Antifungal therapy Flashcards
Amphotericin B: mech
Binds ergosterol (unique to fungi); forms membrane pores that allow leakage of electrolytes. Amphotericin "tears" holes in fungal membrane forming pores
Amphotericin B: uses
Serious, systemic mycoses.
Cryptococcus (with/w/out flucytosine for meningitis), Blastomyces, Coccidioides, Histoplasma, Candida, Mucor.
Intrathecally for fungal meningitis.
Supplement K+ and Mg2+ because of altered renal tubule permeability
Amphotericin B: tox
Fever/chills (“shake and bake”), hypotension, nephrotoxicity, arrhythmias, anemia, IV phlebitis (“amphoterrible”). Hydration decreases nephrotoxicity. Liposomal amphotericin decreases toxicity.
Nystatin: mech
Same as amphotericin B. Topical form because too toxic for systemic use.
Nystatin: use
“Swish and swallow” for oral candidiasis (thrush); topical for diaper rash or vaginal candidiasis.
Azoles:
Fluconazle, ketoconazle, clotrimazole, miconazole, itraconazole, voriconazole.
Azoles mech:
Inhibits fungal sterol (ergosterol) synthesis, by inhibiting the cytochrome P-450 enzyme that converts lanosterol to ergosterol. (14-alpha demethylase)
Azoles: use
Local and less serious systemic mycoses.
Fluconazole: chronic suppression of cryptococcal meningitis in AIDS patients and candidal infections of all types.
Itraconzale: Blastomyces, Coccidioides, Histoplasma.
Clotrimazole and Miconazle for topical fungal infections
Azoles tox:
Testosterone synthesis inhibition (gynecomastia, esp with ketoconazole), liver dysfunction (inhibits cytochrome P-450)
Flucytosine: mech
Inhibits DNA and RNA biosynthesis by conversion to 5-FU by cytosine deaminase
Flucytosine: use
Systemic fungal infections (esp meningitis by Cryptococcus) in combo with Amphotericin B.
Flucytosine: tox
Bone marrow suppression
Echinocandins:
Caspofungin, micafungin, anidulafungin
Echinocandins: mech
Inhibits cell wall synthesis by inhibiting synthesis of Beta-glucan.
Echinocandins: use
Invasive asperillosis, Candida
Echinocandins: tox
GI upset, flushing (by histamine release)
Terbinafine: mech
Inhibits fungal enzyme squalene epoxidase (decreases ergosterol synthesis)
Terbinafine: use
Dermatophytoses (esp onychomycosis - funga infection of finger or toe nails)
Terbinafine: tox
GI upset, HA, hepatotoxicity, taste disturbance
Griseofulvin: mech
Interferes with MT formation; disrupts mitosis. Deposits in keratin-containing tissues (nails)
Griseofulvin: use
Oral treatment of superficial infections; inhibits growth of dermatophytes (tinea, ringworm)
Griseofulvin: tox
Teratogenic, carcinogenic, confusion, HA, increase P-450 and warfarin metabolism, GI
Avoid sunlight
