Nucleoside Antifungals: Flucytosine

Nucleoside Antifungals (F)

Flucytosine (C4H4FN3O)

  • Brand Name: Ancobon®

  • Also Known As: 5-Fluorocytosine, 5-FC

  • Mechanism of Action (MOA):

    • Inhibits DNA and RNA synthesis in fungal cells, which is essential for their growth and reproduction.

    • It is a prodrug, meaning it is converted into its active metabolite, 5-fluorouracil (5-FU), after being taken up by the fungal cells.

  • Pharmacological Properties (ON):

    • Oral Bioavailability: Flucytosine is orally active, making it a convenient option for treatment.

    • Narrow Spectrum of Activity: It has a very narrow spectrum of activity, primarily effective against certain strains of fungi.

  • Resistance:

    • Resistance to flucytosine develops rapidly and is common, limiting its use.

    • Mechanisms of resistance (PCM):

      1. Fungal cell permeability issues: The cell membranes of some fungi become impermeable to flucytosine.

      2. Altered conversion: The enzyme needed to convert flucytosine to 5-FU may be deficient or altered in resistant strains.

      3. Impaired metabolism: The conversion of 5-FU to its active form (uridine monophosphate) may not occur in resistant fungi.

  • Use:

    • It is only recommended for the treatment of serious systemic infections caused by susceptible strains of (CC):

      • Candida spp.: A genus of yeasts that can cause infections in humans.

      • Cryptococcus spp.: A yeast-like fungus responsible for cryptococcosis, particularly in immunocompromised patients, such as those with HIV/AIDS.

    • Due to the risk of resistance, it is often lowered in dose and used in conjunction with other antifungal agents, particularly:

      1. Amphotericin B: A polyene antifungal that is effective against a broad range of fungi and is often used to enhance the efficacy of flucytosine.

  • Clinical Application:

    • Besides its antifungal uses, flucytosine is also employed as an anticancer agent due to its ability to inhibit nucleic acid synthesis.