A patient with AIDS develops disseminated Cryptococcus neoformans meningitis. The induction regimen per current guidelines combines amphotericin B with flucytosine. Flucytosine exerts its antifungal effect by:
- A Binding ergosterol in the fungal membrane, creating pores and causing potassium leakage
- B Inhibiting fungal squalene epoxidase, reducing ergosterol synthesis
- C Being converted intracellularly to 5-fluorouracil (5-FU) and 5-FUMP, inhibiting thymidylate synthase and RNA synthesis ✓
- D Inhibiting beta-1,3-glucan synthase, weakening the fungal cell wall
Correct answer: C. Being converted intracellularly to 5-fluorouracil (5-FU) and 5-FUMP, inhibiting thymidylate synthase and RNA synthesis
Explanation
Flucytosine (5-fluorocytosine) is a prodrug selectively taken up by fungi via cytosine permease. Inside the fungal cell, it is deaminated to 5-fluorouracil (5-FU) by fungal cytosine deaminase (absent in mammalian cells — basis of selectivity). 5-FU is phosphorylated to 5-fluorouridine triphosphate (5-FUTP), which misincorporates into fungal RNA, and to 5-fluorodeoxyuridine monophosphate (5-FdUMP), which inhibits thymidylate synthase, blocking DNA synthesis. Combined with amphotericin B, flucytosine achieves synergistic fungicidal activity against Cryptococcus.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.