Introduction Drugs (all systemic unless otherwise noted) amphotericin B nystatin topical formulation only terbinafine topical or systemic echinocandins anidulafungin caspofungin micafungin azoles topical formulations (too toxic for systemic use) clotrimazole miconazole econazole systemic itraconazole fluconazole isavuconazole ketoconazole (can also be topical) voriconazole griseofulvin flucytosine selenium sulfide topical formulation only Clinical use fungal infections Anti-Fungal Medications Drug Mechanism of Action Adverse Effects of Systemic Treatment Indications Amphotericin B Binds to ergosterol in the membrane that is unique to fungi, forming membrane pores through which electrolytes and other cell content leak Can be fungistatic or fungicidal Fevers, chills, and flu-like reaction Renal toxicity hydrate supplement potassium and magnesium Arrhythmias Anemia IV phlebitis Systemic mycoses Cryptococcus Blastomyces Coccidioides Histoplasma Candida Mucor Nystatin Binds to ergosterol Can be fungistatic or fungicidal Topical formulation only adverse effects are too toxic for systemic use Oral candidiasis Topical yeast infection diaper rash vaginal candidiasis intertrigo Terbinafine Inhibits squalene epoxidase, an enzyme in fungi that is key in lanosterol synthesis Fungicidal Gastrointestinal upset Liver toxicity (rarely, can cause fulminant liver failure requiring liver transplant) Taste disturbance Widespread dermatophyte infections Onychomycosis Echinocandins Disrupts cell wall synthesis by inhibiting beta-glucan synthesis Can be fungistatic or fungicidal Gastrointestinal upset Flushing mediated by histamine Aspergillosis Candida Azoles Inhibits 14-alpha-demethylase, which is key in ergosterol synthesis in fungi Fungistatic Anti-androgen effects via inhibiting testosterone synthesis gynecomastia (in particular, ketoconazole) Inhibits cytochrome P450 Local mycoses Mild systemic mycoses Specific indications fluconazole chronic suppression of Cryptococcus in immunosuppressed patients itraconazole Blastomyces Coccidioides Histoplasma voriconazole Aspergillus Candida isavuconazole Aspergillus Mucor Griseofulvin Disrupts mitosis via microtubule dysfunction Especially targets keratin-containing tissues such as nails Fungistatic Teratogenic Disulfiram-like reaction Neurologic symptoms confusion headaches Induces cytochrome P450 Superficial infections Dermatophytes inhibits growth Flucytosine Converted by fungal enzyme cytosine deaminase to 5-fluorouracil, which then inhibits nucleic acid synthesis Can be fungistatic or fungicidal Bone marrow suppression Systemic mycoses Cryptococcus Selenium sulfide Disrupts mitosis, resulting in decreased turnover of epidermal cells and decreased flaking Also has mild antibacterial and antifungal activity - Seborrheic dermatitis Pityriasis versicolor