Azole Antifungals

Azole antifungals work by inhibiting the fungal enzyme lanosterol 14-alpha-demethylase, which is part of the fungal cytochrome P450 system. This blocks synthesis of ergosterol, a critical component of fungal cell membranes (human cells use cholesterol instead, which is why azoles are selectively toxic to fungi). Without ergosterol, the fungal membrane becomes unstable, inhibiting fungal growth. Azoles are generally fungistatic, not fungicidal — a testable distinction from amphotericin B, which is fungicidal. Fluconazole is the most commonly tested azole — it's used for oropharyngeal and esophageal candidiasis, vaginal yeast infections, and cryptococcal meningitis (especially in immunocompromised clients). It has excellent CNS penetration, which is why it's preferred for cryptococcal disease. Fluconazole is teratogenic at high or prolonged doses and is contraindicated in pregnancy for non-life-threatening infections. The major nursing concern is hepatotoxicity: baseline and periodic LFTs (AST, ALT) are required. Teach patients to report jaundice, dark urine, or RUQ pain and to avoid alcohol. Fluconazole moderately inhibits CYP2C9 and CYP3A4 (ketoconazole and itraconazole are stronger CYP3A4 inhibitors), increasing levels of warfarin, phenytoin, cyclosporine, and oral hypoglycemics. Always review the medication list before administration. Unlike amphotericin B, fluconazole is well tolerated with oral dosing and does not cause nephrotoxicity — this distinction drives drug selection in clinical scenarios.