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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.

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Table 43-3. Drugs Exhibiting Elevated Plasma Concentrations When Co-Administered with Azole Anti-Fungal Agents
Alfentanil Eplerenone Losartan Saquinavir
Alprazolam Ergot alkaloids Lovastatin Sildenafil
Astemizole Erlotinib Methadone Sirolimus
Buspirone Eszopiclone Methylprednisolone Solifenacin
Busulfan Felodipine Midazolam Sunitinib
Carbamazepine Fexofenadine Nevirapine Tacrolimus
Cisapride Gefitinib Omeprazole Triazolam
Cyclosporine Glimepiride Phenytoin Vardenafil
Digoxin Glipizide Pimozide Vinca alkaloids
Docetaxel Halofantrine Quinidine Warfarin
Dofetilide Haloperidol Ramelteon Zidovudine
Efavirenz Imatinib Ranolazine Zolpidem
Eletriptan Irinotecan Risperidone

Mechanism of interaction presumably occurs largely at the level of hepatic CYPs, especially CYPs 3 A4, 2C9, and 2D6, but can also involve P-glycoprotein and other mechanisms. ...

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