Azoles

Summary

The azole drugs are antifungals that share the common -conazole ending. These drugs inhibit ergosterol synthesis to stop fungal growth. They are used to treat a wide variety of different fungal infections. You should remember that the azoles inhibit CYP enzymes, causing potential interactions with other drugs. The azoles, especially ketoconazole, are antiandrogens, so look out for findings like gynecomastia in your patients. These drugs also commonly cause GI upset and liver toxicity.

Key Points

• Triazoles
  • Also known as azole antifungals
  • Drug Names
    • Fluconazole
    • Itraconazole
    • Ketoconazole
    • Voriconazole
    • Isavuconazole
    • Clotrimazole
    • Miconazole
  • Mechanism
    • Inhibit fungal ergosterol synthesis
      • Ergosterol is a unique component of fungal membranes
      • Azoles inhibit 14-alpha-demethylase (a cytochrome P450 enzyme), which normally converts lanosterol to ergosterol
      • Blocking ergosterol synthesis Inhibits formation of fungal cell membrane (note: no effect on fungal cell wall)
  • Clinical Use
    • Local and less serious mycoses
      • Cryptococcal meningitis in AIDS (fluconazole)
      • Candida (fluconazole)
      • Blastomyces, Coccidiodes, Histoplasma, Sporothrix schenckii (itraconazole)
      • Topical fungal infections (clotrimazole, miconazole)
      • Aspergillus (voriconazole, isavuconazole)
  • Adverse Effects
    • GI upset
      • Most common side effect
    • Antiandrogen (Inhibits testosterone synthesis)
      • CYP450 plays a role in testosterone synthesis, in leydig cells and in adrenal cortex
      • Esp. with ketoconazole, which is often used in endocrine settings to reduce testosterone synthesis
      • Can lead to gynecomastia
    • Inhibits CYP450 Enzymes
      • Can lead to drug interactions (e.g. with warfarin, theophylline)
    • Hepatotoxicity
      • Mild hepatitis and liver dysfunction seen in 2-12% of patients