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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
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Nystatin
- Topical form because too toxic systemically
- Use: swish and swallow for oral candidiasis (thrust); topical for diaper rash or vaginal candidiasis
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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
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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
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caspofungin
- inhibits cell wall synthesis by inhibiting synthesis of b-glucan
- Use: invasive aspergillosis and Candida
- Toxicity: GI upset, flushing
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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
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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
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