Flucytosine

**Flucytosine** (also known as 5-FC) is a fluorinated pyrimidine antifungal agent primarily active against strains of *Cryptococcus* and *Candida*. **Key Clinical Points:** * **Combination Therapy is Mandatory:** When used as a monotherapy, fungal resistance develops rapidly (especially with *Cryptococcus*). It is almost exclusively used synergistically with **amphotericin B** or azole antifungals. * **CNS Penetration:** It penetrates the blood-brain barrier exceptionally well, making it highly valuable for treating central nervous system cryptococcosis. * **Toxicity Concerns:** It carries a risk of dose-dependent bone marrow suppression. Dogs are particularly sensitive and may develop severe drug reactions if treated for more than 10-14 days. * **Species Differences:** Mammalian cells generally lack the enzyme needed to convert flucytosine to its toxic metabolite (5-fluorouracil), but gut flora or specific species metabolism (like in rats) can lead to systemic toxicity.

กลไกการออกฤทธิ์: Flucytosine acts as a prodrug that exploits specific fungal enzymes: 1. **Cellular Entry:** Flucytosine enters the fungal cell via the enzyme **cytosine permease**. 2. **Conversion to Active Metabolite:** Inside the fungal cell, it is deaminated by **cytosine deaminase** → **5-fluorouracil (5-FU)**. *(Note: Human and most mammalian cells lack this enzyme, providing selective toxicity).* 3. **RNA Inhibition:** 5-FU acts as an antimetabolite, competing with **uracil** → incorporates into fungal RNA → disrupts pyrimidine metabolism and halts protein synthesis. 4. **DNA Inhibition:** 5-FU is also converted to **fluorodeoxyuridylic acid** → potently inhibits **thymidylate synthetase** → halts DNA synthesis and cell division.

ข้อมูลอ้างอิงยาของ VetSheet มีไว้สำหรับสัตวแพทย์ผู้มีใบอนุญาตเพื่อช่วยในการตัดสินใจทางคลินิก ไม่ใช่สิ่งทดแทนการวินิจฉัยของผู้เชี่ยวชาญหรือฉลากล่าสุดของผู้ผลิต