Journal of Pharmacy Technology

To discuss the mechanism of action, in vitro and in vivo activity, pharmacokinetics, clinical trials, adverse effects, drug interactions, and dosage guidelines of atovaquone.

Pertinent literature published since 1988 was identified via a MEDLINE search. Published proceedings of selected conferences were also used.

All basic science, microbiologic, and pharmacokinetic articles were evaluated. Since only limited data regarding atovaquone are available in the literature, all clinical trials involving the use of atovaquone in the treatment of Pneumocystis carinii pneumonia were reviewed.

Atovaquone is an antiprotozoal agent that was recently approved for the treatment of mild to moderate P. carinii pneumonia (PCP) in patients who are intolerant of trimethoprim/sulfamethoxazole (TMP/SMX). The exact mechanism of action of atovaquone against P. carinii has not been determined. The drug has in vitro and in vivo activity against P. carinii, Toxoplasma gondii, and Plasmodium species. The bioavailability of oral atovaquone is highly variable. The drug must be administered with food to enhance absorption. In a double-blind comparative trial in AIDS patients with mild to moderate PCP, those who were treated with atovaquone had a significantly higher mortality rate than those treated with TMP/SMX. More patients who received TMP/SMX experienced adverse effects that resulted in discontinuation of therapy.

Because of concerns of increased mortality in atovaquone recipients, the drug should be reserved for the treatment of mild to moderate PCP in patients who are unable to tolerate TMP/SMX and trimethoprim-dapsone.

To review the literature discussing the use of angiotensin-converting enzyme (ACE) inhibitors in the treatment of heart failure.

English-language journal articles.

Representative articles discussing the effects of ACE inhibitors on hemodynamics, symptoms, and survival.

Studies selected for review in the text were based on study design and clinical endpoints.

Heart failure results in a series of compensatory responses that, although effective acutely, are ultimately maladaptive. A major mediator in this process is angiotensin II. The production of angiotensin II is dependent on the ACE. Inhibition of this enzyme by ACE inhibitors results in fewer symptoms, improved hemodynamic function, and prolonged survival in patients with heart failure.

ACE inhibitors are beneficial in improving the survival of patients with symptomatic heart failure and of patients who have recently had an acute myocardial infarction (MI) and subsequently have a reduced ejection fraction. There appears to be no advantage for immediately initiating ACE-inhibitor therapy within the first few hours of an MI episode. With respect to patients with a reduced ejection fraction without symptoms of heart failure, current data suggest that ACE inhibitors delay the onset of symptoms of heart failure, reduce the need for hospitalization, and may possibly improve survival.

To describe the roles of the psychopharmacist in the use of neuroleptic therapy.

A geriatric psychiatry ambulatory care clinic in a 400-bed Department of Veterans Affairs Medical Center, San Diego, California.

In the pharmaceutical care model, the pharmacist is involved in several important roles in the provision of neuroleptic therapy. In the ambulatory care program, psychopharmacists provide important drug-related information to patients and consultation regarding potential neuroleptic-induced adverse effects. In addition, psychopharmacists serve as consultants to other clinicians concerning the risks associated with the use of neuroleptics and participate in neuroleptic-discontinuation clinics. Morbidity associated with neuroleptic-induced tardive dyskinesia has exposed healthcare providers to legal repercussions; therefore, pharmacy intervention may aid in the reduction of legal liability.

To report a case of erythromycin-induced ototoxicity and to discuss the occurrence of this event.

A 26-year-old woman was admitted to the medical intensive care unit with a two-day history of progressive shortness of breath, high-grade fever, cough, and pleuritic chest pain. Arterial blood gases on room air showed severe hypoxemia, and a chest X-ray revealed right lower-lobe infiltrates. Provisional diagnosis was atypical pneumonia, for which erythromycin lactobionate 1 g q6h iv was administered. All other chronic medications were maintained at the same dosage and frequency. All laboratory work remained stable. After 36 hours, the patient developed sensorineural hearing loss. Erythromycin was stopped immediately. After 24 hours, there was subjective improvement of hearing, with complete return to pretreatment levels in 72 hours.

A review of the literature showed only 40 reported cases of reversible ototoxicity, mainly with high dosages of erythromycin (4 g/d).

High-dose erythromycin therapy can cause reversible sensorineural hearing impairment. Treatment with erythromycin 4 g/d should be reserved for immunosuppressed patients with Legionnaires' disease and patients with Legionella endocarditis. Patients should have a baseline audiogram and regular monitoring for subjective evidence of sensorineural hearing loss, and the drug should be discontinued if ototoxicity is suspected.