Flucytosine is the only antimetabolite (a substance that closely resembles one required for normal physiologic functioning and that exerts its effect by interfering with metabolism) that acts as an antimycotic. It’s a purine and pyrimidine inhibitor that’s used primarily with another antimycotic drug, such as amphotericin B, to treat systemic fungal infections.
Pharmacokinetics
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.
药动学
口服后，氟胞嘧啶经胃肠道吸收良好，分布广泛，代谢极少，主要经肾排出。
Pharmacodynamics
Flucytosine penetrates fungal cells, where it’s converted to its active metabolite fluorouracil. Fluorouracil then is incorporated into the RNA of the fungal cells, altering their protein synthesis and causing cell death.
Pharmacotherapeutics
Although amphotericin B is effective in treating candidal and cryptococcal 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.
药物治疗学
虽然两性霉素B单独治疗念珠菌和隐球菌脑膜炎也有效，但是，氟胞嘧啶一起使用可以减少其剂量，降低毒性风险。这种联合疗法是隐球菌脑膜炎的首选疗法。 Standing alone
Flucytosine can be used alone to treat candidal infections of the lower urinary tract because it reaches a high urinary concentration. It’s also effective in treating infections caused by T. glabrata, Phialophora, Aspergillus, and Cladosporium.
Drug interactions
Cytarabine may antagonize the antifungal activity of flucytosine, possibly by competitive inhibition. Hematologic, kidney, and liver function must be closely monitored during flucytosine therapy because of the drug’s serious risk of toxicity.
flucytosine – n. 氟胞嘧啶
antimetabolite – n. 抗代谢物/药
fluorouracil – n. 氟尿嘧啶
T. glabrata -- Torulopsis glabrata光滑球拟酵母菌
Phialophora – n. 瓶霉菌
Aspergillus – n. 曲霉菌
Cladosporium – n. 分枝孢子菌
cytarabine – n. 阿糖胞苷
Video Antifungal Drugs Test 1. Which of the following antifungal agents is associated with bone marrow suppression and renal failure?
A. Miconazole
B. Itraconazole
C. Ketoconazole
D. Flucytosine
2. Which of the following antifungal agents interacts with cytochrome P-450 dependent sterol 14 -demethylase to inhibit ergosterol synthesis in many fungal organisms, as well as in gram-positive bacteria and protozoans?
A. Ketoconazole
B. Zidovudine
C. Griseofulvin
D. Amphotericin B
All of the drugs are antifungal agents but only flucytosine has been associated with bone marrow suppression and synergizes with other drugs which suppress bone marrow functions. Miconazole and ketoconazole may produce hepatotoxicity, gastro-intestinal upset and headaches. Amphotericin B may produce nephrotoxicity while itraconazole is associated with gastro-intestinal upset and rare liver dysfunction.
2. A. Ketoconazole
The mechanism of amphotericin B involves ergosterol, but the mechanism is not related to ergosterol synthesis. Amphotericin B binds to ergosterol in the cell membrane, disrupting its permeability to ions. Ketoconazole and other imidazoles interact with cytochrome P-450 to inhibit P-450 dependent synthesis of ergosterol by sterol 14-demethylase. Griseofulvin interacts with microtubular protein to inhibit fungal mitosis. Flucytosine incorporates into RNA and disrupts fungal protein synthesis. Zidovudine is used primarily as an antibiotic and not as an antifungal agent.
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