Antifungal Drugs

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Andrew Street
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Andrew Street
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Give eg's of & indications for antifungal drugs. eg's: nystatin, clotrimazole, fluconazole Indications: • Local fungal infxns - oropharnyx, vagina, skin. They may be applied topically (nystatin, clotrimazole) or taken orally (fluconazole) • Systemic Rx of invasive or disseminated fungal infxn
MOA of antifungal drugs. Fungal cell membranes contain ergosterol. As ergosterol is not seen in animal or human cells it is a target for antifungal drugs. Polyene antifungals (e.g. nystatin) bind to ergosterol in fungal cell membranes, creating a polar pore which allows intracellular ions to leak out of the cell. This can kill or slow growth of the fungi. Imidazole (e.g. clotrimazole) and triazole antifungals (e.g. fluconazole) inhibit ergosterol synthesis, impairing cell membrane synthesis, cell growth & replication. Resistance to antifungals is unusual but can occur during long-term Rx in immunosuppressed pt's. Mechanisms include alteration of membrane synthesis to exclude ergosterol, changes in target enzymes or increased drug efflux.
SE's of antifungal drugs. • Local irritation - topical fluconazole & clotrimazole
CI's, cautions, & important interactions of antifungal drugs. CI's: • Pregnancy - fluconazole Cautions: Fluconazole: • Liver DS - due to risk of hepatic toxicity • Renal failure (reduce dose) Important interactions: There are no significant drug interactions with nystatin or clotrimazole. Fluconazole inhibits cytochrome P450 enzymes, causing an ^in plasma concentrations & risk of adverse effects when prescribed with drugs that are metabolised by P450 enzymes, including phenytoin, carbamazepine, warfarin, diazepam, simvastatin & sulphonylureas. It may reduce the antiplatelet actions of clopidogrel, a pro-drug which requires activation by liver metabolism. It also ^the risk of serious arrhythmias if prescribed with drugs that prolong the QT interval, such as amiodarone, antipsychotics, quinine, quinolone & macrolide antibiotics and SSRI's.
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