Azoles

Snapshot

  • A 30-year-old woman presents to the urgent care clinic after being pricked by a thorn at a flower shop she owns. Yesterday, as she was processing a new shipment of roses, she accidentally poked herself with a sharp thorn, resulting in a scratch on her right upper arm. At that time, she applied some topical bacitracin. Since then, she has developed a rash along the right arm towards the axilla. She denies any fevers or chills. She is given an oral drug for her condition and is counseled about the potential side effects of hepatotoxicity. (Sporotrichosis)

Introduction

  • Drugs
    • topical antifungals (too toxic for systemic use)
      • clotrimazole
      • miconazole
    • systemic
      • itraconazole
      • fluconazole
      • isavuconazole
      • ketoconazole
      • voriconazole
  • Mechanism of action
    • inhibits cytochrome P-450 (CYP450) enzyme, preventing the synthesis of ergosterol, a key component of the fungal cell membrane
  • Clinical use
    • local and systemic mycoses
    • itraconazole
      • Blastomyces
      • Coccidioides
      • Paracoccidioides
      • Sporothrix
      • Histoplasma
    • voriconazole
      • Aspergillus
      • Candida
    • isavuconazole
      • Aspergillus
      • Mucor
    • fluconazole
      • Cryptococcus
        • prophylaxis in patients with AIDS
      • Candida
  • Adverse effects
    • ketoconazole has the highest adverse effect profile
    • inhibition of testosterone synthesis 
      • CYP450 plays a role in testosterone synthesis
      • gynecomastia
    • hepatotoxicity
    • gastrointestinal upset
    • Stevens-Johnson syndrome