Pharm - Fungus Flashcards
most impt card of this deck - flucytosine has one primary indication, what is it?
cryptococcal infections (cryptococcus neoformans)
in general, what is the first line treatment for most fungal species
either an azole (itraconazole) antifungal
or Amphotericin B
What is the main toxicity of Amphotericin B? how does it cause this?
renal toxicity
it causes nephrotoxicity b/c it inserts itself into the membrane, binds ergosterol, forms ion channel pores and renders the kidney dysfunctional
what is a way to reduce the nephrotoxicity associated with Amphotericin B
use lipid formulations
What is the preferred first line treatment for Aspergillus and Bastomyces spp
one of the newer azole drugs, which are effective against these species, rather than amphotericin B
What is azole resistance associated with?
possibly - mutations in the promoter region of CYP51A, which encodes lanosterol-14alpha-sterol demethylase activity (the drug target of the azoles)
there is a trend of moving away from itraconazole to the other newer azole drugs. why?
oral absorption of itraconazole is low and variable from pt to pt
what are the newer azoles (3)?
fluconazole, voriconazole, posaconazole
why are the newer azoles better?
drug levels achieved are much more consistently (better oral bioavailability too)
which is the only azole to penetrate the BBB?
fluconazole
How are azoles metabolized and what interactions are possible
azoles undergo hepatic CYP metabolism and interact w/ concurrent drugs metabolized via CYP2C9, 2C19, and 3A4
What drug interactions should we be worried about with Amphotericin b
other nephrotoxic drugs and drugs producing hypokalemia
What are some side effects of flucytosine? therefore, what drug interactions do we want to avoid?
flucytosine itself can cause anemia, and blood dyscrasias like agrnulocytosis
avoid other hematotoxic drugs
what is the MOA of azole drugs?
prevent conversion of lanosterol to ergosterol - interrupt cell membrane synthesis
what is the MOA of Amphotericin B?
bind ergosterol in fungal cell membranes, punch holes in it increasing membrane permeability
