Fungal Pharmacology Flashcards
azoles moa
inhibit ergosterol synthesis (lanosterol demethylase)
highly selective for fungal enymes
azole toxicities
prolonged QT, teratogenic
ketoconazole has anti-androgenic effects like gynecomastia, lower libido, impotence
azole drug interaction
inhibit 3 CYPs, esp CYP3A4 which metabolizes many drugs
main uses for triazoles and polyenes (ampho B)
dimorphics- blasto, histo, coccidioides
structure/fn of ampho B
hydrophilic and hydrophobic face- binds ergosterol and forms pores in fungal cell membrane
mech of resistance to ampho B
reduced ergosterol in mem, modified ergosterol that reduces ampB binding
administering ampB
iV- poor GIT absorption
only oral for lumenal GI infections
aqueous insolubility- muse be formulated w/ lipids
ampB toxicities acute
“shake and bake”- fever, chills, muscle spasms
hypotension, GI, headache/dizziness
100% of patients, lasts 30-45 min
cumulative ampB toxicities
nephrotoxicity, tubular damage to DCT
dose dependent, can be irreversible
ampB and pregnancy
safest antifungal
Pneumocystis resistance
resistant to most antifungals, less dependent on ergosterol, natural enzyme resistance mutations
rx for PJP
bactrim- TMP/SMX
bactrim moa
sulfa targets pteroate synthase, trimethoprim targets DHFR
both in THF pathway, folate metabolism
mutations in these enzymes confer resistance, extra PABA (substrate) can overwhelm the drug inhibition
SMX/TMP toxicities
SMX- fever, rash, photosensitive, rare Stevens-johnson syndrome
TMP- megaloblastic anemia, leukopenia, granulocytopenia (results of folate deficiency)
first line drug for severe systemic infections /immunocompromised hosts
ampB
