Antifungals Flashcards
amphotericin B and nystatin
polyene antifungals
binds to ergosterol in fungal cell membrane; allows leakage of small molecules; hydrophilic and hydrophobic sides; form pores in cell membrane through which K+ and Mg++ can leak out
polyene antifungals
amphotericin B: fungicidal, fungistatic or both
fungicidal
nystatin: fungicidal, fungistatic or both
both
polyene antifungal: primarily IV, greater than 90% bound to B-lipoprotein; nephrotoxicity (dose limiting)–> less severe with lipid based forms; sodium loading may ameliorate toxicity; fever and chills; preferred treatment for deep fungal infections
amphotericin B
polyene antifungal: topical or oral administration only; candidal infections of oral cavity
nystatin
why doesnt 5-flucytosine (ancobon) block thymidylate synthase in humans?
mammalian cells do not have cytosine deaminase
antimetabolite; inhibits thymidylate synthase and DNA synthesis; fungicidal or static; almost always used in combo with amphotericin B–> penetrates CSF and treats meningitis; reduce dose with renal deficiency
5-flucytosine
inhibit synthesis of ergosterol–> necessary sterol for fungal cell membrane; broad spectrum antifungal
imidazole antifungal agents
azole: inhibits P450 enzyme causing potential increase in serum levels of concurrent drugs
fluconazole
azole: not significant to CSF; mostly bile excretion; potent inhibitor of CYP3A4; broader spectrum than fluconazole
itraconazole
azole: exhibits genetic polymorphism (CYCP2C19 deficiency =increased conc); contraindicated with drugs that induce P450 including rifampin, rifabufin, carbamazapine, long acting barbiturates
voriconazole
which azole? easily crosses to CSF
fluconazole
which azoles? hepatic elimination
itra- and voriconazole
which azole? renal elimination
fluconazole
