1. Amphotericin B
    • binds ergosterol; forms membrane pores that allow leakage of electrolytes
    • Use: serious systemic mycoses, Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor. Intrathecally for fungal meningitis because doesn't cross BBB. Supplement K and Mg because of altered renal tubule permeability
    • Toxicity: nephrotoxicity, arrhythmias, anemia, IV phlebitis ("amphoterrible"). Hydration reduces nephrotoxicity. Liposomal amphotericin reduces toxicity
  2. Nystatin
    • Topical form because too toxic systemically
    • Use: swish and swallow for oral candidiasis (thrust); topical for diaper rash or vaginal candidiasis
  3. Azoles
    fluconazole, ketoconazole, clotrimazole, miconazole
    • inhibit fungal sterol (ergosterol) synthesis, by inhibiting the P-450 enzyme (alpha14demethylase) that converts lanosterol to ergosterol
    • Use: systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients (crosses BBB) and candidal infections of all types. Clotrimazole and miconazole for topical fungal infections. Ketoconazole absorption dec by antacids
    • Toxicity: cholesterol drived hormone synthesis inhibition (gynecomastia, dec libido, menstrual irregularities), liver dysfunction (inhibits cytochrome P450), fever, chills
  4. Flucytosine
    • inhibits DNA synthesis by conversion to 5-fluorouracil by cytosine deaminase of fungus
    • Use: resistance emerges rapidly if used alone. combination w/ amphotericin B for systemic fungal infections (cryptococcus) enters CSF.
    • Toxicity: Bone marrow suppression- inhibits thymidylate synthase --> dec thymine
  5. caspofungin
    • inhibits cell wall synthesis by inhibiting synthesis of b-glucan
    • Use: invasive aspergillosis and Candida
    • Toxicity: GI upset, flushing
  6. Terbinafine
    • inhibits the fungal enzyme squalene epoxidase
    • Use: treat dermatophytoses (nails, skin, hair) especially onychomycosis- fungal infection of finger or toe nails
    • Toxicity: abnormal LFTs, visual disturbances
  7. Griseofulvin
    • interferes w/ microtubule function; disrupts mitosis. deposits in keratin containing tissues
    • Use: oral treatment of suerficial infections, inhibits growth of dermatophytes (tinea, ringworm)
    • Toxicity: Teratogenic, carcinogenic, confusion, headaches, inc P450 and warfarin metabolism; disulfiam-like reaction
Card Set
fungal drugs