Which antifungal drug acts as a prodrug, is converted by fungal cytosine deaminase to 5-fluorouracil within fungal cells, and is used in combination with amphotericin B for cryptococcal meningitis?

• A Fluconazole
• B Caspofungin
• C Flucytosine (5-FC) ✓
• D Voriconazole

Explanation

Flucytosine (5-fluorocytosine, 5-FC) enters fungal cells via cytosine permease and is deaminated by the fungal-specific enzyme cytosine deaminase to 5-fluorouracil (5-FU). 5-FU is then further converted to 5-fluorouridine triphosphate (inhibiting RNA synthesis) and fluorodeoxyuridine monophosphate (inhibiting thymidylate synthase, blocking DNA synthesis). Human cells lack significant cytosine deaminase activity, providing selectivity. It is combined with amphotericin B for cryptococcal meningitis (IDSA guidelines) because the combination is synergistic and reduces resistance emergence. Azoles (fluconazole, voriconazole) and echinocandins (caspofungin) have different mechanisms.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.