Antifungal Drugs (Flucytosine (5-FC))

Question 1

MoA of Flucytosine (5-FC)

Answer 1

Flucytosine decreases dTMP content in fungi, which will inhibit DNA synthesis, as follows:
→ 5-FC enters the cell through Cytosine-specific permease, which are not found in mammalian cells
→ 5-FC will be converted into 5-FU by Cytosine deaminase, then converted into 5-FdUMP
→ 5-FdUMP inhibits the enzyme Thymidylate synthase; lowering the levels of dTMP and inhibiting DNA synthesis

Question 2

Resistance of Flucytosine (5-FC)

Answer 2

Theory #1: fungi will decrease the levels of Cytosine deaminase, or mutate the enzyme
Theory #2: fungi will increase cytosine synthesis to compete with 5-FC; as it mimics its structure

Question 3

RoA / A.D.M.E of Flucytosine (5-FC)

Answer 3

RoA: Oral
D: very good & crosses BBB
E: excreted in kidneys; TDM is a must

Question 4

Indications of Flucytosine (5-FC)

Answer 4

Flucytosine alone [fungistatic - high resistance]
→ Candidiasis UTI
Flucytosine-Amphotericin B [AmB increases 5-FC permeability]
→ Candidiasis
→ Cryptococcus
Flucytosine-Itraconazole
→ Chromoblastomycosis

Question 5

Adverse Effects of Flucytosine (5-FC)

Answer 5

• Neutropenia & Thrombocytopenia
  → patient will be susceptible to infections and bleeding
  → this is due to dose-related bone marrow suppression
  → given with caution in patients given chemotherapy
• Reversible hepatic failure