Chapter 43: Antifungal Agents

Chapter 43: Antifungal Agents

A 43-year-old man is being treated with amphotericin B for esophageal candidiasis. Which of the following serum laboratory tests should be monitored closely?

a. Bilirubin

b. Cholesterol

c. Glucose

d. Creatinine

e. Sodium

Answer is d. Azotemia occurs in 80% of patients who receive C-AMB for deep mycoses. Lipid formulations are less nephrotoxic. Nephrotoxicity is dose-dependent, usually transient, and increased by concurrent therapy with other nephrotoxic agents.

A 56-year-old man with cryptococcal meningitis is being treated with flucytosine and amphotericin B. Flucytosine is metabolized to 5-flurouracil by fungal cells which inhibits DNA synthesis. The selectivity of flucytosine is due to a lack of which enzyme in mammalian cells:

a. Cytosine deaminase

b. N-acetyltransferase

c. Fluorine oxidase

d. Uracil phosphoribosyl transferase

e. Thymidylate synthetase

Answer is a. The selective action of flucytosine is due to the lack of cytosine deaminase in mammalian cells, which prevents the metabolism to 5-flurouracil.

A 48-year-old woman with a history of atrial fibrillation is being treated with warfarin. She has recently developed coccidiodal meningitis and treatment with fluconazole is started. A potential drug–drug interaction that may result in elevated plasma warfarin concentration is likely because fluconazaole inhibits

a. CYP3A4.

b. CYP2D6.

c. CYP2C9.

d. CYP2C19.

e. CYP4.

Answer is c. Fluconazole is an inhibitor of CYP3A4, CYP2C9, and CYP2C19 (see Table 43-3). Warfarin is metabolized by CYP2C9 (see Chapter 19). The inhibition of CYP2C9 would cause an increase in warfarin plasma concentrations unless the warfarin dose is adjusted accordingly.