questions_Pharmacology

Educational objective: Review side effects of amiodarone therapy.

Subclinical hypothyroidism evidenced by small increase in serum TSH and low T4 concentrations occurs in approximately 20% of patients treated with amiodarone. Some patients, particularly those with chronic autoimmune thyroiditis, may become overtly hypothyroid. Symptoms can develop from 2 weeks to as late as 39 months after the initiation of the amiodarone therapy.

About 3% of patients in the U.S. who are treated with amiodarone become hyperthyroid between 4 months and 3 years after initiation of therapy. It is more common in iodine-deficient parts of the world (in about 10% of patients). It is important to note that symptoms may be attenuated by beta-blocking activity of the amiodarone. Serum TSH level is the best test to diagnose this complication.

Pulmonary disease occurs in 5-15% of patients and is the most common cause of death associated with amiodarone therapy. The pathologic changes include alveolar thickening and exudation associated with dense interstitial infiltrates and fibrosis. The mechanism for these changes is not understood. Symptoms may start as soon as 1 month and as late as 5 years after amiodarone is begun. There is a dose response relationship; in one study no cases were seen when maintenance dose was below 305 mg/day.

Amiodarone can directly cause sinus bradycardia and AV block due to its calcium channel blocking activity. However, of greater concern is the prolongation of repolarization and QT interval due to blockade of the potassium channels. Important to note – the incidence of proarrhythmia is very low with amiodarone and the incidence of torsade de pointes is below 1%.

A transient rise in serum aminotransferase level is commonly seen after amiodarone therapy initiation. Patients are usually asymptomatic, but the drug should be stopped if there is more than a two-fold elevation because of the potential for cirrhosis and liver failure.

The rest of the side effects include corneal microdeposits, photosensitivity, and blue-gray discoloration of the skin, sterile epididymitis, etc.

Educational objective: Review medications that interfere with levothyroxine therapy.

Reasons for changing levothyroxine dose in patients on previously stable dosage

Requirement for increased dose:
Pregnancy Further decrease in thyroid function due to Graves’ disease or after radioiodine ablation, or Hashimoto’s thyroiditis. Impaired levothyroxine absorption due to cholestyramine, colestipol Iron sulfate Sucralfate Aluminum hydroxide Short bowel syndrome Augmented levothyroxine metabolism due to Phenytoin Rifampin Carbamazepine

Requirement for decreased dose:
Spontaneous recovery from Hashimoto’s thyroiditis due to disappearance of TSH-receptor-blocking antibodies. Reactivation of Graves’ disease Emergence of autonomous nodule Advanced age Factitious ingestion of levothyroxine.

Educational objective: Review the important features of typical and atypical neuroleptics.

Typical neuroleptics--haloperidol, trifluperazine, thioridazine, etc.-- have been around longer and withstood the test of time; their therapeutic benefit is indeed clear; but the atypical ones - clozapine, risperidone, quetiapine, olanzapine - generally have fewer side effects and their use is considered to be associated with a reduced risk of tardive dyskinesia. Evidence exists that total treatment with atypical neuroleptics may be less expensive even though the cost of the drug itself is significantly higher. The increased compliance with treatment and apparent increased effectiveness against negative symptoms (social withdrawal, impoverishment of affect, etc.) result in fewer re-hospitalizations, which means lower total cost.

Educational objective: Review similarities and differences between delirium and dementia.

• 1- true
• 2- false: Full alertness is quite common in dementia but not in delirium, and such becomes an important factor in distinguishing between the two.
• 3- true
• 4- false: An accurate differential diagnosis between delirium and dementia is often very significant for the treatment and subsequent response to the patient.
• 5- true: A patient often has a debilitating general medical condition and is on several medications, one or more of which may cause a delirous episode.
• 6- false: A delirium does not usually include a disturbance of affect per se, and intense hallucinations, delusions, and agitation must be distinguished from numerous other psychotic episodes such as Brief Psychotic Disorder, Schizophrenia, Schizophreniform Disorder, and Mood Disorder with Psychotic Features.
• 7- false: Disturbances of affect are not included as criteria for a delirium/dementia condition.
• 8- false: Delirium tremens is a substance withdrawal syndrome.
• 9- true

Educational objective: Emphasize low incidence of sexual dysfunction with bupropion and nephazodone.

Bupropion and nephazodone appear to have the least incidence of reported sexual dysfunction side effects. They become, when possible to use them, good choices when patients suffer from sexual dysfunction associated with SSRI's and the patients are willing to risk a change of antidepressants.

Educational objective: Emphasize myositis as a side effect of HMG-CoA reductase inhibitors.

HMG-CoA reductase inhibitors are generally well tolerated, but the risk of myositis increases with the accompanying use of niacin, gemfibrozil, erythromycin and certain immunosuppressive agents such as cyclosporins. HMG-CoA reductase inhibitors and cholestyramine can be combined without much risk of myositis.

Educational objective: Review spectra of cephalosporins.

First generation cephalosporins like cefazolin are best used for gram-positive cocci and for surgical prophylaxis. Cefotetan and cefoxitin have good anaerobic coverage. Ceftazidime, a third generation cephalosporin, is good for gram-negative coverage.

Educational objective: Emphasize lack of sexual side effects with bupropion therapy.

All of the above can be used effectively to treat depressive symptoms. However, bupropion is not associated with sexual dysfunction while the other serotonin reuptake inhibitors (SSRI’s), are all associated with sexual side effects. This patient already has sexual dysfunction and hence would derive the most benefit from treatment with bupropion.

Educational objective: Review side effects of commonly used anticancer drugs.

The important side effects of cisplatin are nephrotoxicity, peripheral neuropathy, ototoxicity and magnesium depletion. Skin pigmentation is an important side effect of bleomycin. Pulmonary fibrosis occurs with busulfan and bleomycin. Cardiomyopathy is a noted side effect of doxorubicin and daunorubicin. Hemorrhagic cystitis occurs with cyclophosphamide.

Educational objective: Review approved medications for Alzheimer’s disease.

Metrifonate remains investigational (at the time of this writing), and both ginko-biloba and tocopherol are dietary supplements.

Educational objective: Review antipsychotic side effects.

Haloperidol, a high potency typical antipsychotic medication, poses the greatest risk of extrapyramidal side effects (EPS). Chlorpromazine is a low potency typical antipsychotic and loxapine is a mid-potency antipsychotic. Risperidone and olanzapine are atypical antipsychotics and associated with lower risk of EPS.

Educational objective: Emphasize sexual dysfunction as an important side effect of MAOI’s.

Sexual dysfunction is a well-known side effect of MAOI’s. The other statements are correct.

Educational objective: Review symptoms of lithium toxicity.

Nausea, vomiting, diarrhea, coarse tremor, sleepiness, sluggishness, vertigo and dysarthria are symptoms of mild lithium toxicity. Cardiac arrhythmias, impaired consciousness, hyperreflexia, nystagmus, seizures and coma can follow with increasing serum levels. Tinnitus is not seen in lithium toxicity.

Educational objective: Review pharmacologic facts about fluoxetine.

Fluoxetine was the first commercially available selective serotonin reuptake inhibitory available in the U.S. (1988). Several others have been released subsequently. The effect exerted by these medications is inhibition of serotonin reuptake. The half-life of fluoxetine in healthy adults is 72 hours, and there is an active metabolite (norfluoxetine) which has a longer half-life. The principle drug interactions pertinent in SSRI’s surround the inhibition of the cytochrome p-450 isoenzymes in the liver, causing elevations of other drugs, including tricyclic antidepressants. Fluoxetine overdose is generally not life threatening. The clinical effect of any antidepressant rarely occurs until the second or third week of therapy.

Educational objective: review medications influencing hepatic cytochrome P450 enzyme system.

If the active form of a drug is eliminated largely by biotransformation, inhibition of its metabolism leads to reduced clearance, prolonged half-life, and accumulation of the drug during maintenance therapy. Fluoxetine and cimetidine are potent inhibitors of the oxidative metabolism of many drugs via inhibition of the cytochrome P450 enzyme system. Cigarette smoking, phenobarbital, rifampin, carbamazepine, alcohol and chloral hydrate induce hepatic metabolism, reducing effective concentration of the drugs.

Educational objective: understanding the mechanism of action for furosemide.

Loop diuretics reduce NaCl reabsorption by inhibiting the Na-K-2Cl carrier in the luminal membrane in the thick ascending limb of the loop of Henle. The efficacy is dose-related and depends on delivery of the diuretic to the site of action. The loop diuretics are highly protein bound and are therefore delivered mostly by tubular secretion rather than by glomerular filtration.

In the subjects with normal renal function diuretic effect can be seen with as little as 10 mg of furosemide given orally. Maximal effect is seen with about 40 mg given intravenously.

The maximum effective dose is, however, higher in patients with heart failure, advanced cirrhosis, or renal failure. In these conditions, decreased renal perfusion (with decreased drug delivery), diminished tubular secretion (because of retention of the anions in renal failure), and enhanced activity of the rennin-angiotensin-aldosterone system (enhancing sodium retention) combine to diminish the diuretic effect.