Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
30 Cards in this Set
- Front
- Back
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
|