USMLE

Flucytosine

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Antifungals
  1. Amphotericin B
  2. Nystatin
  3. Flucytosine
  4. Azoles
  5. Terbinafine
  6. Echinocandins
  7. Griseofulvin

Summary

Flucytosine is an antifungal drug that is converted into 5-fluorouracil, which inhibits both fungal DNA polymerase and RNA polymerase. Flucytosine is most commonly used to treat cryptococcal meningitis in combination with amphotericin B. You should remember that a common side effect of flucytosine is bone marrow suppression.

Key Points

  • Flucytosine
    • Mechanism
      • Inhibits fungal DNA and RNA synthesis
        • Converted into 5-fluorouracil (5-FU) by cytosine deaminase
          • Fluorinated analog of cytosine inhibits DNA and RNA polymerase
        • Inhibits both DNA replication and fungal protein synthesis
      • Cleared renally
    • Clinical Use
      • Systemic fungal infections
        • Cryptococcal meningitis
          • Used in combination with amphotericin B
    • Adverse Effects
      • Bone marrow suppression
        • 5-fluorouracil is used as a chemotherapy with similar effects on bone marrow
        • May present as anemia, thrombocytopenia, or leukopenia
      • Nephrotoxicity
        • Renal toxicity caused by amphotericin may be accentuated by concomitant administration of flucytosine
      • Hepatotoxicity
        • About 5% of patients will develop elevated liver enzymes and evidence of hepatitis
      • Nausea/vomiting
        • Seen in about 6% of patients