Flucytosine antifungal activity

Flucytosine has significant antifungal activity against C. albicans, other Candida spp., C. neoformans, and the fungal organisms responsible for chromomycosis. Not... 

Flucytosine is converted into the anti metabolite 5-fluorouracil that inhibits thymidilate synthetase, thereby disrupting DNA synthesis. It also interferes with protein synthesis by incorporation of fluorouracil into RNA in place of uracil. Although active against most Candida species, its spectrum of antifungal activity, overall, is narrow. Since resistance can develop rapidly it is usually coadministered with another agent and its main value is that it facilitates a reduction in the dose (and, presumably, the toxic effect) of amphotericin when co-prescribed in this way. The main adverse effects are marrow aplasia and hepatotoxicity. 

Mode of action Ketoconazole interacts with C-14 a-demethylase (a cytochrome P-450 enzyme) to block demethylation of lanosterol to ergosterol, the principal sterol of fungal membranes Figure 34.4). This inhibition disrupts membrane function and increases permeability. Ketoconazole acts in an additive manner with flucytosine against Candida, but antagonizes amphotericin B s antifungal activity. 

The suggested interaction of cytarabine with flucytosine, in which there is competitive inhibition of antifungal activity, has not been confirmed (28). 

Amphoteridn is a complex amphoteric polyene antibiotic that binds to cell membranes and forms a pore through which ions can pass, with consequences that include loss of potassium ions from within the cell. Since the antibiotic binds more readily to fungal cell membranes than mammalian, its action is relatively selective. It can potentiate the action of certain other antifungals. and it may be used with flucytosine. Also, it confers antifungal activity on rifampicin (normally antibacterial). As it has an appreciable renal toxicity, it needs to be used with caution in some patients. Nystatin is a polyene antibiotic similar in structure to amphotericin, often used for local treatment. 

Furthermore, the antifungal actions of amphotericin B are enhanced by flucytosine, minocycline, or rifampin, agents otherwise devoid of antifungal activity. 

Flucytosine is converted via fungal cytosine deaminase to the antimetabolite fluorouracil, which causes inhibition of thymidylate synthase. Flucytosine enters the cerebrospinal fluid and has been used in combination with amphotericin B in cryptococcal meningitis. The drug has a narrow spectrum of antifungal activity and is not effective in esophageal candidiasis. The answer is (A). 

Flucytosine is an oral antifungal pro-drug. It has to be enzymatically deaminated by the fungi to the active metabolite, fluorouracil. Fluorouracil inhibits thymidylate synthetase and DNA synthesis. Its indications are treatment of cryptococcal meningitis and serious systemic candidiasis. Resistance develops rapidly, due to altered drug-permeability. For this reason Amphotericin B and flucytosine are often given in combination as they have synergistic effects. 

Flucytosine is an antiinfective/antifungal agent that interferes with DNA and RNA synthesis. It is active against Candida and Cryptococcus. It is indicated in the treatment of serious infections caused by susceptible strains of Candida or Cryptococcus. 

Flucytosine(5-fluorocytosine 5-FC 4-amino-5-fluoro-2-pyrimidone) 217 is an antimetabolite type of antifungal drug. It is activated by deamination within the fungal cells to 177. 

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