquerel equals one decay per second (dps). 1 curie =3.7 x 10m10 bq (dps) The rad is a quantitative measure of radioactivity.

Decay rate is the rate at which atoms undergo radioactive disintegration. The rate of decay (-dn/dt) is proportional to the number of atoms (n) present at any time (t); thus, radioactive decay is a first-order process.

90mTc is available commercially as a technetium generator from various manufacturers in which molybdenum 99Mo is the parent nuclide. The half-life of technetium (6 hours) is long enough to allow completion of usual diagnostic procedures for which it is used, yet short enough to minimize the radiation dose to the patient. Lack of a beta component in its radiation further decreases the dose delivered to the patient. The gamma energy is weak enough to achieve good collimation, yet strong enough to penetrate tissue sufficiently to permit deep-organ scanning.

The OTC product Efidac/24 contains pseudoephedrine for use as an oral-nasal decongestant. The weight-control agent, phenylpropranol amine is present in Acutrim, also an OTC product. Other osmotic tablets include Procardia XL (nifedipine) and Volmax (albuterol). Because the rate-limiting factor in these tablets is the osmotic pressure, drug release is not affected by GI tract pH.

Because of individual patient biologic variation and technologic limitations of precise control of drug release, drugs with either short half-lives or low therapeutic indexes are not suited for sustained-release products. A drug which requires dosing of 500 mg TID is usually not suitable since 1500 mg would be needed in the sustained-release dosage form. Almost all sustained-release products are designed for the treatment of chronic conditions in which acute dosing adjustments are not necessary. Hopefully, sustainedrelease products will improve patient compliance by requiring less frequent dosing.

A common building block for liposomes are (C) phospholipids An artificial microscopic vesicle consisting of an aqueous core enclosed in one or more phospholipid layers, used to convey vaccines, drugs, enzymes, or other substances to target cells or organs. Liposomes are small vesicles of a bilayer of phospholipid encapsulating an aqueous compartment. Since phospholipids have both hydrophilic and hydrophobic portions, either lipophilic or hydrophilic drugs may be incorporated into the structure. Liposomes may vary in shape, usually with sizes between 0.5 and 100 microns. A liposome encapsulates a region on aqueous solution inside a hydrophobic membrane; dissolved hydrophilic solutes cannot readily pass through the lipids. Hydrophobic chemicals can be dissolved into the membrane, and in this way liposome can carry both hydrophobic molecules and hydrophilic molecules. To deliver the molecules to sites of action, the lipid bilayer can fuse with other bilayers such as the cell membrane, thus delivering the liposome contents. By making liposomes in a solution of DNA or drugs (which would normally be unable to diffuse through the membrane) they can be (indiscriminately) delivered past the lipid bilayer.

Liposomal dosage forms may be developed for any route of administration, but their parenteral use is exciting. Liposomal forms of amphotericin B have activity targeted at fungi localized in tissue, thus allowing lower doses and fewer side effects. The chemotherapeutic agent, doxorubicin, has been formulated into parenteral liposomes with reduced cardiotoxicity when compared to the conventional product. Augmentin consists of amoxicillin and clavulanate K. Ziac contains bisoprolol plus hydrochlorthiazide. Zithromax has only azithromycin as an active ingredient.

Aluminum hydroxide is a commonly used antacid because of its nonabsorbability, demulcent activity, and ability to adsorb pepsin. It is somewhat slow in respect to onset of action. A second antacid product with just aluminum hydroxide is Basaljel. Magnesium trisilicate appears to be longer-acting than aluminum hydroxide. When it reacts with hydrochloric acid in the stomach, hydrated silicon dioxide, which may coat ulcers, is formed. Gaviscon and Gaviscon-2 contains alginic acid, which forms a viscous solution, thereby prolonging contact time. The product is claimed to be effective in the relief of gastroesophageal reflux. All of the other Gaviscon products (Extra Strength and Liquid) contain aluminum hydroxide and magnesium carbonate but no magnesium silicate. Calcium carbonate is often considered the antacid of choice because of its rapid onset of action, high neutralizing capacity, and relatively prolonged action. Side effects include constipation, which may be prevented by combining calcium carbonate with either magnesium carbonate or magnesium oxide. Prolonged use of calcium carbonate may result in the formation of urinary calculi. Also, increased blood levels of calcium have been reported. Magnesium hydroxide has been mixed with aluminum hydroxide in an attempt to reduce the incidence of constipation attributed to the aluminum ion and reduce the incidence of diarrhea due to the magnesium ion. Most antacid products on the market consist of this combination.

0. Extension of needle that fits onto the syringe 1. Portion of needle that is ground for sharpness 2. Shaft portion of the needle 3. The hole in the needle 0. (C) The needle hub can be made of plastic or metal. It is fitted onto the syringe body either by a locking system such as the Luer-Lok or by a simple friction fit. 1. (A) The bevel is ground to sharpness, but the back portion (heel) of the bevel is left dull. A dull heel has been shown to decrease the incidence of coring of the rubber closure and the skin. 2. (B) Needle cannulae are made of various grades of steel. Both shaft strength and flexibility are needed. 3. (E) The hole in the shaft is also called the bore.

Alcohol USP, sometimes known as grain alcohol, contains 94.9% V/V or 92.3% W/W of C2H5OH. The remaining portion is water. Diluted Alcohol is prepared by mixing equal volumes of Alcohol USP and Purified Water. Because of some volume shrinkage (about 3%), the final strength is somewhat higher than that calculated by simple alligation.(A) 49% Rubbing alcohol is a form of denatured alcohol containing approximately 70% of absolute alcohol. This product is used as a germicide and an external rubefacient.

1. (E) The normal pH range for the blood is 7.36 to 7.40 for venous samples and 7.38 to 7.42 for arterial samples. It is essential that the blood pH remains within the range of 7.35 to 7.45. Normal acid-base balance is generally maintained by three homeostatic mechanisms using endogenous chemical buffers (eg, bicarbonate and carbonic acid), respiratory control, and renal function. An impairment in any of these mechanisms can result in either acidosis or alkalosis. 2. (E) The pH of the lacrimal fluid is approximately 7.4 but varies with certain ailments. The eye can tolerate a pH from 6 to 8 with a minimum of discomfort. The buffering system of the lacrimal fluid is efficient enough to adjust the pH of most ophthalmic solutions. However, some solutions, particularly those containing strongly acidic drugs, will cause discomfort. 3. (B) The pH of the skin is usually based on measurements of the lipid film that covers the epidermis. Although the value varies greatly between individuals and in various areas of the body, the average value is reported to be 5.5, with a range of 4.0 to 6.5. 4. (A) The acidic pH (3.5 to 4.2) of the vagina discourages the growth of pathogenic microorganisms while providing a suitable environment for the growth of acid-producing bacilli.

(A) encapsulated dissolution (B) ion-exchange (C) matrix diffusion (D) matrix dissolution (E) osmotic pump 5. Drug is bound to a resin and released due to changes in pH B 6. Drug is compressed into tablets with a slowly soluble polymer D 7. Drug particles are microencapsulated and a mixture of the particles is placed into the dosage form

(A) mild sedative (B) improve memory (C) reduce severity of a cold or virus infection (D) inprove urinary flow (E) reduce GI spasms 1. Echinacea 2. Ginkgo biloba 3 . St John's Wort 4. Saw palmetto

1. (C) Echinacea is believed to reduce the severity of cold and flu symptoms, especially if consumed during the early stages of the exposure. 2. (B) Some studies have indicated that Gingko extracts improve blood perfusion. There is hope that the herb will improve memory. A problem may occur if Gingko is taken by individuals being treated with anticoagulants. 3. (A) St. John's Wort may help cases of mild depression. Its active ingredient, hypericin, is believed to cause photodermatitis if lightskinned clients are exposed to direct sunlight. 4. (0) Saw Palmetto may be useful in treating symptoms of BPH (benign prostatic hyperplasia). It appears to improve urinary flow in men with enlarged prostates.

(A) cyanocobalamin B12 (B) pyridoxine B6 (C) thiamine B1 (D) riboflavin B2 (E) pantothenic acid B5

Simethicone is an effective agent when taken orally to reduce gas discomfort in the GI tract. It aids in the coalescence of gas, which then can be discharged by belching or flatus. Infant's Myclicon Drops contain 20 mg of simethicone per 0.3 mL of liquid. There are also several simethicone-containing products for adults including Beano, Gas-X, and Phazyme. 312. (C) Most nasal solutions are mildly buffered at pH's between 5.5 and 7.5 to prevent interference with normal cilia motion. The solutions should also be isotonic if possible.

Transdermal drug delivery systems deliver drugs at an optimal rate through the skin and avoid the hepatic first-pass effect. Since the patch needs replacement only once daily or up to once a week depending upon the drug involved, patient compliance improved. Since most of the drug is in the patch reservoir, relatively large amounts of drugs with short half-lives can be formulated into transdermal patches. One criteria is the ability of the drug to diffuse through the skin.

Controlled studies of ginger root in the form of capsules indicate its ability to counteract mild cases of nausea and vomiting and also to prevent motion sickness.

Gauze that has been coated with a layer of emulsified petrolatum serves well as a primary cover over burns even if exudate is present. Not only will the exudate flow through the gauze, the gauze itself will not adhere to the wound. Typical products include J& J's Adaptic.

The pharmacokinetic and pharmacodynamic parameters are affected by developmental alterations that require critical evaluation. A few examples are cited to illustrate this concept. At birth, the gastric pH ranges between 6 and 8, but declines within hours after birth. The most important factor influencing gastric acid secretion is the initiation of enteral feedings. The gastric emptying time in newborns approaches adult values within the first 6 to 8 months of life.

The activities of all pancreatic enzymes are lower at birth, hence decreasing the bioavailability of drugs (e.g., ester formulation of clindamycin or chloramphenicol palmitate) requiring hydrolysis prior to absorption. The volume of distribution of drugs in newborns is different from that of adults. The percentage of fat that makes up the total body weight is 0.5% in the young fetus, increases to 15% at birth, and 20% by the age of 6 months, and then gradually declines until adolescence. The serum albumin and total protein concentrations are lower in infancy and increase to adult values by the age of 10 to 12 months. The concentration of bilirubin in neonates is much higher than the adult level, due to both increased red cell destruction and the limited capacity of the liver to conjugate bilirubin. Therefore, substantial differences exist in the binding of ampicillin, benzylpenicillin, phenobarbital, and phenytoin to plasma proteins of fetal, neonatal, and adult patients.

Postnatally, the hepatic P450 monooxygenase system matures rapidly, with metabolic capacities similar to those in adults achieved by approximately 5 months of age. On the other hand, alcohol dehydrogenase is detectable by 2 months of age (3 to 4% of adult activity) and approaches adult values after 5 years of age. The hepatic metabolism of certain drugs has also been found to be different in neonates versus children and adults. The N-methylation of theophylline to caffeine occurs in preterm and full-term infants, whereas in adults theophylline is primarily N-demethylated and C-oxidated to monomethylxanthines and methyluric acid, respectively. A glomerular filtration rate of 2 to 4 mL per minute in full-term infants increases to 8 to 20 mL per minute by 2 to 3 days of life and approaches adult values by 3 to 5 months of age. Tubular secretory function matures at a much slower rate.

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IgE-mediated, immediate, inheritable, pollens, fungi, animal fur, carpet mites; dairy products, shellfish, tree nuts, and peanuts; topically applied drugs (procaine), intranenous allergens: insect venoms, cell or plasma protein-bound haptens (penicillin, cephalosprins, vaccines)----these drugs may cause type II or III reactions in patients if they do not hypersecrete IgE in response to these drugs.

an acute systemic (multi-system) and severe Type I Hypersensitivity allergic reaction; Anaphylactic shock, the most severe type of anaphylaxis, occurs when an allergic response triggers a quick release from mast cells of large quantities of immunological mediators (histamines, prostaglandins, leukotrienes) leading to systemic vasodilation (associated with a sudden drop in blood pressure) and edema of bronchial mucosa (resulting in bronchoconstriction and difficulty breathing). Anaphylactic shock can lead to death in a matter of minutes if left untreated.

Urticaria (or hives) is a skin condition, commonly caused by an allergic reaction, that is characterized by raised red skin wheals (welts). Urticarial disease thought to be caused by the release of histamine and other mediators of inflammation (cytokines) from cells in the skin. This process can be the result of an allergic or non-allergic reaction, differing in the eliciting mechanism of histamine release. Allergic urticaria: Type I reaction, Histamine and other pro-inflammatory substances are released from mast cells in the skin and tissues in response to the binding of allergen-bound IgE antibodies to high affinity cell surface receptors. Basophils and other inflammatory cells are also seen to release histamine and other mediators, and are thought to play an important role, especially in chronic urticarial diseases.

Common allergens: (normally blood related---Rh, hemolytic anemia Foreign blood surface antigens to produce transfusion mismatches or Rh disease; Drug allergens: act as cell or plasma protein-bound haptens( penicillin, cephalosporins, vaccines), the leading cause of hemolytic anemia. Self-antigens: in certain autoimmune diseases( myasthenia gravis, autoimmune hemolytic anemia) Hyperacute rejection of transplanted tissue. 7-10 days after initation of drug therapy/ the second exposure within 3 days Transfusion mismatch: 1-2 hr, reach peaks after 12 hr Rh disease: usually in third trimester

Type II hypersensitivity is also known as cytotoxic hypersensitivity and may affect a variety of organs and tissues. The antigens are normally endogenous, although exogenous chemicals (haptens) which can attach to cell membranes can also lead to type II hypersensitivity. Drug-induced hemolytic anemia, granulocytopenia and thrombocytopenia are such examples. In Hashimoto throiditis, antithyroid peroxidase antibodies produce complement-mediated cytotoxicity to thyroid follicle cells. The reaction time is minutes to hours. Type II hypersensitivity is primarily mediated by antibodies of the IgM or IgG classes and complement. Phagocytes and K cells may also play a role (ADCC).

The lesion contains antibody, complement and neutrophils. Diagnostic tests include detection of circulating antibody against the tissues involved and the presence of antibody and complement in the lesion (biopsy) by immunofluorescence. The staining pattern is normally smooth and linear, such as that seen in Goodpasture's nephritis (renal and lung basement membrane) and pemphigus (skin intercellular protein, desmosome). Treatment involves anti-inflammatory and immunosuppressive agents.

The reaction may be general (e.g., serum sickness) or may involve individual organs including skin (e.g., systemic lupus erythematosus, Arthus reaction), kidneys (e.g., lupus nephritis), lungs (e.g., aspergillosis), blood vessels (e.g., polyarteritis), joints (e.g., rheumatoid arthritis) or other organs. This reaction may be the pathogenic mechanism of diseases caused by many microorganisms. Long-term,high-dose therapy may case type III hypersensitivity; The reaction may take 3 - 10 hours after exposure to the antigen (as in Arthus reaction). It is mediated by soluble immune complexes. They are mostly of the IgG class, although IgM may also be involved.

The antigen may be exogenous (chronic bacterial, viral or parasitic infections), or endogenous (non-organ specific autoimmunity: e.g., systemic lupus erythematosus, SLE; rheumatoid arthritis[hhhhhhhhhh]). The most common types of type III are pneumonitis from inhaled fungi and bacteria to which the patient is occupationally exposed (e.g., moldy hay in farmers lung) and reactions to spores borne in aerosol microdroplets from dirty ultrasonic humidifiers(e.g., humidifier lung).

The classical example of this hypersensitivity is tuberculin (Montoux) reaction which peaks 48 hours after the injection of antigen (PPD or old tuberculin). The lesion is characterized by induration and erythema. Type IV hypersensitivity is involved in the pathogenesis of many autoimmune and infectious diseases (tuberculosis, leprosy, blastomycosis, histoplasmosis, toxoplasmosis, leishmaniasis, etc.) and granulomas due to infections and foreign antigens. Another form of delayed hypersensitivity is contact dermatitis (poison ivy , chemicals, heavy metals, etc.) in which the lesions are more papular. Type IV hypersensitivity can be classified into three categories depending on the time of onset and clinical and histological presentation (contact, tuberculin,granuloma) Acute graf rejection, Infections caused by M. tuberculosis and M. leprae are also classified as a Type IV hypersensitivity reaction.

A Type V hypersensitivity reaction occurs when IgG class antibodies directed towards cell surface antigens have a stimulating effect on their target.

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It enhances active reabsorption of calcium from distal tubules and the thick ascending limb

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secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body:

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It enhances the release of calcium from the large reservoir contained in the bones. Bone resorption is the normal destruction of bone by osteoclasts , indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone. Not good for bone.

It enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25Hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D affects the absorption of calcium (as Ca2+ ions) by the intestine via calbindin.

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PTH was one of the first hormones to be shown to use the G-protein, adenylyl cyclase second messenger system. Normal total plasma calcium level is 9.4mg/dl or 2.4mmol/L. Effects on serum phosphate (decrease, with compensation) PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney which means more phosphate is excreted through the urine. However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the bone, slightly more calcium than phosphate is released from the breakdown of bone. In the intestines, which is mediated by an increase in activated vitamin D, the absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result is a small net drop in the serum concentration of phosphate.

Feedback regulation Increased calcium concentration in the blood acts (via feedback inhibition) to decrease PTH secretion by the parathyroid glands.This is achieved by the activation of calciumsensing receptors located on parathyroid cells.

Syndromes A high level of PTH in the blood is known as hyperparathyroidism. If the cause is in the parathyroid gland it is called primary hyperparathyroidism. The causes are parathyroid adenoma, parathyroid hyperplasia and parathyroid cancer. If the cause is outside the gland, it is known as secondary hyperparathyroidism. This can occur in chronic renal failure. A low level of PTH in the blood is known as hypoparathyroidism. Causes include surgical misadventure (eg inadvertent removal during routine thyroid surgery), autoimmune disorder, and inborn errors of metabolism.

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a 32-amino acid polypeptide hormone that is produced in humans primarily by the parafollicular (also known as C-cells) of the thyroid, and in many other animals in the ultimobranchial body.[1] It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH). It has been found in fish, reptiles, birds, and mammals. Its importance in humans has not been as well established as its importance in other animals.

The hormone participates in calcium (Ca2+) and phosphorus metabolism. In many ways, calcitonin has the counter effects of parathyroid hormone (PTH). To be specific, calcitonin affects blood Ca2+ levels in three ways: Inhibits Ca2+ absorption by the intestines Inhibits osteoclast activity in bones Inhibits Ca2+ and phosphate reabsorption by the kidney tubules

Calcitonin can be used therapeutically for the treatment of hypercalcemia or osteoporosis. Calcitonin was extracted from the Ultimobranchial glands (thyroid-like glands) of fish, particularly salmon. Salmon calcitonin resembles human calcitonin, but is more active. At present, it is produced either by recombinant DNA technology or by chemical peptide synthesis. The pharmacological properties of the synthetic and recombinant peptides have been demonstrated to be qualitatively and quantitatively equivalent.

the synapse or junction of the axon terminal of a motoneuron with the motor end plate, the highly-excitable region of muscle fiber plasma membrane responsible for initiation of action potentials across the muscle's surface, ultimately causing the muscle to contract. In vertebrates, the signal passes through the neuromuscular junction via the neurotransmitter acetylcholine. Motor neuron (efferent) axons originating in the spinal cord enter muscle fibers, where they split into many unmyelinated branches. These terminal fibers run along the myocytes to end at the neuromuscular junction, which occupies a depression in the sarcolemma. Each motor neuron can innervate from one to over 25,000 muscle fibers, but muscle fiber receives inputs from only one motor neuron. Upon the arrival of an action potential at the axon terminal, voltage-dependent calcium channels open and Ca2+ ions flow from the extracellular fluid into the motor neuron's cytosol. This influx of Ca2+ triggers a biochemical cascade that causes neurotransmitter-containing vesicles to fuse to the motor neuron's cell membrane and release acetylcholine into the synaptic cleft, a process known as exocytosis. Acetylcholine diffuses across the synaptic cleft and binds to the nicotinic acetylcholine receptors that dot the motor end plate.

The receptors are ligand-gated ion channels, and when bound by acetylcholine, they open, allowing sodium and potassium ions to flow in and out of the muscle's cytosol, respectively. Because of the differences in electrochemical gradients across the plasma membrane, more sodium moves in than potassium out, producing a local depolarization of the motor end plate known as an end-plate potential (EPP). This depolarization spreads across the surface of the muscle fiber into transverse tubules, eliciting the release of calcium from the sarcoplasmic reticulum, thus initiating muscle contraction. The action of acetylcholine is terminated when the enzyme acetylcholinesterase degrades the neurotransmitter and the unhydrolysed neurotransmitter diffuses away.

a neurotransmitter in both the peripheral nervous system (PNS) and central nervous system (CNS) in many organisms including humans. Acetylcholine is one of many neurotransmitters in the autonomic nervous system (ANS) and the only neurotransmitter used in the somatic nervous system. It is also the neurotransmitter in all autonomic ganglia. In the PNS, acetylcholine activates muscles, and is a major neurotransmitter in the autonomic nervous system. When acetylcholine binds to acetylcholine receptors on skeletal muscle fibers, it opens ligand gated sodium channels in the cell membrane. Sodium ions then enter the muscle cell, stimulating muscle contraction. Acetylcholine, while inducing contraction of skeletal muscles, instead induces decreased contraction in cardiac muscle fibers. This distinction is attributed to differences in receptor structure between skeletal and cardiac fibers.

In the CNS, acetylcholine and the associated neurons form a neurotransmitter system, the cholinergic system, which tends to cause excitatory actions.In the central nervous system, ACh has a variety of effects as a neuromodulator, e.g., for plasticity and excitability. Other effects are arousal and reward An inadequate supply of ACh in the brain leads to the breakdown of memory function in what is known as Alzheimer's Disease. There are two main classes of acetylcholine receptor (AChR), nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR). They are named for the ligands used to activate the receptors.

Nicotinic AChRs are ionotropic receptors permeable to sodium, potassium, and chloride ions. They are stimulated by nicotine and acetylcholine. They are of two main types, muscle type and neuronal type. The former can be selectively blocked by curare and the latter by hexamethonium. The main location of nicotinic AChRs is on muscle end plates, autonomic ganglia (both sympathetic and parasympathetic), and in the CNS.

Muscarinic receptors are metabotropic, and affect neurons over a longer time frame. They are stimulated by muscarine and acetylcholine, and blocked by atropine. Muscarinic receptors are found in both the central nervous system and the peripheral nervous system, in heart, lungs, upper GI tract and sweat glands.

the chief inhibitory neurotransmitter in central nervous system. GABA is not an alpha amino acid, nor is it incorporated into proteins. GABA play an important role in regulating neuronal excitability throughout the nervous system. In humans, GABA is also directly responsible for the regulation of muscle tone. In spastic cerebral palsy, GABA cannot be absorbed properly by the damaged nerve rootlets corresponding to affected muscles, which leads to hypertonia in those muscles. In cases besides movement disorders, disrupted GABAergic signaling has been implicated in other numerous and varied neurological and psychiatric pathologies, including anxiety disorders, epilepsy, schizophrenia, and addiction.

Drugs that act as agonists of GABA receptors (known as GABA analogues) or increase the available amount of GABA typically have relaxing, anti-anxiety and anti-convulsive effects. Many of the substances below are known to cause anterograde amnesia and retrograde amnesia. alcohol (ethanol) / avermectinsdoramectin, selamectin, ivermectin / barbiturates / bicucullines - GABA antagonist / benzodiazepines / baclofen / baicalin and baicalein from skullcap / scutellaria lateriflora / carbamazepines / cyclopyrrolone derivatives such as zopiclone / fluoroquinolones / gabazine (SR-95531) / gamma-Hydroxybutyric acid (GHB) / gamma-amino- beta-hydroxybutyric acid / imidazopyridine derivatives such as zolpidem / kavalactones / meprobamate / muscimol / manganese / modafinil / phenytoin / picamilon / picrotoxin / progabide / propofol / phenibut / pyrazolopyrimidine derivatives such as zaleplon / thujoneGABA antagonist / Valerian extract

tiagabinepotentiates by inhibiting uptake into neurons and glia vigabatrinpotentiates by inhibiting GABA-T, preventing GABA breakdown valproatepotentiates by inhibiting GABA-T tetanospasminprimary toxin of tetanus bacteria, blocks release of GABA hyperforininhibits the reuptake of GABA

resides or extends outside the central nervous system (CNS), which consists of the brain and spinal cord, to serve the limbs and organs. Unlike the central nervous system, however, the PNS is not protected by bone, leaving it exposed to toxins and mechanical injuries. The peripheral nervous system is divided into the somatic nervous system and the autonomic nervous system and the enteric nervous system. The main neurotransmitters of the peripheral nervous system are acetylcholine and noradrenaline. However, there are several other neurotransmitters as well, jointly labeled Non-noradrenergic, non-cholinergic (NANC) transmitters. Examples: non-peptides: ATP, GABA, dopamine, NO, and peptides: neuropeptide Y, VIP, GnRH, Substance P and CGRP.

responsible for coordinating the body movements, and also for receiving external stimuli. It is the system that regulates activities that are under conscious control. the part of the peripheral nervous system associated with the voluntary control of body movements through the action of skeletal muscles, and with reception of external stimuli, which helps keep the body in touch with its surroundings (e.g., touch, hearing, and sight). The system includes all the neurons connected with muscles, skin and sense organs. The somatic nervous system consists of efferent nerves responsible for sending brain signals for muscle contraction.

the part of the peripheral nervous system that acts as a control system, maintaining homeostasis in the body. These activities are generally performed without conscious control or sensation. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils, micturition (urination), and sexual arousal. Whereas most of its actions are involuntary, some, such as breathing, work in tandem with the conscious mind. Its main components are its sensory system, motor system (comprised of the parasympathetic nervous system and sympathetic nervous system), and the enteric nervous system.

the sense of the relative position of neighbouring parts of the body. Unlike the six exteroceptive senses (sight, taste, smell, touch, hearing, and balance) by which we perceive the outside world, and interoceptive senses, by which we perceive the pain and the stretching of internal organs, proprioception is a third distinct sensory modality that provides feedback solely on the status of the body internally. It is the sense that indicates whether the body is moving with required effort, as well as where the various parts of the body are located in relation to each other.

a biochemical cascade which helps clear pathogens from an organism. It is part of the larger immune system that is not adaptable and does not change over the course of an individual's lifetime; as such it belongs to the innate immune system. However, it can be recruited and brought into action by the adaptive immune system.

The complement system consists of a number of small proteins found in the blood, normally circulating as inactive zymogens. When stimulated by one of several triggers, proteases in the system cleave specific proteins to release cytokines and initiate an amplifying cascade of further cleavages. The end result of this activation cascade is massive amplification of the response and activation of the cell-killing membrane attack complex. Over 20 proteins and protein fragments make up the complement system, including serum proteins, serosal proteins, and cell membrane receptors. These proteins are synthesized mainly in the liver, and they account for about 5% of the globulin fraction of blood serum.

Three biochemical pathways activate the complement system: the classical complement pathway, the alternative complement pathway, and the mannose-binding lectin pathway. The three pathways all generate homologous variants of the protease C3-convertase. The classical complement pathway typically requires antibodies for activation (specific immune response), while the alternative and mannose-binding lectin pathways can be activated by C3 hydrolysis or antigens without the presence of antibodies (non-specific immune response).

The classical pathway is triggered by activation of the C1-complex (C1q, C1r, and C1s), which occurs when C1q binds to IgM or IgG complexed with antigens (a single IgM can initiate the pathway, while multiple IgG's are needed), or when C1q binds directly to the surface of the pathogen.

The complement system has the potential to be extremely damaging to host tissues meaning its activation must be tightly regulated. The complement system is regulated by complement control proteins, which are present at a higher concentration in the blood plasma than the complement proteins themselves. Some complement control proteins are present on the membranes of self-cells preventing them from being targeted by complement. One example is CD59, which inhibits C9 polymerisation during the formation of the membrane attack complex.

Immunocompetence is the ability of the body to produce a normal immune response (i.e., antibody production and/or cell-mediated immunity) following exposure to an antigen, which might be an actual virus itself or an immunization shot. Immunocompetence is the opposite of immunodeficiency or immuno-incompetent or immunocompromised. Several examples would be a newborn that does not yet have a fully functioning immune system but may have maternally transmitted antibody immunodeficient; A late stage aids patient with a failed or failing immune system - immuno-incompetent; or a transplant reciepient taking medication so their body will not reject the donated organ - immunocompomised. There may be cases of overlap but these terms are all indicators of non fully functioning immune system.

White blood cells, or leukocytes, are cells of the immune system defending the body against both infectious disease and foreign materials. Several different and diverse types of leukocytes exist, but they are all produced and derived from a multipotent cell in the bone marrow known as a hematopoietic stem cell. Leukocytes are found throughout the body, including the blood and lymphatic system.

The number of leukocytes in the blood is often an indicator of disease. There are normally between 410*9 and 1110*9 white blood cells in a litre of blood, making up approximately 1% of blood in a healthy adult. In conditions such as leukemia, the number of leukocytes is higher than normal, and in leukopenia, this number is much lower. The physical properties of leukocytes, such as volume, conductivity, and granularity, may change due to activation, the presence of immature cells, or the presence of malignant leukocytes in leukemia. The name "White blood cell" derives from the fact that after centrifugation of a blood sample, the white cells are found in the Buffy coat, a thin layer of nucleated cells between the sedimented red blood cells and the blood plasma, which is typically white in color. The scientific term leukocyte directly reflects this description, derived from Greek leukos - white, and kytos - cell. Blood plasma may sometimes be green if there are large amounts of neutrophils in the sample, due to the heme-containing enzyme myeloperoxidase that they produce.

There are several different types of white blood cells. They all have many things in common, but are all different. One primary technique to classify them is to look for the presence of granules, which allows the differentiation of cells into the categories granulocytes and agranulocytes:

Granulocytes (polymorphonuclear leucocytes): leukocytes characterised by the presence of differently staining granules in their cytoplasm when viewed under light microscopy. These granules are membrane-bound enzymes which primarily act in the digestion of endocytosed particles. There are three types of granulocytes: neutrophils(54-62%), basophils(<1%), and eosinophils(1-6%), which are named according to their staining properties.

Agranulocytes (mononuclear leucocytes): leukocytes characterized by the apparent absence of granules in their cytoplasm. Although the name implies a lack of granules these cells do contain non-specific azurophilic granules, which are lysosomes. The cells include lymphocytes(25-33%), monocytes(2-8%), and macrophages.

A lymphocyte is a type of white blood cell in the vertebrate immune system. By their appearance under the light microscope, there are two broad categories of lymphocytes, namely the large granular lymphocytes and the small lymphocytes. Functionally distinct subsets of lymphocytes correlate with their appearance. Most, but not all large granular lymphocytes are more commonly known as the natural killer cells (NK cells). The small lymphocytes are the T cells and B cells. Lymphocytes play an important and integral role in the body's defenses. The three major types of lymphocyte are T cells, B cells and natural killer (NK) cells. T cells and B-cells are the major cellular components of the adaptive immune response. Virgin B cells: have not responded to an antigen, their membrane antibodies are of IgM and IgD; Virgin-MD Memory B cells: derived by cell devision from another B cell that has respond to an antigen, membrane antibodies: Ig-A,E,G ; M-EGA B cells principally developed in Bone marrow. All T cells originate from hematopoietic stem cells in the bone marrow. They can be distinguished from other lymphocyte types by the presence of a special receptor on their cell surface called the T cell receptor (TCR) which are membrane proteins (/ or / ). The abbreviation T, in T cell, stands for thymus, since it is the principal organ in the T cell's development. Several different subsets of T cells have been described, each with a distinct function.

Helper T cells (effector T cells or Th cells) are the "middlemen" of the adaptive immune system. Once activated, they divide rapidly and secrete small proteins called cytokines that regulate or "help" the immune response. Depending on the cytokine signals received, these cells differentiate into TH1, TH2, TH17, or one of other subsets, which secrete different cytokines. CD4+ cells associated with MHC class II.

Cytotoxic T cells (TC cells, or CTLs) destroy virally infected cells and tumor cells, and are also implicated in transplant rejection. These cells are also known as CD8+ T cells (associated with MHC class I), since they express the CD8 glycoprotein at their surface. Through SLOB[clarify] interaction with helper T cells, these cells can be transformed into regulatory T cells, which prevent autoimmune diseases such as experimental autoimmune encephalomyelitis.

Memory T cells are a subset of antigen-specific T cells that persist long-term after an infection has resolved. They quickly expand to large numbers of effector T cells upon reexposure to their cognate antigen, thus providing the immune system with "memory" against past infections. Memory T cells comprise two subtypes: central memory T cells (TCM cells) and effector memory T cells (TEM cells). Memory cells may be either CD4+ or CD8+.

Regulatory T cells (Treg cells), formerly known as suppressor T cells, are crucial for the maintenance of immunological tolerance. Their major role is to shut down T cellmediated immunity toward the end of an immune reaction and to suppress auto-reactive T cells that escaped the process of negative selection in the thymus. Two major classes of CD4+ regulatory T cells have been described, including the naturally occurring Treg cells and the adaptive Treg cells. Naturally occurring Treg cells (also known as CD4+CD25+FoxP3+ Treg cells) arise in the thymus, whereas the adaptive Treg cells (also known as Tr1 cells or Th3 cells) may originate during a normal immune response. Naturally occurring Treg cells can be distinguished from other T cells by the presence of an intracellular molecule called FoxP3. Mutations of the FOXP3 gene can prevent regulatory T cell development, causing the fatal autoimmune disease IPEX.

Natural killer T cells (NKT cells) are a special kind of lymphocyte that bridges the adaptive immune system with the innate immune system. Unlike conventional T cells that recognize peptide antigen presented by major histocompatibility complex (MHC) molecules, NKT cells recognize glycolipid antigen presented by a molecule called CD1d. Once activated, these cells can perform functions ascribed to both Th and Tc cells (i.e., cytokine production and release of cytolytic/cell killing molecules).

 T cells represent a small subset of T cells that possess a distinct TCR on their surface. A majority of T cells have a TCR composed of two glycoprotein chains called and - TCR chains. However, in T cells, the TCR is made up of one -chain and one -chain. This group of T cells is much less common (5% of total T cells) than the T cells, but are found at their highest abundance in the gut mucosa, within a population of lymphocytes known as intraepithelial lymphocytes (IELs). The antigenic molecules that activate T cells are still widely unknown. However, T cells are not MHC restricted and seem to be able to recognise whole proteins rather than requiring peptides to be presented by MHC molecules on antigen presenting cells. Some recognize MHC class IB molecules though. Human V9/V2 T cells, which constitute the major T cell population in peripheral blood, are unique in that they specifically and rapidly respond to a small non-peptidic microbial metabolite, HMB-PP, an isopentenyl pyrophosphate precursor.

T cells are involved in cell-mediated immunity whereas B cells are primarily responsible for humoral immunity (relating to antibodies). The function of T cells and B cells is to recognize specific non-self antigens, during a process known as antigen presentation. Once they have identified an invader, the cells generate specific responses that are tailored to maximally eliminate specific pathogens or pathogen infected cells.

B cells respond to pathogens by producing large quantities of antibodies which then neutralize foreign objects like bacteria and viruses. In response to pathogens some T cells, called helper T cells produce cytokines that direct the immune response while other T cells, called cytotoxic T cells, produce toxic granules that induce the death of pathogen infected cells. Following activation, B cells and T cells leave a lasting legacy of the antigens they have encountered, in the form of memory cells. Throughout the lifetime of an animal these memory cells will remember each specific pathogen encountered, and are able to mount a strong response if the pathogen is detected again.

Memory T cells are a specific type of infection-fighting T cell (also known as a T lymphocyte) that can recognize foreign invaders such as bacteria or viruses, that were encountered during a prior infection or vaccination. At a second encounter with the invader, memory T cells can reproduce to mount a faster and stronger immune response than the first time the immune system responded to the invader. This behaviour is utilized in T lymphocyte proliferation assays, which can reveal exposure to specific antigens.

Memory B cells are a B cell sub-type that are formed following primary infection. In wake of first (primary response) infection involving a particular antigen, the responding nave (ones which have never been exposed to the antigen) cells proliferate to produce a colony of cells, most of which differentiate into the plasma cells or the effector B cells (which produce the antibodies) and clear away with the resolution of infection, and the rest persist as the memory cells that can survive for years, or even a lifetime. The facts that all the cells of a single clone elaborate one and only one paratope, and that the memory cells survive for long periods, are what impart a "memory" to the immune response. This is the principle behind vaccination and administration of booster doses.

Phagocytes include macrophages, monocytes, dendritic cells, and granulocytes, Basophil and Eosinophil. Phagocytosis: the engulfment of larger particles, or macromolecules, generally by macrophages Pinocytosis : the engulfment of small solute or fluid volumes. Endocytosis / exocytosis: the movement of macromolecules into and out of the cell, respectively.

The major histocompatibility complex (MHC) is a large genomic region or gene family found in most vertebrates. It is the most gene-dense region of the mammalian genome and plays an important role in the immune system, autoimmunity, and reproductive success. The proteins encoded by the MHC are expressed on the surface of cells in all jawed vertebrates, and display both self antigens (peptide fragments from the cell itself) and nonself antigens (e.g. fragments of invading microorganisms) to a T cell that has the capacity to kill or co-ordinate the killing of pathogens, infected or malfunctioning cells. The antigen receptors of T cells do not recognize antigens alone. Rather they normally recognize peptide epitopes that are chemically combind with MHC proteins on the surface of other body cells. MHC proteins are divided into two major classes: Class I proteins are present on the surfaces of almost all body cells. Class II proteins are present only on the surfaces of APCs.

Antigen-presenting cells are essential for most immune resoponses and are found in the sites at which these responses originate. The best understood APCs are the macrophages and dendritic cells of the lymph nodes, spleen, and other lymphoid tissue.

The complement fixation test is an immunological medical test that can be used to detect the presence of either specific antibody or specific antigen in a patient's serum. It was widely used to diagnose infections, particularly with microbes that are not easily detected by culture methods, and in rheumatic diseases. However, in clinical diagnostics labs it has been largely superseded by other serological methods such as ELISA and by DNA-based methods of pathogen detection, particularly PCR.

(or NK cells) are a type of cytotoxic lymphocyte that constitute a major component of the innate immune system. NK cells play a major role in the rejection of tumors and cells infected by viruses. The cells kill by releasing small cytoplasmic granules of proteins called perforin and granzyme that cause the target cell to die by apoptosis or necrosis. NK-cells are defined as large granular lymphocytes that do not express T-cell antigen receptors (TCR) or Pan T marker CD3 or surface immunoglobulins (Ig) B cell receptor but that usually express the surface markers CD16 (FcRIII) and CD56 in humans, and NK1.1/NK1.2 in certain strains of mice. Up to 80% of NK cells also express CD8. They were named "natural killers" because of the initial notion that they do not require activation in order to kill cells that are missing "self" markers of major histocompatibility complex (MHC) class I.

Perforin is a cytolytic protein found in the granules of CD8 T-cells and NK cells. Upon degranulation, perforin inserts itself into the target cell's plasma membrane, forming a pore. The lytic membrane inserting part of perforin is the MACPF domain. This region shares homology with cholesterol dependent cytolysins from Gram positive bacteria. Although purified perforin is sufficient to lyse cells at high doses, the biology of perforin itself does not explain the ability of CD8 T-cells and NK cells to induce apoptosis in target cells. This induction of apoptosis may require at least one other granule protein, granzyme B.

The percentage by volume of packed red blood cells in a given sample of blood after centrifugation.

The hematocrit (Ht or HCT) or packed cell volume (PCV) or erythrocyte volume fraction (EVF) is the proportion of blood volume that is occupied by red blood cells. It is normally about 46% for men and 38% for women. It is considered an integral part of a person's complete blood count results, along with hemoglobin concentration, white blood cell count, and platelet count.

Polycythemia vera (PV) is associated with elevated hematocrit. PV is a myeloproliferative disorder in which the bone marrow produces excessive numbers of red cells, and reflects excessive numbers of RBC precursors in the bone marrow, as well as some abnormal forms. This condition is called erythroid hyperplasia. Excessive production of both RBCs and WBCs is called bilineage hyperplasia, and if there are excessive numbers of platelets also, trilineage hyperplasia. If PV is present, it is not uncommon to see the serum uric acid level elevated, reflecting an increase in the rate of cell turnover, reflecting increased pyridine metabolism.

Chronic obstructive pulmonary disease (COPD) and other pulmonary conditions associated with hypoxia may elicit an increased production of red blood cells. This increase is mediated by the increased levels of erythropoietin by the kidneys in response to hypoxia. If a patient is dehydrated, the hematocrit may be elevated. Repeat testing after adequate hydration therapy will usually result in a more reliable result.

Lowered hematocrit can imply significant hemorrhage (for example, in an ectopic pregnancy .) The mean corpuscular volume (MCV) and the red cell distribution width (RDW) can be quite helpful in evaluating a lower-than-normal hematocrit, because it can help the clinician determine whether blood loss is chronic or acute. The MCV is the size of the red cells and the RDW is a relative measure of the variation in size of the red cell population. A low hematocrit with a low MCV with a normal RDW suggests a chronic iron-deficient erythropoiesis, but a high RDW suggests a blood loss that is more acute, such as a hemorrhage. Groups of individuals who are at risk for developing anemia include: infants who may not have adequate iron intake children going through a rapid growth spurt, during which the iron available cannot keep up with the demands for a growing red cell mass women in childbearing years who have an excessive need for iron because of blood loss during menstruation pregnant women, in whom the growing baby creates a high demand for iron. patients with chronic kidney disease, as their kidneys no longer secrete sufficient levels of the hormone erythropoietin, which stimulates red blood cell production by the bone marrow.

In the lungs, oxygen diffuses from alveolar air into the blood because the venous blood has a lower partial pressure. The oxygen dissolves in the blood. Only a small amount is carried as a physical solution (0.31 ml per 100 ml). The remainder of the oxygen is carried in chemical combination with the hemoglobin in red blood cells (erthrocytes). Hemoglobin (molecular weight of 68,000) is made from 4 hemes, a porphyrin ring containing iron and globin, a 4 protein chains. Oxygen is bound to the iron for the transport process. Hemoglobin (HHgb) behaves as a weak acid (K = 1.4 x 10-8; pKa = 7.85). Oxyhemoglobin (HHgbO2) also behaves as a weak acid (K = 2.5 x 10-7; pKa = 6.6)

Because both forms of hemoglobin are weak acids, and a relationship of the numerical values of the equilibrium constants, the net reaction for the interaction of oxygen with hemoglobin results in the following equilibrium: HHgb + O2 <===> HgbO2 + H+ If O2 is increased in the blood at the lungs, the equilibrium shifts to the right and H+ ions increase. Oxyhemoglobin can be caused to release oxygen by the addition of H+ ions at the cells. The difference in pH (7.44) of arterial blood and venous blood (pH = 7.35) is sufficient to cause release of oxygen from hemoglobin at the tissue cells.

Based on morphology, animal tissues can be grouped into four basic types. Multiple tissue types comprise organs and body structures. While all animal can generally be considered to contain the four tissue types, the manifestation of these tissues can differ depending on the type of organism. Epithelium / Connective tissue / Muscle tissue / Neural tissue

Epithelium is single layer of cells held together via occluding junctions called tight junctions, to create a selectively permeable barrier. This tissue covers all organismal surfaces that come in contact with the external environment such as the skin, the airways, and the digestive tract. It serves functions of protection, secretion, and absorption, and is separated from other tissues below by a basal lamina. Endothelium, , which comprises the vasculature, is a specialized type of epithelium.

Connective tissue is comprised of cells separated by non-living material, which is called extracellular matrix. Connective tissue holds other tissues together such as in the formation of organs, and has the ability to stretch and contract passively. Bone and blood are examples of specialized connective tissues. Muscle cells form the active contractile tissue of the body known as muscle tissue. Muscle tissue functions to produce force and cause motion, either locomotion or movement within internal organs. Muscle tissue is separated into three distinct categories: visceral or smooth muscle, which is found in the inner linings of organs; skeletal muscle, which is found attached to bone providing for gross movement; and cardiac muscle which is found in the heart, allowing it to contract and pump blood throughout an organism. Cells comprising the central nervous system and peripheral nervous system are classified as neural tissue. In the central nervous system, neural tissue forms the brain, cranial nerves and spinal cord and, in the peripheral nervous system, peripheral nerves inclusive of the motor neurons.

The semifluid secretion of the sebaceous glands, consisting chiefly of fat, keratin, and cellular material. It is the lubricates the surface of the skin and hair; consists of dead cells and fatty substances; in excess may cause seborrhoea.

a sheath of pericytes and epithelial reticular cells around thymic capillaries that prevents the developing T lymphocytes of the cortex of the thymus from being exposed to circulating antigens.

Thyrotropin-releasing hormone (TRH), also called thyrotropin-releasing factor (TRF), thyroliberin or protirelin, is a tripeptide hormone that stimulates the release of thyroidstimulating hormone and prolactin by the anterior pituitary. It is used in pharmacology (brand name Relefact TRH) to test the response of the anterior pituitary gland. Medical preparations of TRH are used in diagnostic tests of thyroid disorders and in acromegaly. TRH is produced by the hypothalamus [7haipEu5WAlEmEs], near the paraventricular nucleus. It travels across the median eminence to the pituitary via the hypophyseal portal system. It is released from cells called thyrotropes. In addition to the brain, TRH can also be detected in other areas of the body including the gastrointestinal system and pancreatic islets.

(also known as TSH or thyrotropin) is a peptide hormone synthesized and secreted by thyrotrope cells in the anterior pituitary gland which regulates the endocrine function of the thyroid gland. TSH stimulates the thyroid gland to secrete the hormones thyroxine (T4) and triiodothyronine (T3). TSH production is controlled by TRH, which is manufactured in the hypothalamus and transported to the anterior pituitary gland via the superior hypophyseal artery, where it increases TSH production and release. Somatostatin is also produced by the hypothalamus, and has an opposite effect on the pituitary production of TSH, decreasing or inhibiting its release.

The level of thyroid hormones (T3 and T4) in the blood have an additional effect on the pituitary release of TSH; When the levels of T3 and T4 are low, the production of TSH is increased, and conversely, when levels of T3 and T4 are high, then TSH production is decreased. This effect creates a regulatory negative feedback loop.

The TSH receptor is found mainly on thyroid follicular cells. Stimulation of the receptor increases T3 and T4 production and secretion. Stimulating antibodies to this receptor mimic TSH action and are found in Graves' disease.

Also known as growth hormone inhibiting hormone (GHIH) or somatotropin release-inhibiting factor (SRIF)) is a peptide hormone that regulates the endocrine system and affects neurotransmission and cell proliferation via interaction with G-protein-coupled somatostatin receptors and inhibition of the release of numerous secondary hormones. Somatostatin is secreted in several locations: the digestive system (stomach, intestine, delta cells of the pancreas); brian (by neuroendocrine neurons of the periventricular nucleus of the hypothalamus).

Somatostatin is classified as an inhibitory hormone: Anterior pituitary gland: Inhibit the release of growth hormone (GH) (thus opposing the effects of Growth Hormone-Releasing Hormone (GHRH)); Inhibit the release of thyroid-stimulating hormone (TSH); Gastrointestinal system: suppresses the release of gastrointestinal hormones [Gastrin, Cholecystokinin (CCK), Secretin, Motilin, Vasoactive intestinal peptide (VIP), Gastric inhibitory polypeptide (GIP), Enteroglucagon]; Lowers the rate of gastric emptying, and reduces smooth muscle contractions and blood flow within the intestine; Suppresses the release of pancreatic hormones; Inhibits the release of insulin; Inhibits the release of glucagon; Suppresses the exocrine secretory action of pancreas.

A hormone synthesized and secreted by gonadotropes in the anterior pituitary gland. FSH and LH act synergistically in reproduction: In females, in the ovary FSH stimulates the growth of immature Graafian follicles to maturation. Graafian follicles are the mature follicle. Primary follicles mature to Graafian follicles. As the follicle grows, it releases inhibin, which shuts off the FSH production. In males, FSH enhances the production of androgen-binding protein by the Sertoli cells of the testes, and is critical for spermatogenesis. ( Follicle-... FSH---Front---anterior pituritary gland) LH/FSH also called interstitial cell-stimulating hormone (ICSH) Lutropin, (LH); In the female, an acute rise of LH the LH surge triggers ovulation. In the male, where LH had also been called Interstitial Cell Stimulating Hormone (ICSH), it stimulates Leydig cell production of testosterone.

" endogenous morphine" Endorphins are endogenous opioid polypeptide compounds. They are produced by the pituitary gland and the hypothalamus in vertebrates during strenuous exercise, excitement, and climax, and they resemble the opiates in their abilities to produce analgesia and a sense of well-being. Endorphins work as "natural fever relievers", whose effects may be enhanced by other medications. In 1999, clinical researchers reported that inserting acupuncture needles into specific body points triggers the production of endorphins.

Adrenocorticotropic hormone (ACTH or corticotropin) is a polypeptide tropic hormone produced and secreted by the anterior pituitary gland. It is an important component of the hypothalamic-pituitary-adrenal axis and is often produced in response to biological stress (along with corticotropin-releasing hormone from the hypothalamus). Its principal effects are increased production of androgens and cortisol from the adrenal cortex. This ultimately results in stimulation of steroidogenesis. ACTH acts at several key steps to influence the steroidogenic pathway in the adrenal cortex: ACTH stimulates lipoprotein uptake into cortical cells; increases the transport of cholesterol into the mitochondria and activates its hydrolysis. stimulates cholesterol side-chain cleavage, which is the rate-limiting step in steroidogenesis. This results in the production of pregnenolone.

The anterior pituitary (also called the adenohypophysis, from Greek adeno, "gland"; hypo, "under"; physis, "growth"; hence, glandular undergrowth) comprises the anterior lobe of the pituitary gland and is part of the endocrine system. Unlike the posterior lobe, the anterior lobe is genuinely glandular, hence the root adeno in its name. Under the influence of the hypothalamus, the anterior pituitary produces and secretes several peptide hormones that regulate many physiological processes including stress, growth, and reproduction. FLAT PEG (FSH, LH, ACTH, TSH, Prolactin, Endorphin and GH).

The hypothalamus links the nervous system to the endocrine system via the pituitary gland (hypophysis). The hypothalamus is responsible for certain metabolic processes and other activities of the Autonomic Nervous System. It synthesizes and secretes neurohormones, often called hypothalamic-releasing hormones, and these in turn stimulate or inhibit the secretion of pituitary hormones. The hypothalamus controls body temperature, hunger, thirst, fatigue, anger, and circadian cycles. Corticotropin-releasing hormone (CRH, corticoliberin), Dopamine, Gonadotropin-releasing hormone (GNRH), Growth hormone-releasing hormone (GHRH), Somatostatin, Thyrotropin-releasing hormone (TRH), Vasopressin Function with vasopressin, stimulates secretion of ACTH inhibits secretion of prolactin stimulates secretion of LH and FSH stimulates secretion of growth hormone inhibits secretion of growth hormone

stimulates secretion of TSH with Corticotropin-releasing hormone, stimulates secretion of ACTH

The posterior pituitary (or neurohypophysis) comprises the posterior lobe of the pituitary gland and is part of the endocrine system. Hormones known classically as posterior pituitary hormones are synthesized by the hypothalamus. They are then stored and secreted by the posterior pituitary into the bloodstream. Insufficient secretion of vasopressin is central to diabetes insipidus, in which the body loses the capacity to concentrate urine. Affected individuals excrete as much as 20 L of dilute urine per day. Oversecretion of vasopressin causes the syndrome of inappropriate antidiuretic hormone. Symbol(s) Target Uterus, mammary glands AVP, ADH Kidneys or Arterioles Effect Uterine contractions; lactation Stimulates water retention; raises blood pressure by contracting arterioles, induces male aggression

The parathyroid glands are small endocrine glands in the neck that produce parathyroid hormone. These glands are usually located behind the thyroid gland and in rare cases are located within the thyroid glands. Most people have four parathyroid glands, but some people have six or even eight. Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood, whereas calcitonin (a hormone produced by the parafollicular cells (C cells) of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body: Effects on serum calcium (raising);

Effect It enhances the release of calcium from the large reservoir contained in the bones.[2] Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH. Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells responsible for creating bone. Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse, forming new osteoclasts which ultimately enhances the resorption of bone. It enhances active reabsorption of calcium from distal tubules[3] and the thick ascending limb. It enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation occurs in the kidney. PTH up-regulates 25Hydroxyvitamin D3 1-alpha-hydroxylase, the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to its active form (1,25-dihydroxy vitamin D). This activated form of vitamin D affects the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. Effects on serum phosphate (decrease, with compensation): PTH reduces the reabsorption of phosphate from the proximal tubule of the kidney which means more phosphate is excreted through the urine. However, PTH enhances the uptake of phosphate from the intestine and bones into the blood. In the intestines, which is mediated by an increase in activated vitamin D, the absorption of phosphate is not as dependent on vitamin D as is that of calcium. The end result is a small net drop in the serum concentration of phosphate.

The adrenal medulla is part of the adrenal gland. It is located at the center of the gland, being surrounded by the adrenal cortex. Composed mainly of hormone-producing chromaffin cells, the adrenal medulla is the principal site of the conversion of the amino acid tyrosine into the catecholamines adrenaline (epinephrine), noradrenaline (norepinephrine), and dopamine. In response to stressors such as exercise or imminent danger, medullary cells release catecholamines into the blood in an 17:3 ratio of adrenaline to noradrenaline. Notable effects of adrenaline and noradrenaline include increased heart rate and blood pressure, blood vessel constriction in the skin and gastrointestinal tract, blood vessel dialation in skeletal muscles, bronchiole dilation, and decreased metabolism, all of which are characteristic of the fight-or-flight response. Release of catecholamines is stimulated by nerve impulses, and receptors for catecholamines are widely distributed throughout the body.

The fight-or-flight response, also called the acute stress response, was first described by Walter Cannon in 1915. His theory states that animals react to threats with a general discharge of the sympathetic nervous system, priming the animal for fighting or fleeing. This response was later recognized as the first stage of a general adaptation syndrome that regulates stress responses among vertebrates and other organisms.

A novel stimulus (a perception of danger or an environmental stressor), once perceived, is relayed from the sensory cortex of the brain through the hypothalamus to the brain stem. That route of signaling increases the rate of noradrenergic activity in the locus ceruleus, and the person becomes alert and attentive to the environment. Similarly, an abundance of catecholamines at neuroreceptor sites facilitates reliance on spontaneous or intuitive behaviors often related to combat or escape. If a stimulus is perceived as a threat, a more intense and prolonged discharge of the locus ceruleus activates the sympathetic division of the autonomic nervous system. This activation is associated with specific physiological actions in the system, both directly and indirectly through the release of epinephrine (adrenaline) and to a lesser extent norepinephrine from the medulla of the adrenal glands. The release is triggered by acetylcholine released from preganglionic sympathetic nerves. The other major factor in the acute stress response is the hypothalamic-pituitary-adrenal axis (Sternberg 2001).

Human chorionic gonadotropin (hCG) is a glycoprotein hormone produced in pregnancy that is made by the embryo soon after conception and later by the syncytiotrophoblast (part of the placenta). Its role is to prevent the disintegration of the corpus luteum of the ovary and thereby maintain progesterone production that is critical for a pregnancy in humans. hCG may have additional functions; for instance, it is thought that hCG affects the immune tolerance of the pregnancy. Early pregnancy testing, in general, is based on the detection or measurement of hCG. Because hCG is produced also by some kinds of tumor, hCG is an important tumor marker, but it is not known whether this production is a contributing cause or an effect of tumorigenesis.

Copper and Manganese are excreted via the biliary tree, and intake should be reduced or eliminated in patients with cholestatic liver disease to prevent toxicity.

(meaning the measuring of breath) is the most common of the Pulmonary Function Tests (PFTs), measuring lung function, specifically the measurement of the amount (volume) and/or speed (flow) of air that can be inhaled and exhaled. Spirometry is an important tool used for generating pneumotachograph to assessing conditions such as asthma, pulmonary fibrosis, cystic fibrosis, and COPD.

A specific gravity bottle; a standard flask for measuring and comparing the densities of liquids. [Also written pyknometer.]

An instrument used to determine specific gravity, especially a sealed, graduated tube, weighted at one end, that sinks in a fluid to a depth used as a measure of the fluid's specific gravity.

A severe, chronic form of diabetes caused by insufficient production of insulin and resulting in abnormal metabolism of carbohydrates, fats, and proteins. The disease, which typically appears in childhood or adolescence, is characterized by increased sugar levels in the blood and urine, excessive thirst, frequent urination, acidosis, and wasting. Also called insulin-dependent diabetes

Diabetes insipidus (DI) is a condition characterized by excretion of large amounts of severely diluted urine, which cannot be reduced when fluid intake is reduced. It denotes inability of the kidney to concentrate urine. DI is caused by a deficiency of antidiuretic hormone (ADH), also known as vasopressin, due to the destruction of the back or "posterior" part of the pituitary gland where vasopressin is normally released from, or by an insensitivity of the kidneys to that hormone. It can also be induced iatrogenically by various drugs.

Excessive urination and extreme thirst (especially for cold water and sometimes ice or ice water) are typical for DI. Symptoms of diabetes insipidus are quite similar to those of untreated diabetes mellitus, with the distinction that the urine is not sweet as it does not contain glucose and there is no hyperglycemia (elevated blood glucose). Blurred vision is a rarity. Signs of dehydration may also appear in some individuals since the body cannot conserve much (if any) of the water it takes in.

The extreme urination continues throughout the day and the night. In children, DI can interfere with appetite, eating, weight gain, and growth as well. They may present with fever, vomiting, or diarrhea. Adults with untreated DI may remain healthy for decades as long as enough water is drunk to offset the urinary losses. However, there is a continuous risk of dehydration.

autopharmacological agents or local hormones, local release and action limited to a specific site: histamine, prostaglandins, serotonin, bradykinin, kallidin

Testosterone is a steroid hormone from the androgen group. In mammals, testosterone is primarily secreted in the testes of males and the ovaries of females, although small amounts are also secreted by the adrenal glands. It is the principal male sex hormone and an anabolic steroid. In both men and women, testosterone plays a key role in health and well-being as well as in sexual functioning. Examples include enhanced libido, increased energy, increased production of red blood cells and protection against osteoporosis. On average, an adult human male body produces about forty to sixty times more testosterone than an adult female body, but females are, from a behavioral perspective (rather than from an anatomical or biological perspective), more sensitive to the hormone.[1] However the overall ranges for male and female are very wide, such that the ranges actually overlap at the low end and high end respectively.

Like other steroid hormones, testosterone is derived from cholesterol. The largest amounts of testosterone are produced by the testes in men. It is also synthesized in far smaller quantities in women by the thecal cells of the ovaries, by the placenta, as well as by the zona reticularis of the adrenal cortex in both sexes. In the testes, testosterone is produced by the Leydig cells. The male generative glands also contain Sertoli cells which require testosterone for spermatogenesis. Like most hormones, testosterone is supplied to target tissues in the blood where much of it is transported bound to a specific plasma protein, sex hormone binding globulin (SHBG).

A prostaglandin is any member of a group of lipid compounds that are derived enzymatically from fatty acids and have important functions in the animal body. Every prostaglandin contains 20 carbon atoms, including a 5-carbon ring. The prostaglandins together with the thromboxanes and prostacyclins form the prostanoid class of fatty acid derivatives; the prostanoid class is a subclass of eicosanoids. prostaglandin types: Prostaglandin I2 (PGI2), Prostaglandin E2 (PGE2) and Prostaglandin F2 (PGF2).

Prostaglandins are found in virtually all tissues and organs. These are autocrine and paracrine lipid mediators that act upon platelet, endothelium, uterine and mast cells, among others. They are synthesized in the cell from the essential fatty acids[3] (EFAs). An intermediate is created by phospholipase-A2, then passed into one of either the cyclooxygenase pathway or the lipoxygenase pathway to form either prostaglandin and thromboxane or leukotriene. The cyclooxygenase pathway produces thromboxane, prostacyclin and prostaglandin D, E and F. The lipoxygenase pathway is active in leukocytes and in macrophages and synthesizes leukotrienes.

Name Gamma-linolenic acid (GLA) via DGLA Arachidonic acid (AA) Eicosapentaenoic acid (EPA)

EFA Type -6 -6 -3

Series series-1 series-2 series-3

Examples of prostaglandin antagonists are: NSAIDs (inhibit cyclooxygenase) Corticosteroids (inhibit phospholipase A2 production) COX-2 selective inhibitors or coxibs However, both NSAIDs and Coxibs can raise the risk of myocardial infarction.

Synthetic prostaglandins are used: To induce childbirth (parturition) or abortion (PGE2 or PGF2, with or without mifepristone, a progesterone antagonist); To prevent closure of patent ductus arteriosus in newborns with particular cyanotic heart defects (PGE1) To prevent and treat peptic ulcers (PGE) As a vasodilator in severe Raynaud's phenomenon or ischemia of a limb In pulmonary hypertension In treatment of glaucoma (as in bimatoprost ophthalmic solution, a synthetic prostamide analog with ocular hypotensive activity) To treat erectile dysfunction or in penile rehabilitation following surgery (PGE1 as alprostadil). To treat egg binding in small birds

Langerhans' cells are dendritic cells abundant in epidermis, containing large granules called Birbeck granules. They are normally present in lymph nodes, and can be found in other organs in the condition Histiocytosis. Specifically, the Langerhans cells are located primarily in the stratum spinosum portion of the epidermis. On infection of an area of skin, the local Langerhans' cells will take up and process microbial antigens to become fully-functional antigen-presenting cells. Generally, dendritic cells in tissue are active in the capture, uptake and processing of antigens. Once dendritic cells arrive in secondary lymphoid tissue however, they lose these properties while gaining the capacity to interact with naive T-cells. Langerhans' cells are derived from the cellular differentiation of monocytes with the marker "Gr-1" (also known as "Ly-6c/G"). The differentiation requires stimulation by colony stimulating factor-1.[1] They are similar in morphology and function to macrophages. In the rare disease Langerhans' cell histiocytosis (LCH), an excess of these cells is produced, which can cause damage to skin, bone and other organs.

The four bases found in DNA are adenine ( A), cytosine (C), guanine (G) and thymine (T). a GC base pair with three hydrogen bonds. but, an AT base pair with two hydrogen bonds. Non-covalent hydrogen bonds between the pairs are shown as dashed lines.

RNA is very similar to DNA, but differs in a few important structural details: In the cell, RNA is usually single-stranded, while DNA is usually double-stranded; RNA nucleotides contain ribose while DNA contains deoxyribose ; and RNA has the base uracil rather than thymine that is present in DNA.

A base is attached to the 1' position, generally adenine (A), cytosine (C), guanine (G) or uracil (U). Adenine and guanine are purines, cytosine and uracil are pyrimidines. A phosphate group is attached to the 3' position of one ribose and the 5' position of the next. The phosphate groups have a negative charge each at physiological pH, making RNA a charged molecule (polyanion). The bases may form hydrogen bonds between cytosine and guanine, between adenine and uracil and between guanine and uracil.

Messenger RNA (mRNA) is the RNA that carries information from DNA to the ribosome, the sites of protein synthesis (translation) in the cell. The coding sequence of the mRNA determines the amino acid sequence in the protein that is produced.

Transfer RNA (tRNA) is a small RNA chain of about 80 nucleotides that transfers a specific amino acid to a growing polypeptide chain at the ribosomal site of protein synthesis during translation. It has sites for amino acid attachment and an anticodon region for codon recognition that binds to a specific sequence on the messenger RNA chain through hydrogen bonding.

Ribosomal RNA (rRNA) is the catalytic component of the ribosomes. Eukaryotic ribosomes contain four different rRNA molecules: 18S, 5.8S, 28S and 5S rRNA. Three of the rRNA molecules are synthesized in the nucleolus, and one is synthesized elsewhere. In the cytoplasm, ribosomal RNA and protein combine to form a nucleoprotein called a ribosome. The ribosome binds mRNA and carries out protein synthesis. Several ribosomes may be attached to a single mRNA at any time.[20] rRNA is extremely abundant and makes up 80% of the 10 mg/ml RNA found in a typical eukaryotic cytoplasm. Transfer-messenger RNA (tmRNA) is found in many bacteria and plastids. It tags proteins encoded by mRNAs that lack stop codons for degradation and prevents the ribosome from stalling.

Several types of RNA can downregulate gene expression by being complementary to a part of an mRNA or a gene's DNA. MicroRNAs (miRNA; 21-22 nt) are found in eukaryotes and act through RNA interference (RNAi), where an effector complex of miRNA and enzymes can break down mRNA which the miRNA is complementary to, block the mRNA from being translated, or accelerate its degradation. While small interfering RNAs (siRNA; 20-25 nt) are often produced by breakdown of viral RNA, there are also endogenous sources of siRNAs in plants. siRNAs act through RNA interference in a fashion similar to miRNAs. Some miRNAs and siRNAs can cause genes they target to be methylated, thereby decreasing or increasing transcription of those genes.

Animals have Piwi-interacting RNAs (piRNA; 29-30 nt) which are active in germline cells and are thought to be a defense against transposons and play a role in gametogenesis.[31][32] Antisense RNAs are widespread among bacteria; most downregulate a gene, but a few are activators of transcription.[33] Antisense RNA can act by binding to an mRNA, forming double-stranded RNA that is degraded by enzymes.[34] There are many mRNA-like large non-coding RNAs that regulate genes in eukaryotes,[35] one such RNA is Xist which coats one X chromosome in female mammals and inactivates it.

Many RNAs are involved in modifying other RNAs. Introns are spliced out of pre-mRNA by spliceosomes, which contain several small nuclear RNAs (snRNA),[14] or the introns can be ribozymes that are spliced by themselves.[38] RNA can also be altered by having its nucleotides modified to other nucleotides than A, C, G and U. In eukaryotes, modifications of RNA nucleotides are generally directed by small nucleolar RNAs (snoRNA; 60-300 nt), found in the nucleolus and cajal bodies. snoRNAs associate with enzymes and guide them to a spot on an RNA by basepairing to that RNA. These enzymes then perform the nucleotide modification. rRNAs and tRNAs are extensively modified, but snRNAs and mRNAs can also be the target of base modification.

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information. Both nucleic acid sequences use complementary language (), and the information is simply transcribed, or copied, from one molecule to the other. DNA sequence is enzymatically copied by RNA polymerase to produce a complementary nucleotide RNA strand, called messenger RNA (mRNA). Transcription is divided into 5 stages: pre-initiation, initiation, promoter clearance, elongation and termination. Enzyme is the start of transcription In the case of protein-encoding DNA, transcription is the first step that usually leads to the expression of the genes, by the production of the mRNA intermediate. The stretch of DNA that is transcribed into an RNA molecule is called a transcription unit, which is translated into protein contains sequences that direct and regulate protein synthesis in addition to coding the sequence that is translated into protein. The regulatory sequence that is before (upstream (-), towards the 5' DNA end) the coding sequence is called 5' untranslated region (5'UTR), and sequence found following (downstream (+), towards the 3' DNA end) the coding sequence is called 3' untranslated region (3'UTR).

Transcription has some proofreading mechanisms, but they are fewer and less effective than the controls for copying DNA; therefore, transcription has a lower copying fidelity than DNA replication. As in DNA replication, RNA is synthesized in the 5' 3' direction (from the point of view of the growing RNA transcript). Only one of the two DNA strands is transcribed. This strand is called the template strand, because it provides the template for ordering the sequence of nucleotides in an RNA transcript. The other strand is called the coding strand, because its sequence is the same as the newly created RNA transcript (except for uracil being substituted for thymine). The DNA template strand is read 3' 5' by RNA polymerase and the new RNA strand is synthesized in the 5' 3' direction. A polymerase binds to the 3' end of a gene (promoter) on the DNA template strand and travels toward the 5' end.

Pre-Initiation: Unlike DNA replication, transcription does not need a primer to start. RNA polymerase simply binds to the DNA and, along with other cofactors, unwinds the DNA to create an initial access to the single-stranded DNA template. However, RNA Polymerase does require a promoter like the ation bubble so that the RNA polymerase has sequence. Initiation: In bacteria, transcription begins with the binding of RNA polymerase to the promoter in DNA. Promoter Clearance: After the first bond is synthesized the RNA polymerase must clear the promoter. Elongation: the template strand (or non-coding strand) is used as a template for RNA synthesis. As transcription proceeds, RNA polymerase traverses the template strand and uses base pairing complementarity with the DNA template to create an RNA copy. Prokaryotic elongation starts with the "abortive initiation cycle". During this cycle RNA Polymerase will synthesize mRNA fragments 2-12 nucleotides long. This continues to occur until the factor rearranges, which results in the transcription elongation complex (which gives a 35 bp moving footprint). The factor is released before 80 nucleotides of mRNA are synthesized.

Termination: Bacteria use two different strategies for transcription termination: in Rho-independent transcription termination, RNA transcription stops when the newly synthesized RNA molecule forms a GC rich hairpin loop, followed by a run of U's, which makes it detach from the DNA template. In the "Rho-dependent" type of termination, a protein factor called "Rho" destabilizes the interaction between the template and the mRNA, thus releasing the newly synthesized mRNA from the elongation complex.

Reverse transcribing viruses replicate their genomes by reverse transcribing DNA copies from their RNA; these DNA copies are then transcribed to new RNA. Retrotransposons also spread by copying DNA and RNA from one another, and telomerase contains an RNA that is used as template for building the ends of eukaryotic chromosomes.

Translation is the first stage of protein biosynthesis (part of the overall process of gene expression). Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA. In translation, messenger RNA (mRNA) is decoded to produce a specific polypeptide according to the rules specified by the genetic code. This uses an mRNA sequence as a template to guide the synthesis of a chain of amino acids that form a protein. Many types of transcribed RNA, such as transfer RNA, ribosomal RNA, and small nuclear RNA are not necessarily translated into an amino acid sequence. Translation proceeds in four phases: activation, initiation, elongation and termination . Amino acids are brought to ribosomes and assembled into proteins. In activation, the correct amino acid is covalently bonded to the correct transfer RNA (tRNA). While this is not technically a step in translation, it is required for translation to proceed.

When the tRNA has an amino acid linked to it, it is termed "charged". Initiation involves the small subunit of the ribosome binding to 5' end of mRNA with the help of initiation factors (IF). Termination of the polypeptide happens when the A site of the ribosome faces a stop codon (UAA, UAG, or UGA). When this happens, no tRNA can recognize it, but a releasing factor can recognize nonsense codons and causes the release of the polypeptide chain. The capacity of disabling or inhibiting translation in protein biosynthesis is used by antibiotics such as: anisomycin, cycloheximide, chloramphenicol, tetracycline, streptomycin, erythromycin, puromycin etc.

Any of various compounds consisting of a sugar, usually ribose or deoxyribose, and a purine or pyrimidine base, especially a compound obtained by hydrolysis of a nucleic acid, such as adenosine or guanine. Adenosine

Nucleotides are organic compounds that consist of three joined structures: a nitrogenous base, a sugar, and a phosphate group. The most common nucleotides can be divided into two groups (purines and pyrimidines) based on the structure of the nitrogenous base. The joined sugar is either ribose or deoxyribose. Any of various compounds consisting of a nucleoside combined with a phosphate group and forming the basic constituent of DNA and RNA.

Steps: Attachment (absorption) --- Penetration --- Uncoating --- Biosynthesis --- Assembly --- Release Single stranded RNA genome: plus (+) strand --- mRNAs, translated directly to peoteins; minus (-) strand --- with RNA-dependent RNA polymerase that copies the genome into a strand of mRNAs then translated directly to peoteins; Double-strand RNA genome: use an RNA-dependent RNA polymerase to transcribe the minus strand of RNA into a mRNA for transcription; Retrovirus: +-strand, use reverse polymerase to transcribe the RNA to double-strand DNA which is integrated into host cell chromosome to form a provirus; it can transcribe to mRNA using host enzymes; DNA genome: maybe double or single stranded, transcribed to mRNA and then translated into peoteins;

An operon is a functioning unit of key nucleotide sequences of DNA including an operator, a common promoter, and one or more structural genes, which is controlled as a unit to produce messenger RNA (mRNA), in the process of transcription by an RNA polymerase. Operons occur primarily in prokaryotes but also in some eukaryotes, including nematodes. An operon is made up of several structural genes arranged under a common promoter and regulated by a common operator. The regulators of a given operon, including repressors, corepressors, and activators, are not necessarily coded for by that operon. The location and condition of the regulators, promoter, operator and structural DNA sequences can determine the effects of common mutations.

Coumarin has appetite suppressing properties, suggesting its widespread occurrence in plants, especially grasses, is because of its effect of reducing the impact of grazing animals. Coumarin has been used in the treatment of lymphedema.

Prostate specific antigen (PSA) is a protein produced by the cells of the prostate gland. PSA is present in small quantities in the serum of normal men, and is often elevated in the presence of prostate cancer and in other prostate disorders. A blood test to measure PSA is the most effective test currently available for the early detection of prostate cancer. Rising levels of PSA over time are associated with both localized and metastatic prostate cancer (CaP).

Renal function, in nephrology, is an indication of the state of the kidney and its role in renal physiology. Glomerular filtration rate (GFR) describes the flow rate of filtered fluid through the kidney. Creatinine clearance rate (CCr) is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR. Both GFR and CCr may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result (eGFR and eCCr).

Where k is a constant that depends on muscle mass, which itself varies with a child's age: In first year of life, for pre-term babies K=0.33, and for full-term infants K=0.45 For infants between ages of 1 and 12 years, K=0.55.

The normal ranges of GFR, adjusted for body surface area, are: Males: 70 14 mL/min/m2 Females: 60 10 mL/min/m2 Normal reference ranges for creatinine clearance are: Gender Low High Units male 55 146 ml/minute/1.73 m2 female 52 134 ml/minute/1.73m2 Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic group. GFR can increase due to hypoproteinemia because of the reduction in plasma oncotic pressure. GFR can also increase due to constriction of the efferent arteriole but decreases due to constriction of the afferent arteriole.

The severity of chronic kidney disease (CKD) is described by 6 stages, the most severe three are defined by the MDRD-eGFR value, and first three also depend whether there is other evidence of kidney disease (e.g. proteinuria): 0) Normal kidney function GFR above 90ml/min/1.73m2 and no proteinuria 1) CKD1 GFR above 90ml/min/1.73m2 with evidence of kidney damage 2) CKD2 (Mild) GFR of 60 to 89 ml/min/1.73m2 with evidence of kidney damage 3) CKD3 (Moderate) GFR of 30 to 59 ml/min/1.73m2 4) CKD4 (Severe) GFR of 15 to 29 ml/min/1.73m2 5) CKD5 Kidney failure (dialysis or kidney transplant needed) GFR less than 15 ml/min/1.73m2

The prothrombin time (PT) and its derived measures of prothrombin ratio (PR) and international normalized ratio (INR) are measures of the extrinsic pathway of coagulation. They are used to determine the clotting tendency of blood, in the measure of warfarin dosage, liver damage and vitamin K status. The reference range for prothrombin time is usually around 12-15 seconds; the normal range for the INR is 0.8-1.2. PT measures factors II, V, VII, X and fibrinogen. It is used in conjunction with the activated partial thromboplastin time (aPTT) which measures the intrinsic pathway.

The prothrombin time is the time it takes plasma to clot after addition of tissue factor (obtained from animals). This measures the quality of the extrinsic pathway (as well as the common pathway) of coagulation. The speed of the extrinsic pathway is greatly affected by levels of factor VII in the body. Factor VII has a short half-life and its synthesis requires vitamin K. The prothrombin time can be prolonged as a result of deficiencies in vitamin K, which can be caused by warfarin, malabsorption or lack of intestinal colonization by bacteria (such as in newborns). In addition, poor factor VII synthesis (due to liver disease) or increased consumption (in disseminated intravascular coagulation) may prolong the PT. A high INR level such as INR=5 indicates that there is a high chance of bleeding, whereas if the INR=0.5 then there is a high chance of having a clot. Normal ranges for a healthy person are 0.9-1.3 and for people on warfarin therapy is 2.0-3.0 (although the target INR may be higher in particular situations, such as mechanical heart valves).

A congenital condition caused by a deficiency of thyroid hormone during prenatal development and characterized in childhood by dwarfed stature, mental retardation, dystrophy of the bones, and a low basal metabolism. Also called congenital myxedema

Cretinism is a condition of severely stunted physical and mental growth due to untreated congenital deficiency of thyroid hormones (hypothyroidism). Congenital hypothyroidism can be endemic, genetic, or sporadic. If untreated, it results in mild to severe impairment of both physical and mental growth and development.

Cretinism arises from a diet deficient in iodine. It has affected many people worldwide and continues to be a major public health problem in many countries. Iodine is an essential trace element, necessary primarily for the synthesis of thyroid hormones. Although iodine is found in many foods, it is not universally present in all soils in adequate amounts. The soils of many inland areas on all continents are iodine deficient, and plants and animals grown there are correspondingly deficient. Populations living in those areas without outside food sources are most at risk of iodine deficiency diseases. Iodine deficiency results in the impairments in varying degrees of physical and mental development. It also causes gradual enlargement of the thyroid gland, referred to as a goitre. It is being combated in many countries by public health campaigns of iodine administration.

three main forms: autolysis, apoptosis, necrosis

Apoptosis (IPA: /5pp7toss/ ) is a form of programmed cell death in multicellular organisms. It is one of the main types of programmed cell death (PCD) and involves a series of biochemical events that lead to a variety of morphological changes, including blebbing, changes to the cell membrane such as loss of membrane asymmetry and attachment, cell shrinkage, nuclear fragmentation, chromatin condensation, and chromosomal DNA fragmentation. Processes of disposal of cellular debris whose results do not damage the organism differentiate apoptosis from necrosis. Apoptosis does not provoke an inflammatory response.

the name given to unnatural death of cells and living tissue. It begins with cell swelling, chromatin digestion, and disruption of the plasma membrane and organelle membranes. Late necrosis is characterized by extensive DNA hydrolysis, vacuolation of the endoplasmic reticulum, organelle breakdown, and cell lysis. The release of intracellular content after plasma membrane rupture is the cause of inflammation in necrosis.

Gastritis is inflammation of the stomach lining. The inflammation can be caused by many factors, including infection, injury, certain drugs, and disorders of the immune system. Infections with bacteria, viruses, or fungi can cause gastritis. Worldwide, the most common cause of gastritis is infection with Helicobacter pylori bacteria. Viral or fungal gastritis may develop in people who have had a prolonged illness or an impaired immune system, such as those who have AIDS or cancer or those who take immunosuppressant drugs. causes the stomach lining to become very thin and to lose many or all of the cells that produce acid and enzymes. This condition can occur when antibodies attack the stomach lining (termed autoimmune metaplastic atrophic gastritis). Atrophic gastritis can also occur in people who are chronically infected with H. pylori bacteria. It also tends to occur in those who have had part of their stomach removed.

Autoimmune metaplastic atrophic gastritis is an inherited autoimmune disease that attacks parietal cells, resulting in hypochlorhydria and decreased production of intrinsic factor. Consequences include atrophic gastritis, B12 malabsorption, and, frequently, pernicious anemia. Risk of gastric adenocarcinoma increases 3-fold. Diagnosis is by endoscopy. Treatment is with parenteral vitamin B12. may result from an allergic reaction to an infestation with roundworms. In other cases, the cause is unknown. In this type of gastritis, eosinophils (a type of white blood cell) accumulate in the stomach wall. People with erosive gastritis must avoid taking drugs that irritate the stomach lining (such as NSAIDs). Some doctors prescribe proton pump inhibitors or misoprostol to help protect the stomach lining. The coxibs (COX-2 inhibitors such as celecoxib) are less likely to irritate the stomach lining than the older NSAIDs, but recent studies have shown that coxibs appear to increase the risk of heart attack and stroke with long-term use. Therefore, caution should be taken with use of coxibs.

There is no cure for postgastrectomy gastritis or atrophic gastritis. People with anemia resulting from decreased absorption of vitamin B12 that occurs with atrophic gastritis must take supplemental injections of the vitamin for the rest of their lives. Corticosteroids or surgery may be needed to relieve a blocked stomach outlet caused by eosinophilic gastritis. Removing part or all of the stomach may cure Mntrier's disease. There is no effective drug treatment.

a class of diseases in which a group of cells display uncontrolled growth (division beyond the normal limits), invasion (intrusion on and destruction of adjacent tissues), and sometimes metastasis (spread to other locations in the body via lymph or blood). These three malignant properties of cancers differentiate them from benign tumors, which are self-limited, do not invade or metastasize. Most cancers form a tumor but some, like leukemia, do not. The branch of medicine concerned with the study, diagnosis, treatment, and prevention of cancer is oncology.

A condition in which cells of the brain and spinal cord are lost. Cells of the brain and spinal cord are not readily regenerated en masse, so excessive damage can be devastating. Neurodegenerative diseases result from deterioration of neurons or their myelin sheath which over time will lead to dysfunction and disabilities resulting from this. They are crudely divided into two groups according to phenotypic effects, although these are not mutually exclusive: conditions causing problems with movements, such as ataxia / conditions affecting memory and related to dementia

Hepatic encephalopathy (sometimes hepatoencephalopathy) is a potentially-reversible neuropsychiatric abnormality in the setting of liver failure, whether chronic (as in cirrhosis), or acutely. It can be diagnosed only after exclusion of other neurological, psychiatric, infectious, and metabolic etiologies. With severe liver impairment, toxic substances normally removed by the liver accumulate in the blood and impair the function of brain cells. If there is also portal hypertension, and subsequent bypassing of the liver filtration system of blood flowing in from the intestines, these toxic substances can travel directly to the brain, without being modified or purified. Signs can include impaired cognition, a flapping tremor (asterixis), and a decreased level of consciousness including coma (hepatic coma or coma hepaticum), cerebral edema, and, ultimately, death.

a condition where bile cannot flow from the liver to the duodenum.

Vomiting results from the activation and release of neurotransmitters such as dopamine, histamine, acetycholine, and serotonin. These act in the emetogenic pathway to stimulate the chemoreceptor trigger zone, which in turn sends afferent input to the vomiting center of the brain, located in the medulla. The resulting efferent impulses induce nausea, retching, and vomiting. The major antiemetics serotonin antagonists, dopamine antagonists, anticholinergics, and antihistamines target the specific neurotransmitters through receptor antagonism. Acute nausea and vomiting occurs within 24 hours of chemotherapy administration. Delayed nausea and vomiting occurs greater than 24 hours after chemotherapy administration and may occur up to 96 hours postchemotherapy. Anticipatory nausea and vomiting is a pychogenic, conditioned response, occurring before chemotherapy is administered.

The advent of serotonin antagonists specific to the 5-hydroxytryptamine-3 receptor (5-HT 3 ) has lead to significant improvements in the treatment of nausea and vomiting and elucidated the role of serotonin in emesis. Interestingly, metoclopramide was thought primarily to be a dopamine antagonist. However, at the high doses used for nausea, it also acts as a serotonin antagonist. Hence, it is believed that cancer chemotherapy triggers the release of both dopamine and serotonin. Unfortunately, at high doses, dopamine antagonist can cause dystonic reactions or extrapyramidal symptoms.

The most effective chemotherapeutic antiemetic is a 5-HT 3 antagonist in combination with a corticosteroid, usually dexamethasone or methylprednisolone. Although the mechanism is not fully understood in emesis, corticosteroids act synergistically and augment the response to anti emetics when used in combination. 5-HT 3 antagonists are effective for acute nausea, but are not effective for anticipatory nausea, and efficacy is low for delayed nausea. Lorazepam is very effective for anticipatory nausea. Other agents used in chemotherapy-induced emesis are dopamine antagonists, scopolamine, and dronabinol. Antihistamines are generally less effective for chemotherapy-induced nausea and vomiting.

Metoclopramide with dexamethasone has been shown to be effective in delayed nausea and vomiting, which occurs more than 24 hours after chemotherapy administration and may last as long as 7 days. Cisplatin is a classic agent that causes significant delayed nausea and vomiting, 5-HT3 antagonists, even in combination with dexamethasone, have not been shown to be effective for delayed nausea and vomiting, Metoclopramide may be given in high doses, but dystonic and EPS reactions often associated with such high doses makes this an undesirable choice (even with coadministration of diphenhydramine).

The application of gold compounds to medicine is called "chrysotherapy" and "aurotherapy."[1] The first reports of research in this area appeared in 1935,[2] primarily to reduce inflammation and to slow disease progression in patients with rheumatoid arthritis. Most chemical compounds of gold, including some of the drugs discussed below, are not in fact salts. Gold compounds find wide use in electroplating,[3] and as reagents in organic chemistry. Gold compounds, which accumulate slowly in the body and, over time, reduce inflammation, especially related to rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis, membranous nephritis, lupus erythematosus and, infrequently, juvenile rheumatoid arthritis (JRA).

Common side effects of oral gold include decreased appetite, nausea, hair thinning and diarrhea, as well as problems affecting skin, blood (thrombocytopenia), kidneys, or lungs. Common side effects of injected gold include an itchy skin rash or mouth sores, with rare instances of kidney problems or suppression of blood cell production.

Any of a group of psychotic disorders usually characterized by withdrawal from reality, illogical patterns of thinking, delusions, and hallucinations, and accompanied in varying degrees by other emotional, behavioral, or intellectual disturbances. Schizophrenia, often associated with dopamine imbalances in the brain and defects of the frontal lobe, may have an underlying genetic cause.

Neurotransmitters are chemicals that are used to relay, amplify and modulate signals between a neuron and another cell. Approximately ten "small-molecule neurotransmitters" are known: Acetylcholine (Ach) Monoamines: norepinephrine (NE), dopamine (DA), serotonin (5-HT), melatonin Amino acids: glutamate, gamma aminobutyric acid (GABA), aspartate, glycine, histamine Purines: Adenosine, ATP, GTP, and their derivatives As explained above, the only direct action of a neurotransmitter is to activate a receptor. Therefore, the effects of a neurotransmitter system depend on the connections of the neurons that use the transmitter, and the chemical properties of the receptors that the transmitter binds to.

Here are a few examples of important neurotransmitter actions: Glutamate is used at the great majority of fast excitatory synapses in the brain and spinal cord. It is also used at most synapses that are "modifiable", i.e. capable of increasing or decreasing in strength. Modifiable synapses are thought to be the main memory-storage elements in the brain. GABA is used at the great majority of fast inhibitory synapses in virtually every part of the brain. Many sedative/tranquilizing drugs act by enhancing the effects of GABA. Acetylcholine is distinguished as the transmitter at the neuromuscular junction connecting motor nerves to muscles. The paralytic arrow-poison curare acts by blocking transmission at these synapses. Acetylcholine also operates in many regions of the brain, but using different types of receptors. Dopamine has a number of important functions in the brain. It plays a critical role in the reward system, but disfunction of the dopamine system is also implicated in Parkinson's Disease and schizophrenia. Serotonin has a number of important functions that are difficult to describe in a unified way, including regulation of mood, sleep/wake cycles, and body temperature.

Off-label use is the practice of prescribing drugs for a purpose outside the scope of the drug's approved label, most often concerning the drug's indication. In the United States, the Food and Drug Administration (FDA) requires numerous clinical trials to prove a drug's safety and efficacy in treating a given disease or condition. If satisfied that the drug is safe and effective, the drug's manufacturer and the FDA agree on specific language describing dosage, route and other information to be included on the drug's label. More detail is included in the drug's package insert.

Actiq (oral transmucosal fentanyl citrate), a Schedule II controlled substance, is used off-label to treat moderate to severe chronic, non-malignant pain even though it is FDAapproved solely for break-through pain in cancer patients. [3] Bevacizumab has been used against Age Related Macular Degeneration, but the evidence for its use is anecdotal.[4] Buprenorphine has been shown experimentally (1982-1995) to be effective against severe, refractory depression. [5] [5] Carbamazepine, or Tegretol, has been used as a mood stabilizer and is accepted treatment for bipolar disorder. [6] Gabapentin, approved for treatment of seizures and postherpetic neuralgia in adults, is used off-label for a variety of conditions including bipolar disorder, essential tremor, hot flashes, migraine prophylaxis, neuropathic pain syndromes, phantom limb syndrome, and restless leg syndrome. [7] Methotrexate (MTX), approved for the treatment of choriocarcinoma, is frequently used for the medical treatment of an unruptured ectopic pregnancy. [8] There is no FDAapproved drug for this purpose and there is little incentive to sponsor an unpatented drug such as MTX for FDA-approval. The SSRI medication sertraline is approved as an anti-depressant. It is also commonly prescribed off-label to help men suffering from Premature ejaculation. [9]

Endotoxins are part of the outer cell wall of bacteria. Endotoxins are invariably associated with Gram-negative bacteria as constituents of the outer membrane of the cell wall, such as E. coli, Salmonella, Shigella, Pseudomonas, Neisseria, Haemophilus, and other leading pathogens. Lipopolysaccharide (LPS) participates in a number of outer membrane functions that are essential for bacterial growth and survival, especially within the context of a host-parasite interaction. The biological activity of endotoxin is associated with the lipopolysaccharide (LPS). Toxicity is associated with the lipid component (Lipid A) and immunogenicity (antigenicity) is associated with the polysaccharide components. The cell wall antigens (O antigens) of Gram-negative bacteria are components of LPS. LPS activates complement by the alternative (properdin) pathway and may be a part of the pathology of most Gram-negative bacterial infections. For the most part, endotoxins remain associated with the cell wall until disintegration of the bacteria. In vivo, this results from autolysis, external lysis, and phagocytic digestion of bacterial cells. It is known, however, that small amounts of endotoxin may be released in a soluble form, especially by young cultures.

Compared to the classic exotoxins of bacteria, endotoxins are less potent and less specific in their action, since they do not act enzymatically. Endotoxins are heat stable (boiling for 30 minutes does not destabilize endotoxin), but certain powerful oxidizing agents such as , superoxide, peroxide and hypochlorite degrade them. Endotoxins, although strongly antigenic, cannot be converted to toxoids. A comparison of the properties of bacterial endotoxins compared to classic exotoxins is shown in Table 5. Table 5. CHARACTERISTICS OF BACTERIAL ENDOTOXINS AND EXOTOXINS PROPERTY CHEMICAL NATURE RELATIONSHIP TO CELL DENATURED BY BOILING ANTIGENIC FORM TOXOID POTENCY SPECIFICITY ENZYMATIC ACTIVITY PYROGENICITY ENDOTOXIN Lipopolysaccharide (mw = 10kDa) Part of outer membrane No Yes No Relatively low (>100ug) Low degree No Yes EXOTOXIN Protein (mw = 50-1000kDa) Extracellular, diffusible Usually Yes Yes Relatively high (1 ug) High degree Usually Occasionally

Lipopolysaccharides are complex amphiphilic molecules with a mw of about 10kDa, that vary widely in chemical composition both between and among bacterial species. In a basic ground plan common to all endotoxins, LPS consists of three components or regions: (1) Lipid A---- (2) Core polysaccharide---- (3) O polysaccharide The Core (R) polysaccharide is attached to the 6 position of one NAG. The R antigen consists of a short chain of sugars. For example: KDO - Hep - Hep - Glu - Gal - Glu GluNAc. In the core polysaccharide. KDO is unique and invariably present in LPS and so has been an indicator in assays for LPS (endotoxin). With minor variations, the core polysaccharide is common to all members of a bacterial genus (e.g. Salmonella), but it is structurally distinct in other genera of Gram-negative bacteria. Salmonella, Shigella and Escherichia have similar but not identical cores. The O polysaccharide (also referred to as the O antigen or O side chain) is attached to the core polysaccharide. It consists of repeating oligosaccharide subunits made up of 3-5 sugars. The individual chains vary in length ranging up to 40 repeat units. The O polysaccharide is much longer than the core polysaccharide and it maintains the hydrophilic domain of the LPS molecule. Often, a unique group of sugars, called dideoxyhexoses, occurs in the O polysaccharide. A major antigenic determinant (antibody-combining site) of the Gram-negative cell wall resides in the O polysaccharide. Great variation occurs in the composition of the sugars in the O side chain between species and even strains of Gram-negative bacteria.

Endotoxins are toxic to most mammals. They are strong antigens but they seldom elicit immune responses which give full protection to the animal against secondary challenge with the endotoxin. They cannot be toxoided. Endotoxins released from multiplying or disintegrating bacteria significantly contribute to the symptoms of Gramnegative bacteremia and septicemia, and therefore represent important pathogenic factors in Gram-negative infections. Regardless of the bacterial source, all endotoxins produce the same range of biological effects in the animal host. The injection of living or killed Gram-negative cells, or purified LPS, into experimental animals causes a wide spectrum of nonspecific pathophysiological reactions related to inflammation such as: fever / changes in white blood cell counts / disseminated intravascular coagulation / tumor necrosis / hypotension / shock / lethality The sequence of events follows a regular pattern: 1. latent period; 2. physiological distress (fever, diarrhea, prostration, shock); 3. death. How soon death occurs varies on the dose of the endotoxin, route of administration, and species of animal. Animals vary in their susceptibility to endotoxin.

Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of hemoproteins found in all domains of life.[1] Cytochromes P450 use a plethora of both exogenous and endogenous compounds as substrates in enzymatic reactions. Usually they form part of multicomponent electron transfer chains, called P450-containing systems. The most common reaction catalysed by cytochrome P450 is a monooxygenase reaction, e.g. insertion of one atom of oxygen into an organic substrate (RH) while the other oxygen atom is reduced to water: RH + O2 + 2H+ + 2e ROH + H2O The name cytochrome P450 is derived from the fact that these are colored ('chrome') cellular ('cyto') proteins, with a "pigment at 450 nm", so named for the characteristic Soret peak formed by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (often with sodium dithionite) and complexed to carbon monoxide.

Alcohol ingestion should be avoided when taking metronidazole. The coadministration of alcohol with metronidazole can result in an uncomfortable disulfiram-like reaction in patients due to inhibition of aldehyde dehydrogenase, leading to an accumulation of acetaldehyde, A disulfiram reaction manifests as flushing, nausea, vomiting, throbbing headache, sweating, and HTN, The effect may last 30 minutes in mild cases to several hours in severe cases,

Glycogen is a polysaccharide of glucose (Glc) which functions as the primary short term energy storage in animal cells. It is made primarily by the liver and the muscles, but can also be made by the brain, uterus, and the vagina. Only the glycogen stored in the liver can be made accessible to other organs. In the muscles, glycogen is found in a much lower concentration (1% of the muscle mass), but the total amount exceeds that in liver. Small amounts of glycogen are found in the kidneys, and even smaller amounts in certain glial cells in the brain and white blood cells The uterus also stores glycogen during pregnancy to nourish the embryo.

Glycogen does not possess a reducing end: the 'reducing end' glucose residue is not free but is covalently bound to a protein termed glycogenin as a beta-linkage to a surface tyrosine residue. Glycogenin is a glycosyltransferase and occurs as a dimer in the core of glycogen. The glycogen granules contain both glycogen and the enzymes of glycogen synthesis (glycogenesis) and degradation (glycogenolysis). The enzymes are nested between the outer branches of the glycogen molecules and act on the nonreducing ends. Therefore, the many non-reducing end-branches of glycogen facilitate its rapid synthesis and catabolism.

As a meal containing carbohydrates is eaten and digested, Insulin acts on the hepatocytes to stimulate the action of several enzymes, including glycogen synthase. Glucose molecules are added to the chains of glycogen as long as both insulin and glucose remain plentiful. In this postprandial or "fed" state, the liver takes in more glucose from the blood than it releases. After a meal has been digested and glucose levels begin to fall, insulin secretion is reduced, and glycogen synthesis stops. About four hours after a meal, glycogen begins to be broken down and converted again to glucose. Glycogen phosphorylase is the primary enzyme of glycogen breakdown. For the next 812 hours, glucose derived from liver glycogen will be the primary source of blood glucose to be used by the rest of the body for fuel. Glucagon is another hormone produced by the pancreas, which in many respects serves as a counter-signal to insulin. When the blood sugar begins to fall below normal, glucagon is secreted in increasing amounts. It stimulates glycogen breakdown into glucose even when insulin levels are abnormally high.

Glycogen synthesis differs from glycogen breakdown. Unlike breakdown, synthesis is endergonic [hhhhhhhhhhh] adj.. Energy for glycogen synthesis comes from UTP, which reacts with glucose-1-phosphate, forming UDP-glucose, in reaction catalysed by UDP-glucose pyrophosphorylase. Glycogen is synthesized from monomers of UDPglucose by the enzyme Glycogen synthase, which progressively lengthens the glycogen chain. As glycogen synthase can only lengthen an existing chain, the protein glycogenin is needed to initiate the synthesis of glycogen.

Glycogen is cleaved from the nonreducing ends of the chain by the enzyme glycogen phosphorylase to produce monomers of glucose-1-phosphate that is then converted to Glucose 6-phosphate. A special debranching enzyme is needed to remove the alpha(1-6) branches in branched glycogen and reshape the chain into linear polymer.

Glycogenolysis (also known as "Glycogenlysis") is the catabolism of glycogen by cleavage of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate. This derivative of glucose is then converted to glucose-6-phosphate, an intermediate in glycolysis. The hormones glucagon and epinephrine stimulate glycogenolysis. Glycogenolysis transpires in the muscle and liver tissue, where glycogen is stored, as a hormonal response to epinephrine (e.g., adrenergic stimulation) and/or glucagon, a pancreatic peptide triggered by low blood glucose concentrations. Liver (hepatic) cells can consume the glucose-6-phosphate in glycolysis, or remove the phosphate group using the enzyme glucose-6-phosphatase and release the free glucose into the bloodstream for uptake by other cells. Muscle cells in humans do not possess glucose-6-phosphatase and hence will not release glucose, but instead use the glucose-6-phosphate in glycolysis.

Glycolysis [^lai5kClisis] The ATP-generating metabolic process that occurs in nearly all living cells by which carbohydrates and sugars, typically glucose, are converted in a series of steps to pyruvic acid. Glycolysis is the sequence of reactions that converts glucose into pyruvate with the concomitant production of a relatively small amount of adenosine triphosphate (ATP).

[7^lu:kE7ni:Eu5dVenisis] The formation of glucose, especially by the liver, from noncarbohydrate sources, such as amino acids and the glycerol portion of fats. Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as pyruvate, lactate, glycerol, and glucogenic amino acids. The vast majority of gluconeogenesis takes place in the liver and, to a smaller extent, in the cortex of kidneys. This process occurs during periods of fasting, starvation, or intense exercise and is highly endergonic. Gluconeogenesis is often associated with ketosis. Gluconeogenesis is also a target of therapy for type II diabetes, such as metformin, which inhibit glucose formation and stimulate glucose uptake by cells.

a chemical substance consisting of a lattice of one type of molecule trapping and containing a second type of molecule. A clathrate therefore is a material which is a weak composite, with molecules of suitable size captured in spaces which are left by the other compounds. They are also called host-guest complexes, inclusion compounds, and adducts (chiefly in the case of urea and thiourea). They used to be called "molecular compounds". The development of clathrate compounds was attained by analyzing crystal structure by Powell (mentioned above), and they were applied to the separation of paraffin using a urea or thiourea host. Thereafter, urea or thiourea host, cyclodextrin, crown ether, and cryptand were found as host molecules (see figure)----- Host and guest

Rheumatic fever is an autoimmune inflammatory disease which may develop two to three weeks after a Group A streptococcal infection (such as strep throat or scarlet fever) and can involve the heart, joints, skin, and brain. Acute rheumatic fever commonly appears in children ages 5 through 15, with only 20% of first time attacks occurring in adults. It gets its name for its similarity in presentation to rheumatism.

Brucellosis, also called undulant fever, or Malta fever, is a highly contagious zoonosis caused by ingestion of unsterilized milk or meat from infected animals, or close contact with their secretions. Brucella spp. are small, gram-negative, non-motile, non-spore-forming rods, which function as facultative intracellular parasites that cause chronic disease, which usually persists for life.

The mean corpuscular volume, or MCV, is a measure of the average red blood cell volume (i.e. size) that is reported as part of a standard complete blood count. In patients with anemia, it is the MCV measurement that allows classification as either a microcytic anemia (MCV below normal range) or macrocytic anemia (MCV above normal range). It can be calculated (in litres) by dividing the hematocrit by the red blood cell count (number of red blood cells per litre). The result is typically reported in femtolitres. If the MCV was determined by automated equipment, the result can be compared to RBC morphology on a peripheral blood smear. Any deviation would be indicative of either faulty equipment or technician error. The normal reference range is typically 80-100 fL. In presence of hemolytic anaemia, presence of reticulocytes can increase MCV. In pernicious anemia (macrocytic), MCV can range up to 150 femtolitres. An elevated MCV is also associated with alcoholism.

The mean corpuscular hemoglobin, or "mean cell hemoglobin" (MCH), is the average mass of hemoglobin per red blood cell in a sample of blood. It is reported as part of a standard complete blood count. It is diminished in microcytic anemias, and increased in macrocytic anemias. It is calculated by dividing the total mass of hemoglobin by the number of red blood cells in a volume of blood. MCH=Hgb/RBC A normal value in humans is 26.3 to 33.8 picograms/cell.

Liver function tests (LFTs or LFs), which include liver enzymes, are groups of clinical biochemistry laboratory blood assays designed to give information about the state of a patient's liver. Most liver diseases cause only mild symptoms initially, but it is vital that these diseases be detected early. Hepatic (liver) involvement in some diseases can be of crucial importance. This testing is performed by a medical technologist on a patient's serum or plasma sample obtained by phlebotomy. Some tests are associated with functionality (eg. albumin); some with cellular integrity (eg. transaminase) and some with conditions linked to the biliary tract (gamma-glutamyl transferase and alkaline phosphatase).

Caused by Calcium ingestion (milk-alkali syndrome), Hyperparathyroid, Hyperthyroid, Iatrogenic (thiazides), Multiple myeloma, Pagets disease, Addisons disease, Neoplasms, Zollinger-Ellison syndrome, Excess vitamin D, Excess vitamin A, Sarcoidosis.

Hyperopia, also known as farsightedness or longsightedness, is a defect of vision caused by an imperfection in the eye (often when the eyeball is too short or when the lens cannot become round enough), causing inability to focus on near objects, and in extreme cases causing a sufferer to be unable to focus on objects at any distance. As an object moves toward the eye, the eye must increase its power to keep the image in focus on the retina. If the power of the cornea and lens is insufficient, as in hyperopia, the image will appear blurred.

Inability of the eye to focus sharply on nearby objects, resulting from loss of elasticity of the crystalline lens with advancing age.

also called near- or short-sightedness, is a refractive defect of the eye in which collimated light produces image focus in front of the retina when accommodation is relaxed. Those with myopia see nearby objects clearly but distant objects appear blurred. With myopia, the eyeball is too long, or the cornea is too steep, so images are focused in the vitreous inside the eye rather than on the retina at the back of the eye.

Age : The likelihood of suffering miosis increases with age. Diseases: Horner syndrome (a set of abnormalities in the nervous supply of the face due to damage to the sympathetic nervous system). Pancoast tumor (a tumor of the apical lung), due to damage to the ascending sympathetic tract that would normally cause the pupil to dilate. Hemorrhage into pons (intracranial hemorrhage); Cluster Headaches with ptosis Drugs: Opioids such as tramadol, codeine, fentanyl, morphine, heroin and methadone Antipsychotics, including haloperidol, thorazine, olanzapine, quetiapine and others Cholinergic agents and nerve gases; pilocarpine, carbachol (Miostat) and neostigmine; Some cancer chemotherapy drugs, including camptothecin derivatives Mirtazapine, a noradrenergic and specific serotonergic antidepressant (NaSSA) Trazodone; Some MAO Inhibitors. In some rare cases, when exposed to mustard gas.

Mydriasis is an excessive dilation of the pupil due to disease, trauma or drugs. There are two types of muscle that control the size of the iris: circular muscle and radial muscle. The former is innervated by the parasympathetic nervous system, the latter by the sympathetic nervous system. Sympathetic stimulation of 1 adrenergic receptors causes the contraction of the radial muscle, and subsequent dilation of the pupil. Conversely, parasympathetic stimulation cause contraction of the circular muscle and constriction of the iris. The mechanism of mydriasis usually involves either a disruption of the parasympathetic nerve supply to the eye (which causes contraction of the pupil), or over activity of the sympathetic nervous system (SNS). Drugs cause mydriasis: Cyclomydril is an ophthalmic medication intended to cause mydriasis Atropine blocks muscarinic acetylcholine receptors. Acetylcholine (ACh) is the neurotransmitter of the parasympathetic nervous system and blocking its action means the pupil cannot constrict. Cocaine inhibits the reuptake of noradrenaline (norepinephrine) within a nerve synapse. When a solution of cocaine is dropped into the eye, noradrenaline is no longer reabsorbed by neurons, and its levels increase. Noradrenaline, the neurotransmitter for the SNS, causes dilation of the pupil. Mydriasis is used as a diagnostic test for Horner's Syndrome, in which it is initiated using a similar mechanism, though cocaine is not usually used in this procedure. Many other drugs such as amphetamines and psychedelic drugs (LSD, psychedelic mushrooms, mescaline, and MDMA) are also known to cause mydriasis. Opiate withdrawal can cause dilated pupils in some people. [3] Opiates normally lead to miosis or the constriction of the pupils. Antihistamines and tricyclic antidepressants may cause mydriasis.

Conjunctivitis (commonly called "Pink Eye" or "Red Eye" in North America) is an inflammation of the conjunctiva (the outermost layer of the eye and the inner surface of the eyelids), most commonly due to an allergic reaction or an infection (usually viral, but sometimes bacterial). The leading cause of a red, inflamed eye is a bacterial infection. A number of different bacteria can be responsible for the infection. Bacterial pink eye symptoms are usually associated with more of a watery discharge that is not green or yellow in color. Often, bacterial "cold-like" symptoms, such as sinus congestion and runny nose, are also present. The eyelids may be swollen. Sometimes looking at bright lights is painful. While bacterial pink eye may not require an antibiotic, those affected should see a doctor, as occasionally this form of pink eye can be associated with infection of the cornea (the clear portion of the front of the eyeball). This infection must be correctly detected and treated. Bacterial pink eye is highly contagious, but usually resolves in seven to 10 days after symptoms appear. Other causes of a red eye includes drug intake. Notably, marijuana use causes the eyes to turn red temporarily.

its concentration is helpful in diagnosis of Acute myocaridial infarctions with similar sensitivity to CK-MB levels from 4-8 hours post MI

a disorder characterized by the presence of a higher than normal level of methemoglobin (metHb) in the blood. Methemoglobin is a form of hemoglobin that does not bind oxygen. When its concentration is elevated in red blood cells, anemia and tissue hypoxia can occur. Methemoglobinemia can be treated with supplemental oxygen and methylene blue[4] 1% solution (10mg/ml) 1-2mg/kg administered intravenously slowly over five minutes followed by IV flush with normal saline. Methylene blue restores the iron in hemoglobin to its normal (reduced) oxygen-carrying state. Signs and symptoms :(methemoglobin >1%) include shortness of breath, cyanosis, mental status changes, headache, fatigue, exercise intolerance, dizziness and loss of consciousness. Arterial blood with elevated methemoglobin levels has a characteristic chocolate-brown color as compared to normal bright red oxygen containing arterial blood. Severe methemoglobinemia (methemoglobin >50%) patients have dysrhythmias, seizures, coma and death.

Cyanosis is a blue coloration of the skin and mucous membranes due to the presence of deoxygenated hemoglobin in blood vessels near the skin surface. It occurs when the oxygen saturation of arterial blood falls below 85-90% (1.5g/dl deoxyhemoglobin).

The D-xylose test involves having a patient to drink a certain quantity of D-xylose, and measuring levels in the urine and blood; if there is no evidence of D-xylose in the urine and blood, it suggests that the small bowel is not absorbing properly (as opposed to problems with enzymes required for digestion). Malabsorption can be detected in this way. Xylose is a sugar that does not require enzymes to be digested.

Any of several disorders of porphyrin metabolism, usually hereditary, characterized by the presence of large amounts of porphyrins in the blood and urine. But acquired porphyria is usually due to lead or heavy metal poisoning or the drugs griseofulvin or apronalide.

Anion gap represents the approximate sum of measured anions minus unmeasured cations (anion gap=Na+ - [Cl- +HCO3-]. When measured, it may indicate lactic acidosis or ketoacidosis if the data is bigger than 30 mmol/L.

p-glycoprotein causes cellular efflux of a variety of drugs causes Na+ retention and K+ excretion

traditionally includes RBC count, WBC count, Hgb, HCT, RBC indices, reticulocyte count, RBC distribution width, and platelet count

MCV: size of red blood cells; (mean corpuscular volume) MCH: weight of hemoglobin per average red blood cell; (mean cell hemoglobin) MCHC: amount of hemoglobin per red blood cell in relation to size; (mean corpuscular hemoglobin concentration) iron deficiency anemia: indices the decreased MCV, MCH and MCHC;

a group of enzymes in many body tissuses, including the liver, bone, small intestine, and kidneys, as well as plasma and leukocytes. Bone disorder such as Paget's disease, anticonvulsants ( phenytoin, phenobarbital) and acromegaly can cause general increases in ALP.

Digoxin, phenytoin, theophylline, cyclosporine: via serum/plasma drug concentrations; Warfarin: via clotting test

CEA is a glycoprotein. In the healthy poulation, the upper limit of CEA is about 3 ng/L for nonsmokers and about 5 ng/L for smokers; It is a nonspecific marker for certain types of carcinoma, including colorectal, breast, gastrointestinal, pancreatic, ovarian, and uterine. In breast cancer, an elevated CEA usually indicates metastatic disease.

allergic reaction to latex, drug hypersensitivity reaction, parasitic infestation may increase its levels

P-glycoprotein (plasma gycoprotein, abbreviated as P-gp or Pgp) is a well-characterized human ABC-transporter of the MDR/TAP subfamily. It is extensively distributed and expressed in normal cells such as those lining the intestine, liver cells, renal proximal tubular cells, and capillary endothelial cells comprising the blood-brain barrier. P-gp is also called ABCB1 and is an ATP-dependent efflux pump with broad substrate specificity. It likely evolved as a defense mechanism against harmful substances. ABCB1 transports various substrates across the cell membrane including: Drugs such as colchicine and tacrolimus; anticancer agents: etoposide, doxorubicin, and vinblastine; Cardiac glycosides like digoxin; Immunosuppressive agents; Glucocorticoids like dexamethasone; Lipids; Steroids; Xenobiotics; Peptides; Bilirubin; HIV-type 1 antiretroviral therapy agents like protease inhibitors and nonnucleoside reverse transcriptase inhibitors. Its ability to transport the above substrates accounts for the many roles of ABCB1 including: Regulating the distribution and bioavailability of drugs The removal of toxic metabolites and xenobiotics from cells into urine, bile, and the intestinal lumen The transport of compounds out of the brain across the blood-brain barrier / Digoxin uptake / The migration of dendritic cells Prevention of ivermectin entry into the central nervous system / Protection of hematopoietic stem cells from toxins.

substances that mimic the effects of the catecholamines epinephrine (adrenaline), norepinephrine (noradrenaline), and/or dopamine. Such drugs are used to treat cardiac arrest, low blood pressure, or even delay premature labor, among other things. These drugs act at the postganglionic sympathetic terminal, either directly activating postsynaptic receptors, blocking breakdown and reuptake, or stimulating production and release of catecholamines. The mechanisms of sympathomimetic drugs can be direct-acting, such as -adrenergic agonists, -adrenergic agonists, dopaminergic agonists; or indirect-acting, such as amphetamines (including MDMA), ephedrine and cocaine; MAOIs, COMTs(catechol-O-methyl transferase.), release stimulants, and reuptake inhibitors. "Parasympatholytic" and "sympathomimetic" are similar, but not identical. For example, both cause mydriasis, but parasympatholytics reduce accommodation (cycloplegia ) while sympathomimetics do not.

A potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation, inflammation, and anaphylaxis. It is produced in response to specific stimuli by a variety of cell types, including neutrophils, basophils, platelets, and endothelial cells. It is an important mediator of bronchoconstriction. It causes platelets to aggregate and blood vessels to dilate. At a concentration of 10^-12 M, PAF causes life threatening inflammation of the airways to induce asthma like symptoms. Toxins such as fragments of destroyed bacteria induce the synthesis of PAF, which causes a drop in blood pressure and reduced volume of blood pumped by the heart, which leads to shock and maybe death.

eicosanoids are signaling molecules made by oxygenation of twenty-carbon essential fatty acids, (EFAs). They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the CNS. The networks of controls that depend upon eicosanoids are among the most complex in the human body. Eicosanoids derive from either omega-3 (-3) or omega-6 (-6) EFAs. The -6 eicosanoids are generally pro-inflammatory; -3's are much less so. The amounts and balance of these fats in a person's diet will affect the body's eicosanoid-controlled functions, with effects on cardiovascular disease, triglycerides, blood pressure, and arthritis. Anti-inflammatory drugs such as aspirin and other NSAIDs act by downregulating eicosanoid synthesis. There are four families of eicosanoidsthe prostaglandins, prostacyclins, the thromboxanes and the leukotrienes. (arachidonic acid is the important precursor)

Macrosomia, also known as big baby syndrome, is sometimes used synonymously with LGA, or is otherwise defined as a fetus that weighs above 4000 grams (8 lb 13 oz) or 4500 grams (9 lb 15 oz) regardless of gestational age. Large for gestational age (LGA) babies are those whose birth weight lies above the 90th percentile for that gestational age. One of the primary risk factors is poorly-controlled diabetes, particularly gestational diabetes (GD), as well as preexisting diabetes mellitus (DM). This increases maternal plasma glucose levels as well as insulin, stimulating fetal growth.

All cellular blood components are derived from haematopoietic stem cells (HSCs) . Approximately 10111012 new blood cells are produced daily.[1] HSCs reside in the marrow and have the unique ability to give rise to all of the different mature blood cell types. HSCs are self renewing: when they proliferate, at least some of their daughter cells remain as HSCs, so the pool of stem cells does not become depleted.

The proliferation and self-renewal of these cells depend on stem cell factor (SCF). Glycoprotein growth factors regulate the proliferation and maturation of the cells that enter the blood from the marrow, and cause cells in one or more committed cell lines to proliferate and mature. Three more factors which stimulate the production of committed stem cells are called colony-stimulating factors (CSFs) and include granulocyte-macrophage CSF (GM-CSF), granulocyte CSF (G-CSF) and macrophage CSF (M-CSF). These stimulate a lot of granulocyte formation. They are active on either progenitor cells or end product cells.

Bradykinin is a peptide that causes blood vessels to enlarge (dilate), and therefore causes blood pressure to lower. A class of drugs called ACE inhibitors increase bradykinin further lowering blood pressure. Bradykinin works on blood vessels through the release of prostacyclin, nitric oxide, and endothelial-derived hyperpolarizing factor. Currently, bradykinin inhibitors are being developed as potential therapies for hereditary angioedema. Icatibant is one such inhibitor.

A drug that blocks one or more of the five subtypes of the enzyme phosphodiesterase (PDE), therefore preventing the inactivation of the intracellular second messengers, cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), by the respective PDE subtype(s). Non-selective phosphodiesterase inhibitors: caffeine, a minor stimulant theophylline, a bronchodilator IBMX (3-isobutyl-1-methylxanthine), used as investigative tool in pharmacological research Vinpocetine

EHNA (erythro-9-(2-hydroxy-3-nonyl)adenine)

Enoximone and milrinone, used clinically for short-term treatment of cardiac failure. These drugs mimic sympathetic stimulation and increase cardiac output. PDE3 is sometimes referred to as cGMP-inhibited phosphodiesterase.

Mesembrine, an alkaloid from the herb Sceletium tortuosum Ibudilast, a neuroprotective and bronchodilator drug used mainly in the treatment of asthma and stroke. It inhibits PDE4 to the greatest extent, but also shows significant inhibition of other PDE subtypes, and so acts as a selective PDE4 inhibitor or a non-selective phosphodiesterase inhibitor depending on the dose. Pentoxifylline, a drug that potentially enhances circulation and may have applicability in treatment of diabetes, fibrotic disorders, peripheral nerve damage, and microvascular injuries PDE4 is the major cAMP-metabolizing enzyme found in inflammatory and immune cells. PDE4 inhibitors have proven potential as anti-inflammatory drugs, especially in inflammatory pulmonary diseases such as asthma, COPD and rhinitis. They suppress the release of cytokines and other inflammatory signals and inhibit the production of reactive oxygen species. PDE4 inhibitors may have antidepressive effects and have also recently been proposed for use as antipsychotics.

Sildenafil, tadalafil and vardenafil, and the newer udenafil and avanafil selectively inhibit PDE5, which is cGMP-specific and responsible for the degradation of cGMP in the corpus cavernosum. These phosphodiesterase inhibitors are used primarily as remedies for erectile dysfunction, as well as having some other medical applications such as treatment of pulmonary hypertension. Dipyridamole also inhibits PDE5. This results in added benefit when given together with NO or statins.

refers to two clinical blood tests used in immunohematology and immunology: direct Coombs test (also known as direct antiglobulin test or DAT), and the indirect Coombs test (IAT). In certain diseases or conditions an individual's blood may contain IgG antibodies that can specifically bind to antigens on the red blood cell (RBC) surface membrane, and their circulating red blood cells (RBCs) can become coated with IgG alloantibodies and/or IgG autoantibodies. Complement proteins may subsequently bind to the bound antibodies. The direct Coombs test is used to detect these antibodies or complement proteins that are bound to the surface of red blood cells; a blood sample is taken and the RBCs are washed (removing the patient's own plasma) and then incubated with antihuman globulin (also known as "Coombs reagent"). If this produces agglutination of RBCs, the direct Coombs test is positive, a visual indication that antibodies (and/or complement proteins) are bound to the surface of red blood cells. The indirect Coombs test is used in prenatal testing of pregnant women, and in testing blood prior to a blood transfusion. It detects antibodies against RBCs that are present unbound in the patient's serum. In this case, serum is extracted from the blood, and the serum is incubated with RBCs of known antigenicity. If agglutination occurs, the indirect Coombs test is positive.

Methyldopa (IgG mediated type II hypersensitivity) Penicillin (high dose) Quinidine (IgM mediated activation of classical complement pathway and Membrane attack complex, MAC) (A memory device to remember that the DAT tests the RBCs and is used to test infants for haemolytic disease of the newborn is: Rh Disease; R = RBCs, D = DAT.)

To be able to perform their biological function, proteins fold into one, or more, specific spatial conformations, driven by a number of noncovalent interactions such as hydrogen bonding, ionic interactions, Van der Waals forces and hydrophobic packing. Biochemistry refers to four distinct aspects of a protein's structure:

Primary structure - the amino acid sequence of the peptide chains. Secondary structure - highly regular sub-structures (alpha helix and strands of beta sheet) which are locally defined, meaning that there can be many different secondary motifs present in one single protein molecule. Tertiary structure - three-dimensional structure of a single protein molecule (or a single polypeptide chain); a spatial arrangement of the secondary structures. It also describes the completely folded and compacted polypeptide chain. Quaternary structure - complex of several protein molecules or polypeptide chains, usually called protein subunits in this context, which function as part of the larger assembly or protein complex. A simple mnemonic for correct L-form is "CORN": when the C atom is viewed with the H in front, the residues read "CO-R-N" in a clockwise direction.

Essential: Isoleucine Leucine Lysine Methionine Phenylalanine Threonine Tryptophan Valine Watch TV TILL PM Nonessential: Alanine Asparagine Aspartate Cysteine* Glutamate Glutamine* Glycine* Proline* Serine* Tyrosine* Arginine* Histidine* cysteine, taurine, tyrosine, histidine and arginine are semiessential amino acids in children,

Many amino acids are used to synthesize other molecules, for example: Tryptophan is a precursor of the neurotransmitter serotonin. Glycine is a precursor of porphyrins such as heme. Arginine is a precursor of nitric oxide. Ornithine and S-adenosylmethionine are precursors of polyamines. Aspartate, glycine and glutamine are precursors of nucleotides. AGG

The genetic code is the set of rules by which information encoded in genetic material (DNA or RNA sequences) is translated into proteins (amino acid sequences) by living cells. Specifically, the code defines a mapping between tri-nucleotide sequences called codons, and amino acids; every triplet of nucleotides in a nucleic acid sequence specifies a single amino acid. There are 64 codons encoding 20 different amino acids as dictated by genetic code; AUG is classified as Initiation codon; Stop-codon: UAG is amber, UGA is opal, and UAA is ochre

A restriction enzyme (or restriction endonuclease) is an enzyme that cuts double-stranded or single stranded DNA at specific recognition nucleotide sequences known as restriction sites.

DNA ligase is a special type of ligase that can link together two DNA strands that have single-strand breaks (a break in both complementary strands of DNA). The alternative, a double-strand break, is fixed by a different type of DNA ligase using the complementary strand as a template but still requires DNA ligase to create the final phosphodiester bond to fully repair the DNA.

The term is sometimes used to refer only to protein translation but more often it refers to a multi-step process, beginning with amino acid synthesis and transcription which are then used for translation. Protein biosynthesis, although very similar, differs between prokaryotes and eukaryotes. Transcription can be divided into 3 stages: Initiation, Elongation and Termination, each regulated by a large number of proteins such as transcription factors and coactivators that ensure the correct gene is transcribed in response to appropriate signals. The DNA strand is read in the 3' to 5' direction and the mRNA is transcribed in the 5' to 3' direction by the RNA polymerase. Translation occurs in the cytoplasm where the ribosomes are located.

Translation proceeds in four phases: activation, initiation, elongation and termination (all describing the growth of the amino acid chain, or polypeptide that is the product of translation). In activation, the correct amino acid (AA) is joined to the correct transfer RNA (tRNA). While this is not technically a step in translation, it is required for translation to proceed. The AA is joined by its carboxyl group to the 3' OH of the tRNA by an ester bond. When the tRNA has an amino acid linked to it, it is termed "charged". Initiation involves the small subunit of the ribosome binding to 5' end of mRNA with the help of initiation factors (IF), other proteins that assist the process. Elongation occurs when the next aminoacyl-tRNA (charged tRNA) in line binds to the ribosome along with GTP and an elongation factor. Termination of the polypeptide happens when the A site of the ribosome faces a stop codon (UAA, UAG, or UGA). When this happens, no tRNA can recognize it, but releasing factor can recognize nonsense codons and causes the release of the polypeptide chain. The capacity of disabling or inhibiting translation in protein biosynthesis is used by antibiotics such as: anisomycin, cycloheximide, chloramphenicol, tetracycline, streptomycin, erythromycin, puromycin etc. The events following biosynthesis include post-translational modification and protein folding to assume native secondary and tertiary structures.

RNAi is a mechanism that inhibits gene expression at the stage of translation or by hindering the transcription of specific genes. RNAi targets include RNA from viruses and transposons (significant for some forms of innate immune response), and also plays a role in regulating development and genome maintenance. Small interfering RNA strands (siRNA) are key to the RNAi process, and have complementary nucleotide sequences to the targeted RNA strand. Specific RNAi pathway proteins are guided by the siRNA to the targeted messenger RNA (mRNA), where they "cleave" the target, breaking it down into smaller portions that can no longer be translated into protein. A type of RNA transcribed from the genome itself, microRNA (miRNA), works in the same way.

complementary DNA (cDNA) is the DNA synthesized from a mature mRNA template in a reaction catalyzed by the enzyme reverse transcriptase. cDNA is often used to clone eukaryotic genes in prokaryotes. cDNA is also produced by retroviruses (such as HIV-1, HIV-2, Simian Immunodeficiency Virus, etc.) which is integrated into its host to create a provirus. A cDNA library is a collection of cloned cDNA (complementary DNA) fragments. cDNA is produced from fully transcribed mRNA found in the nucleus and therefore contains only the coding regions of an organism. While information in cDNA libraries is a powerful and useful tool since gene products are readily identified, the libraries lack information about enhancers, introns, and other regulatory elements found in a genomic DNA library.

gene regulation includes the processes that cells and viruses use to turn the information on genes into gene products. Although a functional gene product may be an RNA or a protein, the majority of known mechanisms regulate protein coding genes. Any step of the gene's expression may be modulated, from DNA-RNA transcription to the posttranslational modification of a protein.

Post-transcriptional regulation is the control of protein synthesis by genes after synthesis of RNA has begun by modulating the Capping, Splicing, addition of a Poly(A) Tail, the sequence-specific nuclear export rates and in several contexts sequestration of the RNA transcript. These processes occur in eukaryotes but not in prokaryotes. This modulation is a result of a protein or transcript which in turn is regulated and may have an affinity for certain sequences.

Up-regulation is a process which occurs within a cell triggered by a signal (originating internal or external to the cell) which results in increased expression of one or more genes and as a result the protein(s) encoded by those genes. Conversely down-regulation is a process resulting in decreased gene and corresponding protein expression. Up-regulation occurs for example when a cell is deficient in some kind of receptor. In this case, more receptor protein is synthesized and transported to the membrane of the cell and thus the sensitivity of the cell is brought back to normal reestablishing homeostasis. Down-regulation occurs for example when a cell is overly stimulated by a neurotransmitter, hormone, or drug for a prolonged period of time and the expression of the receptor protein is decreased in order to protect the cell (see also tachyphylaxis).

A plasmid is an extra-chromosomal DNA molecule separate from the chromosomal DNA which is capable of replicating independently of the chromosomal DNA. In many cases, it is circular and double-stranded. Plasmids usually occur naturally in bacteria, but are sometimes found in eukaryotic organisms

the scientific field of the study of sequencing and analyzing the expression, modification and function of proteins on a genome-wide or global scale.

10 Most Common Side Effects of Steroid Abuse: 1. Liver Tumors 2. Jaundice 3. Fluid Retention 4. High Blood Pressure 5. Baldness 6. Shrinking of the Testicles 7. Infertility and Low Sperm Count 8. Develop Breasts 9. Accelerated Puberty 10. Deepened Voice

category of signaling molecules that, like hormones and neurotransmitters, are used extensively in cellular communication. They are proteins, peptides or glycoproteins. The term cytokine encompasses a large and diverse family of polypeptide regulators that are produced widely throughout the body by cells of diverse embryological origin. Immunoglobulin (Ig) superfamily, which are ubiquitously present throughout several cells and tissues of the vertebrate body, and share structural homology with immunoglobulins (antibodies), cell adhesion molecules, and even some cytokines. Examples: IL-1 receptor types. Haemopoietic Growth Factor (type 1) family, whose members have certain conserved motifs in their extracellular amino-acid domain. The IL-2 receptor belongs to this chain, whose -chain (common to several other cytokines) deficiency is directly responsible for the x-linked form of Severe Combined Immunodeficiency (X-SCID). Interferon (type 2) family, whose members are receptors for IFN and . Tumor necrosis factors (TNF) (type 3) family, whose members share a cysteine-rich common extracellular binding domain, and includes several other non-cytokine ligands like CD40, CD27 and CD30, besides the ligands on which the family is named (TNF).

Hypertrophy is the increase of the size of an organ or in a select area of the tissue. It should be distinguished from hyperplasia which occurs due to cell division increasing the number of cells while their size stays the same; hypertrophy occurs due to an increase in the size of cells, while the number stays the same. Ventricular hypertrophy is the increase in size of the ventricles of the heart. Changes can be beneficial or healthy if they occur in response to aerobic or anaerobic exercise, but ventricular hypertrophy is generally associated with pathological changes due to high blood pressure or other disease states.

Hyperplasia (or "hypergenesis") is a general term referring to the proliferation of cells within an organ or tissue beyond that which is ordinarily seen in e.g. constantly dividing cells. Hyperplasia may result in the gross enlargement of an organ, the formation of a benign tumor, or may be visible only under a microscope. Hyperplasia is considered to be a physiological response to a specific stimulus, and the cells of a hyperplastic growth remain subject to normal regulatory control mechanisms. This stands in contrast to neoplasia (the process underlying cancer and some benign tumors), in which genetically abnormal cells proliferate in a non-physiological manner which is unresponsive to normal stimuli. Hyperplasia may be due to any number of causes, including increased demand, chronic inflammatory response, hormonal dysfunctions, or compensation for damage or disease elsewhere. Hyperplasia may be harmless and occur on a particular tissue.

a substance is described as amphiprotic if it can both donate or accept a proton, thus acting either like an acid or a base (according to Brnsted-Lowry theory of acids and bases: acids are proton donors and bases are proton acceptors. In Lewis theory of acids and bases; acids are electron pair acceptors and bases are electron pair donors). Water, amino acids, hydrogen carbonate ions and hydrogen sulfate ions are common examples of amphiprotic species. Since they can donate a proton, all amphiprotic substances contain a hydrogen atom. Also, since they can act like an acid or a base, they are amphoteric. A common example of an amphiprotic substance is the hydrogen carbonate ion, which can act as a base Or as an acid. Water is the most common example.

also known as the Mantoux (screening) test, Pirquet test, or PPD test for Purified Protein Derivative. It is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test. A standard dose of 5 Tuberculin units (0.1 mL) is injected intradermally (into the skin) and read 48 to 72 hours later. A person who has been exposed to the bacteria is expected to mount an immune response in the skin containing the bacterial proteins. The reaction is read by measuring the diameter of induration (palpable raised hardened area) across the forearm (perpendicular to the long axis) in millimeters. If there is no induration, the result should be recorded as "0 mm". If a person has had a history of a positive tuberculin skin test, another skin test is not needed. A positive result indicates TB exposure.

Small doses of the iodide of potassium iodide represents some expectorant action

chelates lead, copper and other heavy metals to form stable, soluble complexes that are excreted in the urine; e.g., used for Wilson's disease for chelating excess coppers

hypovolemia (also hypovolaemia) is a state of decreased blood volume; more specifically, decrease in volume of blood plasma. Volumetric thirst can be caused by a number of things including bleeding and diarrhea. Common causes of hypovolemia can be dehydration, bleeding, vomiting, severe burns and drugs such as diuretics or vasodilators typically used to treat hypertensive individuals. Rarely, it may occur as a result of a blood donation, sweating, and alcohol consumption. To respond to hypovolemia is a task for the body fluid balance systems as well as osmotic balance systems. Following an acute response, this function is accomplished by two sets of receptors; one in the kidneys and the other in the heart. The first response to hypovolemia is an inversed baroreflex, where a lack of activation of baroreceptors results in elevation of total peripheral resistance and cardiac output via increased contractility of the heart, heart rate, and arterial vasoconstriction,[3]which tends to increase blood pressure.

Renin-angiotensin system in the kidney: angiotensin II stimulates the release of hormones by the posterior pituitary gland (ADH, also known as vasopressin) and the adrenal cortex (aldosterone). Aldosterone causes the kidneys to reabsorb sodium, leading to the reabsorption of water. ADH (vasopressin) also causes the kidneys to reabsorb water. Angiotensin II increases blood pressure by contracting arterial muscles. Both the activation of the renin angiotensin system and the decrease in atrial natriuretic peptide, along with their other functions, contribute to elicit thirst, by affecting the subfornical organ.

Transcription is the synthesis of RNA under the direction of DNA. RNA synthesis, or transcription, is the process of transcribing DNA nucleotide sequence information into RNA sequence information. Both nucleic acid sequences use complementary language, and the information is simply transcribed, or copied, from one molecule to the other. DNA sequence is enzymatically copied by RNA polymerase to produce a complementary nucleotide RNA strand, called messenger RNA (mRNA), because it carries a genetic message from the DNA to the protein-synthesizing machinery of the cell. Transcription is divided into 5 stages: pre-initiation, initiation, promoter clearance, elongation and termination. In eukaryotes, a collection of proteins called transcription factors mediate the binding of RNA polymerase and the initiation of transcription. Only after certain transcription factors are attached to the promoter does the RNA polymerase bind to it.

Some viruses (such as HIV, the cause of AIDS), have the ability to transcribe RNA into DNA. HIV has an RNA genome that is duplicated into DNA. The resulting DNA can be merged with the DNA genome of the host cell. The main enzyme responsible for synthesis of DNA from an RNA template is called reverse transcriptase. Some eukaryotic cells contain an enzyme with reverse transcription activity called telomerase. Telomerase is a reverse transcriptase that lengthens the ends of linear chromosomes. Telomerase carries an RNA template from which it synthesizes DNA repeating sequence, or "junk" DNA.

Translation is the first stage of protein biosynthesis (part of the overall process of gene expression). Translation is the production of proteins by decoding mRNA produced in transcription. Translation occurs in the cytoplasm where the ribosomes are located. Ribosomes are made of a small and large subunit which surrounds the mRNA. In translation, messenger RNA (mRNA) is decoded to produce a specific polypeptide according to the rules specified by the genetic code. This uses an mRNA sequence as a template to guide the synthesis of a chain of amino acids that form a protein. The mRNA carries genetic information encoded as a ribonucleotide sequence from the chromosomes to the ribosomes. The ribonucleotides are "read" by translational machinery in a sequence of nucleotide triplets called codons. Each of those triplets codes for a specific amino acid.

a type of injury that may be caused by heat, cold, electricity, chemicals, light, radiation, or friction. Depending on the location affected and the degree of severity, a burn victim may experience a wide number of potentially fatal complications including shock, infection, electrolyte imbalance and respiratory distress. First-degree burns: limited to redness (erythema), a white plaque and minor pain at the site of injury, only involve the epidermis. Second degree burn: manifest as erythema with superficial blistering of the skin, and can involve more or less pain depending on the level of nerve involvement. Seconddegree burns involve the superficial (papillary) dermis and may also involve the deep (reticular) dermis layer. Third-degree burns occur when the epidermis is lost with damage to the full thickness of the underlying dermis but not the subcutaneous layer. Burn victims will exhibit charring and extreme damage of the epidermis, and sometimes hard eschar will be present. Third-degree burns result in scarring and victims will also exhibit the loss of hair shafts and other adenexal structures including sweat glands and sebaceous glands. These burns will require skin grafting, unless very small. Fourth-degree burns damage muscle, tendon, and ligament tissue, thus result in charring and catastrophic damage of the hypodermis. In some instances the hypodermis tissue may be partially or completely burned away as well as this may result in a condition called compartment syndrome, which threatens both the life and the limb of the patient. Grafting is required if the burn does not prove to be fatal.

m clatu en re

T ition rad al n en om clatu re F irst -degree

ficial

A hernia is a protrusion of a tissue, structure, or part of an organ through the muscle tissue or the membrane by which it is normally contained. The hernia has three parts: the orifice through which it herniates, the hernial sac, and its contents. Hernias often occur when one or both testes are invised through the cavity of the stomach. Predominantly sports related, they can often occur while lifting heavy objects. abdominal hernias diaphragmatic hernias and hiatal hernias (for example, paraesophageal hernia of the stomach) pelvic hernias, for example, obturator hernia anal hernias hernias of the nucleus pulposus of the intervertebral discs intracranial hernias

Cyanide is an inhibitor of the enzyme cytochrome c oxidase (also known as aa3) in the fourth complex of the electron transport chain (found in the membrane of the mitochondria of eukaryotic cells.) It attaches to the iron within this protein. The binding of cyanide to this cytochrome prevents transport of electrons from cytochrome c oxidase to oxygen. As a result, the electron transport chain is disrupted, meaning that the cell can no longer aerobically produce ATP for energy.

Cyanocobalamin, or vitamin B12, is essential for proper growth, cell reproduction, formation of blood components, and many other functions. In order for cyanocobalamin to be absorbed properly from the GI tract, it must combine with a glycoprotein called intrinsic factor. In the absence of proper levels of intrinsic factor, cyanocobalamin is administered parenterally or intranasally.

Old Age / Decreased Blood flow / Diabetes / High Blood Pressure (Hypertension) Pelvic Surgery (Prostate, Bladder, Rectal) Spinal Cord Injury, Multiple Sclerosis and Other Nervous System Disorders Hormonal Problems Depression and Psychological Problems Cigarette Smoking, Excessive Use of Alcohol, Drug Abuse Medications (e.g. b-blockers; antipsychotic; SSRI: sertraline ) Sickle Cell Anemia /Peyronie's Disease / Premature Ejaculation / hyperlipidemia

Having the same number of sets of chromosomes as a germ cell or half as many as a somatic cell.

Red blood cell size: Macrocytic anemia (MCV>100); Normocytic anemia (80<MCV<100); Microcytic anemia (MCV<80) Microcytic anemia is primarily a result of hemoglobin synthesis failure/insufficiency, which could be caused by several etiologies: Heme synthesis defect : Iron deficiency anemia; Anemia of chronic disease (more commonly presenting as normocytic anemia) Globin synthesis defect: Sideroblastic defect : Hereditary; Acquired (including lead toxicity); and Reversible sideroblastic anemia; Iron deficiency anemia is the most common type of anemia overall and it has many causes: insufficient dietary intake or absorption of iron; blood lost during menses; bleeding lesions of the gastrointestinal tract; parasitic infestation (hookworm, amebiasis, schistosomiasis and whipworm) in some country and locations.

the most common cause of macrocytic anemia, is due to a deficiency of either vitamin B12, folic acid (or both). Deficiency in folate and/or vitamin B12 can be due either to inadequate intake or insufficient absorption. Folate deficiency normally does not produce neurological symptoms, while B12 deficiency does; Pernicious anemia is caused by a lack of intrinsic factor. Intrinsic factor is required to absorb vitamin B12 from food; Other causes: Hypothyroidism; Alcoholism; Liver Disease; Methotrexate, zidovudine, and other drugs that inhibit DNA replication.

Iron deficiency anemia occurs when the dietary intake or absorption of iron is insufficient, and hemoglobin, which contains iron, cannot be formed. It is the most common cause of microcytic anemia. It is characterized by pallor (reduced amount of oxyhemoglobin in skin or mucous membrane), fatigue and weakness. In severe cases, dyspnea (trouble breathing) can occur. Unusual obsessive food cravings, known as pica, may develop. Hair loss and lightheadedness can also be associated with iron deficiency anemia. Diagnosis: high red blood cell distribution width (RDW), low MCV, MCH or MCHC, and the appearance of the RBCs on visual examination of a peripheral blood smear will narrow the diagnosis to a microcytic anaemia. The blood smear shows many hypochromatic and rather small RBCs; a low serum ferritin, a low serum iron level, an elevated serum transferrin and a high total iron binding capacity (TIBC). Serum ferritin is the most sensitive lab test for iron deficiency anemia. a blood disorder characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickling decreases the cells' flexibility and results in a risk of various other complications. abnormal hemogloblin Certain oxidant drugs ( aspirin, quine, primaquine, chloroquine, sulfonamide, nitrofuran, nalidixic acid, probenecid, phenacetin, quinidine and dimercaptol, isosorbide dinitrate) may cause G6PD deficiency pts to hemolytic anemia. G6PD (glucose-6-phosphate dehydrogenase) is an enzyme necessary to maintain the reduce glutathione level in red blood cells. Immune hemolytic anemia is most commonly found with methyldopa, also including: Mefenamic acid, levodopa and strptomycin

a granulocyte count is less than 1500 cells / mL;

a granulocyte count is less than 500 cells / mL;

duodenum contact: stomach (through pylorus) pancreas (pancreatic duct) liver (bile duct) jejunum

Clindamycin: AAC (antibiotic associated colitis) and severe diarrhea; Chloramphenicol: aplastic anemia; bone marrow toxicity The follicular phase is dominated by estrogen; Ovulatory phase:

The menstrual cycle is under the control of the hormone system and is necessary for reproduction. It may be divided into several phases: menstruation, the follicular phase, and the luteal phase.[2] Ovulation defines the transition from the follicular phase to the luteal phase. Counted from the first day of menstrual flow, the length of each phase varies from woman to woman and cycle to cycle. The average cycles length is 28 days. Hormonal contraception interferes with these normal hormonal changes with the aim of preventing reproduction.

Stimulated by gradually increasing amounts of estrogen in the follicular phase, the lining of the uterus thickens. Luteal phase is dominated by progesterone (which is released by corpus luteum.

Occurs due to loss of bicarbonate from the body. It stimulates the respiratory center to increase of CO2 from the body. Normal anion gap: due to a loss of bicarbonate from the body such as hypokalemia; Elevated anion gap: due to overproduction of organic acids such as lactic acids and formic acids. It occurrs due to inadequate ventilation of CO2 by the lungs, normally related to asthma, beta-blockers, sleep apnea, use of CNS depressants, pulmonary edema or embolism, Cardiac arrest. (more CO2 retend in the lung, makes the balance to the acid side) associated with increase in excretion of CO2; it is not a severe condition. an increase in bicarbonate concentration; saline-responsive or unresponsive. Normally related to: diuretic therapy, vomiting, high concentration of alkali administration, hypercalcemia Histamine H1 receptor are metabotropic G-protein-coupled receptors expressed throughout the body, specifically in smooth muscles, on vascular endothelial cells, in the heart, and in the central nervous system.

also known as the Mantoux screening test, Tuberculin Sensitivity Test, Pirquet test, or PPD test for Purified Protein Derivative) is a diagnostic tool for tuberculosis. It is one of the two major tuberculin skin tests used in the world, largely replacing multiple-puncture tests such as the Tine test

Honey bees, yellow jackets, fire ants, bumblebees and hornets are members of hymenoptera. Their bites cause fatal hymenoptera sensitivity. Urticaria, angioedema, asthma, anaphylaxis, respiratory death and collapse are signs and symptoms reported within one hour of their sting bites.

It is a complete absence of secretion of HCl acid. It is normally associated with gastritis, gastric carcinoma and pernicious anemia, Epigastric distress, abdominal distention, coated tongue, nausea, vomiting and diarrhea are signs and symptoms of achlorhydria. HCl or its precursors are required to prevent symptoms.

due to excessive production of angrogens. Many tumors produce excessive ACTH that result in an increase in adrenal androgen production. Hirsutism, acne, deepening of voice, decrease in breast size, amenorrhea and enlargement of the clitoris are principal signs and symptoms of the disease.

[9vAskjJ`laItIs]

The inflammatory of in blood vessels can lead to necrosis, thrombosis and obliteration of blood vessels.

A narrowing of the mitral valve, usually caused by rheumatic fever, resulting in an obstruction to the flow of blood from the left atrium to the left ventricle.

The principle site for oxidative phosphorylation reaction in bacteria is Cytoplasmic membrane; in human it is Mitochondria A hereditary disease of the exocrine glands, usually developing during early childhood and affecting mainly the pancreas, respiratory system, and sweat glands. It is characterized by the production of abnormally viscous mucus by the affected glands, usually resulting in chronic respiratory infections and impaired pancreatic function.Also called mucoviscidosis A genetic disorder generally observed in infants. If affects both sexes equally. The most accurate diagostic test is the sweat test. There is ussually a 3-to-5 fold increase in the concentration of chloride in the sweat of patients with cycstic fibrosis. The magnitude of the disease can be reduced by treating pulmonary infection and pancreatic insufficiency. Death in cycstic fibrosis patients is usually due to profound pulmonary infection and respiratory failure.

Defined as staining and subsequent damage of the brain by bile pigment (bilirubin). It is normally occur in severe cases of hemolytic disease of new born. Immature brain cells are affected which result in to uncoordinated movements, deafness, disturbed vision and speech difficulty.

Defined as a cell that undergoes meiosis to form an ovum. Primary oocyte is normally formed in the early stages of meiosis. Only a fraction of the primary oocyte survive untill puberty. At ovulation, the first meiotic division is completed and a secondary oocyte and first polar body are formed. Fertillization stimulates the completion of the second meiotic division, which produces an ovum and secdonary polar body.

a process by which mature spermatozoa are produced in the testis. The whole process takes place within 70-80 days. In the beginning of the cycle, spermatogenium produce primary and secondary spermatocytes after completion of meiotic division. The secondary spermatocyte will produce spermatid or haploid, which are then transformed into mature spermatozoa through the process of spermatogenesis. Epididymis is the place for the spermatozoa becoming mature and capable of fertilization. It is a highly convolated tube about 7 meters long which connects the testis to the vas deferens. The spermatozoa are moved positively along the tube over a periods of 70-80 days. Acrosome is the caplike structure on the front end of a sperm. It breaks down just before fertilization. It releases a number of enzymes that assist penetration between the follcle cells that still surround the ovum. The failure of acrosome reaction is a cause of male infertility. Severe Combined Immunodeficiency: adenosine deaminase is an enzyme involved in purine metabolism. The deficiency of this enzyme results in the absence of antibodyproducing lymphocytes. A baby has no resistance to infection. (bubble boy). defined as a condition in which there is an abnormally low concentration of carbon dioxide. TT4, TT3, RT3U, TSH and FTI Serum TSH assay is a more useful test to find out hypothyroidism, since little decreases in thyroxine hormone in blood stimulate the hypothalamus of pituitary axis to release more TSH. It is recommended to screen for thyroid disease (free T4 test is also recommended). Serum TT4 test provides an idea about concentration of free and bound thyroxine in blood. It is not a reliable test since change in thyroid globulin concentration leads to unreliable results of total thyroxine in blood. Serum TT3 test measures free as well as bond T3. Serum concentration of T3 and TT3 elebated during hyperthyroidism. RT3U test is generally used to differentiate that the rise of the serum T4 level is because of thyroid gland abnormality or because of the abnormality in the thyroid binding protein. Free thyroxine index (FTI) test is generally helpful to find out serum concentration of T4 by putting valuses of RT3 and TT4 in the following equation: FTI = TT4 x RT3U / mean serum RT3U; TT4 = serum total thyroxine; RT3U = serum resin triiodothyronine uptake; Common test to monitor patients receiving replacement therapy for hypothyroidism include: TSH, FTI, RT3U, TT4.

defined as a temporary disturbance in blood clotting caused by vitamin K deficiency in infants, on the second to fourth day of life. The severity varies from mild G.I. bleeding to profuse bleeding into many organs, including the brain. The condition can be prevented by giving all babies Vitamin K, either by injection or orally, shortly after birth.

protein-energy malnutrition (PEM) include Marasmus, kwashiorkor or mixed form, and cachexia

a form of severe protein-energy malnutrition characterized by energy deficiency. Marasmus occurrence increases prior to age 1, whereas kwashiorkor occurrence increases after 18 months.

Kwashiorkor is a type of malnutrition with controversial causes, but it is commonly believed to be caused by insufficient protein intake. It usually affects children aged 14 years, although it also occurs in older children and adults. Symptoms of kwashiorkor include a swollen abdomen known as a pot belly, (see above picture) as well as alternating bands of pale and dark hair (flag sign) and weight loss. Common skin symptoms include dermatitis and depigmented skin.

Cachexia ( /k 5kksi/) is loss of weight, muscle atrophy, fatigue, weakness and significant loss of appetite in someone who is not actively trying to lose weight. It can be a sign of various underlying disorders: the possibility of cancer, metabolic acidosis (from decreased protein synthesis and increased protein catabolism), certain infectious diseases (e.g. tuberculosis, AIDS), and some autoimmune disorders, or addiction to drugs such as amphetamines or cocaine. Cachexia physically weakens patients to a state of immobility stemming from loss of appetite, asthenia, and anemia, and response to standard treatment is usually poor.

[5testikEnd] , non-descent of the testicle, the viable sperm will not be produced in this situation.

Hemochromatosis or iron storage disease, is a hereditary disorder in which there is an excessive absorption and storage of iron. This leads to damage and function impairment of many organs, including the liver, pancreas and endocrine gland. The main clinical symptoms include liver failure, bronze color of the skin and diabetes. The iron chelating agent should be administered. a small group of endocrine cells. Alpha---glucagon; beta---insulin; delta---somatostatin;

Lactic acid is the end product of glucose metabolism in glycilysis absent of oxygen. During strenuous exercise, pyruvic acid is reduced to lactic acid which may accumulate in the muscles and cause cramps. Lactic acid is formed by fermentation of mild. It is an important food preservative and flavor agent for cheese, yogurt and other milk products.

is used to measure the fetal lung maturity. An LS ratio below 2 indicates a higher risk of RDs and can be prevented by administration of cortisone.

due to an underactive thyroid gland. It is classified as hypothyroidism that is reported due to a low secretion of throid hormone. A dry firm waxy swelling of the skin and subcutaneous tissues is found in patients with an underactive thyroid gland. The symptoms may include: Coarsening of the skin, intolerace to cold, weight gain, mental dullness;

Trigeminal neuralgia is a severe burning or stabbing pain often following the course of the Trigeminal nerve. The nerve is present in the face. Carbamazepine is a drug of choice for treatment of pain.

The treatment to remove warts and other lesions in which the epidermis produces excess skin. In this therapy, acid medicine, such as salicylic acid is put on the lesion. Keratolytic therapy thins the skin on and around the lesion. It causes the outer layer of the skin to loosen and shed. Keratolytics can also be used to soften keratin, a major component of the skin. This serves to improve the skin's moisture binding capacity, which is beneficial in the treatment of dry skin. Such agents (keratolytics) include urea, lactic acid, and allantoin. While cytostatic agents such as zinc pyrithione, found in shampoos such as Head and Shoulders are first line, keratolytics (salicylic acid and sulfur) can also be used in the treatment of dandruff and seborrheic dermatitis. Sulfur and salicylic acid can also be used to treat acne and cradle cap, though sulfur products can actually worsen acne in some cases. Resorcinol is another keratolytic that is usually combined with sulfur.

Lactulose and sodium benzoate, and phenylacetate are indicated for the treatment of hyperammonia

Hyperammonemia (or 'hyperammonaemia') is a metabolic disturbance characterised by an excess of ammonia in the blood. It is a dangerous condition that may lead to encephalopathy and death. It may be primary or secondary. Ammonia is a substance that contains nitrogen. It is a product of the catabolism of protein. It is converted to the less toxic substance urea prior to excretion in urine by the kidneys. The metabolic pathways that synthesise urea are located first in the mitochondria and then into the cytosol. The process is known as the urea cycle, which comprises several enzymes acting in sequence. Treatment centers on limiting intake of ammonia and increasing its excretion. Dietary protein (a source of ammonium) is restricted and caloric intake is provided by glucose and fat. Intravenous sodium phenylacetate and sodium benbenzoate are pharmacologic agents commonly used to treat hyperammonemia.

Primary hyperammonemia is caused by several inborn errors of metabolism that are characterised by reduced activity of any of the enzymes in the urea cycle. Secondary hyperammonemia is caused by inborn errors of intermediary metabolism characterised by reduced activity in enzymes that are not part of the urea cycle (e.g .Propionic acidemia, Methylmalonic acidemia) or dysfunction of cells that make major contributions to metabolism (eg hepatic failure).

Addisons disease, Grave's disease, Glomerulonephritis, Hashimoto's thyroiditis, Hemolytic anemia, Junevile diabetes, Myasthenia gravies, Rheumatic fever, Ulcerative colitis;

Goodpasture's syndrome, rheumatoid arthritis, SLE, Sjogren's syndrome, scleroderma and polymyositis

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PRE-CLINICAL STUDIES

Drug Submissions

New Drug Submission

Abbreviated NDS

Supplemental NDS

Drug Identification Number

Classes of Medical Devices

CADTH

Common Drug Review

Adverse Reaction Reporting

deposition

Osmotic Release Oral Systems OROS

Vanishing Creams

Common ointment bases

Ophthalmic Formulaitons

Pharmaceutical equivalence

Therapeutic equivalence

Therapeutic Equivalents

Generic drugs

Bioequivalents

Bioequivalence

Pharmaceutical Alternatives

Onset time

Intensity

Therapeutic window

AUC

Formulary

Plasma Expander

Spans and tweens

Humectant

lyophilic [7laiE5filik] lyophobic [7laiE5fCbik]

Solvate / hydrate

colloid dispersion

Salting out effect

shear stress

shear dependent viscosity

Time- dependent viscosity

thixotropic [7WiksE5trCpik]

time-independent behavior of fluids

flocculation

Stoke's Law

coalescence

Emusion stability
formation of interfacial film lowering of interfacial tension Presence of Charge on the ions

Creaming

Cracking

Natural emulcifying agents

eutectic point

Colligative properties

Osmosis

Heterogeneous system Disperse system

Carbomer

Emulsion

Ointments

Powders

Capsules

Hard gelation

Soft gelation

Levigation

trituration

Pulverization by intervention

Maceration

impalpable

polymorphs

Lyophilization

Sublimation

Benzalkonium chloride

surfactants

sodium-free salt

Tablets excipients

Diluents

Binders and adhesives

Disintegrants

Lubricants, antiadherents and glidants

Tablet processing problems Sticking Mottling Capping Picking granulation

excipient An inert substance used as a diluent or vehicle for a drug

Enteric-coated tablets

Film-coated tablets

Tablets used in the oral cavity

Friability

Controlled-release dosage forms

LaPlace's Law

Raoult's law

Henry's law

Fick's law diffusion

Noyes-Whitney equation

dissolution

Stokes's law

leaching

Sterile Products needles and syringes

gauge numbers.

via 25G 5/8" needle

Winged needles

eccentric tips syringe

(A) bevel (B) cannula (C) hub (D) heel of bevel (E) lumen

French system

Drug delivery systems

drug transport

Active transport:

Paracellular transport

Vesicular transport

Transport proteins

Rate-limiting step in bioavailability

Limulus test

Gastric empty

First pass effect

biological half-life

loading dose: DL

Maintenance dose

Steady state plasma levels

IV infusion plateau protion

Infusion rate

nonlinear pharmacokinetics

Creatinine clearance rate (eCcr)

Cockcroft-Gault formula

Estimated GFR for Children using Schwartz formula

Active tubular secretion

Adsorption Absorption

isotope isotone isobaro

Ion Channel

By gating Voltage-gated

sodium channels:

calcium channels:

potassium channels (KV):

proton channels:

Ligand-gated

Effect of loding dose: 4-5 half-life to reach steady state

IV not related to Absorption, the answer is A

Cl = GFR x F

Loading dose: Vd= 42 L total body water normally for 70 kg adults

Electrolytes, serum Sodium (Na+) Chloride (1-) Bicarbonate (HC0 3 -) Potassium (K+) Magnesium (Mg2+)

Pycnometer

Hydrometer

TLC

Gas chromatography

Western blotting assay

Lecithin

Ferrous: Fe2+ Ferric: Fe3+

Solubility Stated in terms of the parts of solvent needed to dissolve one part of the solute (US): Very soluble Freely soluble Soluble Sparingly soluble Slightly soluble Very slightly soluble Insoluble

Benzalkonium chloride

minibottIes

Intermittent therapy piggyback

subcutaneous injection isotonicity

Intradermal injections

Serum albumin

Active / Passive immunization

Wyeth-Ayerst Norplant system

surfactants

Chlorobutanol

oral / rectal thermometer

Pamabrom

improve the absorption of a drug into the skin

Carbomers

crenation

isotonic

Fluorescein sodium

radioisotope generator

Sustained-release dosage forms

Sterilization

The degree of freedom of a system Blending Naturally Chelates

Bias Precision Accuracy alpha error beta error

Statistical tests

ANOVA t-test

KCl Chromatography

parenteral depot preparation

Gold number

Molar refraction

Depot preparation

page 50-98

As a first step in drug development, pre-clinical studies are carried out to evaluate the safety of a drug and its potential use. These studies are carrie in vitro (test tube testing) and in vivo (using animals) to assess the performance of the drug, including assessment of the existence and extent of toxic effects. The pre-clinical studies provide important information on the potential use of the drug prior to testing on humans in clinical trials. If the pre-clin studies are promising, the sponsor must apply to the HPFB for authorization to conduct a clinical trial involving human subjects in Canada.

If the results of the clinical trial studies indicate that a new drug has potential therapeutic value that outweighs the risks (e.g., adverse effects or toxici associated with its proposed use, the manufacturer may seek authorization to sell the product in Canada by filing a New Drug Submission with HPF (Health Products and Food Branch). (The clinical trials need not have been conducted in Canada.)

A New Drug Submission (NDS), which typically involves between 100 and 800 binders of data, contains scientific information about the product's safe efficacy and quality. It includes the results of both the pre-clinical and clinical studies, details on the production of the drug and its packaging and labe and information about its claimed therapeutic value, conditions for use and side effects. New drugs are commonly referred to as brand-name product because they have been created by companies and patented rather than reproduced by competitors.

An Abbreviated NDS (ANDS) is used for a generic product. The submission must meet the same quality standards as an NDS and the generic produ be shown to be as safe and efficacious as the brand-name product. An ANDS, which typically involves between10 and 20 binders of data, includes s information that shows how the generic product performs compared with the brand-name product, as well as providing details on the production of th generic drug, its packaging and labelling. The generic drug must be shown to deliver the same amount of medicinal ingredient at the same rate as the brand-name product. This comparison is usually done through comparative bioavailability studies.

A Supplemental NDS (SNDS) must be filed by the manufacturer if certain changes are made to already-authorized products. Such changes might inc the dosage form or strength of the drug product, the formulation, method of manufacture, labelling or recommended route of administration. An SNDS also be submitted to HPFB if the manufacturer wants to expand the indications (claims or conditions of use) for the drug product.

A Drug Identification Number (DIN) application must be filed for those products that do not meet the definition of a 'new drug'. In such circumstances substance for use as a drug has been sold in Canada for a sufficient time and quantity to establish the safety and effectiveness of that substance for a drug. DIN application requirements are outlined in regulations, and the information requirements are further clarified in policies and guidelines that a posted on Health Canada's Web site.

Risk Class I Lowest risk Class II Low risk Class III Moderate risk Class IV High risk

Examples Reusable surgical scalpel, Band-Aids, culture media Contact lenses, epidural catheters, pregnancy test kits, surgical gloves Orthopedic implants, glucose monitors, dental implants, haemodialysis systems, HIV test kits, pacemakers, angioplasty catheters

Manufacturers of Class II, III and IV devices must obtain a medical device licence before their products can be legally sold in Canada.

Canadian Agency for Drugs and Technologies in Health (CADTH); Since 1989, CADTH has provided Canadian health care decision makers with unb reliable information about health technologies, focusing on evaluations of clinical effectiveness and cost-effectiveness. As Canada's health technolog agency, the goal of CADTH is to increase access to and use of evidence as a basis for informed decisions about technology use in Canada's publicly funded health care system.

The Common Drug Review (CDR) began in the fall of 2003. CDR involves a single process to assess new drugs for potential coverage by participatin federal, provincial and territorial drug benefit plans. CADTH develops evidence-based clinical and pharmacoeconomic reviews to assess a drug's cos effectivness. These reviews are used by the Canadian Expert Drug Advisory Committee (CEDAC), an independent advisory body of professionals in therapy and evaluation, as the basis for its recommendations on what drugs to include in the formularies of the participating drug plans. Federal, prov and territorial governments (with the exception of Quebec) examine the CDR recommendations but retain the final say over which drugs to include in respective formularies. In 2004, CADTH expanded once again by adding the Canadian Optimal Medication and Prescribing Utilization Service (COMPUS).

An Adverse Reaction Report contains information about the affected patient, the suspected association between the therapeutic product and the adv reaction, and the treatment and final outcomes of the product use. The identities of both the patient and the person reporting are kept confidential by

Patients, health professionals, manufacturers and health product regulatory authorities work together to monitor adverse reactions and medical devic incidents. The most common source of information about adverse reactions is voluntary reporting by health professionals and consumers; but madan manufacturers;

one process of sublimation in which the compound transfers from the vapor state directly to the solid state

An O/W emulsion base; easy to be washed off by water---vanishing. Moisture is necessary to preserve the skin from the ups and downs of the weather. Vanishing Cream keeps the skin moist. It is beneficial for oily and skin. Vanishing Cream contains stearic acid, potassium hydro-oxide, glycerine, di-glycol stearate and water. If used before makeup, Vanishing Cream a glow to the face. Some known brands are: lakme, max-factor, ponds, charmis. Hydrocarbon bases: white petrolatum, white ointment; Absorption bases: hydrophilic petrolatum, cold cream; Water-removable bases: hydrophilic ointment; Water-soluble bases: polyethylene glycol ointment;

_Vehicles: increase viscosity and then enhance contact time of the product ( carboxymethylcellulose (CMC), povidone, polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC)) - Preservatives: antimicrobial activity (benzalkonium chloride (BAK), chlorhexidine, methylparaben, propylparaben, ethylenediaminetetraacetic acid (E and sobic acid. - Antioxidants: prevent product deterioration (edetic acid, sodium bisulfite, sodium metabisulfite, sodium thiosulfate, and thiourea) - Wetting agents: reduce surface tension of the lens (polysorbate 20, polysorbate 80, poloxamer 282, and tyloxapol) - Buffers: maintain pH 6-8 (acetic acid, boric acid, hydrochloric acid, phosphoric acid, potassium bicarbonate, potassium borate, potassium citrate, Na NaHCO3, Na2HPO4, Na borate, Na2CO3, sodium citrate, NaOH, Na3PO4). - Tonicity adjusters: ensure an isotonic agent, equal 0.9 % - 60.2 % NaCl ( dextrose, glycerin, KCl, propylene glycol, NaCl)

Drugs contain the same therapeutically active ingredient(s), are of the same dosage form, route of administration and are identical in strength concentration (e.g., chlordiazepoxide hydrochloride, 5mg capsules). Pharmaceutically equivalent drug products are formulated to contain the same a of active ingredient in the same dosage form and to meet the same or compendial or other applicable standards (i.e., strength, quality, purity, and ide but they may differ in characteristics such as shape, scoring configuration, release mechanisms, packaging, excipients (including colors, flavors, preservatives), expiration time, and, within certain limits, labeling.

Therapeutic equivalence means that a chemical equivalent of a drug product (i.e., containing the same amount of the same drug in the same dosage when administered to the same individuals in the same dosage regimen will provide essentially the same efficacy and toxicity. http://www.hc-sc.gc.ca/dhp-mps/prodpharma/applic-demande/guide-ld/bio/bio-a-eng.php

Drug products are considered to be therapeutic equivalents only if they are pharmaceutical equivalents ???? and if they can be expected to have the clinical effect and safety profile when administered to patients under the conditions specified in the labeling. Generic drug must be a therapeutic equivalent to the reference drug product but may differ in certain characteristics (shape, scoring configuration, packaging, and excipients---colors, flavors, preservatives, expiration date, and minor aspects of labeling.

generic drugs are identical or bioequivalent to the brand name counterpart with respect to pharmacokinetic and pharmacodynamic properties. By exte therefore, generics are identical in dose, strength, route of administration, safety, efficacy, and intended use; The FDA requires the bioequivalence of the generic product to be between 80% and 125% of that of the innovator product. Bioequivalence, however not mean that generic drugs must be exactly the same (pharmaceutical equivalent) as their innovator product counterparts, as chemical differences exist (different salt or ester a pharmaceutical alternative).

a generic drug is considered bioequivalent to the reference listed drug (RLD) product if both are pharmacuutical equivalents and the generic drug pro rate and extent of systemic drug absorption (bioavailability) do not show a statistically significant difference when administered in the same molar dos the active ingredient, in the same chemical form, in a similar dosage form, by the same route of administration, and under the same experimental con The RLD is generally the brand products.

Bioequivalence implies that the drug product can be expected to have the same systemic effects (both therapeutic and adverse) as the reference pro when administered to patients under the conditions specified in the labelling.

Bioequivalence is usually established by measuring the drug, or its metabolites, or both, in plasma (or blood, or serum). In some situations, determina the urinary excretion of the drug, or its metabolites, or both, may be employed to measure bioavailability and establish bioequivalence. In the absence adequate methodology for bioavailability testing, alternate approaches such as pharmacodynamic studies can be used. In some instances, therapeut equivalence should be determined by clinical trials.

BIOAVAILABILITY - The rate and extent of absorption of a drug into the systemic circulation.

BIOEQUIVALENCE - A high degree of similarity in the bioavailabilities of two pharmaceutical products (of the same galenic form) from the same mola dose, that are unlikely to produce clinically relevant differences in therapeutic effects, or adverse effects, or both.

Bioequivalent means that test and reference products containing an identical drug or drugs, after comparison in an appropriate bioavailability study, w found to meet the standards for rate and extent of absorption specified in these guidances.

Drugs contain the same therapeutic moiety, but are different salts, esters, or complexes of that moiety, or are different dosage forms or strengths (e.g tetracycline hydrochloride, 250mg capsules vs. tetracycline phosphate complex, 250mg capsules; quinidine sulfate, 200mg tablets vs. quinidine sulfa 200mg capsules).

Data are generally not available for FDA to make the determination of tablet to capsule bioequivalence. Different dosage forms and strengths within product line by a single manufacturer are thus pharmaceutical alternatives, as are extended-release products when compared with immediate-releas standard-release formulations of the same active ingredient.

The time from drug adm. to the minimum effective concentration (MEC)

the intensity of pharmacological effect is proportional to the number of receptors occupied by the drug up to a maximum pharmacological effect. Maxi pharmacological effect may occur before, after, or at peak drug absorption.

The drug concentration range between the minimum effective concentration (MEC) and the MTC (minimum toxic concentration)

area under the plasma drug concentration versus time curve relates to the amount or extent of drug absorption. The amount of systemic drug absorp directly related to the AUC. The AUC is calculated by the trapezoidal rule.

A formulary is a list of drugs which can be substituted by each other in a positive lists, or should not be substitute for each other in a negtive lists. A restrictive formulary lists only those drugs that may be reimbursed without justification by prescriber.

Dextrans

surface active substances derived from sorbitol; polyoxyakalene derivatives; Emulsions made with tweens are usually O/W; with spans are W/O.

 A humectant is a hygroscopic substance. It is often a molecule with several hydrophilic groups, most often hydroxyl groups, but amines and carboxyl groups, sometimes esterified, can be encountered as well; the affinity to form hydrogen bonds with molecules of water is crucial here. Since hygroscopic substances absorb water from the air, they are frequently used in desiccation. Examples of humectants include glycerine, propylene glycol (E 1520) and glyceryl triacetate (E1518). Others can be polyols like sorbitol (E420), xylito maltitol (E965), or polymeric polyols like polydextrose (E1200) or natural extracts like quillaia (E999), or lactic acid or urea. Lithium chloride is an exce humectant but is toxic.

Characterized by strong attraction between the colloid medium and the dispersion medium of a colloidal system. Characterized by a lack of attraction between the colloid medium and the dispersion medium of a colloidal system.

The incorporation of solvent molecules into the crystal lattice of a solid results in a molecular adduct, it is called solvate; If the solvent is water, it is ca hydrate. Normally, solvates or hydrate exhibit different solubilities and dissolution rates than their unsolvated or anhydrous counterparts.

blood, cell membrane, milk, fog, beer foam

the solubility of a nonelectrolyte is decreased----salting out effect. If it is increased, it is salting in effect. The smller the ionic size, the higher abbility to water and then more potent to reduce the solubilty of nonelcetrolyte. So LiCl > NaCl in salting out effect.

Shear stress in fluids A viscous, Newtonian fluid (including air and water) moving along a solid boundary will incur a shear stress on that boundary. The no-slip condition d that the speed of the fluid at the boundary (relative to the boundary) is 0, but at some height from the boundary the flow speed must equal that of the The region between these two points is aptly named the boundary layer. The shear stress is imparted onto the boundary as a result of this loss of vel

Shear-thickening or dilatancy --increase in apparent viscosity with increasing rate of shear; shear-thinning, or pseudo-plasticity---decrease in viscosity with increasing rate of shear;

the yield value of plastic systems may be time dependent (i.e., may depend on the time scale involved in the application of force). Thxotropic system shear-thining behavior but do not immediatel recover their higher apparent viscosity when the rate of shear is lowered. Thixotropy occurs with heterogeneous systems that involve a three-dimensional structure or network. Under shear, the structure appars more fluidity rest status in which it has a relatively rigid consistency. (gel-sol transformation) Rheopexy (negative thixotropy) occurs when the apparent viscosity of the system continues to increase with continued application of shear up to som equilibrium value at a given shear rate. ( sol-gel transformation)

The distinction between a thixotropic fluid and a shear thinning fluid: A thixotropic fluid displays a decrease in viscosity over time at a constant shear rate. A shear thinning fluid displays decreasing viscosity with increasing shear rate.

These terms refer to the response of a fluid's viscosity to a shearing stress, that is, a force tending to make part of the fluid slide past another part. Th time-independent behavior of fluids falls into 3 general classes:

Shear stress (resistance to flow) is proportional to shear rate (speed of motion of the fluid with respect to nearby fluid elements (in lay terms it means fast am I stirring the stuff) -- this is Newtonian flow. The fluid viscosity is a constant with change in the shear rate. Shear stress decreases with shear rate. The viscosity of the fluid decreases with increasing shear rate. This type of behavior is also referred to as pseudoplastic. (shear-thinning)

Shear stress increases with shear rate. Viscosity increases with increasing shear rate. These types of fluids are referred to as "shear thickening" and "dilatant".

Low molecular weight liquids, like water etc. are usually Newtonian. Water borne latex paints are shear thinning, and wet concrete is an example of a dilatant fluid. Silly Putty is a shear-thickening fluid; ketchup is shear-thinning.

In contrast, but often confused with the above are fluids that become less viscous as a function of TIME. These types of fluids are called thixotropic, although this term is often confused with shear thinning. Fluids that become more viscous as a function of time are called "rheopectic" although again term is often applied when the term dilatant is meant. ) The source of the confusion is that in real uncontrolled situations it is often difficult to separate the time-dependent and time-independent behavior of

Flocculation is a process where a solute comes out of solution in the form of floc or flakes. The action differs from precipitation in that the solute comi of solution does so at a concentration generally below its solubility limit in the liquid.

In colloid chemistry, flocculation refers to the process by which fine particulates are caused to clump together into floc. The floc may then float to the t the liquid, settle to the bottom of the liquid, or can be readily filtered from the liquid.

For emulsions, flocculation describes clustering of individual dispersed droplets together, whereby the individual droplets do not lose their identity. Flocculation is thus the initial step leading to further aging of the emulsion (droplet coalescence and the ultimate separation of the phases). It depend the electrokinetic, or zeta, potential ( ). when is high, the interparticulate repulsive forces exceed the attractive forces, and the dispersion is deflocculated and relatively stable to collision and subsequent aggregation (flocculation). When is low enough, the flocculation occurs.

The properties of flocculated suspension are: Particles form loose aggregates; the rate of sediment is high; A sediment forms very rapidly; A sediment can easily redisperse; Particles do not bond tightly to each other; Particles settle as a floc.

For a dispersion, the particles are not uniformaly sized (not monodisperse). The particles are subject to particulate aggregation, or clumping, and the dispersion becomes more heterogeneous with time.

Stoke's law describes the relationship between the sdimentation rate (separating or creaming of the dispersed phase) and the particle size, dispersi phase viscosy, and difference in density between the dispersed phase and the dispersion medium.

Small partical size, lower particulate concentration, lower density of the dispersion medium, higher viscosity, will slow the rate of settling, but it cann halted.

coalescence occurs in emulsion system when the liquid particle of the dispersed phase merge to form larger particles. It is largely prevented by the interfacial film of surfactant around the droplets.

coalescence occurs when the liquid particles of the dispersed phase merge to form larger particles. It is largely prevented by the interfacial film of sur around the droplets. Emulsifying agent can be used to prevent coalescence and maintains the integrity of the individual droplets. Electrostatic repulsion is also stablize the oil in water(O/W) emulsion. Creaming is the reversible seperation of a layer of emulsified particles. But cracking, or irreversible phase separation is never acceptable.

the reversible separation of a layer of emulsified particles. Mixing or shaking may be sufficient to reconstitute the emulsion system. It is acceptable.

or irreversible phase separation, involves the reversion of an emulsion from an O/W to a water in oil (W/O) form, or vice versa. It is a emulsion-type re It is not acceptable.

Acacia, gelatin, lecitin, cholesterol are naturally availabe emulsifying agents that can help in stablization of emulsion.

eutectic. The melting point of a mixture of two or more solids (such as an alloy) depends on the relative proportions of its ingredients. A eutectic or eu mixture is a mixture at such proportions that the melting point is as low as possible, and that furthermore all the constituents crystallize simultaneousl this temperature from molten liquid solution.

the property of a solution depend on the total number of ionic and nonionic solute molecules in the solution; These properites depend on ionization bu independent of other chemical properties of the solute. Lowering the vapor pressure, depression of the freezing point, elevation of the boiling point, osmotic pressure.

Osmosis is the diffusion of a solvent (frequently water) through a semi-permeable membrane, from a solution of low solute concentration (high water potential) to a solution with high solute concentration (low water potential), up a solute concentration gradient. The osmotic pressure is defined to be the pressure required to maintain an equilibrium, with no net movement of solvent. Osmotic pressure depends molar concentration of the solute but not on its identity.

Suspention: 2 phase system, solid and oily or solid and aq., the particle size is usually >0.5 m;

Emulsion: a system that consists of at least one immiscible liquid that is intimately dispersed in another in the form of droplets. The droplet diameter u exceeds 0.1 m; Stokes's law: describes the rate of settling (separating, or creaming) of the dispersed phase in the dispersion medium

Carbomer is a generic name for synthetic polymers of acrylic acid used as emulsion stabilizers or thickening agents in pharmaceuticals and cosmeti products. They may be homopolymers of acrylic acid, crosslinked with an allyl ether pentaerythritol, allyl ether of sucrose, or allyl ether of propylene. used in the formation of a topical gel.

O/W: water is the External phase, HLB 8-18 W/O: water is the internal phase, HLB 4-6; Wetting agents: HLB 7-9 Detergents: HLB 13-15 Solubilizing agents: HLB 10-18 Natural emulsifying agents: Acacia, Tragacanth, Agar, Pectin, Geltin, Methyl cellulose, Carboxymethylcellulose; Anionic synthetic agents: sulfuric acid esters(Sodium lauryl sulfate); Sulfonic acid derivatives (Dioctyl sodium sulfosuccinate), Soaps (Alkali ~/Monovalent ~: O/W; Metallic ~ / Polyvalent ~: W/O) Cationic synthetic agents: benzalkonium chloride, used as surface-active agents in 1% concentration; incompatible with soaps; Noninoic synthetic agents: Sorbitan esters known as Spans (HLB 1-9); Polysobates known as Tweens (HLB 11-20)

Oleaginous bases: Petrolatum, Synthetic esters (glyceryl monostearate, isopropyl myristate, isopropyl palmitate, butyl stearate, butyl palmitate, longalcohols(cetyl alcohol, stearyl alcohol, PEG)), Lanolin derivatives (Lanolin oil, hydrogenated lanolin); Absorption bases: anhyrous and water insoluble ( wool fat, Hydrophilic petrolatum); Emulsion bases: May be W/O emulsions ( Lanolin, Cold cream), May be O/W emulsions (Hydrophilic ointment, Vanishing cream)

Water-soluble bases: PEG ointment, Propylene glycol and propylene glycol-ethanol form a clear gel when mixed with 2% hydroxypropyl cellulose. Th popular dermatologic vehicle.

Levigation/ Fusion method for incorporation of medicinal agents. In fusion method, start with the highest MP material, the others are added in decrea order of MP.

Trituration is used both to comminute and to mix powders; Geometric dilution is used for mixing with large amount of diluent.

Powder paper: Vegetable parchmet / Glassine / Waxed paper (moisture-resistant paper); White bond (no moisture-resistant); Hygroscopic and vlatile are best protected with waxed paper that is double wrapped and covered with a bond paper.

The hard shells made from a mixture of gelatin, colorants, opacifying agent (e.g., titanium dioxide); Sizes: From largest to smallest (000 - 5) ----( 600 mg - 30 mg) Diluent, lubricant, wetting agent may be used;

May contain a nonaqueous solution, a powder, or a drug suspenstion; The vehicle may be water miscible (e.g. PEG). Glycerin or a polygydric alcohol (e.g., Sorbitol) is added to make them elastic or plastic-like; Preservatives (methyl and propyl parabens, sorbic acid) added to prevent the growth of fungi. is the process of reducing the particle size of solids by adding a small amount of a liquid or an ointment base to make a paste, which is then rubbed spatula on an ointment tile. Levigation---liquid or oil to make a paste first

The term usually refers to reducing the particle size of powders often in a mortar and pestle. However, trituration has also been used to describe the mixing of two or more powders in the mortar.

is a process for reducing particle size by using a second agent that can then be readily removed. For example, camphor is reduced by the interventio alcohol. Intervention---second agent

is an extraction process in which the ground drug is soaked in a solvent until the cellular structure is penetrated and the soluble constituents have bee dissolved.

Powders that are either directly applied to the skin or are incorporated into topical products should be extremely fine or impalpable. Trituration is often needed to reduce particles to an extremely fine size so that the patient will not discern individual particles when the product is rubbed on the skin. Us particle size of 50 microns or smaller is desired.

differ in their melting points, x-ray diffractions, infrared spectra, and dissolution rates. For example, riboflavin has three polymorphs, each with signific different solubilities. Theobroma oil (cocoa butter) can exist in four forms, each differing in melting points. Gentle heating of cocoa butter will favor the formation of the stable beta polymorph. This crystalline form is desired because it melts at 34.50 C, which is close to but lower than body temperature Metabolic rates of a drug's polymorphs will not vary because once the drug has dissolved, the polymorphs no longer exist.

freeze-drying, a form of vacuum drying in which water is removed by sublimation from the frozen product. It is an especially useful process for drying aqueous solutions or dispersions of heat- or oxygen-sensitive drugs and biologicals (e.g., proteins, peptides)

or deposition, a process that direct transition from the vapor state to the solid state.

Benzalkonium chloride is a cationic surface active agent. In the presence of anionic agents such as soaps, benzalkonium chloride and similar cationi agents are inactivated because the combination of large cations with large anions of soaps form inactive products.

Sorbitan monopalmitate is a sorbitan fatty acid ester, commercially available as Span 40. It is classified as nonionic because the molecules would no the tendency to migrate to either pole in an electric field.

Ammonium laurate, dioctyl sodium sulfosuccinate, and triethanolamine stearate are anionic surfactants. This designation implies that the large portion of the surfactant molecule would bear a negative charge and, therefore, would migrate to the anode in an electric field. For example, the stear portion of triethanolamine stearate is considered the active ion. Cetylpyridinium chloride is a cationic surfactant. The active surfactant portion, cetylpyridinium, has a positive charge and migrates to the cathode.

Potassium chloride is an obvious substitute for sodium chloride because it has a similar salty taste, is crystalline, and is an electrolyte already presen body. However, the use of these salt substitutes is contraindicated in patients with severe kidney disease or oliguria. Symptoms such as weakness, n and muscle cramps indicate excessive sodium depletion. Increased sodium intake is warranted.

Fillers fill out the size of a tablet or capsule, making it practical to produce and convenient for the consumer to use. A good filler must be inert, compatible with the other components of the formulation, non-hygroscopic, soluble, relatively cheap, compactible, and pre tasteless or pleasant tasting. Plant cellulose (pure plant filler) is a popular filler in tablets or hard gelatin capsules. Dibasic calcium phosphate is another popular tablet filler. A range of vegetable fats and oils can be used in soft gelatin capsules. Other examples of fillers include: lactose, sucrose, glucose, mannitol, sorbitol, calcium carbonate, and magnesium stearate.

added in either dry or liquid form to promote granulation or to promote cohesive compacts during direct compression; 10-20% aq. preparation of corn 25-50% solution of glucose, molasses, various natural gums (acacia), cellulose derivatives (methylcellulose, carboxymethylcellulose, microcrystalline cellulose), gelatins , povidone (a water-soluble polymer)

to facilitate disintegration when the tablet contacts water in the GI tract by drawing water into the tablet, swelling, and causing the tablet to burst. Including cornstarch and potato starch; sodium statch glycolate, cellulose derivatives, clays (VEEGUM, bentonite), and cation exchange resins

have overlapping function; Lubricants reduce the friciton that occurs between the walls of the tablet and the walls of the die cavity when the tablet is ejected. (Talc, waxes, PEG surfactants, agnesium stearate, and calcium stearate are commonly used;) Antiadherents reduce sticking or adhesion of the tablet granulation or powder to the faces of the punches or the die walls. Glidants promote the flow of the tablet granulation or powder by reducing friction among particle. (cormstarch, silica derivatives, Talc)

adhesion of tablet material to a die wall, caused by excessive moisture or the ingredients with low melting temp. uneven color distribution, caused by poor mixing of the tablet granulation or a degraded colored metabolite of the drug

separation of the top or bottom of a tablet from the main body. Excessive force of compression, use of insufficient binder, worn tablet tooling equipme entrpment of air during processing may be the reason.

adherence of tablet surface material to a punch. Caused by a granulation that is too damp, by a scratched punch , by static charges on the powder, a particulary by the use of a punch tip that is engraved or embossed. The act or process of granulating.

Which one of the following chemicals is NOT suitable as a drug excipient? (A) methyl paraben (B) starch (C) glycerin (D) benzocaine (E) lactose

(D) Pharmaceutical excipients are selected for specific characteristics that will improve the drug formulation. These include solvents (glycerin), ointme bases (petrolatum), tablet diluents (lactose), antioxidants (sodium bisulfite), and antimicrobial preservatives (the parabens). Because they must be re inert therapeutically, the local anesthetic benzocaine would not be suitable. bentonite( an excipient used in preparation of ASA granules.)

Although most drugs in pharmaceutical dosage forms are expected to decompose following first-order kinetics, an exception are drugs formulated (A) capsules (B) oral solutions (C) oral suspensions (D) tablets (E) suppositories

(C) Drugs in suspensions are likely to follow zero-order kinetics because the limiting factor is the amount of drug actually in solution. The classic exa aspirin suspension.

with a coating that ramains intact in the stomach, but dissolves in the intestines to yield the tablet ingredients there. Enteric coatings include various f fatty acids, waxes, shellacs,cellulose acetate phthalate(dissolves only when the pH > 6). Others: povidone, polyvinyl acetate phthalate, hydroxypropy methylcellulose phthalate. coated with a thin layer of a polymer ( water-soluble or insoluble) such as hydroxypropyl methylcellulose, ethylcellulose, povidone, PEG.

Buccal and sublingal tablets allow absorption through the oral mucosa; (sublingal nitroglycerin tablets, buccal progesterone tablets)

Effervescent tablets: prepared by compressing granular effervescent salts or other materials (citric acid, tartaric acid, NaHCO3) that release CO2 gas contacted with water.

Friability is used to evaluate the ability of a tablet to withstand abrasion in packaging, handling and shipping. For this type of test, a Roche fibrialor is normally used.

Coated beads or granules; Microencapsulation: coacervation is the most common method; Shellacs, waxes, gelatin, starches, cellulose acetate phthalate and ethylcellulose are as film-forming substances; Matrix tablets: use insoluble plastics (polyerhylene, polyvinyl aceate), hydrophilic polymers (methylcellulose), or fatty compounds (waxes, glyceryl tristearate); Osmotic systems: an oral osmotic pump composed of a core tablet and a semipermeable coating that have a small hole (0.4 mm) for drug exit. (ORO osmotic pressure release system) Ion-exchange resins; Complex formation: cyclodextrin form

a nonlinear partial differential equation that describes the capillary pressure difference sustained across the interface between two static fluids, such as water and air, due to the phenomenon of surface tension (r) and the diameters of the capillary (R)

the vapor pressure of an ideal solution is dependent on the vapor pressure of each chemical component and the mole fraction of the component pres the solution. Consequently, as the number of components in a solution increases, the individual vapor pressures decrease, since the mole fraction of each compo decreases with each additional component. If a pure solute which has zero vapor pressure (it will not evaporate) is dissolved in a solvent, the vapor pressure of the final solution will be lower than that of the pure solvent.

At a constant temperature, the amount of a given gas dissolved in a given type and volume of liquid is directly proportional to the partial pressure of th in equilibrium with that liquid.

Fick's first law relates the diffusive flux to the concentration field, by postulating that the flux goes from regions of high concentration to regions of low concentration, with a magnitude that is proportional to the concentration gradient (spatial derivative).

decribes the diffustion-controlled rate of drug dissolution.

describes the rate of settling (separating, or creaming) of the dispersed phase in the dispersion medium Related to the radius,density of the particle, the density and viscosity of the medium; Independent of the lipophilic nature of particles

The term "leaching" is used specifically to designate the release of a container ingredient into the product itself. For example, zinc and accelerators m leached from rubber closures into a parenteral vial.

Needle gauge: the outside diameter of the needle shaft, 13-27( largest to smallest). Subcutaneous 24/25 intramuscular 19-22 Bevels:

compounding parenteral 18-20

Hypodermic needle sizes are expressed by a gauge system based on the external diameter of the cannula: the larger the number,the smaller the diameter of the needle. For example, the 21-gauge needle is smaller in diameter than the 19-Gauge needle. Generally, the length of the cannula is a specified. This measurement, expressed in inches, represents the distance from the needle tip to the junction with the hub.

Insulin solutions have low viscosities, and only small volumes are injected. Therefore, small-bore needles (25G up to 30G) may be used. Short (3/8" to 5/8") needles are adequate for the usual subcutaneous route of insulin administration (24 or 25G). Intramuscular injections require 19 and 22-gauge; Needles between 18-20 gauge are commonly used for compounding parenterals. IV normally use (larger bore, capable of higher IV flow rates) or 18G (smaller bore, with slower flow rates, but easier to start).

"Winged" needles are most closely associated with which type of injections? intravenous The winged (scalp-vein, scalp, or butterfly) needle consists of a stainless steel needle with two flexible plastic winglike projections.

The wings serve two purposes: They ease manipulation of the needle during insertion into the vein and then allow the needle to be anchored with tap the skin.

used to minimize venous irritation

280. Extension of needle that fits onto the syringe 281. Portion of needle that is ground for sharpness 282. Shaft portion of the needle 283. The hole in the needle

280. (C) The needle hub can be made of plastic or metal. It is fitted onto the syringe body either by a locking system such as the Luer-Lok or by a sim friction fit. (13:325) 281. (A) The bevel is ground to sharpness, but the back portion (heel) of the bevel is left dull. A dull heel has been shown to decrease the incidence o coring of the rubber closure and the skin. (13:325) 282. (B) Needle cannulae are made of various grades of steel. Both shaft strength and flexibility are needed. (13:325) 283. (E) The hole in the shaft is also called the bore.

The French system is used for designating sizes of both urinary catheters and tubing used for enteral feedings. One French unit equals 1 mm outside circumference. Thus, a catheter with an outside circumference of 20 mm is identified as a 20F or 20Fr size.

a cell membrane is a semipermeable structure composed primarily of lipids and proteins. Passive diffusion, partitioning, carrier-mediated transport, paracellular transport, or vesicular transport. Usually proteins, drugs bond to proteins and macromolucules do not easily cross cell membranes; nonpolar lipid-soluble drugs more easily transport;

Against a concentration gradient; Requires energy; Maybe selective for certain types of drugs; The carrier system may be saturated at a high drug concentration; The process may be competitive;

drugs transport across tight junctions between cells or transendothelial channels; it involves both diffusion and the convective(bulk) flow of water and accompanying water-soluble drug molecules through the paracellular channels. the process of engulfing particles or dissolved materials by a cell. It is the only transport mechanism that does not require a drug to be in an aqueous solution to be absorbed. Pinocytosis and phagocytosis ; Endocytosis and exocytosis. embedded in the lipid bilayer of cell membranes in tandem which can facilitate the efflux of drug molecule from the cell. ATP-dependent pump. For most solid drug: the dissolution rate is the rate limiting step; For controlled- or sustained-release drug, the release of the drug from the delivery system is the rate limiting step

Horseshoe crabs are valuable as a species to the medical research community, and in medical testing. The above-mentioned clotting reaction is use Limulus Amebocyte Lysate (LAL) test to detect bacterial endotoxins in pharmaceuticals and to test for several bacterial diseases.[17] LAL is obtained the animals' blood. ----pyrogens

Gastric emptying appears to be an exponential process with a normal half-life of between 20 and 60 minutes. However, many factors can influence th of this process. It is slowed by the vigorous exercise, fatty foods, hot meals, and emotional stress and is speeded by hunger, mild exercise, cold mea dilute solutions, and lying on the right side.

Because some drugs and some dosage forms (eg, enteric-coated tablets) are absorbed at rather specific sites along the GI tract, alterations in the ra gastric emptying may lead to erratic and unpredictable absorption. For example, if an acid-labile drug that is preferentially absorbed from a portion of small intestine is consumed as an enteric-coated tablet, a greatly reduced gastric emptying rate may permit the tablet to dissolve in the stomach and degraded by the acid fluids of the stomach. Similarly, if the gastric emptying rate is greatly increased, the tablet may not dissolve before it reaches its primary site of absorption.

The first-pass effect (also known as first-pass metabolism or presystemic metabolism) is a phenomenon of drug metabolism whereby the concentra a drug is greatly reduced before it reaches the systemic circulation.

After a drug is swallowed, it is absorbed by the digestive system and enters the hepatic portal system, then into the liver before it reaches the rest of body. The liver metabolizes many drugs, sometimes to such an extent that only a small amount of active drug emerges from the liver to the rest of the circulatory system. This first pass through the liver thus greatly reduces the bioavailability of the drug. Alternative routes of administration like suppos inhalation, nasal, transdermal, intravenous, intramuscular, and sublingual avoid the first-pass effect because they allow drugs to be absorbed directly the systemic circulation.The four primary systems that affect the first pass effect of a drug are the enzymes of the gastrointestinal lumen, gut wall enz bacterial enzymes, and hepatic enzymes. e.g.: Propranolol, morphine, penicillin, nitroglycerin, insulin, estradiol, aspirin, mesalamine, lidocaine.....

The biological half-life of a drug is the time for one-half of the therapeutic activity to be lost. The presence of renal impairment slows the process of excretion and thereby increases the biological half-life of the drug in the blood. If the biological half-life of a drug increases in patients with impaired renal function, the time required to reach steady-state plasma levels will also be increased. This time factor is only dependent on the biological half-life of a given drug in a given individual.

DL = Css VD or R/k ( R: the zero-order rate of infusion; k: elimination rate constant)

When the clearance (Cl) of a drug is known, the maintenance dose required to sustain a desired average steady-state plasma concentration can be calculated by: Where Cp =average steady-state plasma concentration = dosing interval (tau) S = portion of salt that is active drug F = fraction of dose absorbed

If doses are adm. at each half-life of the drug, then maintenance dose is half of the loading dose;

For any drug that is eliminated by first order kinetics, the time required to achieve steady-state plasma levels is dependent only on the biological halfthat drug in a given individual. As a drug is repeatedly administered in constant dosage and at constant time intervals (that are short enough to preclu complete elimination of the drug), the elimination rate of the drug increases as the concentration of drug in plasma increases. The tendency of a drug accumulate on repeated dosing is, therefore, balanced by increased amounts of drug being eliminated. Eventually, a steady state will be reached in w the amount of drug absorbed will equal the amount of drug being eliminated. The time to reach steady state corresponds to about 4 to 5 half-lives and more completely described in the following table:

The time in which the optimum drug blood level is obtained is independent of the infusion rate. It is dependent only on the biological half-life of the particular drug. The time required to reach the plateau (steady state) is approximately four to five half-lives. At the blood concentration plateau, the Ke equals the infusion rate.

R ( infusion rate) = Css x CL

It is obvious that the higher the total clearance rate, the faster the infusion rate to maintain a specific steady-state concentration. Although renal clear predominates for many drugs, hepatic metabolism, or other elimination processes may be present. Nonlinear pharmacokinetics follows zero-order kinetics. It usually reflects the effect of enzymes or the presence of carrier-mediated systems. In these situations, the elimination half-life of the drug will increase when the dose is increased.

Male: 97-137 mL/min Female: 88-128 mL/min

For creatinine in mol/L: Where Constant is 1.23 for men and 1.04 for women.

This employs the serum creatinine (mg/dl), the child's height (cm) and a constant to estimate the glomerular filtration rate: Where k is a constant that depends on muscle mass, which itself varies with a child's age: In first year of life, for pre-term babies K=0.33 and For full-term infants K=0.45 For infants between ages of 1 and 12 years, K=0.55

Carrier-mediated active transport system that require energy; Two system: weak acids and weak bases; There may be competition effects in the same system: probenecid competes for penicillin (longer t 1/2 p-aminohippurate (PAH) used to measure effective renal blood flow (ERBF)

Adsorption is a process that occurs when a gas or liquid solute accumulates on the surface of a solid or a liquid (adsorbent), forming a film of molecul atoms (the adsorbate). It is different from absorption, in which a substance diffuses into a liquid or solid to form a solution. The term sorption encomp both processes, while desorption is the reverse process.

Adsorption is present in many natural physical, biological, and chemical systems, and is widely used in industrial applications such as activated charc synthetic resins, and water purification.

Adsorption, ion exchange, and chromatography are sorption processes in which certain adsorbates are selectively transferred from the fluid phase to surface of insoluble, rigid particles suspended in a vessel or packed in a column.

atoms with the same number of protons atoms with the same number of nuetrons atoms with the same number of mass

Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of all living cells (see potential) by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells. Ion channels regulate the flow of ions across the membrane in all cells. It is an integral membrane protein; or, more typically, an assembly of several prot Because "voltage-gated" channels underlie the nerve impulse and because "transmitter-gated" channels mediate conduction across the synapses, ch are especially prominent components of the nervous system.

Voltage-gated channels open and close in response to membrane potential.

This family contains at least 9 members and is largely responsible for action potential creation and propagation. Both and subunits are extensive glycosylated. sodium channel blocker:Tetrodotoxin (TTX); Saxitoxin (red tide);Conotoxin; Lidocaine and Novocaine

This family contains 10 members, though these members are known to coassemble with 2, , and subunits. These channels play an important ro both linking muscle excitation with contraction as well as neuronal excitation with transmitter release. contains almost 40 members, which are further divided into 12 subfamilies. These channels are known mainly for their role in repolarizing the cell membrane following action potentials. The subunits have six transmembrane segments, homologous to a single domain of the sodium channels. Correspondingly, they assemble as tetramers to produce a functioning channel. K channel blocker: Dendrotoxin; Iberiotoxin;Heteropodatoxin

Voltage-gated proton channels opening with depolarization, but in a strongly pH-sensitive manner. The result is that these channels open only when electrochemical gradient is outward, such that their opening will only allow protons to leave cells. Their function thus appears to be acid extrusion from Another important function occurs in phagocytes (e.g. eosinophils, neutrophils, macrophages) during the "respiratory burst."

Ligand-gated ion channels (LGICs) activate/inactivate depending on binding of ligands to the channel. They are also known as ionotropic receptors. This group of channels open in response to specific ligand molecules binding to the extracellular domai receptor protein. Ligand binding causes a conformational change in the structure of the channel protein that ultimately leads to the opening of the cha gate and subsequent ion flux across the plasma membrane. Examples of LGICs include the cation-permeable "nicotinic" Acetylcholine receptor, ionotropic glutamate-gated receptors and ATP-gated P2X receptors, and the anion-permeable -aminobutyric acid-gated GABA A receptor.

136-145 mEq/L 95-105 mEq/L 22-28 mEq/L 3.5-5.0 mEq/L 1,5-2,0 mEq/L

 also called pyknometer or specific gravity bottle, is a flask, usually made of glass, with a close-fitting ground glass stopper with a capillary tube through it, so that air bubbles may escape from the apparatus. This enables the density of a fluid to be measured accurately, by reference to an appr working fluid such as water or mercury, using an analytical balance.

, an instrument used to measure the specific gravity (or relative density) of liquids; that is, the ratio of the density of the liquid to the d of water.

mechanism of action of TLC is Capillary action; The solid phase is silicagel or allumina, a polar support stationary phase; Ninhydrin is used in TLC as spray reagent for detection of Amino acids, amino sugars and amines.

Mobile phase is inert gas such as Nitrogen or Helium, Argon, CO2, H2 even air, depends on the detector being used. Derivativation permit analysis of compounds with inadequate volatility or stability; improve chromatographic behavior or detectability; and silylation most used technique in derivativation.

Method that separates macromolucules in nucleic acids and proteins on the base of size and electric charge

any of a group of yellow-brownish fatty substances occurring in animal and plant tissues, and in egg yolk, composed of phosphoric acid, cho fatty acids, glycerol, glycolipids, triglycerides, and phospholipids (e.g., phosphatidylcholine, phosphatidylethanolamine, and phosphatidylinositol). How lecithin is sometimes used as a synonym for pure phosphatidylcholine, a phospholipid that is the major component of its phosphatide fraction.

, Ferrous is better!

Solubility of a substance may be expressed in several ways. When a quantitative statement of solubility is given in the USP, it is generally expressed of solvent required to dissolve 1 g of solute;

needed to dissolve one part of the solute (US):

<1 1-10 10-30 30 - 100 100 - 1000 1000 - 10,000 > 10,000

Benzalkonium chloride is a cationic surface active agent. In the presence of anionic agents such as soaps, benzalkonium chloride and similar catio agents are inactivated because the combination of large cations with large anions of soaps form inactive products.

Partially filled glass containers (minibottIes) usually consist of 250-mL bottles containing 50, 100, or 150 mL of either DsW or NS. To these bottles on easily add drug solutions, taking advantage of the vacuum present in the minibottle. Plastic bags are also employed for preparing parenteral admixtur The plastic units do not have a vacuum but are flexible enough to accommodate additionalliquids.

Intermittent therapy refers to administration of parenteral drugs at spaced intervals. One of the most convenient methods for administration is for the pharmacist to prepare a minibottle containing active drug solution such as an antibiotic added to a diluent. This unit is attached to the tubing of a largevolume parenteral (LVP) bottle already hanging on the patient. This "piggyback" concept saves the patient from multiple injections and assures h blood levels of the additive drug because the minibottle solution is infused in a short period of time.

A subcutaneous injection will come into contact with a large number of nerve endings and may remain at the injection site for a long period of time. P be experienced if the solution is not isotonic. The potential effects of hypotonic or hypertonic intravenous solutions are offset by their dilution in the lar volume of blood into which they are injected, provided the volume injected is not excessive and the rate of injection is slow. Even distribution of a drug into the blood after an IV bolus injection can be expected within 4 minutes. Factors affecting the distribution of a drug in the blood after an IV bolus include the blood volume, heart rate, and injection rate. Assuming that even distribution occurs within 4 minutes, drug sampling may be initiated after that time.

Intradermal injections are usually limited to diagnostic determinations, desensitization, or immunization into the forearm. Usually only 0.1 mL volume used.

Lactated Ringer's injection is considered to most closely approximate the extracellular fluid of the human body. (B) Except for the lactate concentration and the absence of sodium bicarbonate, lactated Ringer's (Hartmann's) solution closely approximates the extracellular fluid. Although the injection has a pH of 6 to 7.5, it has an alkalinizing effect because the lactate is metabolized to bicarbonate.

Heparin sodium is given by both IV bolus and infusion as well as by subcutaneous injection. The 1M route is not used since it may be painful and als cause a localized hematoma. (A) intradermal: , 0.1 ml; (B) intramuscular: vaccine (C) intravenous (D) subcutaneous: insulin Serum albumin is the protein in plasma that controls blood volume through its watercontaining capacity. Normal Human Serum Albumin USP, which in the treatment of shock or hemorrhage, is available in either a 6 or 25% sterile solution.

Passive immunizations are usually accomplished by the administration of purified and concentrated antibody solutions (antitoxins) derived from hum animals that have been actively immunized against a live antigen. Active immunizations are usually accomplished by the administration of one of the following: (1) toxoids, (2) inactivated (killed) vaccines, (3) live attenuated vaccines.

Chemicals that are not significantly adsorbed by activated charcoal include boric acid, cyanides, DDT, and ferrous sulfate.

Wyeth-Ayerst Norplant system consists of levonorgestrel in a silastic polymer. The rods are inserted under the skin of the upper arm and slowly rele drug for up to 5 years. It is considered a reversible contraceptive system. However, it is not classified as a targeted delivery system, which would imp delivery of drug only to a specific organ or area.

The inclusion of surfactants in topical preparations appears to enhance the penetration of active drugs through the skin. Contact lens solutions may c surfactants for the cleansing of the lenses before storage or insertion. Nont xic and nonirritating surfactants such as docusate (dioctyl sodium sulfosuccinate) are used as emollient laxatives because they soften stools.

Both ophthalmic and nasal preparations should have only mild buffer capacity so that the organ's natural buffer system can overcome any pH differe Otherwise, irritation might result. Nasal preparations usually have a pH in the range of 5.5 to 6.5. Often, phosphate buffers are used. Rendering the n solution isotonic will decrease potential for damage to the local tissue. The presence of an antimicrobial preservative is important because there may accidental contamination of the dropper or nasal spray tip.

Chlorobutanol is included in some ophthalmic and parenteral solutions as an antioxidant. The three chemicals (ascorbyl palmitate, butylated hydroxytoluene, and vitamin E are oil soluble, thus limiting their use to lipophilic systems. Ascorbic acid is a watersoluble antioxidant.

The rectal thermometer bulb has a strong, blunt shape that facilitates insertion into the rectum and retention by sphincter muscles. The oral bulb is cylindrical, elongated, and thin-walled for quick registration of temperature. Rectal thermometers can be used orally. The oral bulb is too easily broke is not suitable for rectal use. The short, sturdy, security bulb represents a compromise intermediate shape.

Pamabrom, a xanthine derivative is present in several OTC products for the prevention of premenstrual syndrome (PMS), specifically bloating. Its diu activity is obtained with a dose of 25 to 50 mg four times a day. Examples of products containing pamabrom include Midol PMS and Pamprin.

Which one of the following procedures has been recognized by the FDA for the removal of ear cerumen? (A) carbamide peroxide; The carbamide peroxide will effervesce, thereby softening the waxy material. An example of an OTC product is Debrox, which also contains glycerin and propylene glycol that acts as solvents.

Which one of the following procedures would NOT improve the absorption of a drug into the skin? (A) Applying the ointment and covering the area with an occlusive bandage or Saran wrap. (B) Incorporating an oil-soluble drug in polyethylene glycol ointment rather than white ointment. (C) Applying the medicated ointment on the back of the hand rather than on the palms. (D) Increasing the concentration of the active drug in the ointment bases. (E) Using an ointment base in which the active drug has excellent solubility.

Diffusion of a drug from a vehicle into the skin is often related to the solubility of the drug in the vehicle relative to the solubility in the skin, ie, the par coefficient. Drugs that are very soluble in a vehicle will tend to remain in the vehicle and will penetrate more slowly than drugs with poorer solubility in vehicle. Covering the area to which a topical drug product has been applied will often enhance the rate of drug absorption. Sweat accumulation at the vehicle interface induces hydration of the skin, a condition that facilitates penetration of drugs. Poorer solubility of the drug in PEG ointment than in w ointment may lead to faster diffusion. This is the converse of choice E. The thicker epidermis of the palms results in slower drug penetration than that which occurs on the backs of the hands. Higher drug concentrations will increase the rate of diffusion and penetration.

Carbomers may be included in a topical product as thickening agent. Carbomers (Goodrich's Carbopols) are polymers with a number of carboxy groups present. When the pH of a solution containing the carbomer is incr there will be a significant increase in viscosity.

crenated erythrocyte A hypertonic solution will draw water from within the cell until an equilibrium is reached with equal pressure on each side of the cell membrane. Beca the loss of volume, the cell will shrink and take on a wrinkled appearance (crenation).

Sodium chloride equivalents are used to estimate the amount of sodium chloride needed to render a solution isotonic. The sodium chloride equivalen "E" value, may be defined as the (A) amount of sodium chloride that is theoretically equivalent to 1 gram of a specified chemical

All aqueous solutions that freeze at -0.52 C are isotonic with red blood cells. They are also isoosmotic with each other. The second statement is true but the first is false. Aqueous solutions that freeze at the same temperature as blood have the same osmotic pressure as blood (ie, are isoosmotic with blood and each o However, to be isotonic a solution must maintain a certain pressure, or "tone," with the red blood cells. If the chemical in a solution passes freely thro red blood cell membrane, equalized pressure on both sides of the membrane is not possible without changes in the cell volume. Tone will not be maintained, and the solution will not be isotonic, though it might be isoosmotic with blood.

Fluorescein sodium is an ophthalmic diagnostic agent. It is instilled into the eye to delineate scratches and corneal lesions. It would be very dangero place a contaminated solution on a damaged cornea through which microorganisms may easily pass. If Pseudomonas aeruginosa enters the interior eyeball, blindness may occur quickly. Pharmacists should not prepare fluorescein sodium solutions extemporaneously unless sterility can be guarant Pharmaceutical manufacturers supply fluorescein as unitdose solutions or individual paper strips.

A radioisotope generator is a (an) ion-exchange column on which a nuclide has been adsorbed

Although it is desirable to use isotopes with short half-lives to minimize the radiation dose received by the patient, it is evident that the shorter the hal the greater the problem of supply. Radioisotope generators, or "cows," have been developed to deal with this problem. A radioisotope generator is an exchange column containing a resin of alumina on which a long-lived parent nuclide is absorbed. Radioactive decay of the long-lived parent results in production of a short-lived daughter nuclide that is eluted or "milked" from the column by means of an appropriate solvent such as sterile, pyrogenfree saline.

A reconstituted drug solution assays at 1.5 mg/mL after 24 hours. What is the first-order reaction rate if the original sloution concentration was 2.0 m The drug solution lost 0.5 mg of its 2.0 mg/mL concentration in 24 hours. This represents a loss of Because first-order reaction rates are expressed as fraction per unit of time, the value willI be 0.25/ day.

To prepare a buffer system with the greatest buffer capacity at a pH of 4.0, one would use which one of the following acids? lactic acid pKa = 3.86

A buffer system consists of a weak acid or base and its corresponding strong salt. In preparing a buffer system, one should choose an acid or a base pKa close to the desired pH. For example, lactic acid and sodium lactate can be combined to obtain a pH of exactly 4.0. The needed molar concentra each may be calculated by using the Henderson-Hasselbalch equation.

193. (C) Sustained-release dosage forms are intended to reduce dosing frequency while maintaining relatively consistent blood levels of the drug. Th duration of activity of drugs with half-lives between 2 and 8 hours can be extended to obtain convenient once- or twicedaily dosing. Although it would desirable to increase the therapeutic duration of those drugs with half-lives of less than 2 hours, the required high drug-release rates and high drug concentration in the dosage form reservoir usually preclude sustained-release dosage formulation. Also, individual biologic variation could result in ei sub- or hypertherapeutic blood levels. Drugs with halflives greater than 8 hours usually have long intervals between dosing, making sustainedrelease formulations unnecessary.

Because of individual patient biologic variation and technologic limitations of precise control of drug release, drugs with either short half-lives or low therapeutic indexes are not suited for sustained-release products. A drug which requires dosing of 500 mg TID is usually not suitable since 1500 mg be needed in the sustained-release dosage form. Almost all sustained-release products are designed for the treatment of chronic conditions in which dosing adjustments are not necessary. Hopefully, sustainedrelease products will improve patient compliance by requiring less frequent dosing.

Moist heat: most widely used method, coagulation of the cellular protein of the organism. Normal pressure, 121 at least 15 min. Not suitable for petroleum jelly, mineral oil, greases, waxes and talcum powder;

Dry hear: used for oily substances such as mineral oil, waxes, and greases; less efficinet than moixt heat, need prolonged time under high temperatu Oxidation process to make the organism dies. Gaseous: ethylene oxide, formaldehyde and chlorine dioxide were used; Filtration: 0.22 m membrane filter is required, widely used for heat sensitive substances; Radiation: commonly employed in hospitals to sterilize supplies, vitamins, antibiotics, steroids, hormones, medical devices and tissue transplants. Electromagnetic radiation or particle radiation, UV (253 nm) serve as radiation sources.

Cold sterilization: the process of removing 0.2 m or larger particles, including microorganisms from parenteral solution; Also called "polishing the solution".

F = C - P + 2 ( C: number of components; P: number of phases) the increase in mutual solubility of two partially miscible liquids by the addition of a third substance Chlorophyll, hemoglobin, peroxidase, cytochromes, oxidases, ascorbic acid oxidase, insulin, and cyanocobalamin; cisplatin

Boric acid is normally added to epinephrine to stabilize it. The catechol ring of epinephrine si easily attacked by the sulfite and bisulfite in a solution. B acid chelates with the catechol ring of epinephrine and protects it from attack of sulfite and bisufite.

A systematic difference from the true value The reproducibility of a series of measurements The closeness of measurements to their true values

Parametric test: the most popular data analysis procedures that assume that data are from populations that are normally and independently distribu The population of Parametic tests must have the same variances. Examples: t-test, mean, and standard deviation; Non-parametric statistics: distribution free, it does not require assumption of same variances. Their observations are independent. Examples: mod median, chisquare tests; Analysis of Variance (ANOVA) is used to test for significance of difference between two or more group means. The t-test is employed to test for significance of difference between two group means; Regression analysis is the most useful technique for research in behavioral science; KCl causes ulceration in the small intestine, It should be taken in Wax-matrix formulation. Gel permeation chromatography is useful for determining of molecular weight distributions in polymers; Gas chromatography identifies and analyzes trace organic materials.

The minimum weight in milligrams of protective colloid required to prevent the color change from red to violet in 10 mL of gold solution (in presence o 10 percent sodium chloride solution)

Depot (dp) is from the French dpt which means a deposit (as in geology or banking) or a storehouse. In medical terms, a depot injection is a lon acting formulation of an injectable drug.

Celsius Fahrenheit

Non-proprietary drugs

Compendium of Pharmaceuticals and Specialties

PMPRB

Scheduled Drugs Schedule 1: Schedule 2:

NAPRA

Schedule 3:

Alberta

Poinson prevention packaging act (USA )

Orphan Drugs

Refilling presciptions

Pharmacy related literatures Index medicus IPAs SCIs D-list AMA drug evaluation Drugdex PDR Identidex Redbook Bluebook Drug Facts and comparisons Martindale

Pharmacy financial assessment:

profitability: "net profit"

NP:NS NP:NW Return on investment NP:TA

Return on asset investment

NP:IN

Efficiency---"net sales" IN TOR NS:IN NS:NWC NS:NW

A/R CT

A/R RT

Liquidity and solvency "current" "inventory"

Acid test ratio

Current ratio CA:CL

Inventory to Net working capital

IN:NWC

Current assets

Financial position TL:NW FA:NW FD:NWC

Asset turnover

Leverage

Break-even analysis

Retail related Elasticity

Actual Acquisition Cost Capitation

Goodwill

Pricing

Retail price Mark-up

Pricing strategy

Pharmacy Margin Growth Margin Incremental cost

Gross profit margin

Profit margin

Halo effect

Pareto's Law

Triage

QALY

sterilization

BMI

Class A prescription balance

MichaelisMenten equation

Cockcroft-Gault formula

Schwartz formula

Drug-drug / nutrient interacitons

Young's Rule for children >2 years dose

others Clark's rule---weight Fried's rule for infants

1 tbsp ac and hs

gtt i au TID.

1 pint 1 gallon gal 1 gr 1 lb(pound) 1kg

approximate equivalents

Normality (N)

Molarity (M)

Molality (m)

Alligation alternate

Electrolyte solutions Milliequivalents mEq Milliosmoles mOsmol

Isotonic solutions

Sodium chloride equivalents

making tablets

Preparing ointments, creams, pastes, and gels

vitamin D intake

proof gallon

USP alcohol

proof alcohol

proof gallon and wine gallon

non-taxable alcohol

denatured alcohol

kosher alcohol

diluted alcohol USP Rubbing alcohol

ESR

???

page 1 to 17 Pharmacy Practices

Code of Ethics (Values) All pharmacists practising in British Columbia are governed by a Code of Ethics. By entering the profession of pharmacy, every pharmacist commits to moral norms of conduct. We assume a professional commitment to the health and well being of every one of our patients.
Value 1

A pharmacist respects the professional relationship with the patient and acts with honesty, integrity and compassion.

Value 2

A pharmacist honours the individual needs, values and dignity of the patient.
Value 3

A pharmacist supports the right of the patient to make personal choices about pharmacy care.
Value 4

A pharmacist provides competent care to the patient and actively supports the patient's right to receive competent and ethical health care.
Value 5

A pharmacist protects the patient's right of confidentiality.

Value 6

A pharmacist respects the values and abilities of colleagues and other health professionals.
Value 7

A pharmacist endeavours to ensure that the practice environment contributes to safe and effective pharmacy care.
Value 8

A pharmacist ensures continuity of care in the event of job action, pharmacy closure or conflict with moral beliefs.

Transfering equation: 5(F- 50= 9(C-10) ----- 5F =9C + 160----- F = 1.8C+32 or C = (F - 32) / 1.8

When a pharmacist does not counsel a patient for warfarin S/E, he violates: ? A. Non-malfacious B. Beneficience When a pharmacist does not counsel a patient how to use warfarin, he violates: B A. Non-malfacious B. Beneficience Non-proprietary drugs are those that are not Rx but on shelf and their reaction with other proprietary drugs should be checked with the patient before buying these drugs: A. Be sure to councel before buying these drugs (more important) B. Keep an eye on them, be near the pharmacy shelves

CPS, is a book published annually by the Canadian Pharmacists Association (CPhA). It lists commonly used pharmaceuticals in Canada. It is not a comprehensive list of all pharmaceuticals available in Canada. Being Canadian, it exists in a French and English version. Recently, it has become available online; however, it is by registration only.

What is the difference between prescription drugs, over the counter drugs and non-prescription drugs? Prescription drugs are usually prescribed by a physician, dispensed by a pharmacist and received either in hospital or in the community. A prescription drug may or may not be patented. Over the counter drugs or non-prescription drugs are legally available without a prescription but may be prescribed. Usually paid for directly by the consumer but, when prescribed, OTC medicines are sometimes covered by public and private drug plans. Although an over the counter drug may or may not be patented, only a small number of OTC drugs are patented.

What is the Patented Medicine Prices Review Board (PMPRB)? Created in 1987 under the Patent Act as an independent quasi-judicial tribunal, the PMPRB limits the prices set by manufacturers for all patented medicines, new and existing, sold in Canada, under prescription or over the counter, to ensure they are not excessive. The PMPRB reviews the "factory-gate" price, i.e. the price at which the manufacturer sells the patented medicine to wholesalers, hospitals and pharmacies. The PMPRB does not have jurisdiction over prices charged by wholesalers or retailers nor over pharmacists' professional fees. The PMPRB regulates the price of each patented drug product, including each strength of each dosage form of a patented medicine. This is normally the level at which Health Canada assigns a Drug Identification Number (DIN). The PMPRB has no authority to regulate the prices of non-patented drugs, including generic drugs.

Drugs that require a prescription as a condition of sale. Drugs that are available only from the pharmacist and without a prescription. There is no opportunity for patient self-selection. Standards of practice for patient counselling (Standard 7) 3 and documentation (Standard 18) apply to Schedule 2 drugs. Schedule II drugs will be located in the prescription service department or in an area adjacent to the prescription service department ensuring there is no opportunity for self selection by the patient. Schedule III drugs shall be located in an area adjacent to the prescription service department. This area shall provide self selection to the patient but also the opportunity for patient-pharmacist consultation.

Drugs that are available without a prescription form the selfselection area of a pharmacy. Unscheduled: Drugs not listed in Schedule 1, 2 or 3 that may be sold from any retail outlet. These drugs may be sold only from a licensed pharmacy or an institution pharmacy. Schedule 3 drugs must be stored and sold only in the patient services area of the pharmacy. A pharmacist must take reasonable steps to offer assistance to a patient who wishes to purchase a Schedule 3 drug.

As a result of applying the cascading principle, four categories of drugs resulted: Schedule 1: Drugs that require a prescription as a condition of sale. Schedule 2: Drugs that are available only from the pharmacist and without a prescription. There is no opportunity for patient self-selection. Schedule 3: Drugs that are available without a prescription form the selfselection area of a pharmacy. Unscheduled: Drugs not listed in Schedule 1, 2 or 3 that may be sold from any retail outlet.

The exempt drugs list including: sublingual nitroglycerine, methyl prednisolone, Mebendazole, potassium supplement, prednisone, oral contraceptives, colestipol, cholestyramine powder, sublingual and chewable isosorbide, dinitrate.

the class of drugs which is used for treating rare diseases. < 200,000 people in the USA)

The partial supply of a Schedule II controlled drug must be filled within 72 hours of the initial filling; failure to do so requires a nes prescription

international Pharmaceutical Abstracts Science Citation Index

therapeutic and dosage information of drugs therapeutic and dosage information of drugs therapeutic and dosage information of drugs

the complete drug reference

net profit to net worth ratio is the best indicator; the acceptable ratio for a 10 year old pharmacy : 15%, target value: 20%

net profit to net sales; the acceptable ratio: 5-7% net profit to net worth; For a new pharmacies: 40%; 15% would be acceptable for old pharmcies net profit to total assets; It is generally useful for a new pharmacies: 10-20%; net profit to inventory; It is generally useful for a new pharmacies: 10-20%; It is also a good indicator for efficiency of the pharmacy.

Inventory turnover rate; calculated by dividing the cost of the goods sold by the average of beginning and ending inventroy. >6 net sales to inventory: calculated by dividing the net sales by the inventory; >8 net sales to net working capital: calculated by dividing the net sales by net working capital(current assets minus current liabilities); 4 to 8 net sales to net worth: calculated by dividing the net sales by net worth(total assets total liabilities); 3 to 8 accounts receivable collection time; calculated by dividing year end accounts receivable by mean credit sales per day. It is a direct measure of efficient credit management. 30 days.

accounts payable remitance time: calculated by year end accounts receivable devided by mean purchases per day. 21 days

also known as Qucik test ratio; calculated by dividing the sum of cash and accounts receivable by the current liabilities; Acid test ratio = (Current assets Inventory) Current liabilities ( more detailed, see above) 1:1 ratio represents a successful pharmacy; Current assets Inventory = Cash + Accounts receivable

The current ratio: dividing current assets by current liabilities; minimum standard value would be 2 dividing mean inventory (average of the beginning and ending inventory) by net working capital (unencumbered portion of current assets); The higher the value, the lower the liquidity; normall value: 80-100%

Including Cash, accounts receivable, inventory

Total liabilities to Net worth; calculated by dividing the Total liabilities by Net worth ; <50%; Fixed asset to net worth: dividing fixed assets by net worth; target value <20% Funded debt to net working capital; dividing long-term liabilities (liabilities older than 1 year) by net working capital (unencumbered portion of current assets); target value:2025%; the lower the better a measure the sales dollars generated by each dollar invested in the firm's total assets: Asset turnover = SalesTotal assets measure the dollar value in total assets that is being acquired for each dollar of net worth or equity . Leverge = Total assets Net worth (or equity)

The break-even point (BEP) is the point at which cost or expenses and revenue are equal: there is no net loss or gain, and one has "broken even". Therefore has not made a profit or a loss. BEP (in sales) = Fixed expensesMarginal-incom ratio ; Marginal-incom ratio = Gross margin ratioVariable-expense ratio = (Gross marginvariable expenses) total sales; BEP (in Days) = BEP in sales average daily sales

Turnover: = Total Annual Sales / Largest inventory Turnover liability: decrease the cost and increase the turnover can impove the turnover liability

coefficient of elasticity E = Q / P

( Q: % of sales quantities change; P: % of price change)

elastic demand: E > 1 unitary elasticity: E = 1 inelastic demand: E < 1 AAC, the actual price paid by the pharmacy after all treade, volume and cash discounts a form of prospective reimbursement in which the pharmacy is paid a specified amount of money each month for each patient who is assigned to receive prescriptions from that pharmacy. classified as intangible assets which is the assets which are of value to the pharmacy and which may produce income but do not have a readily determinable value. Tangible assets are defined as touchable assets which have physical form and qualities such as inventory, fixtures, etc.

Rx: professional fee + cost price OTC: retail price = markup + cost price----- two methods: markup on cost or markup on retail price; Costcomplements % + markup % = 100% gross margin = expenses + profit; Maintained markup = gross margin - cash discounts from suppliers; Initial markup percentage = (maintained markup + reductions) / (net sales + reductions) R=C/P (C: cost of drug; P: cost complement in %)

Retail price = Cost of drug + Mark-up market-oriented pricing: discount pricing: leader pricing (a "leader store in setting competitive prices), loss-leader pricing (priced below cost); Traditional pricing: markup on cost, gross-margin pricing

The gross profit of pharmacies expressed as a percentage of the pharmacy retail price. Growth Margin = profit / customer price the increase or decrease in costs as a result of one more or one less unit of output

Gross profit margin is a financial ratio used to assess the profitability of a firm's core activities, excluding fixed costs. The general calculation is The gross profit margin is related to the net profit margin, which assesses the profitability of an organization after including fixed costs. Indicates the relationship between net sales revenue and the cost of goods sold. A high gross profit margin indicates that a business can make a reasonable profit on sales, as long as it keeps overhead costs in control.

Net Margin, Net profit margin or Net Profit Ratio all refer to a measure of profitability. It is calculated using a formula and written as a percentage or a number. The profit margin is mostly used for internal comparison. It is difficult to accurately compare the net profit ratio for different entities. Individual businesses' operating and financing arrangements vary so much that different entities are bound to have different levels of expenditure, so that comparison of one with another can have little meaning. A low profit margin indicates a low margin of safety: higher risk that a decline in sales will erase profits and result in a net loss.

a term used to describe a phenomena by which an interviewer is biased in favour of a particular personality or physical attribute on the part of interviewees over other factors which may be more relevant to the position in question; It is a cognitive bias whereby the perception of a particular trait is influenced by the perception of the former traits in a sequence of interpretations The Pareto principle (also known as the 80-20 rule, the law of the vital few and the principle of factor sparsity) states that, for many events, roughly 80% of the effects come from 20% of the causes; In pharmacy retail, it may be a guideline of inventory control which holds that 20% of all products stocked generates 80% of total dollar sales; 15% of inventory generates another 15%, and the ramining 65% of the stock generates only 5%;

A process for sorting injured people into groups based on their need for or likely benefit from immediate medical treatment. Triage is used on the battlefield, at disaster sites, and in hospital emergency rooms when limited medical resources must be allocated. Triage of patients is an example of an expanded role of the pharmacist.

Quality-adjusted life year; QALY is a measure of disease burden, including both the quality and the quantity of life lived . It is used as a means of assessing the value for money of a medical intervention. The QALY model requires utility independent, risk neutral, and constant proportional tradeoff behaviour . The QALY is based on the number of years of life that would be added by the intervention. Each year in perfect health is assigned the value of 1.0 down to a value of 0.0 for death. If the extra years would not be lived in full health, for example if the patient would lose a limb, or be blind or be confined to a wheelchair, then the extra life-years are given a value between 0 and 1 to account for this. The QALY is used in cost-utility analysis to calculate the ratio of cost to QALYs saved for a particular health care intervention. This is then used to allocate healthcare resources, with an intervention with a lower cost to QALY saved ratio being preferred over an intervention with a higher ratio.

Moist-heat sterilization is the most widely used and reliable strilizaition method. h Cellular protein coagulation h Saturated steam under 1 atm pressure at Minimum 121 degree for at least 20-60min; h Autoclave is commonly used; h Cause less product and equipment damage Dry-heat sterilization: appropritate for materials that cannot withstand moist-heat. 160degree and 120 min Chemical sterilization: ethylene oxide combination with moisture and heat Radioactive sterilization: Mechanical sterilization: 1. Depth filters; 2. Screen /membrane filters: particulate filters---microbial filters (0.22m)---final fiters

body mass index

C ategory Severely underw eight U nderweight

The minimum weighable quantity is 120 mg. Normal energy requirement for an health adult is about 2500 Kcal pH of gastrointestin is 0.9-1.5

The MichaelisMenten equation describes how the reaction rate v depends on the position of the substrate-binding equilibrium and the rate constant k2. Michaelis and Menten showed when k2 is much less than k-1 (called the equilibrium assumption) they could derive the following equation: The Michaelis-Menten equation will appear first order when the substrate concentration [S] << Km; The Michaelis-Menten equation will appear zero order when Km << [S]. This is the basis for most single-substrate enzyme kinetics. The Michaelis constant Km is defined as the concentration at which the rate of the enzyme reaction is half Vmax.

Estimated creatinine clearance rate (eCcr)

Estimated GFR for Children using Schwartz formula ( Height in cm, SCr in mg /dL)
Where k is a constant that depends on muscle mass, which itself varies with a child's age: In first year of life, for pre-term babies K=0.33 and for full-term infants K=0.45 For infants between ages of 1 and 12 years, K=0.55

ent interacitons

Fat: 1 gram = 9 calories Protein: 1 gram = 4 calories Carbohydrates: 1 gram = 4 calories Alcohol: 1 gram = 7 calories

Neonates have an age span from birth to 1 month of age. Infants are 1 month to 1 year, early childhood is 1 through 5 years, late childhood is 6 through 12 years.

average weight: 150 lb average BSA: 1.73 m2

1 tablespoon before meal and sleep----15 ml x 4 times

1 drop in each ear(both ears) three times a day Apothecary system / Avoirdupois system

473 ml = 0.5 quart normally take it as 480 ml 3785 ml = 8 pt = 4 quart(qt) 65 mg ( avoir. = apoth.) 454 g (avoir.); 2.2 lb (avoir.) 373 g (apoth.)

1 fluid dram = 1 teaspoonful = 5 ml 1 fluidounces = 30 ml 1 pint = 480 ml 1 cup = 240 ml = 8 fl. oz. 1 gallon = 3785 ml / or 3840 ml

It is defined as the presence of number of gram equivalent weight of solute in 1000 ml or (1L) solution; Normality highlights the chemical nature of salts: in solution, salts dissociate into distinct reactive species (ions such as H+, Fe3+, or Cl-). Normality accounts for any discrepancy between the concentrations of the various ionic species in a solution. For example, in a salt such as MgCl2 (1 M), there are two moles of Cl- for every mole of Mg2+, so the concentration of Cl- is said to be 2 N (read: "two normal").

or molar concentration . It is defined as the presence of number of moles of solute in 1000 ml or (1L) of solution; It must be emphasized that a 0.5 molar solution contains 0.5 moles of solute in 1.0 liter of solution. This is not equivalent to 1.0 liter of solvent. A 0.5 mol/L solution will contain either slightly more or slightly less than 1 liter of solvent because the process of dissolution causes the volume of the liquid to increase or decrease.

It is defined as the presence of number of moles of solute in 1000 gm of solvent the number of moles of solute per kilogram of solvent (not solution). For instance: adding 1.0 mole of solute to 2.0 kilograms of solvent constitutes a solution with a molality of 0.50 mol/kg. Such a solution may be described as "0.50 molal". The term molal solution is used as a shorthand for a "one molal solution", i.e. a solution which contains one mole of the solute per 1000 grams of the solvent.

it is the amount (in milligrams) of a solute equal to 1/1000 of its gram-equivalent weight. Valence the electrolytes is important in this calculation

When 1 g mol wt (M-weight) of any nonelectrolyte is dissolved in 1000g of water, the freezing point of the solution is depressed by 1.86 ; Freezing point depression of body fluids: - 0.52 ; So, the amount needed for preparing isotonic solution: X = 0.52 (M-weight) / 1.86 g

Dissociation values (i) considered as 80% dissociated in weak solutions: two ions (NaCl) 1.8; three ions (CaCl2) 2.6; four ions 3.4 0.9% NaCl is a isotonic fluid: Calculated the mass of NaCl represented by all ingredients; and the mass of NaCl required to prepare an equal volume of isotonic solution; Based on the difference between those two masses, calculate the NaCl equivalent for the prescription component.

methods can be used to make tablet wet granulation, dry granulation or direct compression; Tablet triturates using moistered powders: diluent (usually a mixture of lactose and sucrose) were triturated with the active ingredients and use a moistening agent ( a mixture of ethyl alcohol and water) to form a uniform paste, which was spread into the mold; the tablets are punched out and remain on the pegs until dry.

Mixing can be done in a motar or on an oilment slam or tile; Liquids are incorporated by gradually adding them to an absorption-type base and mixing; Insoluble powders are reduced to a fine powder and then added to the base, using geometric dilution; Water-soluble substances are dissolved with water and then incorporated into the base; the final preparation should be smooth (impalpable) and free of any abrasive particles.

Recommended vitamin D intake In the US, the recommended intake of vitamin D for babies and lactating mothers is 200 IU (5 micrograms) per day, the same as for anyone else under the age of 50. Infants 0-12 months should not exceed 1,000 IU (25 g) per day. Anyone aged 1-50 years should not exceed 2,000 IU (50 g) per day.

What is a proof gallon and how do I convert regular gallons to proof gallons? A proof gallon is one liquid gallon of spirits that is 50% alcohol at 60 degrees F. Distilled Spirits* bottled at 80 proof (40% alcohol) would be 0.8 proof gallons per gallon of liquid. At 125 proof, a gallon of liquid would be 1.25 proof gallons. In the industrial and fuel industries, most alcohol is at 190 or 200 degrees of proof. One gallon of alcohol that is 200 proof is equal to 2.0 proof gallons. Refer to 27 CFR Part 19 and 27 CFR Part 30 concerning procedures for determining proof, gauging spirits to determine quantity by weight or volume, or other procedures and regulations concerning measurement of alcohol.

What is pure USP alcohol? Answer: Pure Alcohol (Ethanol) is commonly referred to as USP (United States Pharmacopeia) alcohol. Not all pure alcohol meets USP standards; only 190 and higher proof alcohol which meets or exceeds the stringent specifications of purity by the USP can be classified as such.

What is 80, 190, 192, or 200 proof alcohol? Answer: All ethanol products have a proof associated with the product description. The proof is a measure of the water content of the ethanol portion of the product, and any level of proof can be manufactured based upon the amount of water added. The proof is calculated as two times (2 x) the actual ethanol concentration by volume. The most common pharmaceutical grade ethanol products are 190 proof and 200 proof. The third most common proof is 192. Vodka, on the other hand, is generally 80 proof.

What is the difference between alcohol proof and alcohol percentage? Answer: Each degree of alcohol proof is equal to 0.5 % alcohol by volume. As an example, 100 proof is the same as 50% alcohol by volume.

What is proof gallon and wine gallon? Answer: A proof gallon and a wine gallon are terms used to describe the same thing. A proof and wine gallon refers to one gallon of one 100 proof alcohol (or 50% by volume). The Federal Government taxes alcohol by the proof gallon. Hence, the proof becomes significant in taxable situations. For example, 200 proof, pure Ethanol has two (2) proof gallons per every one (1) gallon of alcohol. The actual physical quantity of one (1) gallon is then referred to as a wine gallon. 190 proof Ethanol, on the other hand, has 1.9 proof gallon per wine gallon of Ethanol.

What is taxable and what is non-taxable alcohol? Answer: Pure alcohol is considered taxable alcohol. The Federal Government requires an excise tax of $13.50/ proof gallon (200 proof, pure alcohol =$27.00/wine gallon). A tax exempt certificate is required to be on file with Alchemical Solutions for us not to charge the Federal excise tax on pure alcohol. Eligibility for exemption is determined by the BATF (Bureau of Alcohol, Tobacco and Firearms). Alchemical Solutions does not make any profit from collecting the tax, nor do we receive a portion of the tax. All denatured Ethanol products do not require the payment of a federal excise tax.

What is denatured alcohol? Answer: Unlike pure alcohol, denatured alcohol has toxic additives which make it unfit for human consumption.

What is kosher alcohol? Answer: It is alcohol that has been manufactured and packaged under the supervision and guidelines of a duly recognized rabbinical authority. To receive USP-Kosher alcohol from Alchemical Solutions, the product must be specifically requested at the time of ordering. 49% V/V 70% V/V

The erythrocyte sedimentation rate is an estimate of the suspension stability of red blood cells in plasma. A normal blood ESR is 0-15 mm/hout. It is generally affected by anemia and certain disease condition.

68. How much diluted alcohol USP can be prepared from 1 pint of 0.5 proof gallon? 1 pint of 0.5 proof gallon means: 0.25 gallon 1/8 3840 = 120 ml pure alcohol

gray baby syndrome chloramphenicol

red man syndrome red neck syndrome Vancomycin

Conn syndrome hyper-aldosterone

Cushing's syndrome

Symptoms

Symptoms

Addison's disease

Graves' disease

symtoms

Graves' ophthalmopathy

Hashimotos thyroiditis

Myasthenia gravis [5maiAs5Wi : niE]

Reye's syndrome

Down syndrome

Dandy-Walker syndrome (DWS)

Raynaud's phenomenon

Paget's Disease of Bone (Osteitis Deformans)

Hodgkin's disease

Toxic shock syndrome

Goodpasture's syndrome

Zollinger-Ellison syndrome

Tourette syndrome

Fibromyalgia (FM) syndrome [5faibrEJmai5AldViE]

Serotonin Syndrome

Cholinergic syndrome

Alcohol withdraw syndrome

symptoms

Drug withdraw syndrome

Stevens-Johnson syndrome

Causes

Mcardle's disease

Lyell's syndrome

Bright's disease

Respiratory distress syndrome

Nephrotic Syndrome

page 12-22

a rare but serious side effect that occurs in newborn infants (especially premature babies) following the administration of the antibiotic chloramphenicol. Two pathophysiologic mechanisms : 1. The UDP-glucuronyl transferase enzyme system of infants, esp premature infants, is immature and incapable of metabolizing the excessive drug load. 2. Insufficient r of the unconjugated drug.

Toxic levels of chloramphenicol after 29 days result in: Vomiting / Ashen gray colour of the skin / Lim Hypotension / Cyanosis blue discolouration of lips and skin. / Hypothermia / Cardiovascular collapse

Vancomycin must be administered in a dilute solution slowly, over at least 60 minutes (maximum rate mg/minute for doses >500 mg). This is due to the high incidence of pain and thrombophlebitis and to a infusion reaction known as the red man syndrome or red neck syndrome. This syndrome, usually appe 10 minutes after the commencement or soon after the completion of an infusion, is characterized by flu an erythematous rash that affects the face, neck and upper torso . These findings are due to noncell degranulation and are not an IgE mediated allergic reaction. Less frequently, hypotension and an may also occur. Symptoms may be treated with antihistamines, including diphenhydramine.

Primary aldosteronism, also known as primary hyperaldosteronism , is characterized by the overprodu mineralocorticoid hormone aldosterone by the adrenal glands. Aldosterone causes increase in sod retention and potassium excretion in the kidneys, leading to arterial hypertension . Also increase pro mineralocorticoid from the adrenal gland is evident. It is a rare but recognised cause of hypertension.

Cushing's Syndrome (also called hypercortisolism or hyperadrenocorticism) is an endocrine disorder high levels of cortisol in the blood from a variety of causes, including a pituitary adenoma (known as C disease), adrenal hyperplasia or neoplasia, ectopic adrenocorticotropic hormone (ACTH) production (e small cell lung cancer), and iatrogenic (steroid use). Normally, cortisol is released from the adrenal gla to ACTH being released from the pituitary gland. Both Cushing's syndrome and Cushing's disease are by elevated levels of cortisol in the blood, but the cause of elevated cortisol differs between the two dis Cushing's disease specifically refers to a tumour in the pituitary gland that stimulates excessive rele from the adrenal gland by releasing large amounts of ACTH. In Cushing's syndrome, the pituitary glan respond as it should with negative feedback to high levels of cortisol, and continues to produce ACTH

rapid weight gain, particularly of the trunk and face with sparing of the limbs (central obesity), a round f referred to as a "moon face," excess sweating, telangiectasia (dilation of capillaries), thinning of the sk causes easy bruising) and other mucous membranes, purple or red striae (the weight gain in Cushing' skin, which is thin and weakened, causing it to hemorrhage) on the trunk, buttocks, arms, legs or breas muscle weakness (hips, shoulders), and hirsutism (facial male-pattern hair growth). A common sign is the growth of fat pads along the collar bone and on the back of the neck (buffalo hum a lipodystrophy). The excess cortisol may also affect other endocrine systems and cause, for example, insomnia, reduc impotence, amenorrhoea and infertility. Patients frequently suffer various psychological disturbances, ranging from euphoria to psychosis. Dep anxiety are also common.

Other signs include polyuria (and accompanying polydipsia), persistent hypertension (due to cortisol's of epinephrine's vasoconstrictive effect) and insulin resistance (especially common in ectopic ACTH pr leading to hyperglycemia which can lead to diabetes mellitus. Untreated Cushing's syndrome can lea disease and increased mortality. Cushing's syndrome due to excess ACTH may also result in hyperpig This is due to Melanocyte-Stimulating Hormone production as a byproduct of ACTH synthesis from Pro opiomelanocortin (POMC). Cortisol can also exhibit mineralcorticoid activity in high concentrations, wo hypertension and leading to hypokalemia (common in ectopic ACTH secretion). Furthermore, gastroint disturbances, opportunistic infections and impaired wound healing (cortisol is a stress hormone, so it d immune and inflammatory responses). Osteoporosis is also an issue in Cushing's Syndrome since, a before, cortisol evokes a stress-like response. The body's maintenance of bone (and other tissues) is t longer one of its main priorities, so to speak. It is also important to note that Cushing's may elicit hirsut (male-pattern hair growth in a female) and oligomenorrhea (decreased frequency of menstruation) due in androgens (male sex hormones), normally at low levels in women.

Addison's disease (also known as chronic adrenal insufficiency, hypocortisolism or hypocorticism) is a disorder in which the adrenal gland produces insufficient amounts of steroid hormones (glucocorticoids mineralocorticoids). It may develop in children as well as adults, and may occur as the result of a large underlying causes. The symptoms of Addison's disease develop insidiously, and it may take some tim recognized. The most common symptoms are fatigue, muscle weakness, weight loss, vomiting, diarrhe sweating, changes in mood and personality and joint and muscle pains. Some have marked cravings f foods due to the urinary losses of sodium.

Low blood pressure that falls further when standing (orthostatic hypotension) ; darkening (hyperpigme skin, which occurs because melanocyte-stimulating hormone (MSH) shares the same precursor molec adrenocorticotropic hormone (ACTH); an increase in ACTH production also increases MSH. In second forms of Addison's, skin darkening does not occur. Signs of conditions that often occur together with Addison's: goiter and vitiligo

Graves' disease is a thyroid disorder characterized by goiter, exophthalmos, "orange-peel" skin, and hyperthyroidism. It is caused by an antibody-mediated auto-immune reaction, but the trigger for this re unknown. It is the most common cause of hyperthyroidism in the world, and the most common cause o thyroid enlargement in developed countries.

exophthalmos (protuberance of one or both eyes) [7eksCf5WAlmCs] a non-pitting edema (pretibial myxedema ) with thickening of the skin usually found on the lower extre fatigue, weight loss with increased appetite, and other symptoms of hyperthyroidism: rapid heart bea weakness

The two signs that are truly diagnostic of Graves' disease (i.e. not seen in other hyperthyroid condition exophthalmos and non-pitting edema (pretibial myxedema).

Graves' disease is an autoimmune disorder, in which the body produces antibodies to the receptor fo stimulating hormone (TSH). (Antibodies to thyroglobulin and to the thyroid hormones T3 and T4 may a produced.)

These antibodies cause hyperthyroidism because they bind to the TSH receptor and chronically stimul receptor is expressed on the follicular cells of the thyroid gland (the cells that produce thyroid hormone result of chronic stimulation is an abnormally high production of T3 and T4. This in turn causes the clin of hyperthyroidism, and the enlargement of the thyroid gland visible as goiter.

also known as Graves' thyroid-associated or dysthyroid orbitopathy or exophthalmos, is an autoimmu inflammatory disorder affecting the orbit of the eye, with or without thyroid disorder.

Thyroid-associated ophthalmopathy (TAO) is an orbital autoimmune disease. The thyroid stimulating h receptor (TSH-R) is an antigen found in orbital fat and connective tissue, and is a target for autoimmun However, some patients with Graves orbitopathy present with neither anti-microsomal, anti-thyroglobu TSH receptor, the antibodies identified in Graves' disease.

On histological examination there is an infiltration of the orbital connective tissue by lymphocytes, plas mastocytes. The inflammation results in a deposition of collagen and glycosaminoglycans in the muscl leads to subsequent enlargement and fibrosis. There is also an induction of the lipogenesis by fibrobla preadipocytes, which causes orbital volume enlargement due to fat deposition.

an autoimmune disease where the body's own T-cells attack the cells of the thyroid. It was the first dise recognised as an autoimmune disease. This disorder is believed to be the most common cause of prim hypothyroidism in North America. It occurs far more often in women than in men (10:1 to 20:1), and is between 45 and 65 years of age.

Physiologically, antibodies against thyroid peroxidase and/or thyroglobulin cause gradual destruction o thyroid gland. Autoimmune disorder resulting in hypothyroidism (can have thyrotoxicosis during follic Slow course; moderately enlarged, nontender thyroid. Lymphocytic infiltrate with germinal centers. Ant and antithyroglobulin antibodies. Associated with Hrthle cells on histology. Hypothyroidism caused by Hashimoto's Thyroiditis is treated with thyroid hormone replacement.

The disease myasthenia gravis, characterized by muscle weakness and fatigue, occurs when the body inappropriately produces antibodies against acetylcholine nicotinic receptors, and thus inhibits p acetylcholine signal transmission. Over time, the motor end plate is destroyed.

Drugs that competitively inhibit acetylcholinesterase (e.g., neostigmine, physostigmine, or primarily are effective in treating this disorder. They allow endogenously-released acetylcholine more time to int respective receptor before being inactivated by acetylcholinesterase in the gap junction.

Reye's syndrome is a potentially fatal disease that causes numerous detrimental effects to many organ the brain and liver. It is associated with aspirin consumption by children with viral diseases such as chi

The disease causes fatty liver with minimal inflammation, and severe encephalopathy (with swelling of liver may become slightly enlarged and firm, and there is a change in the appearance of the kidneys. J usually present. The precise mechanism by which Reye's syndrome occurs remains unknown. Many studies have dem strong association between aspirin taken for viral illnesses and the development of Reyes syndrom claimed that acetaminophen (paracetamol) is a greater risk, but the only study to suggest this was too according to some sources, the conclusions by the authors seem flawed.

A chromosomal disorder caused by the presence of all or part of an extra 21st chromosome. Often Do is associated with some impairment of cognitive ability and physical growth as well as facial appearanc syndrome can be identified during pregnancy or at birth.

a congenital brain malformation involving the cerebellum and the fluid filled spaces around it. The Dan complex is a genetically sporadic disorder that occurs one in every 25,000 live births, mostly in female

Raynaud's phenomenon is a vasospastic disorder causing discoloration of the fingers, toes, and occas extremities.This condition can also cause nails to become brittle with longitudinal ridges. It comprises b disease (primary Raynaud's), where the phenomenon is idiopathic, and Raynaud's syndrome (seconda Raynaud's), where it is caused by some other instigating factor. Primary Raynaud phenomenon, stemming from Raynaud disease, is an exaggeration of vasomotor res cold or emotional stress. More specifically, it is a hyperactivation of the sympathetic system causing ex vasoconstriction of the peripheral blood vessels, leading to tissue hypoxia. Chronic, recurrent cas phenomenon can result in atrophy of the skin, subcutaneous tissues, and muscle. It can also rarel ulceration and ischemic gangrene.

Drugs: Beta-blockers; cytotoxic drugs - particularly chemotherapeutics and most especially bleom cyclosporin; ergotamine; sulfasalazine may cause this disease.

Paget's disease of bone is a chronic disorder of the adult skeleton in which bone turnover is accelerate areas. Normal matrix is replaced with softened and enlarged bone. The disease may be asymptomatic gradual onset of bone pain or deformity. Diagnosis is by xray. Treatment includes symptomatic measu drugs, usually bisphosphonates.

Five bisphosphonates are currently available. In general, the most commonly prescribed are the three bisphosphonates: Actonel(risedronate sodium), Fosamax(alendronate sodium) and Aredia(pamid disodium) . Didronel (etidronate disodium) and Skelid (tiludronate disodium) may be appropriate thera selected patients but are less commonly used.

As a rule, bisphosphonate tablets should be taken with 68 oz of tap water (not from a source with hig content) on an empty stomach. Contraindicated in people with severe kidney disease.

also known as Hodgkin's lymphoma, is a type of lymphoma first described by Thomas Hodgkin Hodgkin's lymphoma is characterized clinically by the orderly spread of disease from one lymph node another and by the development of systemic symptoms with advanced disease. Pathologically, the dis characterized by the presence of Reed-Sternberg cells (RS cells). Hodgkin's lymphoma was one of the to be cured by radiation. Later it was one of the first to be cured by combination chemotherapy. The su generally around 90% when the disease is detected relatively early,

Toxic shock syndrome (TSS) is a rare but potentially fatal disease caused by a bacterial toxin. The cau bacteria include Staphylococcus aureus and Streptococcus pyogenes. Streptococcal TSS is some to as Toxic shock-like syndrome (TSLS).

TSS resultant of infection with the bacteria Staphylococcus aureus typically manifests in otherwise hea with high fever, accompanied by low blood pressure, malaise and confusion, which can rapidly progres coma, and multi-organ failure. The characteristic rash, often seen early in the course of illness, resemb and can involve any region of the body, including the lips, mouth, eyes, palms and soles. In patients w initial onslaught of the infection, the rash desquamates, or peels off, after 1014 days.

(also known as anti-glomerular basement membrane disease) is a rare condition characterised by rapi of the kidneys and haemorrhaging of the lungs. It is an autoimmune disease produced when the patien system attacks cells presenting the Goodpasture antigen (a type II hypersensitivity reaction), which the kidney and lung, causing damage to these organs.

A disorder where increased levels of the hormone gastrin are produced, causing the stomach to prod hydrochloric acid. Often the cause is a tumor (gastrinoma) of the duodenum or pancreas producing t gastrin. Beta-adrenergic agents, cholinergic agents, gastrin-releasing peptide (GRP) can also stim secretion. Gastrin then causes an excessive production of acid which can lead to peptic ulcers (in almo patients)

Gastrin-secreting tumor of pancreas or duodenum. Causes recurrent ulcers. May be associated with M

Proton pump inhibitors (such as omeprazole and lansoprazole) and histamine H2-receptor antagonists famotidine and ranitidine) are used to slow down acid secretion. If possible the tumours should be su removed, or treated with chemotherapy. Octreotide can be used to slow down acid secretion.

an inherited neuropsychiatric disorder with onset in childhood, characterized by the presence of multip (motor) tics and at least one vocal (phonic) tic; these tics characteristically wax and wane. Tourette's is part of a spectrum of tic disorders, which includes transient and chronic tics.

a disorder classified by the presence of chronic widespread pain and tactile allodynia.The disorder is n threatening. The degree of symptoms may vary greatly from day to day with periods of flares (severe w symptoms) or remission; however, the disorder is generally perceived as non-progressive.

The defining symptoms of fibromyalgia are chronic, widespread pain and tenderness to light touch. Oth can include moderate to severe fatigue, a heightened and painful response to gentle touch (allodynia tingling of the skin, muscle aches, prolonged muscle spasms, weakness in the limbs, nerve pain, fun disturbances, and chronic sleep disturbances.

Serotonin Syndrome is a potentially life-threatening adverse drug reaction that may occur following the use, inadvertent interactions between drugs, or the recreational use of certain drugs. It is not a spontan reaction; it is a consequence of excess serotonergic activity at central nervous system (CNS) and perip serotonin receptors. This excess serotonin activity produces a specific spectrum of clinical findings wh from barely perceptible to fatal. The symptoms are often described as a clinical triad of abnormalities (): Cognitive effects: mental confusion, hypomania, hallucinations, agitation, headache, coma. Autonomic effects: shivering, sweating, fever, hypertension, tachycardia, nausea, diarrhea. Somatic effects: myoclonus (muscle twitching), hyperreflexia (manifested by clonus), tremor.

Drugs may cause serotonin syndrome: Antidepressants: Monoamine oxidase inhibitors (MAOIs), TCAs, SSRIs, SNRIs, bupropion

Opioids: tramadol, pethidine, fentanyl, pentazocine CNS stimulants: phentermine, diethylpropion, amphetamines, sibutramine, methylphenidate, methamp cocaine 5-HT1 agonists: triptans Psychedelics: MDMA, MDA, MDEA, PMA, Psilocybin, LSD Herbs: St John's Wort, Yohimbe, Boswellia, Panax ginseng, Ginkgo biloba

Others: tryptophan, valproate, montelukast, buspirone, kanna, lithium, linezolid, dextromethorphan, 5Hydroxytryptophan, chlorpheniramine, risperidone, olanzapine, ondansetron, granisetron, metoclopram

(Cholinergic too much you will get a SLUDGE(Salivation, Lacrimation, Urination, Defecation, Gastr upset, Emesis) A syndrome of pathological effects indicative of massive discharge of the parasympathetic nervous sys common cause of SLUDGE is exposure to organophosphorus insecticides, including parathion, malath diazinon. These agents phosphorylate acetylcholinesterase, thereby raising acetylcholine levels and c SLUDGE which may be treated with Atropine or other anticholinergics.

Alcohol withdrawal syndrome is the set of symptoms seen when an individual reduces or stops alcoho after prolonged period of excessive alcohol intake. Excessive abuse of alcohol leads to tolerance, phys dependence, and an alcohol withdrawal syndrome. Unlike most withdrawals from drugs, alcohol withdr deadly.

Chronic use of alcohol leads to changes in brain chemistry especially in the GABAergic system: chang expression and down regulation of GABAa receptors.

The severity of the alcohol withdrawal syndrome can vary from mild symptoms such as mild sleep distu mild anxiety to very severe and life threatening including delirium, particularly visual hallucinations in s and convulsions (which may result in death).

Agitation, Alcoholic hallucinosis, Anorexia, Anxiety and panic attacks, Catatonia, Confusion, Delirium tremens, Depression, Derealization, Diaphoresis, Diarrhea; Euphoria, Fear, Gastrointestinal u Hallucinations, Headache, Hypertension, Insomnia, Irritability, Nausea and vomiting, Palpitations, Psyc Rebound REM sleep, Palpitations, Restlessness, Seizures and death, Sweating, Tachycardia, Tremor

A protracted alcohol withdrawal syndrome occurs in many alcoholics where withdrawal symptoms cont the acute withdrawal stage but usually at a subacute level of intensity and gradually decreasing with se time.

Treatment of alcohol withdrawal syndrome can be managed with various pharmaceutical medications Barbiturates: phenobarbital; benzodiazepines: diazepam, lorazepam, chlordiazepoxide; antipsych haloperidol; antiepileptics: phenytoin Others: Baclofen, clonidine, carbamazepine, trazodone, low dose ethanol, Vitamin deficiency is common in alcoholic: most import B1 and B9 (thiamine and folic acid)

Stevens-Johnson syndrome (SJS) is a life-threatening condition affecting the skin in which cell death c epidermis to separate from the dermis. It is a severe form of erythema multiforme. In addition to the top affects mucous membranes. The skin usually becomes hemorhagic and serious ocular lesions are form

The syndrome is thought to be a hypersensitivity complex affecting the skin and the mucous membr the majority of cases are idiopathic, the main class of known causes is medications, followed by infecti (rarely) cancers.

SJS can be caused by infections (usually following viral infections such as herpes simplex virus, influe cat-scratch fever, histoplasmosis, Epstein-Barr virus, or similar), adverse effects of drugs (allopurinol, fluconazole, valdecoxib, sitagliptin, penicillins, barbiturates, sulfonamides, phenytoin, azithromycin, mo lamotrigine, nevirapine, ibuprofen, ethosuximide, carbamazepine), malignancy (carcinomas and lymp idiopathic factors (up to 50% of the time). SJS has also been consistently reported as an uncommon herbal supplements containing ginseng. SJS may also be caused by cocaine usage.

The leading cause appears to be the use of antibiotics and sulfa drugs. Medications that have tradi known to lead to Stevens Johnson Syndrome, Erythema Multiforme, Lyell's Syndrome, and Toxic Epid Necrolysis include sulfonamides, penicillins, barbiturates, lamotrigine, and phenytoin - Dilantin. Combining lamotrigine with sodium valproate increases the risk of Stevens-Johnson Syndrome oc

Glycogen storage disease type V (GSD-V) is a metabolic disorder, more specifically a glycogen stor caused by a deficiency of myophosphorylase. It is the most common of the various types of glycogen s disease, but is still considered rare (1 in 100,000). GSD type V is also known as McArdle's disease or phosphorylase (myophosphorylase) deficiency. The disease was first reported in 1951 by Dr. Brian Mc Hospital, London. McArdles Disease is an inborn error and inherited. Symptoms include exercise intolerance with myalgia, early fatigue, painful cramps, weakness of exerc and myoglobinuria. Myoglobinuria, the condition where myoglobin is present in urine, may result from s damage to the muscles, or rhabdomyolysis, where muscle cells breakdown, sending their contents into bloodstream.

Oral vitamin B6 appears to impart greater resistance to fatigue. No specific therapy exists, but combine exercise programs and high-protein diets may help. Some patients learn the limits of their exercise and their restrictions, going on to live fairly normal lives. Supervised exercise programs have been recomm lessen the risks of extended inactivity. Sucrose treatment is now being recommended prior to exercise.

also called Toxic Epidermal Necrolysis (TEN), it is caused by certain drugs and phase II group staphyl characterized by large areas of erythema involving most of the skin surface. Phenylbutazone, sulfon allopurinol and penicillin are responsible for causing drug induced TEN.

Glomerulonephritis, it is an autoimmune diasease.

RDS, is seen in newborn infants. It is also known as hyaline membrane disease. It is a condition of new which the lungs are imperfectly expanded. Initial inflation and normal expansion of the lungs requires t a surfactant that reduces the surface tension of the air sacs and prevents the collapse of the small airw the surfactant the airway collapses, leading to inefficient and still lungs. Breathing is rapid, labored, and microscopic examinations of the lung tissue in fatal cases has revealed the presence of hyaline materi collapsed air sacs.

A condition in wich there is a great loss of protein in the urine. This reduces the level of albumin in the Patients may sulffer from edema due to swelling of the tissues. Glomerulonephritis is a principal caus administration of corticosteroid may help in controlling the disease.

page 1 -17 http://www.psychresidentonline.com/CYP450%20drug%20interactions.htm

CYP450 INHIBITORS
1A2
amitriptyline imipramine

2B6
fluvoxamine

2C19
amitriptyline
imipramine

2D6
All TCAs fluoxetine

3A4
nefazodone
norfluoxetine fluoxetine

TCAs SSRIs / SNRIs

fluvoxamine duloxetine
ciprofloxacin norfloxacin ofloxacin

clopidogrel ticlopidine

fluoxetine fluvoxamine paroxetine

paroxetine bupropion SSRIs sertraline > 100-150mg duloxetine fluvoxamine citalopram

fluvoxamine
haloperidol pimozide

PPIs ketoconazole

ciprofloxacin norfloxacin chlorpromazine fluphenazine haloperidol perphenazine thioridazine

cimetidine

Erythromycin PPIs
ketoconazole and itraconazole diltiazem verapamil

aripiprazole
lansoprazole is the most potent in vitro inhibitor of 2C19

clozapine risperidone cimetidine protease inhibitors NNRTIs

Metronidazole (Flagyl)
methadone valproic acid mild

*quinidine* ritonavir cimetidine diphenhydramine Vistaril

CYP 450

present in

Acute alcohol Inhibitors Inducers

inhibitor

metoclopramide

Flagyl, Allopurinol, Cimetidine, Erythromycin, Dextropropoxyphene, Imipramine, (the) pill (FACE DIP). Queen Barb takes Phen-Phen and Refuses Greasey Carb Shakes and Smokes with St John's Chronic alcohol inducer

CYP450 INDUCERS

1A2
modafinil
cruciferous vegetables charbroiled foods

2B6

2C19
carbamazepine valproic acid

2D6

3A4
carbamazepine
oxcarbazepine

topiramate >200mg
phenobarbital phenytoin rifampin phenobarbital cyclophosphamide No Inducers! phenobarbital phenytoin rifampin ritonavir efavirenz St. John's Wort modafinil

smoking

cigarrettes, antiepileptics (carbamazepine & phenytoin), rifampicin, griseofulvin, alcohol and spironolactone (CAR GAS) [also barbiturates].

Drugs / Foods that Induce or Inhibit Various Cytochrome P-450 Systemsand the Drugs that are effected by this Induction or Inhibition.
http://www.edhayes.com/CYP450-4.html (in details for the interactions of drugs)

Cytochrome P450 http://www.medicine.iupui.edu/Flockhart/table.htm

Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of hemoproteins found in all domains of life.[1] Cytochromes P both exogenous and endogenous compounds as substrates in enzymatic reactions. Usually they form part of multicomponent electron transfer chains, called P450-cont

The most common reaction catalysed by cytochrome P450 is a monooxygenase reaction, e.g. insertion of one atom of oxygen into an organic substrate (RH) while the o reduced to water: RH + O2 + 2H+ + 2e ROH + H2O

The name cytochrome P450 is derived from the fact that these are colored ('chrome') cellular ('cyto') proteins, with a "pigment at 450 nm", so named for the characterist by absorbance of light at wavelengths near 450 nm when the heme iron is reduced (often with sodium dithionite) and complexed to carbon monoxide.

Many drugs may increase or decrease the activity of various CYP isozymes in a phenomenon known as enzyme induction and inhibition. This is a major source of adve since changes in CYP enzyme activity may affect the metabolism and clearance of various drugs. Such drug interactions are extra important to take into account when importance to the patient, drugs with important side effects and drugs with small therapeutic windows, but any drug may be subject to an altered plasma concentration d metabolism. A classical example includes anti-epileptic drugs, Phenytoin, for example, induces CYP1A2, CYP2C9, CYP2C19 and CYP3A4. Substrates for the latter may be drugs w amiodarone or carbamazepine, whose blood plasma concentration may decrease because of enzyme induction.

In addition, naturally occurring compounds may cause a similar effect. For example, bioactive compounds found in grapefruit juice and some other fruit juices, including dihydroxybergamottin, and paradisin-A, have been found to inhibit CYP3A4-mediated metabolism of certain medications, leading to increased bioavailability and thus th overdosing.[11] Because of this risk, avoiding grapefruit juice and fresh grapefruits entirely while on drugs is usually advised. Other examples: Saint-John's wort, a common herbal remedy induces CYP3A4. Tobacco smoking induces CYP1A2 (example substrates are clozapine/olanzapine)

Inhibitors compete with other drugs for a particular enzyme thus affecting the optimal level of metabolism of the substrate drug which in many cases affect the indivi
that particular medication, e.g. making it ineffective. A Strong inhibitor is one that cause a > 5-fold increase in the plasma AUC values or more than 80% decrease in clearance. A Moderate inhibitor is one that cause a > 2-fold increase in the plasma AUC values or 50-80% decrease in clearance. A Weak inhibitor is one that cause a > 1.25-fold but < 2-fold increase in the plasma AUC values or 20-50% decrease in clearance. All other inhibitors. FDA preferred1 and acceptable2 inhibitors for in vitro experiments.* 1A2 2B6 2C8 2C19 2C9

fluvoxamine

thiotepa

gemfibrozil2

PPIs:

fluconazole2

ciprofloxacin

ticlopidine2

lansoprazole

trimethoprim2

omeprazole2

amiodarone

cimetidine

pantoprazole

glitazones

rabeprazole

fenofibrate

amiodarone

montelukast1

fluvastatin

fluoroquinolones

quercetin1

chloramphenicol

fluvoxamine2

furafylline1

cimetidine

isoniazid

interferon

felbamate

lovastatin

methoxsalen

fluoxetine

phenylbutazone

mibefradil

fluvoxamine

probenicid

indomethacin

sertraline

ketoconazole

sulfamethoxazole

modafinil

sulfaphenazole1

oxcarbazepine

teniposide

probenicid

voriconazole

ticlopidine2

zafirlukast

topiramate

INDUCERS

Inducers stimulate the production of the enzyme thus increasing the rate of metabolism causing the substrate drug to clear out of the system faster. This will also affect the individual's response to the medication, i.e. m because it has not been in the system long enough to have an effect. FDA preferred1 and acceptable2 inducers for in vitro experiments.*

1A2

2B6

2C8

2C19

2C9

broccoli

phenobarbital

carbamazepine

rifampin

brussel sprouts

rifampin

norethindrone

secobarbital

char-grilled meat

NOT pentobarbital

insulin

prednisone

methylcholanthrene1

rifampin1

modafinil

nafcillin

beta-naphthoflavone1

omeprazole1

rifampin1

tobacco rifampin1

norfluoxetine fluoxetine fluvoxamine duloxetine sertraline bupropion citalopram patoxetine

Cimetidine
Omeprazole _prazoles

present in gastrointestinal tract

griseofulvin spironolactone

barbiturates].

d in all domains of life.[1] Cytochromes P450 use a plethora of lectron transfer chains, called P450-containing systems.

nto an organic substrate (RH) while the other oxygen atom is

t 450 nm", so named for the characteristic Soret peak formed d to carbon monoxide.

inhibition. This is a major source of adverse drug interactions, xtra important to take into account when using drugs of vital ject to an altered plasma concentration due to altered drug

Substrates for the latter may be drugs with critical dosage, like

ce and some other fruit juices, including bergamottin, g to increased bioavailability and thus the strong possibility of

rug which in many cases affect the individual's response to

nce.

2D6

2.00E+01 3A4,5,7

H I V A n t diethyl-dithiocarbamate2 i v i r a l s :

bupropion

fluoxetine

disulfiram

indinavir

paroxetine

nelfinavir

quinidine1

ritonavir

duloxetine

clarithromycin

terbinafine

itraconazole1

ketoconazole1

amiodarone

nefazodone

cimetidine

saquinavir

sertraline

telithromycin

celecoxib

aprepitant

chlorpheniramine

erythromycin

chlorpromazine

fluconazole

cinacalcet

grapefruit juice

citalopram

verapamil2

clemastine

diltiazem

clomipramine

cocaine

cimetidine

diphenhydramine

doxepin

amiodarone

doxorubicin

NOT azithromycin

escitalopram

chloramphenicol

goldenseal

delaviridine

halofantrine

histamine H1 receptor antagonists

diethyl-dithiocarbamate

hydroxyzine

fluvoxamine

levomepromazine

gestodene

methadone

imatinib

metoclopramide

mibefradil

mibefradil

mifepristone

midodrine

norfloxacin

moclobemide

norfluoxetine

perphenazine

star fruit

ranitidine

voriconazole

red-haloperidol ritonavir ticlopidine

tripelennamine

ct the individual's response to the medication, i.e. making he drug ineffective

2D6

2.00E+01 3A,4,5,7
H I V A n t i v i r a l s :

dexamethasone

ethanol

rifampin

isoniazid

efavirenz

nevirapine

barbiturates

carbamazepine

efavirenz

glucocorticoids

modafinil

nevirapine

oxcarbazepine

phenobarbital2

phenytoin2

pioglitazone

r i f a b u t i n

rifampin1

St. John's wort

troglitazone1

page 1 -4 (take note-7)

Partial list of prescription abbreviations Abbreviation aa ad a.c. a.d. ana ad ante cibum auris dextra ad libitum admove agita alternis horis Latin

ad lib.
admov. agit alt. h. a.m. amp amt aq a.l., a.s. A.T.C. a.u. bis b.d./b.i.d. B.M. bol. B.S. B.S.A BUCC cap., caps. c c cc cf comp. cr., crm D5W D5NS D.A.W. dc, D/C, disc dieb. alt. dil. disp.

Ante Meridiem

aqua auris laeva, auris sinistra

auris utraque bis bis in die

bolus

capsula cum cibos cum cibos

diebus alternis

div. d.t.d. D.W. elix. e.m.p. emuls. et ex aq fl., fld. ft. g gr gtt(s) H h, hr h.s. ID IM inj. IP IV IVP IVPB L.A.S. LCD lin liq lot. M. m, min mcg mEq mg mist. mitte mL nebul N.M.T. noct. non rep. NS 1/2NS N.T.E. o_2 nocte non repetatur nebula mistura mitte misce minimum linimentum liquor injectio hora hora somni gutta(e) fiat ex modo prescripto emulsum et ex aqua dentur tales doses

o.d. o.s. o.u. oz per p.c. p.m. prn p.o. p.r. pulv. q q.a.d. q.a.m. q.d.s. q.p.m. q.h. q.h.s. q.1h q.d. q.i.d. q.o.d. qqh q.s. QWK R rep., rept. RL, R/L s s.a. SC, subc, subcut, subq, SQ sig SL sol s.o.s., si op. sit ss stat supp

oculus dexter oculus sinister oculus uterque oculo utro per post cibum Post Meridiem pro re nata per os pulvis quaque quoque alternis die quaque die ante meridiem quater die sumendus quaque die post meridiem quaque hora quaque hora somni quaque 1 hora quaque die quater in die quater quaque hora quantum sufficiat

repetatur

sine secundum artum

solutio si opus sit semis statim suppositorium

susp syr tab tal., t tbsp troche tsp t.i.d. t.d.s. t.i.w. top. T.P.N. tr, tinc., tinct. u.d., ut. dict. ung. U.S.P. vag w w/o X Y.O. ut dictum unguentum ter in die ter die sumendum trochiscus syrupus tabella talus

list of prescription abbreviations Meaning of each up to before meals right ear use as much as one desires; freely apply stir/shake every other hour morning, before noon ampule amount water left ear "a a" like ears

around the clock both ears twice twice daily bowel movement as a large single dose (usually intravenously) blood sugar body surface areas inside cheek capsule with (usually written with a bar on top of the "c") food with food, (but also cubic centimetre) with food compound cream dextrose 5% solution (sometimes written as D5W) dextrose 5% in normal saline (0.9%) dispense as written discontinue every other day dilute dispense

divide give of such doses distilled water elixir as directed emulsion and in water fluid make; let it be made gram grain drop(s) hypodermic hour at bedtime intradermal intramuscular (with respect to injections) injection intraperitoneal intravenous intravenous push intravenous piggyback label as such

coal tar solution

liniment solution lotion mix a minimum microgram milliequivalent milligram mix send millilitre a spray not more than at night no repeats normal saline (0.9%) half normal saline (0.45%) not to exceed both eyes, sometimes written as o2

right eye left eye both eyes each eye ounce

"O O", like eyes

by or through after meals evening or afternoon as needed by mouth or orally by rectum powder every every other day every day before noon four times a day every day after noon every hour every night at bedtime every 1 hour; (can replace "1" with other numbers) every day four times a day every other day every four hours a sufficient quantity every week rectal repeats Ringer's lactate without (usually written with a bar on top of the "s") use your judgement subcutaneous write on label sublingually, under the tongue solution if there is a need one half immediately

Lactated Ringer's solution is a solution that is isotonic wit blood and intended for intravenous administration. One liter of Lactated Ringer's Solution contains: 130 mEq of sodium ion = 130 mmol/L. 109 mEq of chloride ion = 109 mmol/L. 28 mEq of lactate = 28 mmol/L. 4 mEq of potassium ion = 4 mmol/L. 3 mEq of calcium ion = 1.5 mmol/L .

suppository

suspension syrup tablet such

tablespoon
lozenge

teaspoon
three times a day three times a day three times a week topical

total parenteral nutrition

tincture as directed ointment

United States Pharmacopoeia

vaginally with without times years old

ion that is isotonic with administration.

on contains: /L. l/L.

. .

evaluating personal health or relied on to make healthcare decisions.

HEMATOLOGY VALUES Red Blood Cell Values RBC (Male) RBC (Female) RBC (Child) White Blood Cell Values WBC (Male) WBC (Female) WBC (Child) Hemoglobin Values Hgb (Male) Hgb (Female) Hgb (child) Hgb (Newborn) Hematocrit Values Hct (Male) Hct (Female) Hct (Child) MCV MCH MCHC Neutrophils Bands Lymphocytes Monocytes Eosinophils Basophils CARDIAC MARKERS

Troponin I

Troponin T Myoglobin (Male) Myoglobin (Female) GENERAL CHEMISTRY Acetone Albumin Alkaline Phosphatase Anion gap Ammonia

Amylase AST, SGOT (Male) AST, SGOT (Female) Bilirubin, Direct Bilirubin, Indirect Bilirubin, Total BUN Calcium (total) Carbon dioxide Carbon monoxide Chloride Creatine (Male) Creatine (Female) Creatinine Ethanol Folic acid Glucose HDL (Male) HDL (Female) Iron Iron binding capacity Lactic acid Lactate Lipase Magnesium Osmolarity Parathyroid hormone Phosphorus Potasssium Protein (total) SGPT Sodium T3 Thyroglobulin Thyroxine (T4) total Total protein TSH Urea nitrogen Uric acid (Male) Uric acid (Female) LIPID PANEL (ADULT) Cholesterol (total) Cholesterol (HDL) Cholesterol (LDL) Triglycerides (Male) Triglycerides (Female) URINE VALUES Color

Specific Gravity pH Na K Cl Protein Osmolality 24 HOUR URINE VALUES Amylase Calcium Chloride Creatinine Creatine Clearance (Male) Creatine Clearance (Male) Creatine Clearance (Female) Creatine Clearance (Female) Magnesium Osmolality Phosphorus Potassium Protein Sodium Urea nitrogen Uric acid COAGULATION ACT APTT Platelets Plasminogen PT PTT FSP Fibrinogen Bleeding time Thrombin time CEREBRAL SPINAL FLUID Appearance Glucose Osmolality Pressure Protein Total cell count WBC's HEMODYNAMIC PARAMETERS Cardiac Index Cardiac Output Left Ventricular Stroke Work Index Mean Arterial Pressure Pulmonary Vascular Resistance

Pulmonary Vaslular Resistance Index Right Ventricular Stroke Work Index Stroke Volume Stroke Volume Index Systemic Vascular Resistance Systemic Vascular Resistance Index Systolic Arterial Pressure Diastolic Arterial Pressure Central Venous Pressure Ejection Fraction Left Arterial Pressure Pulmonary Artery Systolic Pulmonary Artery Diastolic Pulmonary Artery Pressure Pulmonary Artery Wedge Pressure Pulmonary Artery End Diastolic Pressure Right Atrial Pressure Right Ventricular End Diastolic Pressure NEUROLOGICAL VALUES Cerebral Perfusion Pressure Intracranial Pressure ARTERIAL VALUES pH PaCO2 HCO3 O2 sat PaO2 BE VENOUS VALUES pH PaCO2 HCO3 O2 sat PaO2 BE

or relied on to make healthcare decisions.

4.2 - 5.6 M/L 3.8 - 5.1 M/L 3.5 - 5.0 M/L 3.8 - 11.0 K / mL 3.8 - 11.0 K / mL 5.0 - 10.0 K / mL 14 - 18 g/dL 11 - 16 g/dL 10 - 14 g/dL 15 - 25 g/dL 39 - 54% 34 - 47% 30 - 42% 78 - 98 fL 27 - 35 pg 31 - 37% 50 - 81% 1 - 5% 14 - 44% 2 - 6% 1 - 5% 0 - 1% MCV = (Hct% x 10) / RBC MCH = (Hgb x 10) / RBC MCHC = [ (Hgb x 100) / Hct ] %

0 - 0.1 ng/ml (onset: 4-6 hrs, peak: 12-24 hrs, return to normal: 4-7 days)

0 - 0.2 ng/ml (onset: 3-4 hrs, peak: 10-24 hrs, return to normal: 10-14 days) 10 - 95 ng/ml (onset: 1-3 hrs, peak: 6-10 hrs, return to normal: 12-24 hrs) 10 - 65 ng/ml (onset: 1-3 hrs, peak: 6-10 hrs, return to normal: 12-24 hrs)

0.3 - 2.0 mg% 3.5 - 5.0 gm/dL 32 - 110 U/L 5 - 16 mEq/L 11 - 35 mol/L

50 - 150 U/dL 7 - 21 U/L 6 - 18 U/L 0.0 - 0.4 mg/dL total minus direct 0.2 - 1.4 mg/dL 6 - 23 mg/dL 8 - 11 mg/dL 21 - 34 mEq/L symptoms at greater than or equal to 10% saturation 96 - 112 mEq/L 0.2 - 0.6 mg/dL 0.6 - 1.0 mg/dL 0.6 - 1.5 mg/dL 0 mg%; Coma: greater than or equal to 400 - 500 mg% 2.0 - 21 ng/mL 70 - 110 mg/dL (diuresis greater than or equal to 180 mg/dL) 25 - 65 mg/dL 38 - 94 mg/dL 52 - 169 g/dL 246 - 455 g/dL 0.4 - 2.3 mEq/L 0.3 - 2.3 mEq/L 10 - 140 U/L 1.5 - 2.5 mg/dL 276 - 295 mOsm/kg 12 - 68 pg/mL 2.2 - 4.8 mg/dL 3.5 - 5.5 mEq/L 6.0 - 9.0 gm/dL 8 - 32 U/L 135 - 148 mEq/L 0.8 - 1.1 g/dL Less than 55 ng/mL 5 - 13 g/dL 5 - 9 gm/dL Less than 9 U/mL 8 - 25 mg/dL 3.5 - 7.7 mg/dL 2.5 - 6.6 mg/dL Less than 200 mg/dL desirable 30 - 75 mg/dL Less than 130 mg/dL desirable Greater than 40 - 170 mg/dL Greater than 35 - 135 mg/dL Straw

1.003 - 1.040 4.6 - 8.0 10 - 40 mEq/L Less than 8 mEq/L Less than 8 mEq/L 1 - 15 mg/dL 80 - 1300 mOsm/L 250 - 1100 IU / 24 hr 100 - 250 mg / 24 hr 110 - 250 mEq / 24 hr 1 - 2 g / 24 hr 100 - 140 mL / min 16 - 26 mg / kg / 24 hr 80 - 130 mL / min 10 - 20 mg / kg / 24 hr 6 - 9 mEq / 24 hr 450 - 900 mOsm / kg 0.9 - 1.3 g / 24 hr 35 - 85 mEq / 24 hr 0 - 150 mg / 24 hr 30 - 280 mEq / 24 hr 10 - 22 gm / 24 hr 240 - 755 mg / 24 hr 90 - 130 seconds 21 - 35 seconds 140,000 - 450,000 / ml 62 - 130% 10 - 14 seconds 32 - 45 seconds Less than 10 g/dL 160 - 450 mg/dL 3 - 7 minutes 11 - 15 seconds clear 40 - 85 mg/dL 290 - 298 mOsm/L 70 - 180 mm/H2O 15 - 45 mg/dL 0 - 5 cells 0 - 6 / L 2.5 - 4.2 L / min / m squared 4 - 8 LPM 40 - 70 g / m squared / beat 70 - 105 mm Hg 155 - 255 dynes / sec / cm to the negative 5

255 - 285 dynes / sec / cm to the negative 5 7 - 12 g / m squared / beat 60 - 100 mL / beat 40 - 85 mL / m squared / beat 900 - 1600 dynes / sec / cm to the negative 5 1970 - 2390 dynes / sec / cm to the negative 5 90 - 140 mm Hg 60 - 90 mm Hg 2 - 6 mm Hg; 2.5 - 12 cm H2O 60 - 75% 4 - 12 mm Hg 15 - 30 mm Hg 5 - 15 mm Hg 10 - 20 mm Hg 4 - 12 mm Hg 8 - 10 mm Hg 4 - 6 mm Hg 0 - 8 mm Hg

70 - 90 mm Hg 5 - 15 mm Hg or 5 - 10 cm H2O 7.35 - 7.45 35 - 45 mm Hg 22 - 26 mEq/L 96 - 100% 85 - 100 mm Hg -2 to +2 mmol/L 7.31 - 7.41 41 - 51 mm Hg 22 - 29 mEq/L 60 - 85% 30 - 40 mm Hg 0 to +4 mmol/L

page 1-8

Antiseizure Drugs in Canada

Drug Lorazepam Valproic Acid Acetazolamide

Marketed in Canada ATIVAN DEPAKENE DIAMOX

Common Use (Seizure Types) Status epilepticus. Atonic, myoclonic, infantile spasms, absence, tonic-clonic, simple partial, complex partial. Absence.

Possible Side Effects Excessive drowsiness, weakness, mental confusion. Nausea/vomiting, indigestion, sedation, dizziness, hair loss, tremor, change in liver function, weight gain, loss of coordination. Loss of appetite, thirst, headache, drowsiness.

Phenytoin

DILANTIN

Body hair increase, gum overgrowth, tremor, anemia, Tonic-clonic, simple partial, complex partial. loss of coordination, double vision, nausea/vomiting, confusion, slurred speech. Atonic, myoclonic, infantile spasms, absence, tonic-clonic, simple partial, complex partial. Nausea/vomiting, indigestion, sedation, dizziness, hair loss, tremor, change in liver function, weight gain, loss of coordination.

Divalproex Sodium

EPIVAL

Colbazam, Benzodiazepine

FRISIUM

Adjunctive therapy in broad range of seizures, including atonic, myoclonic, Sedation, tiredness, drowsiness, unsteadiness, infantile spasms, absence, generalized irritability, muscle weakness, weight gain. tonic-clonic, complex parial, simple partial.

Levetiracetam

KEPPRA

Partial (including secondary tonic-clonic). Somewhat effective against primary generalized tonic-clonic. Also effective against photoparoxysmal response.

Drowsiness, fatigue, asthenia (lack or loss of strength).

Lamotrigine

LAMICTAL

Simple partial, complex partial, generalized, Clumsiness, diplopia (blurred vision), sedation, epileptic syndromes. dizziness.

Phenobarbital, Barbiturate

LUMINAL

Myoclonic, partial and tonic-clonic.

Lethargy, drowsiness, hyperactivity (in children), mood changes, depression, behavioural/learning problems. Abrupt discontinuation produces withdrawal convulsions, and another GABA-A agonist such as benzodiazepine, paraldehyde should be substituted

Nitrazepam

MOGADON

Myoclonic and infantile spasms such as Wests Syndrome.

Drowsiness, fatigue, dizziness, mental confusion and lack of co-ordination.

Primidone

MYSOLINE

Drowsiness, appetite loss, irritability, nausea, Tonic clonic, simple partial, complex partial. dizziness, loss of coordination, hyperactivity, mood or personality changes, depression. Simple partial, complex partial, secondarily Drowsiness, dizziness, fatigue, clumsiness, generalized tonic clonic. weakness, trembling, increased appetite/weight gain. Lethargy, dizziness, nausea/vomiting, increase in salivation, increase in bronchial secretions, weight loss, slurred speech. Blurred vision, drowsiness, weakness/tiredness, increased appetite, hyperactivity, depression, dizziness, headache. With caution in pts with bone marrow depression and glaucoma. Drowsiness, dizziness, blurred vision, double vision, lethargy, nausea/vomiting, change in liver function, hyponatremia (low blood sodium).

Gabapentin

NEURONTIN

Clonazepam, Benzodiazepine

RIVOTRIL

Adjunctive therapy with atonic, myoclonic, infantile spasms, absence.

Vigabatrin

SABRIL

Simple partial, complex partial.

Carbamazepine

TEGRETOL

Tonic-clonic, simple partial, complex partial

Topiramate

TOPAMAX

Adjunctive therapy with partial and secondarily generalized seizures. Also effective with absence, tonic/atonic and Lennox-Gastaut Syndrome. Partial seizures (including secondary generalized tonic-clonic).

Difficulty concentrating, drowsiness, dizziness, loss of coordination, weight loss, numbness of the extremities. Drowsiness, fatigue, hyponatremia (low blood sodium), diplopia (blurred vision).

Oxcarbazepine

TRILEPTAL

Diazepam, Benzodiazepine Ethosuximide, Succinimide

VALIUM ZARONTIN

Acute and status epilepticus. Absence.

Drowsiness, fatigue, ataxia, also: confusion, slurred speech, blurred vision, tremors, headache, nausea, depression. Drowsiness, hyperactivity, nausea/vomiting, sleep disturbance. Drowsiness, fatigue, gastrointestinal upset (nausea/vomiting, diarrhea, loss of appetite), depression, reduced sweating, difficulty with concentration and speech.

Zonisamide

ZONEGRAN

Partial seizures (including secondary tonicclonic), primary generalized tonic-clonic. Somewhat effective against absence, myoclonic and tonic/atonic seizures.

Seizure type Simple partial

choice 1 Carbamazepine (alone or combination) Carbamazepine Lamotrigine Valproic acid Lamotrigine Lamotrigine Ethosuximide valproic acid Valproic acid diazepam Phenytoin

choice 2 Phenytoin

choice 3 Primidone Lamotrigine Oxacarbazepine Phenobarbital Zonisamide Oxcarbazepine Phenytoin

complex partial

Phenytoin

Tonic clonic

Carbamazepine

Absence myoclonic atonic status epilepticus Psychomotor

Zonisamide clonazepam Phenytoin Zonisamide Phenobarbital

Barbiturates Hydantoins Succinimides Sulfonamides

Phenobarbital / Primidone / Mephobarbital phenytoin / Mephenytoin / Ethotoin / Fosphenytoin (water-soluble prodrug of phenytoin) Ethosuximide / Methsuximide / Phensuximide Zonidamide / Trimethadione

Oxazolidinediones Benzodiazepine Micellaneous

Paramethadione / Diazepam / Lorazepam Clonazepam / Felbamate / Clorazepate dipotassium Carbamazepine / valprioc acid / Topiramate / Tiagabine / Levetiracetam Lamotrigine /Gabapentin / Oxcarbazepine / Pregabalin

Drug interactions of Phenytoin

Antilepileptic drugs increase its metabolism and then decrease the level of phenytoin; Increases the conversion of primidone to phenobarbital; Disulfiram, isoniazid, chloramphenicol, propoxyphene increase the level of phenytoin (decrease metabolism) Impair the efficacy of : corticosteroids, digitoxin, dozycycline, estrogens, furosemide, oral contraceptives, quinidine, rifampin, theophylline, tricyclic antidepressant, nutritional therapy. Coumarin and warfarin anticoagulants increase the serum phenytoin levels and prolong the serum half-life of phenytoin by inhibiting its metabolism. Interacts with diabetes and arthritis medications

4. Guide to Adult Dosing based predominantly on drug half-life. Initial Usual Dose Increment Maximum Primary AED ----------diphenylhydantoin 300 mg qd 50-100 mg/1-2week 400 mg (Dilantin) phenobarbital (Luminal) carbamazepine (Tegretol) primidone (Mysoline) ethosuximide (Zarontin) Secondary AED ------------90 mg qd 30 mg/2 wks 180 mg

200 mg tid 200 mg/3 days

1200 mg

250 mg tid

250 mg/2 wks

1500 mg

250 mg tid

250 mg/2 wks

1500 mg

valproate (Depakote) clorazepate (Tranxene) methosuximide (Celontin) clonazepam (Klonopin) gabapentin (Neurontin) lamotrigine (Lamictal) felbamate (Felbatol) tiagabine (Gabitril) topiramate (Topamax)

250 mg tid

250 mg/3 days

1500 mg

7.5 mg tid

7.5 mg/3 days

45 mg

300 mg tid

300 mg/week

1800 mg

0.5 mg tid

0.5 mg/3 days

3 mg

300 mg tid

300 mg/3 days

3600 mg

25 mg qd

25 mg/week

300 mg

4 mg qd

4 mg/week

32 mg

25 mg qd

25 mg/week

1600 mg

1. Drug Selection a. First correctly diagnose the type of epilepsy you are treating . This influences treatment, prognosis and genetic counseling. b. Second, be aware that no prospective, double-blind, cross-over (or randomized) study with sufficient numbers of patients followed long-term has been done to define which AED is best for most seizure types. c. Use the least expensive AED (all things being equal, like efficacy).

d. Use AEDs which can be taken once daily over bid/tid as this improves compliance. AEDs almost never need qid dosing (based on half-life or side-effects). e. For absence epilepsy (petit mal), ethosuximide (Zarontin) is the AED of choice. Valproate is equally effective--BUT--fatal complications (rare) make it an unacceptable first choice. f. Use valproate for absence plus myoclonic/clonic/tonic/atonic. g. Phenobarbital, primidone, phenytoin and carbamazepine are all equally effective against complex partial seizures. h. Valproate, clorazepate are second line drugs for partial seizures. i. Newer is not better, and almost certainly more expensive (Neurontin, Lamictal, Topamax, Gabitril)

2. Monotherapy a. No good study has been done to prove that multiple AED's are synergistic in the treatment of epilepsy. Of course, no good study says monotherapy is best either. b. Polypharmacy is expensive, increases side effects and increases the complexity of adjusting AEDs in the refractory patient. c. Recommend - Start with one AED and push the dose to clinical toxicity or seizure control. d. Recommend - Withdraw AED's that are not effective.

e. Recommend - Arbitrarily never have a patient on more than three (3) AED's. f. Recommend - Don't use combinations meds (e.g., Dilantin with phenobarbital). 3. Monitoring a. The quoted "therapeutic" range of blood levels for AED's is a

compromise between toxicity and efficacy. In fact, therapeutic means seizure control, which does not apply most of the time. If you must use blood levels, consider them a TARGET range when first instituting treatment. b. AED levels can never substitute for clinical judgment.

5. Pearls a. Administer two (2) multiple vitamin pills (800 IU vit.AED levels to assess: c. Use D) qd to prevent anticonvulsant osteomalacia. i. Poor clinical control (compliance, metabolism) b. Use bromides to treat epilepsy in porphyria. ii. Dose-related side effects iii. Drug or disease interaction REFERENCES iv. "Routine" levels on controlled, nontoxic patients are not 1. International League Against Epilepsy. Proposal for Revised Clinical and indicated. Electroencephalographic Classification of Epileptic Seizures, Epilepsia 1981;22:489-501. (Highly recommended.) 2. Coatsworth, J.J. Studies on the Clinical Efficacy of Marketed Antiepileptic Drugs, NINDS Monograph No. 12, 1971. 3. Reynolds, E.H., et al. Phenytoin Monotherapy for Epilepsy, Epilepsia 1981;22:475-488. 4. Olanow, C.W. and Finn, A.L. Phenytoin, Pharmacokinetics and Clinical Therapeutics, Neurosurgery 1981;8:112-117. (Required reading - illustrates all important principles about ANY AED.) 5. Woodbury, D.M., Penry, J.K, and Schmidt, R.P. Antiepileptic Drugs, Raven Press, NY, 1972. (A reference book.) 6. Beran, R.G., et al. Doctors' Perspectives of Epilepsy, Epilepsia 1981;22:397-406. 7. Hahn, T.J. and Avioli, L.F. Anticonvulsant Osteomalacia, Arch Intern Med 1975;135:997-1000. 8. Bonkowsky, H.L., et al. Seizure Management in Acute Hepatic Porphyria,

Neurology 1980;30:588-592.

Severe Side Effects May intensify feelings of depression. Hypersensitivity, allergic reaction, impaired liver function, low blood platelet count, stupor, coma. Hypersensitivity to sun, allergic rash, fever, urinary difficulties. Hypersensitivity, allergic reaction

Hypersensitivity, allergic reaction, impaired liver function, low blood platelet count, stupor, coma.

Hypersensitivity, allergic reaction.

Generally well tolerated. Slightly decreased red and white blood cell counts occasionally seen.

Allergic reaction, severe skin rash.

Hypersensitivity, allergic reaction.

Hypersensitivity, allergic reaction.

Hypersensitivity, allergic reaction.

(Rare) CNS toxicity, vision disturbances, rhinitis, pharyngitis.

Hypersensitivity, allergic reaction.

Allergic reaction, partial loss of vision.

Hypersensitivity, allergic reaction, impaired liver function, low white blood cell count.

Allergic reaction, 1.5 % incidence of kidney stones.

Allergic reaction.

Allergic rash, hallucinations, rage, anxiety, haematological effects, respiratory depression. Hypersensitivity, allergic reaction.

Kidney stones, allergic rash.

choice 4 Gabapentin levetiracetam Zonisamide valproic acid Primidone Topiramate Tiagabine Phenobarbital Topiramate Tiagabine

Felbamate (alone or combination)

mpin, theophylline, tricyclic antidepressant, vitamin D, and enteral

by inhibiting its metabolism.

ontoxic patients are not

pg 1-4

Drug

Pronunciation

Target/Mechanism

Nitrogen Mustards

Mechlorethamine Melphalan Chlorambucil Cyclophosphamide Ifosfamide Carmustine Lomustine Streptozotocin Thiotepa Mitomycin C Bisulfan Procarbazine Dacarbazine Cisplatin

me-klor-ETH-a-meen mel-FAL-an klor-AM-bu-sill sye-klo-FOSS-a-mide eye-FOSS-fa-mide car-MUS-teen loe-MUS-teen strep-toe-ZOE-toe-sin thi-o-TEE-pa mi-to-MYE-sin C bi-SUL-fan pro-KAR-ba-zeen da-KAR-ba-zeen SIS-pla-tin KAR-bow-pla-tin camp-toe-THEE-sin toe-poe-TEA-can eye-RIN-o-TEA-can

bifunctional, bind to DNA bases, crosslink same as mechlorethamine, less reactive same as mechlorethamine, less reactive bifunc, must be activated by p450 structural analog of cyclophosphamide lipophilic, (aka BCNU) lipophilic antibiotic deriv. specific to beta-islet cells antibiotic deriv. (streptomyces) alkane sulfonate methylating agent, inhibits DNA/RNA synthesis methylating agent, inhibits DNA/RNA synthesis crosslinking of DNA to itself or other macromols crosslinking of DNA to itself or other macromols intercalation, blocks ligation of DNA intercalation, blocks ligation of DNA intercalation-prodrug activated by carboxyesterase investigational, minor groove binding agents aka Dactinomycin, intercalates, causes DNA bends, may inhibit RNA pol, antibiotic non-intercalative, topo-II drug non-intercalative, topo-II drug intercalative, topo-II, anthracycline antibiotic intercalative, topo-II, anthracycline antibiotic same as anthracyclines, less cardiac toxicity (aka Oncovin), block mitosis in metaphase block mitosis, decrease dynamics of MTs less toxic, same mechanism as other vincas decrease MT dynamics, may polymerize MTs decrease MT dynamics, may polymerize MTs folate mimic, no prod. THF (DHFR inhib), no A,G, T

Aziridines Nitrosoureas

Alkylating Agents

Platinum Compounds

Carboplatin Camptothecin

topo-I

Topotecan Irinotecan(CPT-11) MGBA's Actinomycin D Etoposide

Mitotic Spindle poisons Topoisomerase targeted drugs

ac-TIN-o-mye-sin D ee-TOE-pa-zide ten-IH-poe-zide DOX-a-roob-i-sin DAWN-a-roob-i-sin MITE-o-ZAN-trone vin-CRIS-teen vin-BLAS-teen vyn-NO-rel-bean pac-li-TAX-il doe-si-TAX-il meth-o-TREX-ate

topo-II

Teniposide Doxorubicin Daunorubicin Mitoxantrone

vinca alkaloids

Vincristine Vinblastine Vinorelbine

taxanes
folate

Pacitaxel Docetaxel Methotrexate

r Therapy Drugs

Hydroxyurea

hy-DROX-ee-u-ree-a 5-F U ??? 5- d F-U cap-ih-SIT-a-bean 6 thye-o-GUA-neen A-za-THYE-o-PUR-een gem-SITE-a-bean err-a-BIN-o-side flu-DARE-a-bean A-za-CITE-ih-deen

inhibits ribonucleotide reductase, NDPs and dNDPs 5F-dUMP binds to TS -> no TMP. Also ds breaks " " TP activated, generates 5-FU at site of tumor inhibit purine synthesis, get incorporated into DNA converted to mercaptopurine -then same action disrupt DNA pol, incorporate for C, inhibit elongation (aka Cytarabine, ara-c), pyrimidine antag, inhib elong purine antagonist, incorporates in DNA/RNA

purine synth pyrimidine synth

Antimetabolite Cancer Therapy Drugs

5-fluorouracil (5-FU) ftorafur 5-dFU Capecitabine 6-thioguanin 6-mercaptopurine Azathiopurine Gemcitabine Cytosine arabinoside Fludarabine 5-azacytidine 2-chlorodeoxyadenosine Gleevec Anti-angiogenesis

6-mer-CAP-toe-PUR-een "

Nucleoside analogs

New Therapies

GLEE-vec

signal transduction (TK) inhibitor protease inhibitors, endothelial proliferation inhibitors

proteosome

Bortezomib Velcade

BOAR-te-ZO-mib VEL-cade

targets proteosome, possible prevents degredation of regulatory apoptotic proteins

Significant Side effects

Administration

BMS, severe nausea/vomit, vessicant BMS, amenorrhea, sterility BMS, amenorrhea, sterility Hemorrhagic cystitis(from acrolein, MESNA prevents), BMS HEMORRHAGIC CYSTITIS (even more), BMS BMS BMS BMS, nephrotoxicity, hepatotoxicity, DM BMS fever, mod nausea/vomit, BMS, diarrhea, hemolytic uremic syndrome (HUS), nephotox, hepatic veno-occlusive dx. BMS, pulmonary fibrosis, hepatic v-o, skin pigment changes BMS, peripheral neuropathy, sterility, 2 leukemia BMS, "flu-like" sx, Budd Chiari sx, photosensitivity severe nausea/vomit, nephrotox, ototox, neurotox BMS, much less toxic than cisplatin myelosuppression (neutropenia), diarrhea myelosuppression (neutropenia), diarrhea myelosupp (neutropenia),hepatotoxicity in Gilbert's dx

IV only oral oral IV/oral IV only IV oral IV

oral/parenteral IV, IP IV IV

myelosuppression, oral and gastrointestinal ulceration myelosuppression (leukopenia), mucositis, anaphylaxis myelosuppression, mucositis, anaphylaxis cardiotoxicity, BMS, mucositis, anaphylaxis, severe alopecia cardiotoxicity, BMS, mucositis, anaphylaxis, severe alopecia same as anthracyclines, less cardiac toxicity peripheral neuropathy, hepatotox, phlebitis, cellulitis potent myelosuppression potent myelosuppression myelosupp (neutropenia), periph neurop, hypersensitivity less periph neurop, neutropenia, also hypersensitivity mucositis,nephro-,hepato-pulmono-neurotox"Leucovorin rescue"

IV IV/oral IV IV IV IV IV IV/IM/oral

BMS. Tx enhanced w/ leucovorin (enhances 5F-dUMP to TS) giving 5-ethynyluracil enhances oral delivery of 5-FU by inhibiting dihydropyrimidine dehydrogenase in intestines. " BMS. Drug inactivated by XO, caution when coadministered with allopurinol. myelosuppression myelosuppression (granulosytopenia) myelosuppression

IV/oral oral oral oral oral oral oral IV IV IV

BMS: bone marrow suppression

Therapeutic Uses

Hodgkins (MOPP) mycosis fungoides (lymphoma multiple myeloma CLL, indolent lymphomas, Waldenstrom's Sx, macroglobulinemia non-Hodgkins (CHOP), breast cancer, also autoimmune dx. sarcomas and other cancers brain tumors brain tumors insulinomas, islet cell tumors breast cancer, bladder ca as an intravesical instillate rectal and pancreatic ca. bladder ca. as intravesical instillate used in high dose for BMT preparation MOPP for Hodgkins ABVD for Hodgkins epithelial and testicular - in combo w/ vinblastine and bleomycin, ovarian ca. in combo w/cyclophosphamide, alone for bladder ca solid tumors, colorectal, ovarian, lung other adult cancers solid tumors, metastic ovarian cancer solid tumors, in combo with 5-FU for advanced colorectal ca.

in combo w/ surgery and vincristine for Wilm's tumor, w/methotrexate for gestational choriocarcinoma, Ewing's sarcoma, embryo rhabdosarcoma

oat cell carcinoma of lung, refractory testicular ca. breast ca, lymphomas, Hodgkins, sarcomas, ALL AML and ALL ALL, lymphomas, Hodgkins (MOPP), other childhood malign. germ cell ca,w/bleomycin,cisplatin for test.ca, Hodg/nonH lymph non small-cell lung and breast cancer ovarian and breast cancer metastatic breast cancer breast, colorectal, lymphoma (Burkitt's), ALL, osteogenic sarc

leukemias, head and neck ca colorectal and breast ca, combo with others " " metastatic breast cancer resistant to first line druge used for leukemias, maintanance of remission in ALL ALL/AML in combo w/daunorubicin and cytarabine " locally advanced or metastatic pancreatic ca AML in combo w/6-TG and daunorubicin CLL , hairy cell leukemia

BCR-ABL CML

myeloma - upregulates NF-kappaB