Antifungal Agents Study Notes

  • ANTIFUNGAL AGENTS

    • Antifungal agents (also known as antimycotic drugs) are used to prevent and treat fungal infections (mycosis) like athlete's foot, ringworm, candidiasis, and serious systemic infections (e.g., Cryptococcal meningitis).
    • Types of Fungi
      • Yeasts
      • Yeast-like fungi
      • Dimorphic fungi
      • Molds
    • Fungi are eukaryotic cells; they differ from prokaryotic bacterial cells and share similarities with mammalian cells, leading to less selective toxicity of antifungal drugs, making them often more toxic than antibacterial agents.

  • HISTORICAL BACKGROUND

    • Fluconazole (1990): First broad-spectrum triazole; enhanced antifungal treatment by overcoming issues with imidazoles.
    • Itraconazole (1992): Extended the activity spectrum of triazoles; replaced ketoconazole for many systemic mycoses.
    • Mid-90s saw formulation improvements for Itraconazole and enhanced formulations of polyenes like Amphotericin B and Nystatin.

  • CLASSIFICATION OF ANTIFUNGAL AGENTS

    • By Mechanism of Action:
      1. Inhibition of fungal cell wall synthesis (Echinocandins): Caspofungin, Micafungin, Anidulafungin
      2. Inhibition of ergosterol and lanosterol synthesis: Terbinafine
      3. Inhibition of ergosterol synthesis: Fluconazole, Itraconazole, Voriconazole
      4. Inhibition of nucleic acid synthesis: 5-Flucytosine
      5. Disruption of mitotic spindle: Griseofulvin
      6. Miscellaneous agents: Ciclopirox, Tolnaftate, Naftifine
    • By Chemical Structure:
      • Polyenes: Amphotericin B, Nystatin
      • Echinocandins:
      • Azoles:
        • Imidazoles (Clotrimazole, Econazole, Miconazole)
        • Triazoles (e.g., Fluconazole, Voriconazole)
      • Allylamines: Terbinafine
      • Other agents: Tolnaftate, Ciclopirox olamine, etc.

  • MECHANISM OF ACTION

    • Three Main Mechanisms:
      1. Inhibition of cell wall formation
      2. Disruption of cell membrane integrity
      3. Inhibition of cell division and nucleic acid synthesis
    • Polyene Antibiotics:
      • Mechanism: Binds to ergosterol forming membrane pores leading to leakage of cellular components.
      • Examples include Amphotericin B, Nystatin, Griseofulvin.