Azole antifungal

Azole Antifungal

Azole antifungals are a class of antifungal drugs that are used to treat a variety of fungal infections. They are characterized by their ability to inhibit the synthesis of ergosterol, a critical component of fungal cell membranes. This disruption in ergosterol synthesis leads to increased membrane permeability and ultimately the death of the fungal cell.

Mechanism of Action

Azole antifungals work by inhibiting the enzyme lanosterol 14α-demethylase, which is involved in the conversion of lanosterol to ergosterol. This enzyme is a member of the cytochrome P450 family, and its inhibition results in the accumulation of toxic sterol intermediates and a decrease in ergosterol levels, compromising the integrity of the fungal cell membrane.

Types of Azole Antifungals

Azole antifungals are divided into two main groups:

• Imidazoles: These include drugs such as clotrimazole, ketoconazole, and miconazole. Imidazoles are typically used for topical infections.
• Triazoles: These include drugs such as fluconazole, itraconazole, voriconazole, and posaconazole. Triazoles are often used for systemic infections and have a broader spectrum of activity compared to imidazoles.

Clinical Uses

Azole antifungals are used to treat a variety of fungal infections, including:

• Candidiasis
• Aspergillosis
• Cryptococcal meningitis
• Dermatophytosis

Side Effects

Common side effects of azole antifungals include:

• Gastrointestinal disturbances (nausea, vomiting, diarrhea)
• Hepatotoxicity (liver damage)
• QT prolongation (a heart rhythm disorder)
• Drug interactions due to inhibition of cytochrome P450 enzymes

Resistance

Fungal resistance to azole antifungals can occur through several mechanisms, such as:

• Mutations in the target enzyme, lanosterol 14α-demethylase
• Overexpression of efflux pumps that remove the drug from the fungal cell
• Alterations in the ergosterol biosynthesis pathway

Also see

• Antifungal
• Ergosterol
• Cytochrome P450
• Fungal infection