azoler

Azoler (azoles) are a class of antifungal medications that exert their effect by inhibiting the fungal cytochrome P450 enzyme 14α-demethylase (CYP51). This enzyme is involved in converting lanosterol to ergosterol, an essential component of the fungal cell membrane. Inhibition disrupts membrane synthesis and function, leading to inhibition of fungal growth and, in some cases, fungal death.

Azoles are divided into imidazoles and triazoles. Imidazoles (such as miconazole and clotrimazole) are largely used topically for skin and mucosal infections. Triazoles (including fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole) are suitable for systemic therapy and have broader clinical use.

Spectrum and indications: Topical azoles treat dermatophyte infections of the skin, candidiasis of the skin and mucosa, and onychomycosis in some cases. Systemic azoles are used for a range of invasive infections: fluconazole for candidiasis and cryptococcal meningitis; itraconazole for histoplasmosis and certain endemic mycoses; voriconazole for invasive aspergillosis and some molds; posaconazole and isavuconazole for invasive fungal infections including mucormycosis and aspergillosis. Choice depends on organism, site, and patient factors.

Pharmacology and safety: Azoles vary in oral bioavailability and are largely hepatically metabolized, with potential for drug–drug interactions via cytochrome P450 enzymes. Adverse effects can include hepatotoxicity, gastrointestinal symptoms, rash, and, for some agents, QT prolongation. Use in pregnancy is cautious or avoided depending on the agent.

Resistance and stewardship: Resistance arises mainly through mutations in ERG11, encoding 14α-demethylase, and through efflux mechanisms, with cross-resistance within the class possible. Efficacy depends on susceptibility, site of infection, and host factors.