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Ketoconazole Pharmacology

Ketoconazole Pharmacology

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 Ketoconazole is an imidazole antifungal that works by inhibiting fungal cytochrome P450 14α-demethylase, an enzyme essential for ergosterol synthesis, which disrupts fungal cell membrane integrity. Common adverse effects of ketoconazole include nausea, vomiting, abdominal pain, and elevated liver enzymes, with hepatotoxicity being a notable concern. Ketoconazole carries a boxed warning for severe hepatotoxicity, including cases of liver failure and death, and should not be used as a first-line treatment for fungal infections when other safer antifungals are available. Another boxed warning highlights ketoconazole’s potential to prolong the QT interval, increasing the risk for life-threatening ventricular arrhythmias such as torsades de pointes. Ketoconazole is a strong inhibitor of CYP3A4 and can cause significant drug interactions by increasing serum concentrations of medications metabolized by this pathway, including statins, certain benzodiazepines, and some antiarrhythmic.

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