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30 Cards in this Set

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Amphotericin B specs

amphoteric polyene macrolide; nearly insoluble in water; poor GI aborsorption
Amphotericin B MOA
binds ergosterol and alters permeability of cell by forming pores
amphotericin B current clinical use
often initial induction regimen then replaced by newer, less toxic azole drugs for chronic therapy or prevention of relapse
adverse rxns of amphotericin B
1) immediate rxns related to infucion 2) occuring more slowly
infusion related toxicity of amphotericin B
fever, chills, muscle spasms. Vomiting, headache, hypotension
cumulative toxicity of amphotericin B
renal damage-reversible (decreased renal perfusion) and irreversible (renal tubular injury); LFT abnormalities, varying degree of anemia
how does renal damage manifest in amphotericin B use
renal tubular acidosis and severe K+ and Mg2+ wasting
Flucytosine specs
oral; >90% Gi absorption; gets in CSF; glomerular filtration; half-life 3-4 hours
Flucytosine MOA
taken up by fungal cells via cytosine permease and converted to 5-FU and then 5-flurodeoxyuridine monophosphate and FUTP which inhibit DNA and RNA synthesis respectively
uses of Flucytosine
restricted to C neoformans, some candida, and dematiaceous molds that cause chromoblastomycosis
toxic effects of flucytosine
due to metabolism to toxic antineoplastic cmpd fluorouracil=anemia, leukopenia, and thrombocytopenia
imidazoles (2 nitrogens in ring)
ketoconazole, miconazole, and clotrimazole
trizoles (3 nitrogens in ring)
itroconazole, fluconazole, voriconazole, and posaconazole
MOA of azoles
reduction of ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes; imidazoles have less degree of selectiveity, hence higher incidence of drug interactions and side effects
uses of azoles
broad: candida species, C neoformans, endemic mycoses (blasto, coccidio, and histoplasmosis), dermatophytes, some aspergillus infections; amphotericin-resistent organisms like P boydii
adverse effects of azoles
relatively nontoxic; minor GI upset; liver enzyme disruption, rarely hepatitis
ketoconazole
greater propensity to inhibit mammalian cytochrome P450 enzymes (less selective)
itraconazole
reduced bioavailability when taken with rifamycins; ; drug of choice for dimorphic fungi histoplasma, Blastomyces, and sporothrix
fluconazole
higher water solubility and CSF penetration and oral bioavailability; least effect of all azoles on hepatic microsomal enzymes; drug of choice for secondary prophylaxis and treatment of cryptococcal meningitis, mucocutaneous candidiasis
voriconazole
good oral absorption; hepatic metabolism; inhibitor of mammalian CYP3A4; rash and elevated hepatic enzymes as effects along with visual disturbances; similar spectrum to itraconazole; treatment of choice for invasive aspergillosis
posaconazole
rapid high tissue levels with low blood levels; drug interactions via CYP3A4; broadest spectrum azole:candida and aspergillus, zygomycosis and mucormycosis
Echinocandins
large cyclic peptides linked to a long-chain fatty acid; active against candida and aspergillus
MOA of echinocandins
inhibit synthesis of B(1-3)-glucan; results in disruption of fungal cell wall and cell death
adverse effects of echinocandins
minor GI and flushing
uses of echinocandins
Caspofungin=disseminated and mucocutaneous candida and emperic antifungal therapy during febrile neutropenia; Micafungin=mucocutaneous candidiasis, candidemia, and prophylaxis of candida in bone marrow transplant patients; Anidulafungin=esophageal candidiasis and invasive candidiasis
Griseofulvin
insoluble fungistatic; use as systemic treatment of dermatophytosis; MOA unclear-deposited in newly forming skin where it binds keratin and protects from new infection
terbinafine
synthetic allylamine; treatment of dermatophytoses (onychomycosis); keratophilic medication and is fungalcidal-interferes with ergosterol via inhibition of squalene epoxidase
nystatin
polyene macrolide (like amphotericin); only used topically-too toxic parenterally; no significant absorption through skin, mucous membranes, or GI; commonly used for candida local infections
topical azoles
clotrimazole and micronazole most common-vulvovaginal candidiasis
topical allylamines
terbinafine and naftifine-tinea cruris and corporis