Clinical pharmacy最新文献

Standard pharmacologic management of cystic fibrosis is discussed and the role of new agents in the treatment of this disease is explored. Cystic fibrosis is a recessive, fatal genetic disease involving multiple organ systems, in which patients develop pancreatic insufficiency, malabsorption, and repeated pulmonary infections. Pharmacotherapy to date has included broad-spectrum antimicrobials and aggressive nutritional management with microencapsulated pancreatic enzymes. Acute pulmonary exacerbations, caused by Pseudomonas aeruginosa, require combination i.v. antimicrobial therapy for 14 to 21 days. With the recent discovery of the genetic defect responsible for cystic fibrosis, as well as the cellular mechanism, new pharmacologic approaches are being explored to improve treatment. Aerosolized amiloride is being tested to modify the basic defect in the chloride channel. Dornase, a new mucolytic, is used to decrease sputum viscosity and increase mucociliary clearance. Leukoprotease inhibitors are currently being evaluated for decreasing the acute inflammatory reaction in the lung. Gene therapy has been promising, but its role in the management of cystic fibrosis is many years away. Drug therapy for cystic fibrosis has been primarily directed at treating infections with antibiotics and supplementing digestive enzymes and vitamins. New agents and gene therapy may substantially change the morbidity and mortality of this disease.

The mechanism of action, pharmacokinetics, and use of flumazenil in benzodiazepine overdose, as well as in the management of other disease states, are reviewed. Flumazenil interacts at the central benzodiazepine receptor to antagonize or reverse the behavioral, neurologic, and electrophysiologic effects of benzodiazepine agonists and inverse agonists. Flumazenil has been studied for a variety of indications, including as an antidote to benzodiazepine overdose and for awakening of comatose patients, reversal of sedation after surgery and in critically ill patients, and management of hepatic encephalopathy. It improves the level of consciousness in patients with benzodiazepine overdose; however, resedation may occur within one to two hours after administration, so repeated doses or a continuous infusion may be required to maintain therapeutic efficacy. It appears to be effective in reversing sedation induced by midazolam or diazepam, and case reports suggest that it is useful in awakening comatose patients, although its clinical utility is questionable. Flumazenil has proved useful in reversing conscious sedation in critically ill patients, although response may be dose dependent. Animal models indicate that flumazenil is of some benefit in hepatic encephalopathy, but until well-designed clinical trials are conducted, hepatic encephalopathy must be considered an investigational indication for flumazenil. Adverse reactions include CNS manifestations, resedation, cardiovascular effects, seizures, and alterations in intracranial pressure and cerebral perfusion pressure. Hepatic dysfunction results in a substantial change in the pharmacokinetic profile of flumazenil; therefore, dosage adjustment may be necessary in patients with hepatic dysfunction or in those receiving medications that alter flumazenil metabolism. Flumazenil has been shown to reverse sedation caused by intoxication with benzodiazepines alone or benzodiazepines in combination with other agents, but it should not be used when cyclic antidepressant intoxication is suspected. It may be beneficial after surgery when benzodiazepines have been used as part of anesthesia and after a diagnostic or surgical procedure when assessment of CNS function is necessary.

The mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy, adverse effects, and dosage of atovaquone in the management of mild to moderate Pneumocystis carinii pneumonia (PCP) are reviewed. Atovaquone has a novel mechanism of action that has been hypothesized to result in microbicidal rather than microbistatic activity against Pneumocystis carinii. Absorption of the drug is significantly enhanced by the presence of food, particularly food with a high fat content. In comparative trials, atovaquone was slightly less effective than trimethoprim-sulfamethoxazole and as effective as pentamidine isethionate in treating mild to moderate PCP. Atovaquone is associated with a lower incidence of treatment-limiting adverse reactions than are trimethoprim-sulfamethoxazole and pentamidine isethionate. The most commonly occurring adverse effect in patients receiving atovaquone is rash, and the drug does not appear to cause bone marrow suppression. The FDA-approved dosage regimen for atovaquone in treating mild to moderate PCP is 750 mg (three 250-mg tablets) administered orally three times daily with food for 21 days. Atovaquone may be considered a first-line treatment for patients with the acquired immunodeficiency syndrome who have mild to moderate PCP and have demonstrated an intolerance to trimethoprim-sulfamethoxazole.

The mechanisms of magnesium action and the possible benefits of its use in treating acute myocardial infarction are reviewed. Magnesium is an essential cofactor in more than 300 enzymatic reactions, including those responsible for the production, storage, and use of energy. It influences impulse generation and action potential propagation of the cardiac and pacemaker cells and affects muscular contraction within the myocardium and arterial smooth muscle. Magnesium has been used successfully for the treatment of arrhythmias and has been shown to produce hemodynamic changes including suppression of vasospasm and reduction of vascular resistance. In clinical trials to assess the usefulness of intravenous magnesium in the treatment of acute myocardial infarction, several beneficial effects were found, including a smaller mean infarction size, a reduction in the occurrence of supraventricular tachycardia, fewer occurrences of serious ventricular arrhythmias, and a lower incidence of early mortality. A bolus dose of magnesium followed by a prolonged infusion to maintain elevated serum magnesium levels appears necessary to obtain the beneficial effects. Studies indicate that magnesium may reduce the incidence of early mortality after acute myocardial infarction. The mechanism of action is still unclear, but it may be a direct cardioprotective effect.

Characteristics and diagnosis of photosensitivity are discussed, and drugs available in the United States that cause photosensitivity are identified. In phototoxic reactions, the drug absorbs energy from ultraviolet A (UVA) light and releases it into the skin, causing cellular damage. In photoallergic reactions, light may cause a structural change in a drug so that it acts as a hapten, possibly by binding to proteins in the skin. Once a hapten-protein complex is formed, Langerhans' cells residing in the epidermis can present the antigen to immunocompetent cells, causing hypersensitivity. Phototoxicity is much more common than photoallergy. Drugs that can cause phototoxic reactions include amiodarone, quinolones, and tetracyclines. Drugs that have been associated with photoallergic reactions include thiazides and benzocaine. Pharmacists should be aware of drugs that can cause photosensitivity and should counsel patients taking these drugs to avoid excessive exposure to sunlight.