PharmacologyTest #2 Review: Know Insulins: Onset, Peak, & Duration.

Insulin Duration Routes

Lispro Insulin (Humalog) Aspart Insulin (NovoLog) Regular Insulin (Humulin R) (Novolin R) Rapid 3-6.5 hours Rapid 3-5 hours Short (slower acting) 6-10 hours SC SC Infusion Pump SC SC Infusion Pump

AC Meals Time 15 min ac

Onset Rapid 15-30 min 10-20 min

Peak to 2 hours

5-10 min ac

to 3 hours

NPH Insulin (Humulin-N) (Novolin-N) Glargine Insulin (Lantus)

SC SC Infusion Pump IH IM IV Intermediate SC 16-24 hours Injection Long 24 hours SC Injection

30 min ac Bolus 30 min ac 20 min ac

30-60 min

1 to 5 hours

Administer 2 times per day (Same Time) Administer 1 time per day (Same Time)

1-2 hours

6-14 hours

70 min

None

*Insulin: Converts glucose to glycogen. *Insulin: Moves potassium into cells (along w/ glucose) Therapeutic Uses: *Insulin: Used for glycemic control of diabetes mellitus (type 1 & II)(gestational) *Clients w/ type II diabetes may require insulin when: __Oral hypoglycemics, diet, and exercise are unable to control BG levels. __Severe renal or liver disease is present __Painful neuropathy is present __Undergoing surgery or diagnostic tests __Experiencing severe stress such as infection and trauma. *Emergency treatment of diabetes ketoacidosis (DKA) and hyperosmolar hyperglycemic nonketotic syndrome (HHNS) *Treatment of Hyperkalemia Insulin Side/Adverse Effects: ~~Risk for hypoglycemia (too much insulin~~ Nursing Interventions: ***Monitor patient for signs of hypoglycemia. If abrupt onset, client will experience sympathetic nervous system symptoms (tachycardia, palpitations, diaphoresis, shakiness) If gradual onset, client will experience CNS symptoms (headache, tremors, weakness, diaphoresis.) ***Administer glucose. For conscious clients, admninister a fast acting source (glucose tablet, orange juice, non diet soda, candy) If the client is not fully conscious, do not risk aspiration and instead administer glucose parenterally (IV, SC/IM glucogon)

***Encourage the client to wear a medical alert bracelet. ~~~Lipohypertrophy~~~ ***Instruct the client to systematically rotate injection sites and to allow 1 in between injection sites. Medication/Food Interactions Nursing Interventions/Client Education Sulfonylureas, Meglitinides, beta-blockersMonitor the clients serum glucose levels for hypoglycemia (<50 additive glucose reducing effects with mg/dl) and adjust insulin or oral hypoglycemic dosages accordingly. concurrent use. Thiazide diuretics and glucocorticoidsMonitor the clients serum glucose levels for hyperglycemia and concurrent us will decrease glucose-reducing adjust insulin doses accordingly. Higher insulin doses may be effects or insulin. indicated.

Nursing Interventions and Client Education: Adjust the clients insulin dosage to meet insulin needs. ~~~Increase the clients dosage in response to the clients increase in caloric intake, infection, stress, growth spurts, and in the second and third trimesters of pregnancy. ~~~Decrease the clients dosage in response to the clients exercise and first trimester of pregnancy. *When mixing insulin, if you dont draw the short acting first,you can accidentally inject some of the longer acting insulin into the shorter acting insulin vial and it would pose a risk for unexpected insulin effects with subsequed usus of the vial. ~~~For insulin suspensions, the nurse should gently rotate the vial between palms to disperse the particles throughout the vial prior to withdrawing insulin. Do not administer short acting insulins if they appear cloudy or discolored. ~~Insulin glargine is not administered IV and should not to be mixed in a syringe with any other insulin. ~~Instruct the client to administer SC insulin in one general locale to have consistent rates of absorption. Absorption rates from subcutaneous tissue increases from thigh to upper arm to abdomen. ~~Select an appropriate needle length to ensure insulin is injected into subcutaneous tissue versus intradermal. (too short) or intramuscular (too long). ~~Encourage clients to enhance their diabetes medication therapy with a proper diet and consistent exercise. Nursing Evaluation of Medication Effectiveness: ~~Glucose levels of 90-130 mg/dl preprandial and <180 mg/dl Post prandial ~~HgA1c<7% ~~Normotensive (<130/80 mm Hg) ~~Cholesterol levels within normal ranges.

Oral Hypoglycemia: Which stimulates insulin. Which decreases absorption of glucose in intestine. Oral Hypoglycemics-Sulfonylureas 1st generation-tolbutamide (orinase) 2nd generation-glipizide (Glucotrol, Glucotrol XL)

Medication/Food interactions Alcohol-use of alcohol can result in disulfiram-like reaction (intense nausea and vomiting, flushing, palpitations) Alcohol, NSAIDS, sulfonamide antibiotics, ranitidine (zantac), and cimetidine (Tagamet)additive hypoglycemic affect.

Nursing Interventions/Client Education Inform the client about the risk and encourage the client to avoid alcohol.

~~Inform the client of risk of additive hypoglycemic effect. Encourage the client to avoid alcohol. ~~Instruct the client to closely monitor glucose levels when these other agents are concurrently used. ~~If the client is taking a medication with an additive hypoglycemic effect, dosage adjustment of the oral hypoglycemic medication may be indicated.

other meds: 1st generation: chlorpropamide (Diabinese) 2nd generation: glyburide (DiaBeta, Micronase) glimepiride(Amaryl) ~~Oral Hypoglycemics-sufonylureas promote insulin release from the pancreas. ~~Therapeutic uses: Oral hypoglycemics-sulfonylureas control blood glucose levels in clients with type 2 diabetes mellitus. ~~Oral hypoglycemics-sulfonylureas are usedin conjuction with diet and exercise life-syle changes. Side/Advers Effects Nursing Interventions/Client Education Hypoglycemia ~~Monitor the client for signs of hypoglycemia. If abrupt onset, the client will experience SNS symptoms (tachycardia, palpitation, diaphoresis, shakiness) If gradual onset, the client will experince CNS symptoms (headache, tremors, weakness, diaphoresis). ~~Instruct patient to self-administer a fast acting source (glucose tablets, orange juice, non-diet soda, candy). ~~Instruct the client to notify the primary care provider if there is a recurrent problem. ~~If severe hypoglycemia occurs, IV glucose may be needed. ~~Encourage the client to wear a medical alert bracelet.

Contraindications/Precautions: ~~Pregnancy Risk Category C ~~Avoid use in pregnancy and lactation (risk for fetal/infant hypoglycemia) ~~Use is ineffective in clients with type 1 diabetes since the pancreatic islet are not capable of producing insulin. ~~Contraindicated in the treatment of diabetic ketoacidosis (DKA) ~~Use cautiously in clients with renal or hepatic dysfunction due to the risk of medication accumulation and resulting hypoglycemia.
Concurrent use of Beta-Blockers may mask the typical awareness symptoms of hypoglycemia, specifically the SNS symptoms of tachycardia, palpitations, and diaphoresis. ~~Advise the client fo the importance of monitoring glucose levels and not relying on SNS symptoms as an alert to developing hypoglycemia.

Therapeutic Nursing Interventions and Client Education: ~~Encourage clients to consistently exercise and to follow appropriate dietary guidelines. ~~Encourage clients to maintain a log of glucose levels and to note patterns that impact glucose levels (like increased dietary intake, infection) ~~Consider referring the client to a dietician and/or diabetes educator. Nursing Evaluation of Medication Effectiveness: ~~Glucose levels of 90-130 mg/dl preprandial and <180 mg/dl post prandial) ~~HgA1c <7% ~~Normotensive (<130/80 mm Hg) ~~Cholesterol levels within normal ranges. Oral hypoglycemics:Promote insulin release from pancreas: They are: *** Meglinides family(can be used in combination with metformin) -repaglinide (Prandin) ***Sulfonylureas family ~1st generation: tolbutamide (Orinase) ~2nd generation: glipizide (Glucotrol, Glucotrol XL) ***Biguanides Family ~metformin (Glucophage)(these reduce the production of glucose within the liver through suppression of gluconeogenesis. Also they increase muscles glucose uptake and use. Also treat PCOS.) ***thiazolidinediones Glitazones ~~rosiglitazone (Avandia)

***Oral Hypoglycemics-biguanides metformin HCI (Glucophage) Other meds: none ```````Oral hypoglycemics-biguanides reduce the production of glucose within the liver through suppression of gluconeogenesis. ``````Oral Hypoglycemics-biguanides increase muscles glucose uptake and use. Therapeutic uses: ~~Oral Hypoglycemics-bigunides control blood glucose levels in clients with type II diabetes. ~~Oral Hypoglycemics-bigunides are used in conjunction with diet and exercise lifestyle changes. ~~Oral hypoglycemics-biguanides are used to treat polycystic ovary syndrome (PCOS) Side/Adverse Effects Nursing Interventions/Client Education GI effects (anorexia, N/V, which ~~Monitor the client for severity of these effects. frequently results in weight loss of 3 - ~~D/C the clients medication if necessary. 4 kg (6-8 lbs) Vitamin B12 and folic acid deficiency ~~Provide the client supplements as needed. due to altered absorption. Lactic Acidosis (hyperventilation, ~~Instruct the client to D/C use of metformin if these myalgia, sluggishness)-50% mortality symptoms occur, and to inform the doc immediately. Sever rate. lactic Acidosis can be treated with hemodialysis.

Contraindications/Precautions: ~~Pregnancy Risk Category B ~~Contraindicated in the treatment of diabetic ketoacidosis (DKA) ~~Clients w/ Renal, hepatic, and/or cardiac failure are at greater risk for medication accumulation and resulting lactic acidosis, therefore use if generally contraindicated. ~~Clients with severe infection, shock, and any hypoxic condition. Medication/Food Interactions Nursing Interventions/Client Education Alcohol-Increase the risk of lactic ~~Encourage the client to avoid consuming alcohol. Warn client acidosis with concurrent use. of the risks.

Therapeutic Nursing Interventions and Client Education: ~~Instruct the client to take immediate release tablets twice a day with breakfast and dinner and to take sustained release tablets once a day with dinner. ~~Nursing Evaluation of Medication and Client Education: *For Pancreas test function: Do Amilase & Lipase. (this is not on ATI. This is form M. R notes.) *Glucose levels of 90-130 mg/dl preprandial and <180postprandial. *HgA1c <7% *Normotensive )<130/80 mm Hg) *Cholesterol levels within normal ranges.

For Insulin Overdose: Glucagon ~~For an insulin overdose, glucagon increases glucose levels by: *****Increasing the breakdown of glycogen into glucose. *****Decreasing glycogen synthesis (decrease storage of glucose) *****Stimulating synthesis of glucose. ~~Therapeutic Uses: *****Hypoglycemia secondary to insulin overdose in clients (not conscious and not able to take oral glucose or to receive IV glucose) *****Decreases in GI motility in clients undergoing radiological procedures of the stomach and intestines. Side/Adverse Effects: Nursing Interventions and Client Education: Side/Adverse Effets: GI Distress (N/V) Nursing Intervention/Education: Turn the client onto the left side following administration to reduce risk of aspiration if emesis occurs. Contraindications/Precautions: ~~Ineffective for hypoglycemia due to starvation (no glycogen stores) ~~Contraindicated for clients with pheochromocytoma due to catecholamine stimulating effects. Nursing Interventions and Client Education: ~~Administer glucagon SC, IM, or IV immediately following reconstitution parameters. ~~Provide food as soon as the client regains full consciousness and is able to swallow. ~~Instruct the client to maintain access to a source of glucose and glucagon kit at all times. Nursing Evaluation of Medication Effectiveness: ~~Elevation in blood glucose level to greater than 50 mg/dl. Insulin Side Notes: ~~Rapid Insulins: Lispro (Humalog) & Aspart (Novolog)---both Clear ~~Rapids can be mixed w/ Intemediates NPH, Lente, & UltraLente.(Cloudy) ~~~Long Acting cannot be mixed! Glargine (Lantus) ~~Must check blood glucose level before administering Humalog or Novolog. ~~Insulin is best kept refridgerated but once opened, can be kept at room temperature up to one month. Oral Hypoglycemics:thiazolidinediones Glitazones family ~~rosiglitazone (Avandia) ~~Increases response to insulin by decreasing insulin resistance.(works on liver decreasing glucose) ~~side/advers effects~~fluid retention: Monitor for edema, weight gain, and s/s of chf. S/A effect: Elevations in low density lipoproteins (LDL) cholesterol. Monitor cholesterol levels. S/A effect: Hepatotoxicity: Baseline and periodic liver function tests should be performed, and the client should be instructed to report any hepatotoxicity symptoms (jaundice, dark urine) ~~pregnancy Risk C. Contraindicated in DKA and in Severe heart failure due to retention effects. Interactions with: Gemfibrozil (Lopid) can cause inhibition of rosiglitazone metabolism, which leads to increase risk for hypoglycemia. Nursing intervention/education: pt should avoid concurrent use. If used monitor for s/s of hypoglycemia.

S/A effects: Insulin: increases risk for hypoglycemia with concurrent us. : Monitor for s/s of hypoglycemia. Cancer: Cell cycle specific:When the drug is selectively toxic when the cell is in a specific phase of growth, and therefore is schedule dependent. Cell cycle non specific: drugs are active throughout the cell cycle and may be more effective against slowly proliferating neoplastic tissue. These agents are not schedule dependent but are dose dependant. Once implication of cell cycle specificity is the importance of correlating the dosage schedule of anticancer therapy with the known cellular kinetics of that type of neoplasm. Combination therapy: using cell cycle specific and cell cycle nonspecific agents is superior in therapeutic effect than the use of single agent chemotherapy. The use of combination drug therapy allows for cell death during different phases of the cell cycle, but the agents often have toxic effects on different organs at different time intervals after administration. Epoetin alpha (Procrit, Epogen): Stimulates the production of RBCs. It is used to treat anemia in patients with chronic renal failure or those receiving chemotherapy. Epoetin is administered by subcutaneous IV injection three times weekly. Filgrastim (Neopogen) (subcu and IV) Also known as a human granulocyte colony stimulating factor (GCSF). It stimulates production of neutrophilic white blood cells. It is used to reduce the neutropenia interval in bone marrow transplantation, to stimulate white blood cell production in patients receving myelosuppressive chemotherapy, and to treat neutropenia in acute myelogenous leukemia. Oprelvekin (Neumega) Stimulates platelet production at the stem cell level. Oprelvekin is used to prevent severe chemotherapy induced thrombocytopenia in nonmyeloid malignancies and to decrease the need for platelet transfusions. Darbepoetin (Aranesp): (subcu) Darbepoetin stimulates erythropoiesis (production of red blood cells). It is used to treat anemia in patients receiving chemotherapy. Increased hemoglobin levels are not generally observed until 2-6 weeks after initiating treatment with darbepoetin. Darbepoetin is administered by weekly subcutaneous injection. Chemo thereapy works best during: Rapid Difussion. Chemotherapy can cause:extravascation. So we do not give peripherally only through central line (ex: Huber needle will be used for central line) Signs/Symptoms of Thrombocytopenia: ~~~Pinpoint Red Rash ~~Increase Menstrual Flow ~~Coffee Ground Emesis Power point questions: Advantage of combination therapy using cell cycle nonspecific & specific? Answer: Increased rate of treatment success. Why is Bone Marrow stimulants used in treatment of cancer? Answer: To enhance the patients immune system during treatment What is stomatitis (Also known as: Mucositis): Severe inflammation of gums. >Lidocaine swish can be given (local mouth anithetic)Given after food. Can also give antimetics before chemo.

What is Canver? Disorder of cellular growth, life span, and death. Abnormal proliferation of the cells. Schedule oral hygiene measures using prescribed local anesthetic and antimicrobial solutions. Perform before and after meals and at bedtime if symptoms are mild. With moderate lesions, increase the frequency to every two hours. Severe, the mouth should be rinsed hourly while the patient is awake. Chemotherapy administration: should be performed by qualified registered nurse or prescribers with specific skills in the correct handling and administration techniques for chemo agents. Specifically: anti Cancer/Therapeutic Agents (serious Adverse Effects) (Common Side Affects)---Chemo: Ask for symptoms of anemia, bleeding, stomatitis (mucositis), altered bowel patterns (diarrhea, constipation) alopecia, neurotoxicity, anorexia, nausea, or vomiting. Also obtain rating pain level. (pain meds with relaxation and guided imagery helpful)

Does patient wish to modify smoking habits? Provide smoking cessation education. Plan interventions consistent with assessment data and identified individual needs of the patient: nutritional support, blood component therapy, growth factor therapy, fatigue alopecia, anemia, constipation, diarrhea, nausea and vomiting, neutropenia, pain, and thrombocytopenia)

Patient Teaching----Chemo and also what to look for when taking albuterol or anticolinergic agent.

Muskuloskeletal: Muscle relaxant: Flexeril ~~cyclobenzaprine (Flexeril) 10 mg 3 X daily. Most commonly used. Commonly causes GI discomfort; may be hepatotoxic. Baclofen (Lioresal and Kemstro) Not exactly centrally acting. It interrupts the _________synaptic reflexes at the level of the spinal cord. Baclofen is a skeletal muscle relaxant that acts bit differently from centrally acting agents. It is a gamma-aminobutyric acid derivative that interrupts the polysynaptic reflexes at the level of the spinal cord. Used: is used in the management of muschle spasticity resulting from multiple sclerosis, spinal cord injuries, cerebral palsy and other spinal cord diseases. (not recommended for parkinsons) Use this med with caution for all the patients who must use spasticity to maintain an upright posture and balance in moving. Therapeutic relief: primarily expected to relieve muscle spasm. Interactions : with CNS depressants including sleep aids, analgesics, tranquilizers, and alcohol, potentiate the sedative effects of baclofen. Muscle spasms: are often associated with musculoskeletal trauma or inflammation. (strains, sprains, sciatica, herniated disks). Spasms are sudden alternating contractions and relaxations or sustained contractions of muscle. Antispasmodic agents used to treat muscle spasms are the benzpdiazepines (diazepam) cyclobenzaprine, carisoprodol, metaxalone, chlorzoxazone, methocarbamol, tizanidine, and orphenadrine. The centrally acting skeletal muscle relaxants act within the brainstem, basal ganglia, and spinal cord to induce muscle relaxation. Dantrolene is a muscle relaxant that acts directly on the skeletal muscle to reduce the force of muscle contractions. Centrally Acting Skeletal Muscle Relaxants: CASMR belong to a class of compouds used to relieve acute muscle spasm. The exact mechanism of actionof the centrally acting skeletal muscle relaxants is not known, except that they act by central nervous system (CNS) depression. ******** They do not have any direct effect on muscles, nerve conduction, or neuromuscular junctions. Beware and question antibiotic orders that prescribe aminoglycosides or tetracycline when neuromuscular blockers have been used. These drugs may potentiate the neuromuscular blocking activity. ~~~dantrolene (Dantrium) is a muscle relaxant that acts directly on skeletal muscle. This med produces generalized mild weakness of skeletal muscles and decreases the force of reflex muscle contractions, hyperreflexia, clonus, muscle stiffness, involuntary muscle movements and spasticity. Uses: Used to control the spasticity of chronic disorders such as cerebral palsy, ms, spinal cord infury, and stroke syndrome. It is also FDA approved to treat neuroleptic malignant syndrome associated with the use of antipsychotic agents and unusual reactions to neuromuscular agents used with balanced anesthesia. ~~~Neuro: weakness, drowsiness, dizzy, lightheadedness. ~~~GI diarrhea ~~~photosensitivity ~~~Hepatotoxicity

~~~~~*******Overdose treatment*******~~~~~~~ >>>>>>>>>>>Treatment of overdose includes artificial respiration with oxygen and antidotes such as neostigmine methylsulfate,(Prostigmin), pyridostigmine bromide (Mestinon, Regonol), and edrophonium chloride (Tensilon). Atropine sulfate is usually administered with neostigmine or pyridostigmine to block bradycardia, hypotentsion, and salivation induced by these agents. There is no antidote for the early blockade induced by succinylcholine. Fortunately, it is of short duration and does not require reversal. *****Can be used to treat Myasthenia Gravis and overdose to Neuromuskular Blocker. (neostigmine, prostigmin, mestinon, and tensilon.) ~~~~2 Neuromuscular Blocking Agents~~~~ **mivacurium chloride (Mivacron)**** & ***vecuronium (Norcuron) SIDE NOTE: hypercapnia is tachycardia, hypotension, and cyanosis all together. (need to do Arterial blood gas levels (ABGs). SIDE NOTE: Neuromuscular blocking agents with anesthesia decrease acetlycoline Common Adverse Affects of Neuromuscular Blocking Agents: ~~~~Histamine release: Neuromuscular Blocking agents cause histamine release, which may cause bronchospasm, bronchial and salivary secretions, flushing, edema, and urticaria. Ensure that airway is patent and that secretions are suctioned regularly to prevent obstruction. Report evidence of bronchospasm, edema, and urticaria immediately. Peripheral Nervous System: Mild to moderate discomfort, particularly in the neck, upper back, and lower intercostal and abdominal muscles, will be noted when patient first ambulates after use. ***~~~SERIOUS ADVERSE EFFECTS****~~~ >>>>>Signs of Respiratory distress. Monitor vital signs for a prolonged period after administration of neuromuscular blocking agents. ~~~~Drug Interactions: General anesthetics. Also aminoglycosides: Kanamycin, gentamicin, neomycin, streptomycin, etc..) AB: tetracycline, clindamycin, quinidine, quinine, procainamide, lidocaine, beta adrenergic blocking agents like propranolol, pindolol nadolo, and agents that deplete potassium :thiazide diuretics, furosemide, torsemide, bumetanide, ethacrynic acid, amphotericin b, corticosteroids.

Benzodiazepines: lorazepam (Ativan) :act as antiemetics through a combination of effects, including sedation, reduction in anxiety, possible depression of the vomiting center, and an amnesic effect. Of these, the amnesic effect appears to be most important in treating cancer patients, and in this respect lorazepam and midazolam are superior to diazepam. Uses: Benzodiazepines (Lorazepam, midazolam, diazepam) are effective in reducing not only the frequency of nausea and vomiting but also the anxiety often associated with chemotherapy. Clinically, Benzodiazepines are most useful in combination with other antiemetics, such as metoclopramide, dexamethasone, and serotonin antagonists.

Therapeutic Outcome: The primary therapeutic outcome expected from benzodiazepine

antiemetics is relief of nausea and vomiting. Benzodiazepines have been extremely successful products from a therapeutic and safety standpoint. A major advantage over the barbiturate and other nonbarbiturate sedative hypnotic is the wide safty margin between therapeutic and lethal doses. Intentional and unintentional overdoses well above the normal therapeutic doses are well tolerated and not fatal. **schedule IV habit forming drug. *****THIS IS THE DRUG OF CHOICE FOR STATIS EPILECTICUS*********** Nursing Process for benzodiazepines: ~~Collect date regarding emesis: type, amount, frequency, on a continuum. ~~Assess data relative to the underlying cause of nausea and vomiting such as pregnancy, post surgical state, chemo, radiation, bowel obstruction etc ~~Obtain baseline data about the patients degree of alertness before initiation of therapy because these medications tend to produce some degree of sedation.

Sedative-Hypnotics: Drugs used in conjuction with altered patterns of sleep. Hypnotic: drug that produces sleep ~~~~~~~~~~Sedative: quiets the patient and gives a feeling of relaxation and rest, not necessarily accompanied by sleep. Sedatives used to produce relaxation and rest and hpnotic used to produce sleep are not always different drugs. Their effects depends on the dosage and condition of the patient. A small dose of a drug may act as a sedative, whereas a larger dose of the same drug may act as a hypnotic and produce sleep. The sedative-hypnotics may be classified into three groups: >>>Barbiturates-benzodiazepines >>>Nonbarbiturate-nonbenzodiazepines >>>Misc. sedative-hypnotic agents. Uses: The primary uses for sedative-hypnotics are to improve sleep patterns for the temporary of insomnia, and decrease the level of anxiety, and increase relaxation or sleep prior to diagnostic or operative procedure. CNS Function: Because sedative hypnotics depress overall central nervous system function, identify the patients level of alertness and orientation and ability to perform motor functions. Vital Signs: Obtain current blood pressure, pulse, and respirations before initiating drug therapy. Sleep Pattern: Assess the patients usual pattern of sleep and obtain information on the pattern of sleep disruptionsuch as difficulty falling asleep, inability to sleep the entire night, or awakening in the early morning hours unable to return to a restful sleep. Ask about the amount of sleep hours that the patient considers normal and how insomnia is managed at home. Does the patient have a regular time to go to bed and wake up? If the patient is taking medications, determine the drug, dosage, and frequency of administration and whether this may be contributing to sleeplessness. Medicines that induce or aggravate insomnia include theophylline, caffeine, pseudoephedrine, ephedrine, nicotine, levodopa, corticosteroids, and selective serotonin reuptake inhibitor (SSRI) antidepressants. Other things to consider: Anxiety level, Environmental Control, Nutritional Needs (make sure they dont usually have too much coffe or caffeine products), Alcohol intake, Exercise, Respiratory status (People with respiratory disorders and thos who snore heavily may have low respiratory reserves and should not receive hypnotics because of the potential for causing respiratory depression.******** Planning: ~~CNS assessment and monitor vital signs every 8 hours. ~~Sleep pattern: Many sedatives are offer PRN basis. Do not offer until you see patient is having difficulty sleeping. ~~Anxiety level: Paradoxical response. ~~Environmental control: plan for safety needs, protect from injury. Call light within reach, and place bed in low position with side rails up. Leave night light on. Organize nursing activites so that the patient is disturbed as infrequently as possible while maintaining safe patient care. ~~Nutritional Needs: Offer protein foods and dairy products at a specific time before sleep. Drug Interations: Drugs that increase toxic effects. Drugs that increase effects include antihistamines, alcohol, analgesics, anesthetics, tranquilizers, valproic acid, monoamine oxidase inhibitors, and other sedative hypnotics. Monitor the patient for excessive sedation and reduce the dosage of barbiturate if necessary.

Barbiturates: The first barbiturate placed on market as sedative hypnotic 1903. Became very successful that chemists identified some 2500 compounds of which more than 50 were distributed commercially. Barbiturates became such a mainstay of therapy that fewer than a dozen other sedative hypnotic agents were successfully marketed through 1960. The release of the first benzodiazepine in 1961..started to decline barbiturates. However, several barbiturate compounds are still prescribed. Actions: Barbiturates can reversibly depress the activity of all excitable tissues. The CNS is particularly sensitive, but the degress of depression ranging from mild sedation to deep coma and death depends on the dose, route of administration, tolerance from previous use, degree of excitability of the CNS at the time of administration, and condition of the patient. When used for hypnosis, barbiturates supprees REM and stages III and IV sleep patterns. Because barbiturates have long half lives, residual daytime sedation is a common adverse effect. (still feel sleepy in the day time) Uses: Barbiturates are now rarely used for sedation-hypnosis, but when used, therapy should be limited to two weeks because tolerance to sedation and hypnosis develops during this time. The ultra short acting agents (methohexital and thiopental) may be administered IV as general anesthetics. The short acting barbiturates (amobarbital pentobarbital, secobarbital) are used for sedation before diagnostic procedures. The long acting barbiturate Phenobarbital is also used as an anticonvulsant. ~~~Note:Rapidly d/c barbiturates after long term use of high dosages may result in symptoms similar to those of alcohol withdrawal. These may vary from weakness and anxiety to delirium and grand mal seizures. Treatment consists of cautions and gradual withdrawal over 2-4 weeks. General adverse effects of barbiturates include dowsiness, lethargy, headache, muscle or joint pain, and mental depression. Common Adverse Effects: CNS: Hangover, sedation, lethargy, diminished alertness. Patients may complain of morning hangover, blurred vision, and transient hypotension on arising. Hangover commonly occurs after the administration of hypnotic doses of long acting barbiturates. Patients may display a dulled affect, subtle distortion of mood, and impaired coordination. Explain to the patient*****the need to first rise to a sitting position, equilibrate, and then stand.******** Assistance with ambulation may be required. If hangover becomes troublesome, there should be a reduction in the dosage, a change in the medication, or both. Drug Interactions: Drugs that increase toxic effects: Drugs that increase toxic effects include antihistamines, alcohol, analgesics, anesthetics, tranquilizers, valproic acid, monoamine oxidase inhibitors, and other sedative hypnotics. Monitor the patient for excessive sedation and reduce the dosage of the barbiturate if necessary.

The parasympathetic nervous system (PSNS) is one of the two main divisions of the autonomic nervous system (ANS). The ANS is responsible for regulation of internal organs and glands, which occurs unconsciously. The parasympathetic system specifically is responsible for stimulation of "rest-and-digest" activities that occur when the body is at rest, including sexual arousal, salivation, lacrimation (tears), urination, digestion and defecation. Its action is described as being complementary to that of one of the other main branches of the ANS, the sympathetic nervous system, which is responsible for stimulating activities associated with the fight-or-flight response.

Relation to sympathetic nervous system

Sympathetic and parasympathetic divisions typically function in opposition to each other. This natural opposition is better understood as complementary in nature rather than antagonistic. For an analogy, one may think of the sympathetic division as the accelerator and the parasympathetic division as the brake. The sympathetic division typically functions in actions requiring quick responses. The parasympathetic division functions with actions that do not require immediate reaction. A useful acronym to summarize the functions of the parasympathetic nervous system is SLUDD (salivation, lacrimation, urination, digestion and defecation).

Physical location
The parasympathetic nerves (PSNS) are autonomic (aka "visceral"[1][2]) branches of the peripheral nervous system (PNS). Parasympathetic nerve fibers arise from the central nervous system with the S2, S3, and S4 spinal nerves and from the third, seventh, ninth, and tenth cranial nerves. Because of its location the parasympathetic system is commonly referred to as having "craniosacral outflow", which stands in contrast to the sympathetic nervous system which is said to have "thoracolumbar outflow". The parasympathetic nerves that arise from the S2, S3, and S4 spinal nerves are commonly referred to as the pelvic splanchnic nerves or the "nervi erigentes".

Pathways
As is true in the sympathetic nervous system, efferent parasympathetic nerve signals are carried from the central nervous system to their targets by a system of two neurons. The first neuron in this pathway is referred to as the preganglionic or presynaptic neuron. Its cell body sits in the central nervous system and its axon usually extends to a ganglion somewhere else in the body where it synapses with the dendrites of the second neuron in the chain. This second neuron is referred to as the postganglionic or postsynaptic neuron. The axons of presynaptic parasympathetic neurons are usually long: they extend from the CNS into a ganglion that is either very close to or embedded in their target organ. As a result, the postsynaptic parasympathetic nerve fibers are very short.[3] In the cranium, preganglionic PSN (CN III, CN VII, and CN IX) usually arise from specific nuclei

in the Central Nervous System (CNS) and synapse at one of four parasympathetic ganglia: ciliary, pterygopalatine, otic, or submandibular. From these four ganglia the PSN complete their journey to target tissues via CN V (trigeminal) branches (ophthalmic nerve CN V1, maxillary nerve CN V2, mandibular nerve CN V3). The vagus nerve (CN X) does not participate in these cranial ganglia as most of its PSN fibers are destined for a broad array of ganglia on or near thoracic viscera (esophagus, trachea, heart, lungs) and abdominal viscera (stomach, pancreas, liver, kidneys). It travels all the way down to the midgut/hindgut junction, which occurs just before the splenic flexure of the transverse colon at "Cannon-Bhm point". The pelvic splanchnic efferent preganglionic nerve cell bodies reside in the lateral gray horn of the spinal cord at the S2-S4 spinal levels.[4] Their axons continue away from the CNS to synapse at an autonomic ganglion. The PSN ganglion where these preganglionic neurons synapse will be close to the organ of innervation. This differs from the sympathetic nervous system, where synapses between pre- and post-ganglionic efferent nerves generally occur at ganglia that are farther away from the target organ. [edit]

Sensation
The afferent fibers of the autonomic nervous system, which transmit sensory information from the internal organs of the body back to the central nervous system, are not divided into parasympathetic and sympathetic fibers as the efferent fibers are.[5] Instead, autonomic sensory information is conducted by general visceral afferent fibers. General visceral afferent sensations are mostly unconscious visceral motor reflex sensations from hollow organs and glands that are transmitted to the CNS. While the unconscious reflex arcs normally are undetectable, in certain instances they may send pain sensations to the CNS masked as referred pain. If the peritoneal cavity becomes inflamed or if the bowel is suddenly distended your body will interpret the afferent pain stimulus as somatic in origin. This pain is usually non-localized. The pain is also usually referred to dermatomes that are at the same spinal nerve level as the visceral afferent synapse. [edit]

Cranial Nerve Parasympathetic Paths and Control

The oculomotor nerve is responsible for several parasympathetic functions related to the eye. The oculomotor PNS fibers originate in the Edinger-Westphal nucleus in the CNS and travel through the superior orbital fissure to synapse in the ciliary ganglion located just behind the orbit (eye). From the ciliary ganglion the postganglionic PSN fibers leave via short ciliary nerve fibers, a continuation of the nasociliary nerve (a branch of ophthalmic division of the trigeminal nerve,

CN V1). The short ciliary nerves innervate the orbit to control the ciliary muscle (responsible for accommodation) and the sphincter pupillae muscle which is responsible for miosis or constriction of the pupil (in response to light or accommodation). The parasympathetic aspect of the facial nerve controls secretion of the sublingual and submandibular salivary glands, the lacrimal gland, and the glands associated with the nasal cavity. The preganglionic fibers originate within the CNS in the superior salivatory nucleus and leave as the intermediate nerve (which some consider a separate cranial nerve altogether) to connect with the facial nerve just distal (further out) to it surfacing the CNS. Just after the facial nerve geniculate ganglion (general sensory ganglion) in the temporal bone, the facial nerve gives off two separate parasympathetic nerves. The first is the greater petrosal nerve and the second is the chorda tympani. The greater petrosal nerve travels through the middle ear and eventually combines with the deep petrosal nerve (sympathetic fibers) to form the nerve of the pterygoid canal. The PSN fibers of the nerve of the pterygoid canal synapse at the pterygopalatine ganglion, which is closely associated with the maxillary division of the trigeminal nerve (CN V2). The postganglionic PSN fibers leave the pterygopalatine ganglion in several directions. One division leaves on the zygomatic division of CN V2 and travels on a communicating branch to unite with the lacrimal nerve (branch of the ophthalmic nerve of CN V1) before synapsing at the lacrimal gland. These PSN to the lacrimal gland control tear production. A separate group of PSN leaving from the pterygopalatine ganglion are the descending palatine nerves (CN V2 branch) which include the greater and lesser palatine nerves. The greater palatine PSN synapse on the hard palate and regulate mucus glands located there. The lesser palatine nerve synapses at the soft palate and controls sparse taste receptors and mucus glands. Yet another set of divisions from the pterygopalatine ganglion are the posterior, superior, and inferior lateral nasal nerves; and the nasopalatine nerves (all branches of CN V2, maxillary division of the trigeminal nerve) that bring PSN to glands of the nasal mucosa. The second PSN branch that leaves the facial nerve is the chorda tympani. This nerve carries secretomotor fibers to the submandibular and sublingual glands. The chorda tympani travels through the middle ear and attaches to the lingual nerve (mandibular division of trigeminal, CN V3). After joining the lingual nerve the preganglionic fibers synapse at the submandibular ganglion and send postganglionic fibers to the sublingual and submandibular salivary glands. The glossopharyngeal nerve, CNIX, has parasympathetic fibers that innervate the parotid salivary gland. The preganglionic fibers depart CNIX as the tympanic nerve and continue to the middle ear where they make up a tympanic plexus on the cochlear promontory of the mesotympanum. The tympanic plexus of nerves rejoin and form the lesser petrosal nerve and exit through the foramen ovale to synapse at the otic ganglion. From the otic ganglion postganglionic parasympathetic fibers travel with the auriculotemporal nerve (mandibular branch of trigeminal, CN V3) to the parotid salivary gland.

The vagus nerve, named from the Latin word vagus means literally "Wandering", since the nerve controls such a broad range of target tissues, has PSN that originate in the dorsal nucleus of the vagus nerve and the nucleus ambiguus in the CNS. The vagus nerve is an unusual cranial PSN in that it doesn't join the trigeminal nerve in order to get to its target tissues. Another peculiarity is that the vagus has an autonomic ganglion associated with it at approximately the level of C1 vertebra. The vagus gives no PSN to the cranium. The vagus nerve is hard to track definitively due to its ubiquitous nature in the thorax and abdomen so the major contributions will be discussed. Several PSN nerves come off the vagus nerve as it enters the thorax. One nerve is the recurrent laryngeal nerve, which becomes the inferior laryngeal nerve. From the left vagus nerve the recurrent laryngeal nerve hooks around the aorta to travel back up to the larynx and proximal esophagus while, from the right vagus nerve, the recurrent laryngeal nerve hooks around the right subclavian artery to travel back up to the same location as its counterpart. These different paths are a direct result of embryological development of the circulatory system. Each recurrent laryngeal nerve supplies the trachea and the esophagus with parasympathetic secretomotor innervation for glands associated with them (and other fibers that are not PSN). Another nerve that comes off the vagal nerves approximately at the level of entering the thorax are the cardiac nerves. These cardiac nerves go on to form cardiac and pulmonary plexuses around the heart and lungs. As the main vagus nerves continue into the thorax they become intimately linked with the esophagus and sympathetic nerves from the sympathetic trunks to form the esophageal plexus. This is very efficient as the major function of the vagus nerve from there on will be control of the gut smooth muscles and glands. As the esophageal plexus enter the abdomen through the esophageal hiatus anterior and posterior vagal trunks form. The vagal trunks then join with preaortic sympathetic ganglion around the aorta to disperse with the blood vessels and sympathetic nerves throughout the abdomen. The extent of the PSN in the abdomen include the pancreas, kidneys, liver, gall bladder, stomach and gut tube. The vagal contribution of PSN continues down the gut tube until the end of the midgut. The midgut ends 2/3 of the way across the transverse colon near the splenic flexure.[6]

Pelvic Splanchnic Control

The pelvic splanchnic nerves, S2-4, work in tandem to innervate the pelvic viscera. Unlike in the cranium, where one PSN was in charge of one particular tissue or region, for the most part the pelvic splanchnics each contribute fibers to pelvic viscera by first traveling to one or more plexuses before being dispersed to the target tissue. These plexuses are composed of mixed autonomic nerve fibers (PSN and SN) and include the vesical, prostatic, rectal, uterovaginal and inferior hypogastric plexus. The preganglionic neurons in the neurons do not synapse in named ganglion as in the cranium but rather in the walls of the tissues or organs that they innervate. The fiber paths are variable and each individual's autonomic nervous system in the pelvis is unique. The visceral tissues in the pelvis that the PSN control include: urinary bladder, ureters,

urinary sphincter, anal sphincter, uterus, prostate, glands, vagina and penis. Unconsciously, the PSN will cause peristaltic movements of the ureters helping to move urine from the kidneys into the bladder and move feces down the intestinal tract and upon necessity, the PSN will assist excreting urine from the bladder or defecation. Stimulation of the PSN will cause the detrusor muscle (urinary bladder wall) to contract and simultaneously relax the internal sphincter urethrae muscle to relax allowing void of urine. Also, PSN stimulation to the internal anal sphincter will relax this muscle and allow defecation. There are other skeletal muscles involved with these processes but the PSN play a huge role in continence. Another role that the PSN play in the pelvis is in sexual activity. In males, the cavernous nerves from the prostatic plexus stimulate smooth muscle in the fibrous trabeculae of the coiled helicene arteries to relax and allow blood to fill the corpora cavernosum and the corpus spongiosum of the penis, making it rigid to prepare for sexual activity. Upon emission of ejaculate, the sympathetics participate and cause peristalsis of the ductus deferens and closure of the internal urethral sphincter to prevent semen from entering the bladder. At the same time, parasympathetics cause peristalsis of the urethral muscle, and the pudendal nerve causes contraction of the bulbospongiosus (skeletal muscle is not via PSN), to forcibly emit the semen. During remission the penis becomes flaccid again. In the female, there is erectile tissue analogous to the male yet less substantial that plays a large role in sexual stimulation. The PSN cause release of secretions in the female that decrease friction. Also in the female, the parasympathetics innervate the fallopian tubes which helps peristaltic contractions and movement of the oocyte to the uterus for implantation. The secretions from the female genital tract aids in semen migration. The PSN (and SN to a lesser extent) play a huge role in reproduction.[7] [edit]

Clinical Significance
The parasympathetic nervous system promotes digestion and the synthesis of glycogen, and allows for normal function and behavior. [edit]

Receptors
The parasympathetic nervous system uses chiefly acetylcholine (ACh) as its neurotransmitter, although other peptides (such as cholecystokinin) may act on the PSNS as a neurotransmitter.[8][9] The ACh acts on two types of receptors, the muscarinic and nicotinic cholinergic receptors. Most transmissions occur in two stages: When stimulated, the preganglionic nerve releases ACh at the ganglion, which acts on nicotinic receptors of postganglionic neurons. The postganglionic nerve then releases ACh to stimulate the muscarinic receptors of the target organ.

[edit]

Types of muscarinic receptors

The five main types of muscarinic receptors: The M1 muscarinic receptors (CHRM1) are located in the neural system. The M2 muscarinic receptors (CHRM2) are located in the heart, and act to bring the heart back to normal after the actions of the sympathetic nervous system: slowing down the heart rate, reducing contractile forces of the atrial cardiac muscle, and reducing conduction velocity of the sinoatrial node (SA node) and atrioventricular node (AV node). Note, they have a minimal effect on the contractile forces of the ventricular muscle due to sparse innervation of the ventricles from the parasympathetic nervous system. The M3 muscarinic receptors (CHRM3) are located at many places in the body, such as the endothelial cells of blood vessels, as well as the lungs causing bronchoconstriction. The net effect of uninnervated M3 receptors on blood vessels is vasodilation, as acetylcholine causes endothelial cells to produce nitric oxide, which diffuses to smooth muscle and results in vasodilation. They are also in the smooth muscles of the gastrointestinal tract (GIT), which help in increasing intestinal motility and dilating sphincters. The M3 receptors are also located in many glands that help to stimulate secretion in salivary glands and other glands of the body. They are also located on the detrusor muscle of the bladder, causing contraction of the bladder. The M4 muscarinic receptors: Postganglionic cholinergic nerves, possible CNS effects The M5 muscarinic receptors: Possible effects on the CNS

Autonomic Nervous System: >>>>Controls most tissue in body. >>>>Maintains constant internal environment (homeostasis) >>>>Responds to emergency situations. ~~~Made up of two major neurotransmitters: >>>>Norepinephrine: Liberated by adrenergic fibers >>>>Acetylcholine: Liberated by cholinergic fibers. >>>>Cholinergic Response (Parasympathetic Nervous System): All secretions; Digestion, peristalsis. If we make heart beat faster, such as in the cold, we are pushing Epinephrine. (sympathetic response) Meds will be considered (based on) either one of the following: >>Adrenergic blocker or Adrenergic Stimulator >>Cholinergic blocker or cholinergic Stimulator Cholinergic Response: PARASYMPATHETIC (all secretions are going, hearing, etcc) What will kick in when we want to stop all these responses? >>>Answer: Our Adrenergic Response/Norepinephrine.(adrenaline) (the fight response) Side note: To activate parasympathetic response we need Acetylcholine which is liberated by the cholinergic fibers. Note: (The trick is to keep them well balancedone kicks in when needed to balance the other.) They have to be in perfect harmony. Some neuromuscular problems are related to the imbalance of the parasympathetic and sympathetic responses. Parasympathomimetic: mimicking the parasympathetic response. (cholinergic drugs: salivation, urination, etc.) Sympathomimetic: mimicking the sympathetic response. (Adrenergic drugs) Lytic: means inhibiting or blocking. Parasympatholytic: Blocks the parasympathetic response. (blocks parasympathetic neuro system) (Inhibiting the response of Acetylcoline (acetylcolinesterase???) Sympatholytic: Inhibits Norepinephrine. (?) Parasympatholytic drugs are sometimes used to treat slow heart rhythms (bradycardias or bradydysrhythmias) caused by myocardial infarctions or other pathologies, as well as to treat conditions which cause bronchioles in the lung to constrict, such as asthma. By blocking the parasympathetic nervous system, parasympatholytic drugs can increase heart rate in patients with bradycardic heart rhythms, and open up airways and reduce mucous production in patients suffering from asthma. >>>>Bronchial Muscle: B2~~~~smooth muscle relaxation; opens airway (adrenergic-sympathetic) >>>>Bronchial Muscle: B2~~~~smooth muscle contraction: closes airway (cholinergice-parasympathetic) >>>Heart: B1~~~Increase Heart Rate; force of contraction (Adrenergic-sympathetic) >>>Heart: B1~~~Decreased Heart Rate (Cholinergic-Parasympathetic) >>>Uterus: a; B2: Pregnancy: contraction (a) Relaxation (B2) (Variable)

Catecholamines: Bodys naturally occurring neurotransmitter catcholamines are norepinephrine, epinephrine, and dopamine. Norepinephrine is screted primarily from nerve terminals, epinephrine primarily from the adrenal medulla, and dopamine at primarily selected sites in the brain, kidneys, and gi tract. All three agents are also synthetically manufactured and may be administered to produce the same effects as those naturally secreted. Noncatecholamines have actions that are somewhat similar to those of the catcholamines but are more selective for certain types of receptors, are not quite as fast acting, and have a longer duration of action. ANS can be subdivided into the alpha, beta, and dopaminergic receptors. When stimulated by chemicals of certain shapes, produce action. In general, stimulation of alpha 1 receptors causes vasoconstriction of blood vessels. The alpha2 receptors appear to serve as mediators of negative feedback, preventing further release of norepinephrine. Stimulation of beta1 receptors causes an increase in the heart rate, and stimulation of beta2 receptors causes relaxation of smooth mucle in the bronchi (bronchodilation) uterus (relaxation) and peripheral arterial blood vessels (vasodilation). Stimulation of the dopaminergic receptors in the brain improves the symptoms associated with parkinsons. Dopamine also increases urine output because of stimulation of specific receptors in the kidneys that results in better renal perfusion. Adrenergic agents may cause: generally mild, adrenergic agents may cause some degree of orthostatic hypotension manifested by dizziness and weakness, particularly when therapy is initiated. Monitor BP daily in both the supine and standing position. Anticipate the development of postural hypotension and take measures to prevent an occurrence. Teach patient to rise slowly. Side not: Albuterol is an Adrenergic Drug. (Proventil) (Beta-2) (Bronchodilator) (asthma/emphesema) >>>>Drug Interactions: Agents that may increase therapeutic and toxic effects: These include monoamine oxidase inhibitors (phenelzine, tranylcypromine) tricclic antidepressants, atropine, and halothane anesthesia. Many OTC drugs such as cold remedies and appetite suppressants, diet pills (ephedrine) contain adrenergic meds that can have an additive effect when taken with a prescribed adrenergic agent. Monitor patients for tachycardia, serious dysrhythmias, hypotension, hypertension, and chest pain. Beta blockers can be subdivided into nonselective and selective beta antagonists. The nonselective blocking agents have an equal affinity for beta 1 and beta 2 receptors and inhibit both. These are propranolol, nadolol, etcpg 204 text. Some cholinergic agents act by directly stimulating the parasympathetic nervous system whereas others inhibit acetylcholinestrerase. Anticolinergics: Blocks Acetylcoline (pulmonary drugs) (copd including bronchitis & emphysema) (Atrovent) Anticolinergic drugs promote: broncho constriction The vagus nerve along the airways release acetylcoline which bind to muscurinic receptros in the smooth muscle and airway submucosal glands. Adrenergic Blockers (antiadrenergic): Blocks norepinephrine.

Myasthenic crisis is a life-threatening condition, which is defined as weakness from acquired myasthenia gravis (MG) that is severe enough to necessitate intubation or to delay extubation following surgery [1]. The respiratory failure is due to weakness of respiratory muscles. Severe bulbar (oropharyngeal) muscle weakness often accompanies the respiratory muscle weakness, or may be the predominant feature in some patients. When this results in upper airway obstruction or severe dysphagia with aspiration, intubation and mechanical ventilation are necessary. PRECIPITANTS Myasthenic crisis may be precipitated by a variety of factors, most often a concurrent infection. It can also follow a surgical intervention, pregnancy, childbirth, or tapering of immunosuppressive medications. In addition, myasthenic crisis can occur spontaneously as part of the natural history of myasthenia gravis (MG) itself. A number of drugs can increase the weakness in myasthenia and should be considered as possible precipitants in this setting. This is of more concern with certain antibiotics (aminoglycosides, erythromycin and azithromycin), cardiac drugs (beta-blockers, procainamide, and quinidine), and magnesium. A potential major side effect of excessive anticholinesterase medication is weakness, which can be difficult to distinguish from worsening MG. This paradoxical weakening with anticholinesterase medications is called "cholinergic crisis." However, cholinergic crisis is rarely if ever seen with dose limitation of pyridostigmine to less than 120 mg every three hours. Cholinergic crisis is so rare that it should not be the presumed cause of increasing weakness unless the doses taken are known to significantly exceed this range. Otherwise, even in the presence of cholinergic side effects, it should be assumed that the patient's underlying MG is worsening and appropriate treatment should be initiated.

Mestinon&PrednisonearemedsusedtotreatMG.Prostigman is antedote for neuromuscular blocking agent.

MECHANISM OF ACTION!The neuromuscular blocking activity of aminoglycosides results from a decreased sensitivity at the postjunctional membrane and interfere with transmitter release.(1) These actions produce a synergistic effect with anesthetic agents that produce neuromuscular blockade.(2,3) Some anesthetics cause renal failure due to release of fluoride ion. Aminoglycosides cause nephrotoxicity when high doses are given.(4,5) DISCUSSION!Aminoglycosides including kanamycin(6,11), streptomycin(6,13), amikacin(13), gentamicin(7,13-15), neomycin, and tobramycin(13) have been documented to have neuromuscular blocking activity. There is no documentation with netilmicin and paromomycin, though it is assumed that they produce the same effects as the other members of this class. Neomycin has been shown to interact with cyclopropane(8,9), halothane(6), methoxyflurane(6), and nitrous oxide(6). Enflurane, ethylene, and isoflurane share similar properties to the previous inhalation anesthetics and would likely interact with neomycin. Kanamycin(6,11) and streptomycin (6,12) are known to interact with ether. Gentamicin has been reported to potentiate atracurium.(16) Therefore it is hypothesized that all aminoglycosides interact with the inhaled anesthetics. One study evaluating gentamicin and halothane in animals did not exhibit a decrease in muscle strength.(17) Aminoglycosides have been proven to be nephrotoxic at high doses. Anesthetics containing flouride also produce renal dysfunction. Nephrotoxicity occured more often when gentamicin or tobramycin were given with enflurane than when enflurane was given alone or in patients who received nitrous oxide and narcotic anesthesia.(4)
SIDE NOTE: MG IS WHEN ACH DESTROYED AT RECEPTORSITE. NOT ENOUGH ACH. TO TREAT WE HAVE TO BLOCK ACETYLCOLINESTERASE. >>>>>>>ATROPINE WILL REVERSE COLLINERGIC CRISIS!!!<<<<<<<<< CHOLINERGIC: HYPOSTENSION MYASTHENIC: HYPERTENSION (TENSILON TEST) TREAT WITH AROPINE IF OVERDOSED W/ NEOSTIGMIN/PROSTIGNAN OR NESTINON (ANTICOLINERGIC AGENTS)

Treatment Treatment is by medication and/or surgery. Medication consists mainly of cholinesterase inhibitors to directly improve muscle function and immunosuppressant drugs to reduce the autoimmune process. Thymectomy is a surgical method to treat MG. For emergency treatment, plasmapheresis or IVIG can be used as a temporary measure to remove antibodies from the blood circulation.

Medication Neostigmine, chemical structure. Acetylcholinesterase inhibitors: neostigmine and pyridostigmine can improve muscle function by slowing the natural enzyme cholinesterase that degrades acetylcholine in the motor end plate; the neurotransmitter is therefore around longer to stimulate its receptor. Usually, doctors will start with a low dose, e.g. 3x20mg pyridostigmine, and increase until the desired result is achieved. If taken 30 minutes before a meal, symptoms will be mild during eating. Side effects, such as perspiration and diarrhea, can be countered by adding atropine. Pyridostigmine is a short-lived drug, with a half-life of about four hours.

Azathioprine, chemical structure Immunosuppressive drugs: prednisone, cyclosporine, mycophenolate mofetil and azathioprine may be used. Patients are commonly treated with a combination of these drugs with a cholinesterase inhibitor. Treatments with some immunosuppressives take weeks to months before effects are noticed. Other immunomodulating substances, such as drugs that prevent acetylcholine receptor modulation by the immune system, are currently being researched.[16] [edit] Plasmapheresis and IVIG If the myasthenia is serious (myasthenic crisis), plasmapheresis can be used to remove the putative antibodies from the circulation. Also, intravenous immunoglobulins (IVIGs) can be used to bind the circulating antibodies. Both of these treatments have relatively short-lived benefits, typically measured in weeks.[17] [edit] Surgery Main article: thymectomy Thymectomy, the surgical removal of the thymus, is essential in cases of thymoma in view of the potential neoplastic effects of the tumor. However, the procedure is more controversial in patients who do not show thymic abnormalities. Although some of these patients improve following thymectomy, some patients experience severe exacerbations and the highly controversial concept of "therapeutic thymectomy" for patients with thymus hyperplasia is disputed by many experts, and efforts are underway to unequivocally answer this important question. There are a number of surgical approaches to the removal of the thymus gland: transsternal (through the sternum, or breast bone), transcervical (through a small neck incision), and transthoracic (through one or both sides of the chest). The transsternal approach is most common and uses the same length-wise incision through the sternum (breast bone)used for most open-heart surgery. The transcervical approach, a less invasive procedure, allows for removal of the entire thymus gland through a small neck incision. There has been no difference in success in symptom improvement between the transsternal approach and the minimally invasive transcervical approach.[18] For patients with a thymoma, though, complete tissue removal is important, as thymic tissue can regrow. Thymomas can be malignant and are thought to be the onset of other diseases, as well, so many surgeons will only recommend the full sternotomy approach to a thymectomy.

Thymoma is relatively rare in younger (<40) patients, but especially younger patients with generalized MG without thymoma benefit, paradoxically, from thymectomy. Resection is also indicated for those with a thymoma, but it is less likely to improve the MG symptoms. A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as of a result of the inactivity (perhaps even inhibition) of the AChE enzyme, which normally breaks down acetylcholine. This is a consequence of some types of nerve gas, (e.g. sarin gas). In medicine, this is seen in patients with myasthenia gravis who take too high a dose of their cholinergic treatment medications, or seen in some surgical cases, when too high a dose of a cholinesterase inhibitor is given to reverse surgical muscle paralysis. As a result of cholinergic crisis, the muscles stop responding to the bombardment of ACh, leading to flaccid paralysis, respiratory failure, and other signs and symptoms reminiscent of organophosphate poisoning. Other symptoms include increased sweating, salivation, bronchial secretions along with miosis. This crisis may be masked by the concomitant use of atropine along with anticholinesterase inhibitors in order to prevent side effects. Flaccid paralysis resulting from cholinergic crisis can be distinguished from Myasthenia gravis by the use of the drug Edrophonium which worsens the paralysis if its a cholinergic crisis but strengthens the muscle in the case of myasthenia gravis.(Edrophonium is an anticholinesterase hence increases the concentration of acetylcholine present). >>>>>Cholinergic crisis can be treated with antimuscarinic drugs like Atropine.<<<<<<

Treatment for meds pt with myasthenia gravis. Meds for Myasthenia Crisis Meds for Colinergic Crisis Specific Reversal Anesthesia Aminoglycosides and Anesthesia