Pharmacology

I. Introduction & Basic Principles

Pharmacology & Toxicology
Study of substances that interact with living systems through chemical
processes especially by:
Modifying the function of regulatory molecules
Activating normal body processes
Inhibiting normal & abnormal body processes
For pharmacists, the focus of pharmacology is on substances used to prevent,
diagnose and treat diseases.
Toxicology is the branch of pharmacology that deals with the undesirable effects of
chemicals on living systems
General Principles
Drugs
Substances that bring about changes in biological functions through chemical
actions by agonizing or antagonizing a biologic function.
Maybe endogenous or exogenous.
Poisons
Drugs that have almost exclusively, harmful effects.
Toxins
Poisons of biological origin.
Pharmacogenomics
Studies the one drug does not fit all concept
Looks at the inherited variations in genes that dictate drug response
Drug-Body Interactions
Pharmacodynamics studies the fundamental action of drugs on a
physiological or biochemical level.
(What the drug does to the body)

Pharmacokinetics studies drug concentration in body fluids and tissues and

the factors that influence how these concentrations vary with time.
(What the body does to the drug)

Drug-Receptor Interactions
Direct-acting Agonists
Bind and activate receptors to bring about the effect.
Indirect-acting Agonists
Inhibit molecules responsible for terminating the action of an endogenous agonist.
Partial Agonists
Bind and activate receptors in a much more weaker fashion.
Inverse Agonists
Bind to receptors and promote the formation and stabilization of inactive receptors.

Antagonists
Bind to receptors and competitively prevent binding of other molecules; can be
reversible or irreversible.
Allosteric Activators and Inhibitors
Bind to the receptor but do not prevent the binding of agonists.

Transport Mechanisms
1.) Passive Diffusion
2.) Active Transport
3.) Facilitated Diffusion
4.) Endocytosis and Exocytosis
5.) Pinocytosis
6.) Convective Transport

Special Carriers: p-glycoprotein, re-uptake proteins

Drug Receptors are Macromolecules

Most receptors are proteins and its polypeptide sequence and composition mediates
preferential binding of ligands.
Traditionally, receptors were more recently discovered than the drugs that bind them.
Now, due to the advancements in molecular biology, receptors are more abundantly
discovered compared to ligands that bind them.
Key Terms
Therapeutic Dose - Produces the desired drug response

Toxic Dose - Above the therapeutic dose and produces the undesirable
effects/deleterious effects
Margin of Safety/Therapeutic Index: Ratio of the minimum dose that produces
toxicity and the minimum dose that gives the therapeutic response in a patient
population
*When = or < 2: high risk of toxicity
Affinity - Measure of the tightness by which a drug binds to the receptor.
Intrinsic Activity - Measure of the ability of a drug to produce an effect once bound
to its receptor.
Dose-response Curves

Efficacy
Ceiling Dose
Potency
ED
50
TD
and LD
50
50
In most physiological conditions, all receptors may not be necessarily occupied to
produce maximum effect.

Variations in Responsiveness
Variations maybe due to:
1) Idiosyncracy
Genetic differences in drug metabolism
Immunologic reactions i.e. drug allergy
2) Hyporeactivity and Hyperreactivity
3) Tolerance
Response decreases due to continued drug administration
When the response diminishes rapidly after drug administration, it is
termed as tachyphylaxis.
Factors that may cause variations in response
Ability of drug to induce tolerance or tachyphylaxis
Age
Sex
Body size
Disease states
Genetic factors
Co-administered drugs
Protein-mediated Pharmacodynamics
I. Structural Proteins
Usually the cytoskeleton especially tubulin

Tubulin is essential for:

o Chemotaxis
o Cell structure and localization of organelles
o Migration of divided chromosomes during mitosis
Sample Drugs that Target Tubulin:
o Colchicine
o Griseofulvin
o Vinca Alkaloids
o Albendazole, Mebendazole, Thiabendazole
Regulatory Proteins

II.

1) Voltage-gated Ion Channels

E.g. Voltage-gated Sodium, Potassium & Calcium Channels
2) Carrier/Transport Proteins
E.g.

+ +
+ +
Na -K ATPase Pump and H -K ATPase

Pump

3) Enzymes
E.g.

COX, MAO, ACE, AChesterase

4) Receptors
a. Type I: Ligand-Gated Ion Channels/Ionotropic Receptors

Onset of action is quick.

E.g.
Nicotinic ACh Receptors (NAChRs), GABA

Receptors

b. Type II

GTP-binding Signal Transducer Protein (G-protein) Coupled

Receptors (GPCRs)/Metabotropic Receptors

Can be:
b.1

G : E.g. and Adrenoreceptors

s
1
2

b.2

G : E.g. Central Pre-synaptic Adrenoreceptors

i
2
G : E.g. Adrenoreceptor and M Cholinoceptor
q
1
3

b.3
c. Type III

Enzyme-Linked Receptors

Subject to down-regulation by ligand-induced endocytosis with

subsequent receptor degradation

E.g. Insulin Receptor

d. Type IV

Gene-Transcription Receptors

Onset of action is usually from 30mins to several hours

E.g. Glucocorticoids, Mineralocorticoids, Steroidal Hormone

Receptors

Secondary Messengers:
a. cAMP & cGMP
b. IP3 & DAG
cAMP
Synthesized by adenylyl cyclase and degraded by phosphodiesterase
Increases contractile force of heart, increased heart rate and bronchial smooth
muscle relaxation via -receptor agonism
Conserves water through kidneys via Vasopressin agonism
cGMP
Synthesized by guanylyl cyclase and degraded by phosphodiesterase
Relaxes vascular smooth muscles
NO activates guanylyl cyclase
IP3 & DAG
Hydrolytic products obtained from Phosphatidylinositol-4,5-bisphosphate (PIP2)
via phospholipase C (PLC)
DAG remains membrane bound and activates Ca2+-dependent protein kinase
C.
IP3 diffuses to the cytoplasm and stimulates release of Ca2+ from the
sarcoplasmic reticulum.
IP3 is inactivated by dephosphorylation while DAG is inactivated by
phosphorylation which are converted back to phospholipids.
Non-protein-mediated Pharmacodynamics
I. Direct Chemical Interactions:
a. Neutralization Reactions
E.g. Antacids
b. Complexation/Chelation
E.g. Deferoxamine, Penicillamine
II.

Colligative Mechanisms
E.g. Mannitol

III.

Counterfeit Incorporation Mechanisms

E.g. Purine and Pyrimidine Analog Antivirals, Flucytosine

Antagonism

Classified according to:

I. Reversibility
II.
Competitive Nature
III. Mechanism of Antagonistic Action
Reversibility
1) Reversible Antagonists
Effect is limited by time and agonist concentration.
Involves weak bonds
Sometimes considered as competitive
2) Irreversible Antagonists
Effect is permanent.
Involves strong covalent bonds
Not reversed by increasing agonist concentration
Sometimes considered as non-competitive
Competitive Nature
1) Competitive Antagonists
Antagonist binds to same receptor site as the agonist and the effect can
be reversed by increasing agonist concentration.
2) Non-competitive Antagonists
Antagonist may bind to the same receptor site or a different receptor site
as compared to the agonist.
The effect is only reversed if the antagonist is weakly bound to a different
receptor site.
Mechanism of Antagonistic Action
1) Physiologic Antagonists
Antagonist exerts an effect exactly the opposite of an agonist by binding
to a different receptor system.
2) Pharmacologic/Pharmacodynamic Antagonists
Antagonist blocks the effect of an agonist by competitively binding to the
same receptor system.
3) Chemical Antagonists
Antagonist reduces or diminishes the effect of another drug by chemical
interactions
4) Pharmacokinetic Antagonists
Antagonist reduces or diminishes the effect of another drug either by:
Impairing its absorption and distribution
Enhancing metabolic degradation and elimination
Some Pharmacokinetic Principles:
Kinetic Orders

Volume of Distribution (Vd)

Relates the amount of drug in the body to the concentration of drug in blood or
plasma
Clearance (CL)
Predicts rate of elimination in relation to drug concentration
Half-life (t 1/2)
Time required to change the amount of drug in the body by one-half during
elimination or during a constant infusion.
Bioavailability (F)
Fraction of unchanged drug reaching the systemic circulation following any route of
administration.
Biotransformation
Biotransformation converts drugs and xenobiotics into more water soluble
metabolites.
Some drugs are metabolized to equally active metabolites or even more active
Some metabolites produced even have a different pharmacological effect.
Drug metabolizing enzymes have been exploited in the design of prodrugs.
General Pathways of Drug Biotransformation

Phase I: (Functionalization Reactions)

Oxidation, Reduction and Hydrolysis

Polar functional groups are introduced to produce a more water-soluble
compound out of the drug or xenobiotic. (e.g. OH, COOH, NH2, SH)
This can be achieved by direct introduction of the functional groups or by
unmasking existing functional groups.
Provides handles for Phase II Reactions

Phase II: (Non-functionalization Reactions)

Attach small, polar, and ionizable endogenous compounds to handles
provided by phase I reactions or parent compounds that already have suitable,
existing functionalities.
*Endogenous molecules include glucuronic acid, sulfate, glycine or other amino
acid
Also attenuate or terminate biologic activity
Or protect the body from chemically reactive metabolites
(Glutathione Conjugation)
Dominant Phase I : Oxidation

Can be CYP-mediated or non-CYP mediated (MAO and dehydrogenases)

Some Key Features of Some CYP Isozymes:

CYP 1A2 - Induced by Benzo[]pyrene, Cruciferous Veggies and

Omeprazole

CYP 2C9, 2C19 and 2D6 - Subject to genetic polymorphisms

CYP 3A4
o Most Dominant CYP
o Accounts for the metabolism of >60% of drugs
o Inhibited by Grapefruit Juice

Dehydrogenases are also subject to genetic polymorphisms

Dominant Phase II: Glucuronic Acid Conjugation

Most common conjugative pathway in drug metabolism because:

a. Readily available supply of glucose.
b. Numerous functional groups can combine with glucuronic acid.
c. UDP-glucuronyltransferase is the most dominant transferase

Glucuronide conjugates may be excreted in the bile and maybe susceptible to

hydrolysis by glucuronidases in the GIT hence, may undergo enterohepatic
recycling.

Glucuronidating processes in neonates are not fully developed and are subject
to genetic polymorphisms.

II. Autacoids & Eicosanoids

Histamine
Biosynthesized from histidine via histidine decarboxylase
Most histamine is synthesized & stored in mast cells & basophils.
Released by antigens, xenobiotics or via interaction of IgE-antigen complexes
with membranes of storage cells
In gastric mucosa, Histamine is released from enterochromaffin-like cells via
gastrin & ACh.
General Pharmacological Considerations:
Symptomatic treatment of rhinitis, chronic idiopathic urticaria & other
histamine-related diseases.
Some have anti-emetic actions and anti-vertigo effects.
Some produce pronounced sedation

 Some have strong anti-cholinergic properties due to affinity for muscarinic

receptors.
First Generation (Classical) Antihistamines are lipophilic hence they can cross
BBB.
Second Generation Antihistamines are less sedating.
First

Generation Antihistamines:
Aminoalkylethers/Ethanolamines
Ethylenediamines
Piperazines (Cyclizines)
Alkylamines/Propylamines/ Monoaminopropyl Derivatives
Phenothiazines

Aminoalkylethers/Ethanolamines
Most sedating class of antihistamines
Strongest anti-muscarinic properties
1) Diphenhydramine (Allerin, Benadryl AH)
Also used for Parkinsons Disease & as a Sedative-Hypnotic
2) Dimenhydrinate (Dramamine)
8-chlorotheophyllinate salt of Diphenhydramine
For prevention of motion-sickness & hyperemesis gravidarum
3) Doxylamine (Unisom)
Sedative-Hypnotic
4) Carbinoxamine
5) Clemastine (Tavegyl, Tavist)
Ethylenediamines
1) Tripelennamine
2) Pyrilamine
3) Antazoline (+ Tetrahydrozoline: Spersallerg)
Applied ocularly

Piperazines (Cyclizines)
1) Cyclizine & Meclizine (Bonamine, Dizitab)
primarily in the prophylaxis & treatment of motion sickness
2) Chlorcyclizine
3) Hydroxyzine (Iterax)
Also used as a sedative-hypnotic
4) Buclizine (Appebon, Propan)
Appetite stimulant
Alkylamines/Propylamines/ Monoaminopropyl Derivatives
Most active H Antagonists
1
1) Pheniramine
Least potent; used as an ocular decongestant in conjunction with -1
agonists (Naphazoline: Naphcon-A , Optaphen)
2) Chlorpheniramine & Brompheniramine
Common components of OTC cold medications
3) Dimethindene (Fenistil Gel)
Phenothiazines

1) Promethazine (Phenergan)
Added with other anti-psychotics
Also for motion-sickness & as an anti-emetic
2) Cyproheptadine (Periactin)
For Carcinoid Syndrome
Second Generation Antihistamines
First Members include Terfenadine & Astemizole (Arrhythmogenic: Banned)
1) Fexofenadine (Fenafex, Sensitin, Telfast)
Metabolite of Terfenadine, non-arrhythmogenic
2) Acrivastine(+ Pseudoephedrine)
3) Loratadine (Allerta, Claritin; +Pseudoephedrine: Clarinase)
Desloratadine is the active metabolite & is now also marketed as Aerius,
Clarinex
4) Cetirizine (Virlix, Alnix, Zyrtec)
Metabolite of Hydroxyzine
Levocetirizine is its active metabolite & is also marketed as Xyzal
Serotonin
Biosynthesized from tryptophan via tryptophan hydroxylase and 5hydroxytryptophan decaboxylase.
In the pineal gland, serotonin serves as a precursor for melatonin, a
melanocyte-stimulating hormone.
Serotonin is metabolized by MAO to 5-hydroxyindoleacetaldehyde and is further
oxidized by aldehyde dehydrogenase to 5-hydroxyindoleacetic acid (5-HIAA).
Important neurotransmitter, a local hormone in the gut, a component of the
platelet clotting process, and plays a role in migraine headache
CNS Effects: mood, sleep, appetite and temperature regulation, pain perception,
blood pressure regulation and, vomiting.
Serotonin Syndrome
Condition associated with skeletal muscle contractions and is commonly
precipitated when MAO inhibitors are given with serotonin agonists, especially
SSRIs
Although the hyperthermia of serotonin syndrome results from excessive
muscle contraction, serotonin syndrome is probably caused by a central
nervous system effect of these drugs.
Precipitated by: SSRIs , Second Generation Antidepressants, MAOIs , Linezolid,
Tramadol, Meperidine, Fentanyl, Ondansetron, Sumatriptan, MDMA, LSD, St.
John's Wort, Ginseng
Serotonin Agonists
1) 5-HT
1A
Buspirone (Buspar) (partial agonist): Sedative-hypnotic and Anxiolytic
2) 5-HT
1B/1D
Sumatriptan (Imigran), Naratriptan, Rizatriptan, Zolmitriptan (Zomig),
Almotriptan, Frovatriptan & Eletriptan: For migraine HA
3) 5-HT
2A
Ergotamine (Partial Agonist): For migraine HA; co-administered with
Caffeine
Methylergometrine and Ergonovine (Partial Agonist): Oxytocic
4) 5-HT
4

Tegaserod, Cisapride, Prucalopride: For irritable bowel syndrome (IBS)

Serotonin Antagonists
1) 5-HT
2
Phenoxybenzamine and Cyproheptadine: For Carcinoid Syndrome
Ketanserin and Ritanserin: Anti-platelet Agents
2) 5-HT
2A
Methysergide (Partial Agonist): Tocolytic
3) 5-HT
3
Ondansetron (Zofram), Granisetron (Kytril), Ramosetron (Nasea),
Tropisetron (Navoban), Dolasetron and Palonosetron: Anti-emetic for
Chemotherapy-Induced N&V (CINV)
Alosetron: for IBS
Ergot Alkaloids
Produced by Claviceps purpurea
In medieval times, ergot poisoning was called St. Anthony's Fire.
Accidental ingestion in contaminated grains: Ergotism.
Effects of poisoning: dementia with hallucinations, prolonged vasospasm and
stimulation of uterine smooth muscle contraction.
1) Bromocriptine, Pergolide and Cabergoline
Has central and pituitary dopamine receptor agonistic activity
2) Methysergide, Ergonovine & Ergotamine
3) Lysergic Acid Diethylamide (LSD)
Agonizes dopamine and serotonin receptors in the CNS
Prostaglandins
20-carbon fatty acid derivatives produced by oxidative metabolism of
eicosatetraenoic acid
Eicosanoid Biosynthesis

Precursor is released via PLA2 w/c is stimulated by tissue damage, toxin exposure or by
hormone stimulation

Also released by combinatorial actions of PLC & Diacylglycerol/Diglyceride Lipase.

PLA2 is inhibited via Glucocorticoid-induced synthesis of lipocortins or annexins.

o COX is widely distributed while COX is expressed by inflammatory & immune

1
2
cells.
o COX gene expression is also inhibited by Dexamethasone.
2

Eicosanoid Analogues
1) PGF2 Analogues:
a. Dinoprost

Oxytocic; no longer for human use

b. Carboprost

Oxytocic; also for glaucoma

c. Latanoprost (Xalatan; + Timolol: Xalacom), Bimatoprost (Lumigan), Travoprost,

Unoprostone, Tafluprost

For glaucoma

2) PGE2 Analogue:
a. Dinoprostone

Natural PG used to terminate pregnancy from 12 th week to 3rd trimester & to

evacuate the uterus after miscarriage

3) PGE1 Analogues
a. Alprostadil

Naturally occuring PG and is used to patent ductus arteriosus in infants with

congenital defects that restrict pulmonary blood flow.

b. Misoprostol

Gastroprotective/cytoprotective and anti-hypersecretory properties

Formerly used for NSAID induced ulcers; abortifacient

4) PGI2 Analogues:
a. Epoprostenol, Treprostinil, Iloprost, & Beraprost (Dorner)

For primary pulmonary HTN (PPH)

b. Uniprost

For critical limb ischemia

III. Autonomic Nervous System Drugs

Adrenergic Agents

Enhance or reduce various components of the sympathetic nervous system.

Drugs that stimulate or mimic the effects of sympathetic nervous activity: adrenergic
stimulants, adrenergic agonists or sympathomimetics

Drugs that decrease or block the effects of sympathetic nervous activity: adrenergic
blockers, anti-adrenergics, adrenergic antagonists, sympathetic antagonists,
sympathoplegics or sympatholytics

Adrenergic neurotransmitters include: Dopamine, Norepinephrine, & Epinephrine

Drug Inhibiting Catecholamine Biosynthesis:

Metyrosine

Metyrosine

MOA: Inhibits tyrosine hydroxylase

Pre-operative mgt of pheochromocytoma

S/E: Sedation (Most Common), Crystalluria

Drugs Inhibiting Catecholamine Storage

Reserpine
Reserpine (Centrally & Peripherally-Acting)
Prototype; inhibits storage of catecholamines & 5-HT at pre-synaptic vesicles of the CNS &
Epi in the adrenal medulla
S/E: Sedation & Depression
Drugs Inhibiting Catecholamine Release
Guanethidine & Guanadrel
Guanethidine & Guanadrel (Pure Peripherally-Acting)
Inhibit release of catecholamines by making storage vesicles less responsive to nerve
impulses & undergo uptake into pre-synaptic terminals and replace NE from storage
vesicles
S/Es: Orthostatic Hypotension
Other Drugs Acting on Neurotransmission
1) Release Stimulants
Amphetamine, Methamphetamine, Hydroxyamphetamine, Tyramine &
Pseudoephedrine
2) Reuptake Inhibitors
TCAs & Cocaine
3) Metabolic Degradation Inhibitors
MAOIs & COMTIs
Direct Acting Sympathomimetics:
Endogenous Catecholamines
Selective -agonists
1
Non-selective , -agonists
1 2
Selective -agonists (Centrally-Acting)
2
Selective -agonist
1
Non-Selective , -agonist
1

Selective 3-agonist
Selective 2-agonists

Endogenous Catecholamines
1) Dopamine

2) Norepinephrine
3) Epinephrine
Dopamine (Docard)
Management of cardiogenic shock/acute CHF especially if complicated w/ decreased urine
output (CC) & increased blood volume.
Dose
Receptor Effect
(Infusion
Selectivit
Rate)
y
1-3
D1 & D5
Renovasodilation
g/kg/min
2-5
1
Inotropism
g/kg/min
> or = 5
1
Vasoconstriction
g/kg/min
Norepinephrine (Levophed)
DOC: septic shock; alternative cardiac stimulant for acute CHF
Epinephrine

DOC: Anaphylactic Shock

1st Line Cardiac Stimulant in ACLS (1mg every 3-5mins)

Added to local anesthetics

Management of open-angle glaucoma

*Dipivefrin

Epi prodrug with hydroxyl groups esterified with tert-pentanoic acid/pivalic acid
(lipophilicity)

Selective -agonists
1
Phenylephrine
Nasal decongestant, mydriatic & management of acute hypotension
Methoxamine & Midodrine (Prodrug converted to Desglymidodrine)
Symptomatic treatment of orthostatic hypotension

Non-selective , -agonists
1 2

Naphazoline, Tetrahydrozoline (Visine, Eye-Mo), Xylometazoline (Otrivin) &

Oxymetazoline (Drixine)

Nasal & opthalmic decongestants

S/E:

HTN, Urinary Retention, Tolerance w/in 5 days

Selective -agonists (Centrally-Acting)

2
1) Clonidine (Catapres)
May briefly exert an initial vasoconstricting effect followed by a much longer lasting
anti-hypertensive effect
Nasal decongestant when administered as a nasal spray
S/E: Rebound Hypertension
2) Guanfacine & Guanabenz
Guanfacine & Clonidine are now also indicated for ADHD.
3) Methyldopa (Aldomet)

Converted to -methyldopamine (false neurotransmitter) to -methylnorepinephrine

Management of HTN in pregnant patients

S/Es: Sedation (Most Common), (+) Coombs Test, Hepatotoxic

4) Tizanidine (Sirdalud)

For muscle spasms due to MS or spinal injury

5) Apraclonidine & Brimonidine (Alphagan)

For open-angle glaucoma

Selective -agonist
1
1) Dobutamine (Dobuject, Inocard)

Management of cardiogenic shock/acute CHF

Non-Selective , -agonist
1 2
1) Isoproterenol

Formerly used for asthma, now an inotropic

Selective -agonist
3
1. Mirabegron

For overactive urinary bladder

S/Es: HTN, UTI

Selective -agonists
2
A. For Asthma:
1. Salbutamol/Albuterol (Ventolin), Levalbuterol, Metaproterenol/Orciprenaline
(Alupent), Pirbuterol (Maxair) & Terbutaline (Bricanyl)
Relievers for acute attacks of asthma
2. Formoterol (Foradil, + Budesonide; Symbicort ), Arformoterol, Salmeterol
(+Fluticasone; Seretide), Bambuterol, Clenbuterol & Indacaterol
Longer acting hence used as preventers/controllers of asthmatic attacks & COPD
B. For Tocolysis & Mgt of Fetal Distress
1. Isoxsuphrine (Duvadilan), Terbutaline & Ritodrine
Indirect-Acting Sympathomimetics
1. Amphetamine, Methamphetamine, & Hydroxyamphetamine
2. Pseudoephedrine (+Loratadine; Clarinase)
Nasal decongestant & principally acts indirectly unlike Ephedrine
3. Tyramine
Mixed Direct-Indirect-Acting Sympathomimetics
1. Ephedrine/Ma Huang
Bronchodilator, management of hypotension & narcolepsy
2. Phenylpropanolamine
Sympatholytics:
Non-selective -antagonists
Selective 1-antagonists
Selective 2 Antagonists
-antagonists (Non-selective)
Selective 1-antagonists
Non-selective -antagonists
1. Tolazoline & Phentolamine
Reversible antagonists
1st Line for HTN due to Pheochromocytoma
Management of Raynauds Syndrome
Phentolamine is also used in erectile dysfunction and in the diagnosis of
Pheochromocytoma.
2. Phenoxybenzamine
Irreversible antagonist

Pre-operative mgt of HTN in Pheochromocytoma

Management of Raynauds Syndrome & Carcinoid Syndrome

Selective -antagonists
1
Prazosin, Terazosin (Hytrin), Doxazosin (Alfadil), Tamsulosin (Prozelax) & Alfuzosin (Xatral)

1o use: Urinary Retention and HTN in patients w/ BPH

Also used for Pheochromocytoma

Tamsulosin is available in a fixed-dose combination w/ Dutasteride

S/Es: First-Dose Phenomenon & Syncope

Selective Antagonists
2
1. Yohimbine
Used for hypotension due to autonomic insufficiency & also for erectile dysfunction
2. Mirtazapine
Antidepressant

-antagonists (Non-selective)

Propranolol (Inderal), Penbutolol, Pindolol (Visken), Carteolol, Carvedilol (Dilatrend)

Sotalol, Labetalol, Timolol (Nyolol), Nadolol, Metipranolol (Beta-Ophtiole)
Not for patients with bradycardia or conduction disorders, asthma, DM, and patients with
peripheral vascular insufficiency
Causes rebound HTN on withdrawal
+
Sotalol has K channel blocking capabilities.
Timolol, Metipranolol & Carteolol are used for glaucoma.

Beta-blockers: General Clinical Uses

1. HTN
2. Arrhythmia (Propranolol, Esmolol, Acebutolol)
3. Chronic Stable Angina Pectoris (Metoprolol)
4. CHF (Carvedilol, Bisoprolol, Metoprolol & Nebivolol)
5. MI and Post MI (Metoprolol)
6. Glaucoma (Timolol, Metipranolol, Carteolol, Betaxolol)
7. Hyperthyroidism (Propranolol)
8. Migraine Prophylaxis (Propranolol)
Selective 1-antagonists

Betaxolol (Kerlone), Bisoprolol (Concore) Esmolol , Acebutolol, Atenolol (Tenormin),

Metoprolol (Neobloc), Celiprolol, Nebivolol

Advantage:

Somewhat good for patients w/ asthma & COPD.

Betaxolol is the only one approved for glaucoma.

Esmolol has the shortest half-life

Most commonly used: Metoprolol & Atenolol

-blockers w/ Intrinsic Sympathomimetic Activity

Pindolol, Acebutolol, Carteolol, Penbutolol, Labetalol, Oxprenolol, Bopindolol, Celiprolol

Advantage:

Less associated with reflex tachycardia on d/c of therapy.

Good for patients with bradycardia and peripheral vascular disease

Most commonly used: Pindolol, Acebutolol, Penbutolol

-blockers w/ Membrane Stabilizing Effect

Propranolol, Metoprolol, Pindolol, Betaxolol, Acebutolol, Esmolol, Labetalol

Advantage: Good for arrhythmia

-blockers w/ Mixed & Blocking Effect

Carvedilol, Labetalol, Medroxalol, Bucindolol

Advantage:

Highly useful for hypertensive emergencies & pheochromocytoma

*Nebivolol has vasodilating properties via activation of NOS

-blockers for Congestive Heart Failure

Carvedilol, Bisoprolol, Metoprolol, Nebivolol

Works by up-regulation of beta-receptors, and by blocking catecholamine-induced

apoptosis and catecholamine-induced mitosis (remodeling)

-blockers for HTN in DM

Carvedilol, Celiprolol

Improves Insulin sensitivity, increase HDL-C and decrease TAGs

Cautions & C/Is w/ -blocker Use

Patients w/ bronchospastic disease
Patients w/ allergic history to -blockers
Patients w/ heart block or bradycardia
Patients on Calcium Channel Blockers
Absolutely C/I in patients w/ unstable CHF and/or unstable angina
Relatively C/I in patients with PAOD
Diabetic Patients
General S/Es:
Bradycardia, Heart Block, Bronchospasm, Dyslipidemia & Reflex Tachycardia (esp.
in Chinese patients)
Cholinergic Agents
Enhance or reduce various components of the autonomic nervous system &
motor (efferent) nerves of the somatic nervous system.
Drugs that stimulate or mimic the effects of parasympathetic nervous activity:
cholinergic stimulants, cholinergic agonists, cholinomimetics or
parasympathomimetics.
Drugs that decrease or block the effects of parasympathetic nervous activity:
cholinergic blockers, anticholinergics, antimuscarinics, antinicotinics (if it blocks
ACh receptors in ganglia), cholinergic antagonists, parasympathetic antagonists
or parasympatholytics.
Direct-Acting Parasympathomimetics:
Choline Esters & Cholinergic Alkaloids
Choline Esters & Cholinergic Alkaloids
1. Acetylcholine
Cardiac depressant & vasodilator but causes severe asthma
2. Methacholine
Diagnosis of asthma
3. Carbachol (Miostat)
Management of glaucoma
4. Pilocarpine
Cholinergic alkaloid, also used for glaucoma
5. Bethanechol (Uriflow)
Management of urinary retention & non-obstructive paralytic ileus
Indirect-Acting Parasympathomimetics:
Reversible Anti-AChE or Cholinesterase Inhibitors (Organocarbamates)
Reversible Anti-AChE or Cholinesterase Inhibitors (Amino Alcohol &
Miscellaneous Agents)
Irreversible Anti-AChE or Cholinesterase Inhibitors
Reversible Anti-AChE or Cholinesterase Inhibitors (Organocarbamates)
1. Physostigmine

st
1 used for glaucoma (with Pilocarpine) & as antidote to Atropine & other drugs w/
anticholinergic properties.
2. Neostigmine (Prostigmin)
Management of Myasthenia Gravis
3. Pyridostigmine (Mestinon)
Most widely used anti-AChE for MG

4. Rivastigmine (Exelon)

For Alzheimers Disease

5. Ambenonium

For patients w/ MG who are refractory to Neostigmine & Pyridostigmine

6. Demecarium

For glaucoma

Reversible Anti-AChE or Cholinesterase Inhibitors (Amino Alcohol &

Miscellaneous Agents)
1. Edrophonium (Tensilon)
Used in the diagnosis of MG & in reversing effects of non-depolarizing
neuromuscular blockers after surgery
2. Miscellaneous Agents:
Tacrine
Donepezil (Aricept)
Galantamine (Reminyl)
Irreversible Anti-AChE or Cholinesterase Inhibitors (Organophosphates)
1. Isofluorphate & Echothiophate
2. Malathion & Parathion
Insecticides and was also used in biological warfare.
3. Schradan, HETP & TEPP
Insecticides for plants, hydrolyzed rapidly to non-toxic products
Remedies for Parasympathomimetic Toxicities
1. Atropine for all cases except irreversible cholinesterase inhibitors
2. Pralidoxime & Diacetylmonoxime
AChE regenerators
*Atropine is the 1st Line for all cases
Parasympatholytics/Antimuscarinics/ Anticholinergics:
Solanaceous Alkaloids
Synthetic Agents (Amino Alcohol Esters)
Synthetic Agents (Amino Alcohol Ethers)
Synthetic Agents (Amino Amides)
Miscellaneous Synthetic Agents
Solanaceous Alkaloids
1. Atropine
Management of cholinergic poisoning

 Management of symptomatic heart block or bradycardia

Mydriatic-cycloplegic in fundoscopy
Added to Diphenoxylate
2. Homatropine (Homatal)
Less toxic, acts more rapidly
Hydrobromide salt: Mydriatic-cycloplegic; Methylbromide salt: Anti-spasmodic for the
GIT
3. Hyoscyamine

Antispasmodic for bladder disorders

4. Scopolamine/Hyoscine

Anti-motion sickness

Induces twilight sleep (when given w/ Morphine)

5. Ipratropium (Atrovent, + Fenoterol; Berodual, + Salbutamol; Combivent) Oxytropium &

Tiotropium (Spiriva) (Synthetic Amino Alcohols)

Bronchodilators

Synthetic Agents (Amino Alcohol Esters)

1. Cyclopentolate
Mydriatic-cycloplegic
2. Dicyclomine/Dicycloverine (Relestal), Glycopyrrolate, Oxybutinin (Driptane),
Methantheline, Propantheline, Clidinium & Aclidinium
o For GIT & genitourinary spasms/hypermotility
o Aclidinium is indicated for COPD.
o Not for G6PD Deficient patients
*Absolute C/Is for Use of All Antimuscarinics: BPH & Glaucoma
Synthetic Agents (Amino Alcohol Ethers)
1. Benztropine (Cogentin)
Resembles Diphenhydramine
2. Orphenadrine (+ Paracetamol: Norgesic)
Also resembles Diphenhydramine but has lower antihistaminic properties
Also for local muscle spasms
Synthetic Agents (Amino Alcohols)

Biperiden (Akineton), Procyclidine, Trihexyphenidyl (Artane)

Synthetic Agents (Amino Amides)

1. Isopropamide
o Add on therapy for ulcer & GIT spasms
2. Tropicamide (Mydracyl)
o Mydriatic-cycloplegic

Miscellaneous Synthetic Agents

Tolterodine, Fesoterodine, Trospium, Solifenacin

For over reactive urinary bladder

Remedies for Parasympatholytic Toxicities

1. Cooling blankets
2. Diazepam for seizures
3. Administer Neostigmine
4. Physostigmine for severe cases
Anti-nicotinics/Ganglionic Blockers
Formulated for emergency treatment of HTN
Now are obsolete due to low specificity
1. Hexamethonium
2. Mecamylamine
3. Trimethaphan
Neuromuscular Blockers
Adjuvants in anesthesia for skeletal muscle relaxation & for muscle spasms
A. Depolarizing Neuromuscular Blockers
Succinylcholine & Decamethonium
*Succinylcholines action is prolonged by anti-AChEs
B. Non-depolarizing Neuromuscular Blockers
1. Curiums Isoquinolines
a.) Tubocurarine (South American Arrow Poison)
Action antagonized by anti-AChEs (Neostigmine, Edrophonium) in respiratory
involvement
b.) Metocurine
c.) Atracurium (Tracrium), Doxacurium, Mivacurium
2. Curoniums Steroid derivatives
a.) Pancuronium
b.) Pipecurium
c.) Vecuronium (Vecuron)
d.) Rocuronium (Esmeron, Rocuron)

Cautions & S/Es Associated with Neuromuscular Blocker Use

1. Paralysis of diaphragmatic muscles (give anti-AChE)
2. Isoquinolines may trigger allergic/anaphylactic reactions
3. Myopathy & rhabdomyolysis
4. Halothane augments actions of depolarizing blockers
5. Enflurane augments actions of non-depolarizing blockers
6. Isoflurane produces the greatest augmentation of actions of neuromuscular blockers
7. Malignant Hyperthermia
III. Central Nervous System Drugs
Sedative-Hypnotics & Anxiolytics

Sedatives Agents that decrease activity & moderate excitement

Hypnotics Agents that produce drowsiness & facilitates the onset & maintenance of sleep
Anxiety Unpleasant state of fear or tension of an unknown source

Etiology: Increased catecholamine activity in the brain

General Clinical Uses of Sedative Hypnotics

Anxiety

Insomnia

Sedation & amnesia prior to surgical procedures

Epilepsy & seizure management

Withdrawal from alcohol & other sedatives that are substances of abuse

Muscle relaxants in neuromuscular disorders

Sedative-Hypnotics:
Benzodiazepines (BZDs)
Buspirone
Zolpidem (Stilnox) & Zaleplon
Barbiturates
Benzodiazepines (BZDs)

MOA: Potentiates GABA at GABAA Receptors

All are completely absorbed except Chlorazepate which requires conversion to

Nordiazepam which is completely absorbed.

First line sedative hypnotics along with Buspirone.

Have higher margin of safety than barbiturates & have fewer drug interactions.

Also used as pre-anesthetics (short acting agents) & in alcohol withdrawal (long acting
agents)

Benzodiazepine Classifications
1. Short-Acting

o Midazolam (Dormicum) & Triazolam

2. Intermediate-Acting
o Alprazolam (Xanor), Lorazepam (Ativan), Oxazepam, Temazepam, Estazolam
(Esilgan)
o Lorazepam & Oxazepam have the least amount of side effects in geriatrics
o Lorazepam is used in the initial management of status epilepticus
3. Long-Acting
o Chlorazepate (Tranxene), Chlordiazepoxide, Clonazepam (Rivotril), Clobazam,
Flurazepam
o Diazepam (Valium): DOC for status epilepticus in adults

Benzodiazepine Side Effects

1. Morphine-Like S/Es: (but lesser incidence of respiratory depression compared to
Barbiturates)
CNS, Cardiac Depression, Confusion & Impaired Judgement
2. Paradoxical Excitement
3. Anterograde Amnesia
4. Potential for Abuse & Dependence
Antidote for BZD Toxicity: Flumazenil
Buspirone

MOA: Partial 5-HT and Dopamine receptor agonist

Also a first line sedative hypnotic, no muscle relaxant property

Zolpidem (Stilnox) & Zaleplon

MOA: Activates BZD receptors

Prolong sleep time in insomnia, strong sedative & a weak anxiolytic

S/Es: Nightmares, Hang-Over Effect/Daytime

Sedation

Barbiturates
MOA: potentiates GABA at GABA Receptors and
enhances Cl ion flux
A
No longer used as sedative hypnotics due to low margin of safety.
Now are used as pre-anesthetics, anti-epileptics & emergency treatment of convulsions.
Classifications:
1. Ultra-Short-Acting: Used as pre-anesthetics
Thiamylal, Methohexital (Brevital), Thiopental (Pentothal)
2. Short-Acting Barbiturates
Secobarbital, Pentobarbital, Hexobarbital

3. Intermediate-Acting

Butabarbital, Amobarbital, Vinbarbital

4. Long-Acting

Phenobarbital (Luminal)

DOC for febrile seizures and status epilepticus in children, but is now
being replaced by rectal Diazepam

C/I in porphyria

Potent enzyme inducer, capable of auto-induction

Toxicity Management: Hemodialysis, Activated Charcoal, & NaHCO3

Barbiturate Side Effects

1. Morphine-Like S/Es but with Severe Respiratory Depression: Chief Complication
2. Megaloblastic Anemia on chronic use
3. Paradoxical Excitement
4. Stevens-Johnson Syndrome
5. Abuse & Dependence Potentials
Other Sedative Hypnotics
1. Chloral Hydrate (Knock-Out Drops)
MOA: Converted to trichloroethanol
S/Es: Leukopenia, Hepatotoxic
2. Antihistamines
Hydroxyzine, Dimenhydrinate, Diphenhydramine, Doxylamine
3. Ramelteon (Rozerem)
MOA: MT and MT receptor agonist
1
2
4. Eszopiclone
5. Glutethimide, Ethchlorvynol
6. Meprobamate, Carisoprodol, Methocarbamol, Baclofen: Centrally acting skeletal muscle
relaxants
Ethanol

MOA: Potentiates GABA & blocks cationic channels coupled to NMDA receptors

Antidote for methanol toxicity (Now, Fomepizole, an alcohol dehydrogenase inhibitor)

Chronic alcoholism causes foreign induction

Harmful Effects: Liver Disease, Wernicke-Korsakoff Syndrome

Alcohol Dependence Treatment:

Disulfiram

Naltrexone & Nalmefene: Decrease craving

Acamprosate: GABA analogue & NMDA antagonist

Seizure Disorders

Seizures

Excessive, hypersynchronous discharge of cortical neurons of the cerebral cortex &

thalamus which can be measured by EEG

Convulsions

Violent involuntary contractions of voluntary muscles

Occurs with a seizure or epileptic episode

Epilepsy

Chronic or group of recurrent seizures which are periodic & unpredictable, maybe
determined by MRI

May occur without a convulsion.

Etiology of Seizure Disorders

1. Impairment in voltage-dependent ion channels
2. Dysregulation Theory
Increased ACh, Glu & NE & decreased GABA & Gly
3. Genetics
Seizure Types
1. Partial
Occurs in one of two cerebral hemispheres
a. Simple Partial
o Least complicated; no alterations of consciousness
b. Complex Partial
o Alterations of consciousness either before or after a seizure episode
2. Generalized
Affects both cerebral hemispheres
a. Absence (Petit Mal)
Common in children aged 3-16 y/o
Alterations of consciousness for 10-30 seconds; staring with occasional
blinking & loss of postural tone
b. Myoclonic
Abnormal muscle movements usually of face & limbs

c. Clonic
Muscle jerking; salivation, incontinence & tachycardia
d. Tonic
Muscle rigidity, patient falls to the ground
e. Generalized Tonic-Clonic (Grand Mal/GTC)

Causes sudden loss of consciousness

3 Phases:
1. Prodromal abnormal sensations occur

2. Ictal Phase seizure episode itself

3. Post-Ictal occurs immediately after seizure

Confusion, HA, muscle soreness & drowsiness

f. Status Epilepticus
Series of grand mal seizures with no recovery of consciousness in between
episodes
Always an emergency case as this may cause permanent brain damage
g. Atonic
Sudden loss of postural tone
h. Febrile Seizures
High fever causing seizures and convulsions
Common in children aged 3 mos. 5y/o
i. Juvenile Myoclonic Epilepsy
Most common generalized epileptic syndrome characterized by myoclonic,
tonic-clonic and absence seizures
j. Lennox-Gaustaut Syndrome
Severe epilepsy w/ mental retardation of unknown cause & is refractory to
some agents
*Catamenial Seizures
Seizure exacerbations during menses
*Eclampsia
Convulsions due to HTN during pregnancy
st
1

Line Treatment & Drugs of Choice depend on Seizure Type

Partial

Pregabalin, Ezogabine, Gabapentin, Vigabatrin, Felbamate, Chlorazepate, Levetiracetam,

Lamotrigine, Perampanel

Adjuncts: Tiagabine, Lacosamide, Zonisamide,

Partial with GTC

1st Line Agents: CBZ & Phenytoin

Alternatives: Lamotrigine, Topiramate,

Adjunct: Zonisamide

Absence

DOC: Ethosuximide (Oxazolidinediones, former DOCs)

Alternatives: Clonazepam, Topiramate

Absence with GTC

VPA

Myoclonic, Juvenile Myoclonic Epilepsy & Atonic

VPA, Lamotrigine

Status Epilepticus

Initial Management: Lorazepam

DOC: Diazepam (adults), Phenobarbital (children) rectal Diazepam

Mainstay Tx: Phenytoin Fosphenytoin

Febrile Seizures

DOC: Phenobarbital rectal Diazepam

Lennox-Gaustaut Syndrome

DOC: VPA, Clobazam

Alternative: Topiramate

Adjunct: Rufinamide

Catamenial Seizures

Carbonic Anhydrase Inhibitors: Acetazolamide

Eclamptic Convulsions

MgSO

Drugs Acting on Voltage-Gated Ion Channels

General S/Es: GIT upset, HA, Dizziness, Alteration in Cognition & Cardiotoxicity
1. Phenytoin (Dilantin)
Chemically a diphenylhydantoin
+
MOA: Blocks Na Channels
o Formerly an antiarrythmic (DOC for Digoxin Induced Arrhythmia)
st
o At low doses, exhibits 1 Order Kinetics but at higher doses exhibits 0 Order
Kinetics
o Highly protein bound & a potent enzyme inducer
S/Es: Ataxia & Diplopia (early signs of toxicity), Gingival Hyperplasia (Most
Common),Megaloblastic Anemia, Cosmetic Changes, Hirsutism, Nystagmus &
Osteomalacia
2. Fosphenytoin
Phenytoin produg for patients who cant tolerate Phenytoin
Less irritating at injection site & does not contain propylene glycol
3. VPA (Depakene) Divalproex Na (Depakote)
+
2+
MOA: Blocks Na channels & T-type Ca channels
o Also good for bipolar disorders/mania
o Enzyme inhibitor
S/Es: Hepatotoxic, False (+) Urine Ketone Tests,
Teratogenic (Spina Bifida)
4. Carbamazepine/CBZ (Tegretol)

Chemically an ethylene bridged 1,1-diphenylurea

MOA: Blocks Na+ channels

o Also good for bipolar disorders (1st line in patients refractory to Li+ salts)
o Potent enzyme inducer & capable of autoinduction

S/E: Ataxia & Diplopia (early signs of toxicity), SJS,

*Oxcarbazepine (less toxic & fewer D/Is)

Others: Zonisamide, Rufinamide, Lacosamide, Ezogabine

SLE & Aplastic Anemia

Drugs Altering Neurotransmission & Acting on Neurotransmitter Receptors

1. Phenobarbital
2. Primidone

 Prodrug converted to Phenobarbital & Phenylethylmalonamide (PEMA)

3. Clonazepam, Chlorazepate & Diazepam
4. Others:
Levetiracetam (Keppra), Tiagabine, Perampanel, Vigabatrin
Drugs with Mixed Actions & Miscellaneous Actions
1. Gabapentin (Neurontin)
2+
MOA: GABA analog but increase GABA release & blocks Ca channels
2. Pregabalin (Lyrica)
MOA: Resembles Gabapentins MOA
Also used for painful diabetic neuropathy
3. Succinimides
Phensuximide, Methsuximide & Ethosuximide (Zarontin)
MOA: Inhibits endogenous gamma-hydroxybutyrate formation & blocks T-type
2+
Ca channels
4. Topiramate (Topamax)

+
MOA: Blocks Na channels, KA & AMPA receptors & potentiates GABA

S/Es: Myopia & Glaucoma (warrants d/c of use), High incidence of kidney stones

5. Lamotrigine (Lamictal)

+
MOA: Blocks Na channels & Glu release

S/Es: Life Threatening Pruritus (can be avoided via

st

line agent in bipolar disorders along with Li

6. Felbamate

+
MOA: Blocks Na channels & NMDA receptors

7. Carbonic Anhydrase Inhibitors: Acetazolamide (Diamox)

MOA: Inhibits HCO3- induced depolarization

S/Es: Metabolic Acidosis

8. MgSO4

For eclamptic convulsions

Anesthetics

slow IV infusion)

Agents that cause reversible CNS Depression resulting in loss of response &
decreased perception to all external stimuli

Major Types:
1. General Anesthetics

Induces combined state of amnesia, analgesia, loss of consciousness & reflexes, &
skeletal muscle relaxation

2. Local Anesthetics

Agents that cause loss of sensation at a limited part of the body without loss of
consciousness & central functions & are not intended to be absorbed from
administration site

General Anesthetics
Can be inhalational or intravenous
Ideal Characteristics:
o Rapid & smooth induction of anesthetic effect
o Rapid recovery
o High margin of safety
Stages of General Anesthesia
I.
(Production of Analgesia)
Followed by amnesia
II.
(Excitement or Delirium)
Loss of consciousness, irregular respiration, involuntary activity
(Surgical)

III.

Begins with restoration of regular breathing & ends with cessation of spontaneous
breathing
Absence of eye motion
IV.

(Medullary Depression)
Depression of circulatory & respiratory centers

Minimum Alveolar Concentration (MAC)

Median concentration that results in immobility in 50% of patients when exposed to noxious
stimuli

Standard of comparison of general anesthetics potency

Classification of Inhalational Anesthetics Based on MAC:

o Methoxyflurane

o Halothane
o Enflurane
o Isoflurane
o Sevoflurane
o Desflurane
o Nitrous Oxide

Inhalational Anesthetics/Volatile Anesthetics

+
MOA: Activates GABA & Gly receptors, & opens K
channels
All have bronchodilating properties especially Halothane, Enflurane & Sevoflurane
All have tocolytic effects except methoxyflurane.
All can trigger malignant hyperthermia except N O
2
1. Inorganic Gases
a. N O
2
Low potency, good analgesic effects & poor skeletal muscle relaxation
S/Es: Bone Marrow & Cardiac Depression
b. Xenon
MOA: Blocks NMDA receptors
Potent inducer of stage IV anesthesia
2. Halogenated Hydrocarbon: Halothane

Non-irritating to the larynx & produces bronchiolar dilation

Can augment neuromuscular blocking effects of depolarizing neuromuscular

blockers

S/Es: Halothane Hepatitis, Sensitizes myocardium to catecholamines

3. Ethers/Fluorinated Hydrocarbons
a. Methoxyflurane
Most potent & most toxic
Inhalational anesthetic of choice for labor (intermittently)
S/E: Resp. & Circulatory Depression, Renal Damage
b. Enflurane (Ethrane)
Old anesthetic of choice for patients with asthma
Can augment the action of non- depolarizing neuromuscular blockers
c. Isoflurane (Forane)
Preferred in neurosurgery
Produces the greatest augmentation of neuromuscular blockers effects
S/E: Coronary Steal Phenomenon
d. Sevoflurane (Sevorane)
New anesthetic of choice for patients with asthma
e. Desflurane
Widely used for outpatient surgery

Intravenous Anesthetics/Non-volatile Anesthetics

Produces relaxation & drowsiness before induction of general anesthesia
Only Ketamine & Opioid Analgesics have analgesic properties
1. Aqueous Solutions
a. Ultra-Short-Acting Barbiturates
b. BZDs: Midazolam, Lorazepam & Diazepam
c. Ketamine/Super K (Ketaject)
MOA: NMDA antagonist
Dissociative anesthetic agent, structural congener of Phencyclidine
***Memantine is also an NMDA antagonist but used for Alzheimers dementia.
d. Opioid Analgesics
Morphine, Meperidine, Fentanyl, Sufentanil, Alfentanil, Remifentanil
e. Butyrophenones
Droperidol & Haloperidol
Droperidol + Fentanyl Neuroleptanalgesia
Droperidol + Fentanyl + 65% N2O in O2 Neuroleptanesthesia

f. Fospropofol: Propofol prodrug

2. Propylene Glycol Solution Etomidate

MOA: Activates GABA receptors

Potent ultra-short-acting non-barbiturate without analgesic properties

S/Es: Addisons Disease, Electrolyte Imbalance

3. Emulsion Propofol (Diprivan)

MOA: Activates GABA receptors

Most commonly used & most popular IV anesthetic

DOC for inducing anesthesia in ambulatory surgery

S/Es: Pain at Injection Site (Most Common), Hyperlipidemia, Acidosis

Local Anesthetics
1. Amides
Prilocaine (Emla), Ropivacaine (Naropin), Bupivacaine (Sensorcaine),
Lidocaine (Xylocaine) Levobupivacaine, Etidocaine, Mepivacaine, Dibucaine
2. Esters
A. Esters of Benzoic Acid
Meprylcaine, Piperocaine, Cyclomethicaine Hexylcaine, Isobucaine, Cocaine
B. Esters of p-amino Benzoic Acid (PABA)
Benoxinate, Benzocaine, Butacaine, Chlorprocaine, Procaine, Proparacaine
(Alcaine), Propoxycaine, Tetracaine (Pontocaine)
+
MOA: Blocks Na channels
S/Es: All can cause cardiac depression & vasodilation on absorption except cocaine
Esters of PABA commonly cause hypersensitivity reactions & are antagonistic with
sulfonamides
Some important points:

1. Prilocaine
Causes methemoglobinemia due to formation of o-toluidine
2. Etidocaine, Ropivacaine & Bupivacaine
Cardiotoxic
3. Lidocaine

Most widely used; excreted via saliva

Also has anti-arrhythmic properties

4. Cocaine

1st natural local anesthetic, was used in ophthalmology

Toxicity: Arrhythmia, MI, Cerebral Hemorrhage & Euphoria

5. Procaine: 1st synthetic local anesthetic

6. Tetracaine: Spinal anesthetic

Surface Anesthetics

For skin & mucous membranes & other topical applications

1. Dyclonine
2. Pramoxine

Common in hemorrhoidal preparations

Used as a substitute when patients experience allergy to a particular local

anesthetic

3. Dibucaine

Psychosis & Schizoprenia

Psychosis

Impairment in cognitive function

Thinking becomes illogical, bizarre & disorganized usually with hallucinations & delusions

Schizoprenia

Group of chronic idiopathic psychotic disorders

Same symptoms + social withdrawal, apathy & anhedonia (negative symptoms)

Etiology of Psychosis
1. Neurophysiologic Theories:
a. Dopamine Hypothesis
Dopamine in mesolimbic pathway
b. 5-HT in other areas of the brain
2. Genetics
3. Drug-Induced
4. Psychosocial Triggers
Antipsychotics
st
1 agts include Reserpine & Chlorpromazine
Typical Agents/Traditional Agents:
MOA: Dopamine antagonists
Classification:
1. Phenothiazines
A. Aliphatics
B. Piperidines
C. Piperazines
2. Butyrophenones
Aliphatics
a. Chlorpromazine (Thorazine)
Causes strong sedation hence good for violent patients
Commonly associated with seizures
b. Promethazine, Promazine, Trifluopromazine Levomepromazine (Nozinan)

Piperidines
a. Thioridazine (Mellaril)

Causes retinal & corneal deposits & fatal quinidine-like arrhythmias

b. Mesoridazine

More potent metabolite of Thioridazine, more toxic

Piperazines
a. Fluphenazine (Sydepres) most potent
b. Prochlorperazine rectal anti-emetic

c. Trifluoperazine, Thiethylperazine, Perphenazine

Toxicity: Hypotension, Arrhythmias & Hypothermia

Butyrophenones high potency

a. Haloperidol (Haldol)

Prototype & more widely used for psychosis

b. Droperidol
More used as pre-anesthetic

*Diphenylbutylpiperidines: Modified butyrophenones

Penfluridol & Pimozide

Thioxanthenes
a. Piperazine analogues: Thiothixene, Clopentixol, Zuclopentixol & Flupentixol (Fluanxol)
b. Chlorpromazine Analogue: Chlorprothixene

Atypical Antipsychotics
MOA: 5-HT antagonists except Aripiprazole (w/c is a partial dopamine & 5-HT
agonist) and Risperidone (D and 5HT antagonist)
1. Benzisoxazole Risperidone (Risperdal), Paliperidone
(Invega), Iloperidone
2. Benzothiazole - Lurasidone
3. Dibenzodiazepine Clozapine (Leponex)
4. Dibenzoxazepine Loxapine, Asenapine
5. Dibenzothiazepine Quetiapine (Seroquel)
6. Dihydrocarbostyrol Aripiprazole (Abilify)
7. Dihydroindolone Molindone, Ziprasidone
8. Fluorophenylindole Sertindole
9. Thienobenzodiazepine Olanzapine (Zyprexa)
10. Benzamide Sulpiride (Dogmatil), Amisulpride (Solian)
Antipsychotic Side Effects
1. Due to dopamine blockade: in high potency agents

a. Extrapyramidal S/Es

Acute Dystonia , Akathisia, Pseudoparkinsonism, Tardive Dyskinesia

b. Neuroleptic Malignant Syndrome

Combination of EPS, hyperthermia, altered consciousness & autonomic changes

2+
due to increased Ca release from sarcoplasmic reticulum (Tx: Dantrolene &
Bromocriptine)

2. Due to 5-HT blockade: weight gain in Clozapine & Olanzapine

3. Endocrinal: gynecomastia, amenorrhea, hyperprolactinemia (Risperidone)
4. Fatal Agranulocytosis: Clozapine

Mood Disorders
Mood
Sustained emotion or behavior
Mood Disorder
Sustained elevation or depression in mood impairing ones ability to function normally
Normal Mood
Unsustained elevation or depression of mood
Mood Conditions:
1. Euthymia: range of normal fluctuations in mood
2. Euphoria: mood elevation above normal range
Can be: Mania & Hypomania
3. Dysphoria: mood depression below normal range
Can be: Dysthymia & Depression
Drugs for Major Depression
Major Depression/Unipolar Affective Disorder
One of the most common psychiatric disorders in w/c symptoms are subtle & unrecognized
Etiology:
1. Biogenic Amine Theory dec Monoamines
2. Neurotransmitter Dysregulation
3. Genetics
Anti-depressants
Clinical Response is often delayed (4-8 weeks)
Treatment is only declared ineffective if there is no response after 8 weeks.
If found ineffective, shift from one class of agent to another.
Classification:
1. Selective Serotonin Reuptake Inhibitors (SSRIs)
2. Tricyclic Antidepressants
3. 2nd Generation Anti-depressants
4. 3rd Generation Anti-depressants
5. MAO-Inhibitors (MAO-Is)

Selective Serotonin Reuptake Inhibitors (SSRIs)

1st line treatment of major depression
No dose titration is required but down titration is required
Fluoxetine (Prozac)
1st to reach clinical use, converted to Norfluoxetine & is given once a week.
Fluvoxamine (Faverin)
More used for OCD; potent enzyme inhibitor

Sertraline (Zoloft), Citalopram (Lupram), Paroxetine (Seroxat), Escitalopram

(Lexapro), Vilazodone

S/Es: Transient Insomnia, Sexual Dysfunction

SP: Do not withdraw abruptly (5-HT Withdrawal Syndrome)

5-HT Syndrome with serotoninergics

Tricyclic Antidepressants (TCAs)

1st Generation Antidepressants

MOA: Inhibits NE & 5-HT Reuptake

o Doxepin, Dothiepin, Imipramine (Tofranil), Desipramine, Trimipramine
(Surmontil), Clomipramine (Anafranil), Protryptiline

Amitryptiline

Metabolized to Nortryptiline & has high anticholinergic effects

Effective in multiple sclerosis with pseudobulbar palsy

Nortryptiline

S/Es: Wt Gain (Most Common), Quinidine-Like,

Anticholinergic S/Es, Seizures

2nd Generation Anti-depressants Inc. NE, 5-HT & Dopamine

Amoxapine, Bupropion/Amfebutamone, Maprotiline Trazodone

3rd Generation Anti-depressants Inc. NE, 5-HT & Dopamine

Venlafaxine (Efexor), Nefazodone, Mirtazapine, Duloxetine (Cymbalta)

MAO-Inhibitors (MAO-Is)

Drugs of last choice for treatment of severe depression.

Phenelzine, Isocarboxazid , Clorgyline, Tranylcypromine, Moclobemide (Aurorix),

Brofaromine/Brofamine, Selegiline/Deprenyl (Jumex)
o Selective MAO-A Inhibitors: Moclobemide, Brofamine, Clorgyline
o Selective MAO-B Inhibitor: Selegiline
o Non-Selective: Phenelzine, Isocarboxazid, Tranylcypromine

S/Es: HTN Crisis when taken with Tyramine-Rich Foods

C/Is & D/Is: Serotoninergics, Sympathomimetics, Dopaminergics & Agents that decrease
Monoamines

Bipolar Disorders
Bipolar Disorders Characteristic mood swings
Etiology:
1. Genetics Most Recognized
2. Neurotransmitter Dysregulation
3. G-protein Dysregulation
4. Ca2+ imbalance in CSF
5. Psychosocial Triggers
Drugs for Bipolar Disorders
1. Li Salts (Carbonate, Citrate)
MOA:
o Replaces Na+ for its action potentials
o Decreased NE receptor sensitivity
o Increased NE metabolism & uptake
With Lamotrigine, DOC for mania & bipolar disorders except mixed & rapid cycling
S/Es: Fine Hand Tremors (Most Common),
Electrolyte Imbalance, Leukocytosis,
Thyroid Enlargement & Sick Sinus Syndrome
C/I: Cardiovascular Diseases, Acute Renal Failure,
Teratogenic & Thyroid
Disorders

SP: Do not restrict salt & fluid intake

Li+ Toxicity Signs:

o Confusion, Hyperreflexia, Ataxia, Tremors, Abdominal Pain & Albuminuria

2. Lamotrigine
3. VPA
4. CBZ & Oxcarbazepine

5. Gabapentin

Parkinsons Disease

Parkinsons Disease/Paralysis Agitans

1st described by Dr. James Parkinson in 1871 & described it as shaking palsy.

Slowly progressive, neurodegenerative disorder characterized by TRAP.

Degeneration/depigmentation of substantia nigra/extrapyramidal system due to low

dopamine input into the basal ganglia.

May cause death due to immobilization of pulmonary system

Etiology of Parkinsons Disease

1. ACh-Dopamine imbalance
2. Damage to basal ganglia causing decreased Dopamine sensitivity
3. Drug-Induced
4. Encephalitis
Signs & Symptoms of Parkinsons Disease

Tremors: Initial complaint

o Resting Tremor/ Pill Rolling Tremor
o Action Tremor

Rigidity: Usually of the limbs

Akinesia: Difficulty in initiating movements

Bradykinesia: Slowness in performing voluntary muscle movements

Postural Instabilities: Stooped posture, diminished arm swings & shuffling gait

Antiparkinsonism Agents
1. Anticholinergics
Orphenadrine
Trihexyphenidyl
Benztropine
Diphenhydramine
Biperiden
Procyclidine
2. Dopaminergics
a. Dopamine Precursor
Levodopa + Benserazide (Madopar); + Carbidopa (Sinemet)
MOA:

o Crosses BBB then converted to Dopamine by DOPA Decarboxylase

DOC and is the only agent that improves TRAP.

Perpheral S/Es:
o N&V, Granulocytopenia, Arrhythmias, Brownish Coloration of Urine &
Saliva & Hemolytic Anemia

Remedy: Addition of Peripheral DOPA Decarboxylase Inhibitors

Central S/Es: Acute Psychosis, Anxiety, Fluctuations in Response

Drugs C/I in Patients on Levodopa:

1. Reserpine & Guanethidine
2. Physostigmine & Other Cholinesterase Inhibitors
3. Phenothiazines & Other Typical Antipsychotics
4. Pyridoxine

b. Direct Acting Dopamine Agonists

b.1
Ergot Derivatives
Bromocriptine (Parlodel)
Treatment of choice for NMS & useful for hyperprolactinemia
Pergolide
S/Es: Arrhythmia (warrants d/c of use),
Retroperitoneal Fibrosis
b.2
Non-Ergot Derivatives
Pramipexole (Sifrol) & Ropinirole

Good as initial treatment for young patients

c. Indirect Acting Dopamine Agonists

c.1 Amantadine (Symmetrel)
MOA: Inhibits dopamine reuptake, increase dopamine synthesis & release
S/Es: Livedo Reticularis, Peripheral Edema
c.2 Selegiline & Apomorphine
d. COMT-Is
d.1 Tolcapone: peripherally & centrally-acting

S/Es: Hepatotoxic, Orange Discoloration of Urine

d.2 Entacapone (Comtan): peripherally-acting

S/Es: Retroperitoneal Fibrosis, Orange Discoloration of Urine
e.
Central Sympathomimetic Agents
1. Amphetamine, Methampethamine, Dextroamphetamine & Lisdexamfetamine (prodrug)
For ADHD, narcolepsy & as an anorexiant
Acidification of urine causes necrosis of kidney cells & rhabdomyolysis.

2. Fenfluramine & Dexfenfluramine

Banned appetite suppresants
3. Phenmetrazine & Phendimetrazine
4. Phentermine & Sibutramine
5. For ADHD

Methylphenidate (Concerta)
-

DOC

Marketed in its threo racemate form which is more potent

Releaser and blocks reuptake

Dexmethylphenidate is a new derivative (a pure d-threo-enantiomer)

Others: Atomoxetine (Strattera), Pemoline, Dextroamphetamine & Lisdexamfetamine,

Nortryptiline

Drugs of Abuse
1. Cannabinoids Source: Marijuana; Cannabis sativa
Psychoactive Principle 9-THC
o Relaxation, Euphoria, Decreased Memory, Pulmonary Toxicity on Chronic Use
Dronabinol & Tabilone
o Synthetic analogues approved for CINV & as appetite stimulant
*Rimonabant cannabinoid antagonist
2. Hallucinogens/Psychedelic Agents
Mescaline, Psilocybin & Psilocin, Dimethyltryptamine, LSD, Ecstasy
3. Phencyclidine/PCP/Angel Dust

Not a true hallucinogen, pharmacologically similar to Ketamine

4. Nicotine

Cigarette component that causes dependence & abuse

*Varenicline is a relatively new drug approved for nicotine addiction

5. Liquid Ecstasy/Gamma Hydroxybutyrate

6. Narcotics especially Heroin

Most widely abused narcotic & most rapidly acting

7. Methamphetamine & Cocaine

V. Analgesic Agents, Drugs for Rheumatoid & Gout Arthritis

Pain
Most common complaint for which patients seek treatment.
Major Types:
Nociceptive Pain/Tissue Pain
Arises from damage to tissues other than nerve fibers.
Somatic Pain:
Results from injury to muscles, tendons and ligaments. (Localized)
Visceral Pain
Results from injury to the internal organs like stomach, gall bladder
and urinary bladder. (Diffused)
Pain Subtypes
Neuropathic Pain
- Caused by lesions in the nervous system when damaged.
- Can be central or peripheral
Other Subtypes:
Malignant Pain
- Can be either due to the CA itself or due to the treatment given for CA
- Breakthrough Pain
- Aggravation of chronic pain needing adjustments in treatment to obtain
relief.
The WHO Ladder

Opioid Analgesics
Morphine is the prototype & is obtained from Opium Poppy.
Opium also contains Codeine, Noscapine (Narcotine) & Papaverine.
Used to treat chronic & breakthrough pain; even relieves the affective
component of pain
Endogenous Opioid Peptide Transmitters:
o -Endorphins, Enkephalins (Met & Leu), & Dynorphins (A & B)

Receptor

Mu ()
Major Receptor
Subtype

Kappa ()

Predominan
t
Agonist
Endorphins

Dynorphins

Effects

Analgesia,
Psychotomimetic
Effects, Resp.
Dep, Peristalsis,
Cough
Suppression,
Miosis & N&V
Analgesia
(predominant)

MOA & Clinical Uses

MOA of Endogenous Opiods:
-

Binds to opioid receptors causing closure of Ca

channels

2+

MOAs of Opioid Analgesics:

-

Mimics the effect of endogenous opioids

Stimulates the release of endogenous opioids

Clinical Uses:
-

Analgesics

Acute MI

Anesthetics (Preoperative Sedatives)

Antitussives

Acute Pulmonary Edema

Diarrhea

Classifications Accdg. To Chemistry of Nucleus:

1. Phenanthrenes
2. Piperidines
3. Phenylheptylamines
4. Morphinans & Benzomorphan

channels & opening of K

Phenanthrenes
1. Morphine
Principal active alkaloid of opium poppy
Standard at which all analgesic drugs are compared
Prototype narcotic agonist
1IV:4PO
2. Hydromorphone & Oxymorphone
3. Apomorphine
4. Codeine
Methylated Morphine; more used as antitussive
5. Hydrocodone, Oxycodone & Dihydrocodeine
6. Tramadol (Tramal, TDL; + Paracetamol: Dolcet )
Codeine analogue
7. Nalbuphine (Nubain)
Mixed agonist-antagonist
8. Buprenorphine
Also a mixed agonist-antagonist
9. Heroin
Piperidines
1. Meperidine/Pethidine (Demerol)
Main use is in lessening the severity of labor pains
Good for severe pain of biliary colic
2. Diphenoxylate
Old generic of (Lomotil )
Meperidine congener
Anti-motility agent
3. Loperamide (Lomotil )
Diphenoxylate congener but is more specific
4. Fentanyl (Sublimaze)
5. Alfentanil, Remifentanil & Sufentanil
Phenylheptylamines
1. Methadone
More potent as an analgesic than Morphine & Meperidine but more toxic
2. Levomethadyl (LAAM)
For withdrawal of heroin & narcotic addicts
3. Propoxyphene
(-) isomer is more used & is an antitusssive.
4. Noscapine
First isolated by Pierre Robiquet.
Originally named as Narcotine, changed to Anarcotine
Used as an antitussive
Morphinans & Benzomorphan
Morphinans
1. Levorphanol & Butorphanol:
Mixed agonist-antagonist
2. Dextromethorphan
(+) isomer of methylated levorphanol
Antitussive like Codeine but has no morphine-like properties
3. Levallorphan

Narcotic antagonist; used in overdose

Benzomorphan
1. Pentazocine
Oldest mixed agonist-antagonist
Classifications According to Receptor Actions
1. Strong Full Agonists

Morphine, Hydromorphone, Oxymorphone, Methadone, Meperidine,

Fentanyl, Alfentanil, Sufentanil, Remifentanil, & Levorphanol

2. Mild to Moderate Agonists

Codeine, Hydrocodone, Oxycodone, Dihydrocodeine, Tramadol, Diphenoxylate &
Loperamide
3. Mixed Agonist-Antagonists
May act as antagonists in the presence of full agonists
a. Buprenorphine
agonist, & antagonist
b. Nalbuphine
agonist, antagonist
c. Pentazocine
agonist, agonist-antagonist
d. Butorphanol
predominantly agonist, agonist-antagonist
*Miscellaneous Analgesics:
- Tapentadol: NET & SERT Inhibitor
2+
- Ziconotide: blocks Ca
channels
Side Effects of Opioid Analgesics/Agonists
-

Hyperactivity in Dysphoric Patients

Respiratory Depression

Nausea & Vomiting

Increased Intracranial Pressure

Constipation

Urinary Retention

Pruritus

Tolerance to All Effects EXCEPT: Miosis, Constipation & Convulsions

Classifications According to Receptor Actions: The Opioid Antagonists

1. Naloxone
DOC for narcotic overdose; prototype narcotic antagonist

2. Naltrexone
Naloxone analogue for long term use
Also used for alcohol withdrawal
3. Nalorphine
Has strong analgesic properties but has high incidence of psychosis
4. Nalmefene
Analogue of Naloxone, longer acting than Naltrexone
More used for alcohol withdrawal
Orally Administered Antagonists: Methylnaltrexone & Alvimopan
NSAIDs:
1. Salicylates
2. N-arylanthranilic Acid Derivatives/Fenamates & Pyrazolone
3. Arylacetic Acid Derivatives
o Indole Acetic Acid
o Pyrrole Alkanoic Acid
o Oxicams
o Propionic Acid
o Phenylacetic Acid Derivative
o Napthylacetic Acid Derivative
4. Selective COX2 Inhibitors
5.
Salicylates
1. Na Salicylate, Na Thiosalicylate, Mg Salicylate, Mg Choline Salicylate
2. Salol/Phenyl Salicylate
3. Salicylamide
Useful for patients allergic to Salicylates
4. ASA
Hydrolyzed by moisture to acetic acid & salicylic acid
Causes gastric hemorrhage
Antipyretic (0.3-2.4g/d), Anti-inflammatory (3.2-4g/d), Analgesic (<0.6g/d)
& Anti-platelet (<.325g/d)
Salicylate of Choice for Rheumatism

Low dose ASA (Baby ASA; 81mg) is recommended as daily dose for reduction of MI or
Stroke
Salicylates & Tolmetin are not for gouty arthritis.
S/Es: Erosive Gastritis (added with Omeprazole), Hypersensitivity Reactions, Reyes
Syndrome

Others: Diflunisal & Salsalicylic Acid/Salicylsalicylic Acid

N-arylanthranilic Acid Derivatives/Fenamates & Pyrazolone

Fenamates
1. Mefenamic Acid (Ponstan, Dolfenal )

Good analgesic but is not given for children & pregnant patients (more toxic than
ASA)

Use should be NMT 5-7 days

Good analgesic for primary dysmenorrhea

2. Meclofenamic Acid

More used for arthritic pain

Pyrazolone
1. Phenylbutazone

Its active metabolite Oxyphenbutazone was also once marketed as an anti-inflammatory

Other examples include Antipyrine, Dipyrone/Azapropazone/Apazone,

Propyphenazone: + Paracetamol & Caffeine (Saridon)

Arylacetic Acid Derivatives

Indole Acetic Acid
1. Indomethacin (Indocin )

Best NSAID for mgt. of acute pain due to gout

Selective COX1 Inhibitor

2. Etodolac

Good for post-op pain

3. Sulindac

For OA, RA , GA & ankylosing spondylitis

Pyrrole Alkanoic Acid

1. Tolmetin (Tolectin )
2. Ketorolac (Toradol)

Good for post-op pain

Oxicams
1. Piroxicam (Feldene )

Selective COX1 Inhibitor

2. Meloxicam (Mobic )

Selective COX2 Inhibitor

3. Tenoxicam

Non-selective COX Inhibitor

Propionic Acid
1. Ibuprofen (Advil, Motrin, Nuprin)

Safer than ASA for arthritic & bone pain

Good for primary dysmenorrhea

2. Naproxen (Naprosyn, Flanax)

Has analgesic properties comparable to Opioids

Also used for Gout

Other Examples:

Fenoprofen, Ketoprofen, Flurbiprofen, Tiaprofen, Carprofen & Oxaprozin

S/Es: Nephrotoxic (esp. Fenoprofen), GI Irritation

ASAs actions

& Ibuprofen antagonizes

Napthylacetic Acid Derivative

1. Nabumetone

Structurally similar to Naproxen

Only non-acidic NSAID in use but converted to acid in vivo

Phenylacetic Acid Derivative

1. Diclofenac

Voltaren: sodium salt; Cataflam: potassium salt; Cataflam QS: with

Cholestyramine

For OA, RA, GA & ankylosing spondylitis

Potassium salt is shorter acting & good for PD

Selective COX

Inhibitors

1. Celecoxib (Celebrex)
2. Etoricoxib (Arcoxia)
3. Rofecoxib (Vioxx)
4. Valdecoxib (Bextra):
5. Parecoxib (Dynastat) is a pro-drug
6. Meloxicam (Mobic)

Less ulcerogenic but have no effect on platelet aggregation hence are now marketed with a
black box warning

S/Es: Peripheral edema, Worsening of HTN, DM, Thrombosis & Cardiac Deaths

Aniline & p-aminophenol-Derived Antipyretic Analgesics

1. Acetanilide & Phenacetin

Obsolete

2. Acetaminophen/Paracetamol (Biogesic, Aeknil)

Antipyretic, Analgesic

S/E:

Antidote: N-acetylcysteine

Hepatic necrosis due to GSH depletion via

NAPQI

DMARDs/SAARDs
1. Methotrexate (Zexate)

MOA: Inhibits AICAR transfromylase & thymidylate synthase

st
DMARD of 1 choice at low doses

S/E: Dose related hepatotoxicity, GIT mucosal ulcerations (Remedy: coadminister Leucovorin/Levoleucovorin & B )
9

2. Azathioprine (Imuran)

MOA: Converted to 6-thioguanine w/c inhibits B & T-cell function & IL-2
production

3. Chlorambucil (Leukeran)

MOA: cross-links DNA

4. Cyclophosphamide (Cytoxan)

MOA: Same with Chlorambucil

5. Cyclosporine (Restasis)

MOA: Decreases IL-1 & IL-2 receptor genetic expression

S/E: Nephrotoxic

6. Mycophenolate Mofetil (Cellcept, Myfortic)

MOA: Inhibits CMP dehydrogenase

7. Chloroquine & Hydroxychloroquine

8. Au Preparations

Auranofin, Aurothioglucose & Aurothiomalate

o MOA: Alters morphology & function of macrophages

9. Penicillamine
MOA: Interferes with DNA encoding of macrophages
10. Leflunomide (Arava)
MOA: Metabolized to A77 1726 which inhibits ribonucleotide synthesis
11. TNF- Blocking Agents

Adalimumab, Infliximab (Remicade) & Etanercept

S/E: Increased susceptibility to macrophage dependent infections or

reactivation of latent infections

12. Tocilizumab
MOA: Anti-IL-6 receptor mAb
13. Miscellaneous Agents:

a. Abatacept & Rituximab

-

MOA: Inhibit lymphocyte activation

b. Glucocorticoids Prednisone

Drugs for Gouty Arthritis

1. Colchicine (Goutnil)

MOA: Inhibits microtubule synthesis

DOC for acute gout; (Now; NSAIDs except Salicylates & Tolmetin)

S/Es: Bone Marrow Suppression, Bloody Diarrhea

& Burning Throat

2. Uricosurics

Probenecid, Sulfinpyrazone & Penicillamine

MOA: Enhance uric acid secretion via urine

S/E: Renal Stones

3. Allopurinol (Zyloprim, Purinase)

MOA: Purine analog which inhibits xanthine

DOC for chronic gout

oxidase

4. Febuxostat

MOA: Non-purine analog that also inhibits xanthine oxidase

5. rDNA Derived Uricases

Pegloticase & Rasburicase

MOA: Enzymes that convert uric acid to allantoin

S/Es: N&V, Anaphylaxis