antifungals 4-16-06
Terms
undefined, object
copy deck
- 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.