Flucytosine
Flucytosine is the only antimetabolite (a substance that
closely re-sembles one required for normal physiologic functioning and that
exerts its effect by interfering with metabolism) that acts as an an-timycotic.
It’s a purine and pyrimidine inhibitor that’s used primar-ily with another
antimycotic drug, such as amphotericin B, to treat systemic fungal infections.
After oral administration, flucytosine is well
absorbed from the GI tract and widely distributed. It undergoes little
metabolism and is excreted primarily by the kidneys.
Flucytosine penetrates fungal cells, where it’s
converted to its ac-tive metabolite fluorouracil. Fluorouracil then is
incorporated into the RNA of the fungal cells, altering their protein synthesis
and causing cell death.
Although amphotericin B is effective in treating candidal and
cryp-tococcal meningitis alone, flucytosine is given with it to reduce the
dosage and the risk of toxicity. This combination therapy is the treatment of
choice for cryptococcal meningitis.
Flucytosine can be used alone to treat candidal
infections of the lower urinary tract because it reaches a high urinary
concentra-tion. It’s also effective in treating infections caused by T. glabrata,Phialophora, Aspergillus, and Cladosporium.
Cytarabine may antagonize the antifungal activity
of flucytosine, possibly by competitive inhibition. Hematologic, kidney, and
liver function must be closely monitored during flucytosine therapy be-cause of
the drug’s serious risk of toxicity. (See Adverse
reactionsto flucytosine.)
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