1. A. Nephrotoxicity is the most common and most serious toxicity associated with amphotericin B administration. This is manifested by azotemia (elevated serum blood urea nitrogen and creatinine), and by renal tubular acidosis, which results in the wasting of potassium and magnesium in the urine (leading to hypokalemia and hypomagnesemia, requiring oral or intravenous replacement therapy). Normochromic normocytic anemia is also seen with long-term amphotericin B administration. Elevation of liver enzymes is not associated with the use of amphotericin B.
2. B. Oral fluconazole is well absorbed from the gastrointestinal tract, and 80% of drug is excreted into the urinary tract, allowing effective treatment of Candida cystitis. Subtherapeutic concentrations of itraconazole and ketoconazole are excreted into the urine; these agents are not effective in the treatment of Candida cystitis. Topical clotrimazole would be effective in the treatment of Candida vaginitis, which can cause dysuria, but would not be an effective treatment for cystitis. While 90% of 5-flucyto-sine is excreted unchanged in the urine, this more toxic agent is usually used only in combination therapy with a second antifungal agent (usually ampho-tericin B) in the treatment of systemic candidiasis or cryptococcal meningitis.
3. B. Amphotericin B remains the drug of choice in the treatment of disseminated or invasive fungal infections in immunocompromised hosts; bone marrow transplant recipients are the most heavily im-munocompromised patients encountered in the hospital setting. 5-Flucytosine has no significant activity against Aspergillus spp., and it has bone marrow toxicity as a common adverse effect; it should not be used in this setting. Fluconazole has not been shown to be effective in the treatment of aspergillo-sis. Itraconazole has been reported to be effective as salvage treatment in patients with aspergillosis if amphotericin B therapy fails; it should not be used as initial treatment in this setting. Capsofungin, a new echinocandin antifungal agent recently approved by the U. S. Food and Drug Administration for the treatment of refractory aspergillosis when standard therapy with amphotericin B fails, should also not be used to treat invasive aspergillosis until more data showing efficacy are available.
4. C. Patients receiving multiple medications may have adverse drug reactions when a new medication is added to the regimen. Itraconazole requires an acidic gastric environment for absorption; any drug reducing gastric acid production (H2 blockers, proton pump inhibitors) or neutralizing gastric acid (antacids) will significantly reduce itraconazole absorption. Itraconazole inhibits the metabolism of lovastatin and simvastatin and should not be prescribed with these p-hydroxy-p-methyglutaryl-coenzyme A reductase inhibitors. Itraconazole will raise serum cyclosporin levels, resulting in cy-closporin toxicity, unless cyclosporin levels are closely monitored with dose reductions as indicated.
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