Flucytosine

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Contents

[edit] BRAND NAMES

  • Ancobon
  • Ancotil

[edit] STRUCTURE

Flucytosine.jpg

[edit] MECHANISM OF ACTION

Flucytosine is an analogue of a pyrimidine. It is relatively deaminated in the fungi by cytidine deaminase to form 5-Fluorouracil (an important anticancer agent). Thus, flucytosine is a precursor of 5-FU, but does not behave like an anticancer drug, because the cytidine deaminase is not present in the human cells. However, it is still toxic for the normal (human) tissue.

In order for 5-FU to be active or incorporated into the DNA, it must be converted to 5-FdUMP. In this form, it is able to inhibit thymidylate synthase, thus reducing the pool of thymidylate. Consequently, when the non-correct nucleotide is incorporated into the DNA, upon activation of the repair system that is to replace the wrong base pair, there will be a depletion or lack of the correct dTMP to replace the base.

Spectrum:

  • Candida albicans
  • Cryptococcus

Resistance

  • Due to reduced activation of Flucytosine

Pharmacokinetics

  • Can be administered orally (unlike Amphotericin B)
  • Can cross BBB (unlike Amphotericin B)
  • Eliminated mostly by the kidney

[edit] INDICATIONS

Flucytosine can be used in combination with Amphotericin B for the treatment of cryptococcal meningitis. This is an example of synergism – by disrupting the fungal membrane, Amphotericin B will facilitate the entrance of flucytosine. This synergism allows the use of a reduced dose of both drugs. Flucytosine is not commonly used because of its very narrow spectrum. It is mainly used in combination with Amphotericin B.

[edit] DOSAGE

[edit] CONTRAINDICATIONS

[edit] PRECAUTIONS

[edit] INTERACTIONS

[edit] PREGNANCY AND LACTATION

[edit] SIDE EFFECTS

Flucytosine has systemic side effects that includes bone marrow depression. Its side effects are also similar to those observed with anticancer drugs.

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Antifungals
Ergosterol target : Cell membrane target Azoles (lanosterol 14 alpha-demethylase inhibitors) : Ergosterol inhibitors Imidazoles Topical: Bifonazole   Clotrimazole   Econazole   Fenticonazole   Ketoconazole   Isoconazole   Miconazole   Sertaconazole   Tioconazole
Triazoles Topical: Fluconazole   Terconazole
Systemic: Fluconazole   Itraconazole   Posaconazole   Voriconazole
Polyene antimycotics (ergosterol binding; they form pores in the membrane) Topical: Nystatin
Systemic: Amphotericin B
Allylamines (squalene epoxidase inhibitors) : Ergosterol inhibitors Topical: Amorolfine   Naftifine   Terbinafine
Systemic: Terbinafine
Echinocandins (β-glucan synthase inhibitors) : Cell wall target Anidulafungin   Caspofungin   Micafungin
Pyrimidine analogues / Thymidylate synthase inhibitors : Nucleic acid inhibitors Flucytosine
Mitotic inhibitors Griseofulvin
Others Ciclopirox