Antifungal Drugs Flashcards
(9 cards)
Amphotericin B
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Binds to ergosterol in the fungal cell membrane and causes formation of pores in membrane that leads to cell death
Clinical uses: Broad-spectrum antifungal used to treat systemic mycoses caused by Cryptococcus, Coccidioides, Aspergillus, Blastomycoses, Candida, Histoplasma, and Mucor.
Must be given intrathecally when used to treat fungal meningitis because it does not cross the blood-brain-barrier
Side effects: Nephrotoxicity
Nystatin
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Binds to ergosterol in the fungal cell membrane and causes formation of pores in membrane that leads to cell death
Clinical uses: “Swish and swallow” for oral Candidiasis (treats thrush). Topical administration for diaper rash or vaginal candidiasis.
Side effects: Very toxic - not used systemically, only topically for oral and cutaneous candidiasis
Azoles
Drug examples?
Mechanism of action?
Drug examples: Fluconazole, Ketoconazole, Clotrimazole, Miconazole, Itraconazole, Voriconazole
Mechanism: Blocks fungal ergosterol synthesis by inhibiting the fungal cytochrome P450 that converts lanosterol into ergosterol
Azoles
Clinical uses?
Side effects?
Clinical uses:
Fluconazole for cryptococcal meningitis in AIDS patients and candidal infections of all types (such as Candida sepsis)
Itraconazole for Blatsomycoses, Coccidioides, and Histoplasma
Clotrimazole and Miconazole only for topical fungal infections such as vulvovaginal candidiasis, tinea pedis, tinea cruris (because they’re highly toxic if given systemically)
Side effects: Liver dysfunction and increased levels of other drugs (via inhibition of cytochrome P450’s) and testosterone synthesis inhibition leading to gynecomastia (especially with ketoconazole)
Flucytosine
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Inhibits fungal DNA and RNA synthesis after its conversion to 5-FU (nucleotide analog that inhibits thymidylate synthetase) by cytosine deaminase
Clinical uses: Used in combination (usually Amphotericin B) for treatment of systemic fungal infections and fungal meningitis (especially that caused by Cryptococcus)
Side effects: Bone marrow suppression
Caspofungin
Related drugs?
Mechanism of action?
Related drugs: Micafungin, Anidulafungin
Mechanism: Inhibits fungal cell wall synthesis by blocking production of Beta-glucan
Caspofungin
Clinical uses?
Side effects?
Clinical uses: Invasive aspergillosis, Candida
Side effects: Flushing (from histamine release)
Terbinafine
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Inhibits squalene epoxidase (fungal enzyme involved in ergosterol synthesis)
Clinical use: Dermatophytoses (especially onychomycosis of nails)
Side effects: Taste disturbances
Griseofulvin
Mechanism of action?
Clinical uses?
Side effects?
Mechanism: Interferes with microtubule function to disrupt fungal mitosis (especially in keratin rich tissues such as skin, nails, hair)
Clinical uses: Oral agent used to treat superficial (topical) dermatophytic infections such as tinea and ringworm
Side effects: Teratogenic, carcinogenic, confusion, increased P450 activity (and increased Warfarin metabolism - possibly leading to clots)
