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What is the mechanism of action of the antifungals?
- Polyene (AMB):
- Binds to fungal cell membrane and causes leak of electrolytes
- Azole (fluconazole, itraconazole, posaconazole, voriconazole):
- Inhibit 14-alpha-demethylase
- Prevents conversion of lanosterol to ergosterol
- Echinocandin (anidulafungin, caspofungin, micafungin):
- Inhibit 1,3-beta-glucan synthase
- Inhibit glucan synthesis causing osmotic lysis
- Antimetabolites (flucytosine):
- Inhibit fungal protein synthesis by replacing uracil with 5-FU in RNA
- Allylamines (terbinafine):
- Inhibit ergosterol synthesis through inhibition of squalene epoxidase
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What are the main toxicities of the Antifungals?
- Polyene (AMB):
- Nephrotoxicity
- Infusion rxn
- Azoles:
- Hepatotoxicity
- Transient visual disturbances (Voriconazole)
- Echinocandin (anidulafungin, casp, mica):
- ↑ LFTs
- Antimetabolites (flucytosine):
- Bone marrow suppression
- NV
- Allylamines (terbinafine): agranulocytosis
- GI intolerance
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What is the treatment for C. albicans?
- Static: flucon, itra, posa, vori
- Cidal: AMB, caspo
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What is the treatment for C. glabrata?
Cidal: AMB, caspo
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What is the treatment for C. krusei?
- Static: itra, posa, vori
- Cidal: AMB, caspo
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What is the treatment for C. tropicalis?
- Static: flucon, itra, posa, vori
- Cidal: AMB, caspo
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What is the treatment for Cryptococcus?
- Static: flucon, itra, posa, vori
- Cidal: AMB (DOC)
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What is the treatment for Aspergillus?
- Static: itra, posa, vori, caspo
- Cidal: vori (DOC), AMB
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