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Glossary of antifungals 4-16-06

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Mechanism of action of the anti-fungal therapy polyenes.
Form artificial pores in the cytoplasmic membrane.
Mechanism of action of the anti-fungal therapies terbinafine and azoles.
Terbinafine blocks the conversion of squalene to lanosterol. Azoles block the conversion of lanosterol to ergosterol.
Mechanism of action of the anti-fungal therapy flucytosine.
Inhibits DNA synthesis by conversion to fluorouracil, which competes with uracil.
Mechanism of action of the anti-fungal therapy griseofulvin.
Disrupts microtubles. Deposits in keratin-containing tissues.
Mechanism of action of Amphotericin B.
Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes and disrupt homeostasis. "Amphotericin 'tears' holes in the fungal membrane by forming pores."
Clinical uses of Amphotericin B.
Used for a wide spectrum of sytemic mycoses. Cryptococcus, Blastomyces, Coccidioides, Aspergillus, Histoplasma, Candida, Mucor (systemic mycoses). Intrathecally for fungal meningitis; does not cross blood-brain barrier.
Symptoms of Amphotericin B toxicity.
Fever/chills ("shake and bake"), hypotension, nephrotoxicity, arrhythmias ("amphoterrible").
Mechanism of action of Nystatin.
Binds to ergosterol, disrupting fungal membranes.
Clinical use of Nystatin.
Swish and swallow for oral candidiasis (thrush). Topical for diaper rash or vaginal candidiasis.
Mechanism of action for fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
Inhibits fungal steroid (ergosterol) synthesis. Blocks: lanosterol -> ergosterol
Clinical uses of fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole.
Systemic mycoses. Fluconazole for cryptococcal meningitis in AIDS patients and candidal infections of all types (i.e., yeast infections). Ketoconazole for Blastomyces, coccidioides, Histoplasma, Candida albicans; hypercortisolism.
Symptoms of fluconazole, ketoconazole, clotrimazole, miconazole, itraconazole, voriconazole toxicity.
Hormone synthesis inhibition (gynecomastia), liver dysfunction (inhibits cytochrome P-450), fever, chills.
Mechanism of action of Flucytosine.
Inhibits DNA synthesis byconversion to fluorouracil, which competes with uracil.
Clinical uses of Flucytosine.
Used in sytemic fungal infections (e.g. Candida, Cryptococcus).
Flucytosine toxicity.
Nausea, vomitting, diarrhea, bone marrow suppression.
Mechanism of action for Caspofungin.
Inhibits cell wall synthesis.
Clinical use of Caspofungin.
Invasive aepergillosis.
Symptoms of Caspofungin toxicity.
GI upset, flushing.
Mechanism of action of Terbinafine.
Inhibits the fungal enzyme squalene epoxidase. Inhibits squalene -> lanosterol
Clinical use of Terbinafine.
Used to treat dermatophytoses (especially onychomycosis).
Mechanism of action of Griseofulvin.
Interfers with microtubule function; disrupts mitosis. Deposits in keratin-contianing tissues (e.g. nails).
Clinical use of Griseofulvin.
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm).
Symptoms of Griseofulvin toxicity.
Teratogenic, carcinogenic, confusion, headaches, increase warfarin metabolism.

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