Oral Azole anti-fungal medications

Medications prescribed as treatment for dermatophyte, mucocutaneous, or systemic fungal infections.

All azole antifungal agents have the potential to induce acute liver injury, characterized by elevations of liver aminotransferase levels or more serious cases by dysfunction manifested by coagulopathy, hyperbilirubinemia, or acute liver injury.

Risk of acute liver injury is higher for ketoconazole than other Azole antifungals.

Risks and rates of the acute liver injury are low for fluconazole, ketocanazole, and intracoazole, and were more common with voricanazole and posaconazole(Lo Re V et al).

The azole antifungals include two classes, imidazoles and triazoles, which share the same mechanism of action.

Imidazoles have a two-nitrogen azole ring.

Imidazoles are predominantly used topically and have been replaced for systemic administration by triazoles, which have three nitrogens in the azole ring.

Triazoles have a more favorable pharmacokinetic profile than imidazoles and do not significantly inhibit human sterol synthesis.

Triazoles include fluconazole, itraconazole, voriconazole, and posaconazole.

Triazoles inhibit the cytochrome P450 enzyme 14-α-sterol-demethylase.

This enzyme is implicated in the biosynthetic pathway of ergosterol, which is an essential molecule of the fungal cell membrane.

Inhibition of this enzyme leads to accumulation of 14-a-methylsterols on the fungal surface, which results in arrest of fungal growth.

Triazoles are generally considered fungistatic.

The inhibition of P-glycoprotein by azoles may lead to increased systemic exposure of drugs affected by this transport system.

Among the most significant common drug interactions of triazoles are drug elevations of cyclosporine, tacrolimus, and sirolimus, most Ca channel blockers, most benzodiazepines, many statins and steroids, and warfarin.

Carbamazepine, phenobarbital, phenytoin, and rifampin significantly decrease azole concentrations.

Increased blood levels of terfenadine, astemizole, and quinine can cause Q-Tc prolongation and predispose to torsades de pointes.

Increased cytotoxic chemotherapy-related toxicity can be caused by concomitant treatment with triazoles and vinca alkaloids, cyclophosphamide, vinorelbine, and busulfan.

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