antifungal medchem Flashcards
2 most common mechanisms of antifungal agents
- prevention of biosynthesis
- binding of ergosterol
secondary mechanisms of antifungals
- cell wall disruption
- similar to cancer drugs
amphotericin B MoA
binds ergosterol
*conjugated double bonds increases specificity
amphotericin class
polyene membrane disrupter, increasing leakiness
nystatin MoA
binds ergosterol
nystatin class
polyene membrane disrupter, increasing leakiness
amphotericin use
systemic fungal infection
nystatin use
topical or oral (thrush)
two enzymes involved in biosynthesis
squalene epoxide
14alpha demethylase
fluconazole MoA
14alpha demethylase inhibitor
triazole rings bind to p450 heme
ketoconazole MoA
14alpha demethylase inhibitor
avoid what with ketoconazole
divalent cations
terconazole MoA
14 alpha demethylase inhibitor
terconazole route
topical
itraconazole route
oral
voriconazole MoA
14 alpha demethylase inhibitor
issue with voriconazole
extensive p450 metabolism so many drug interactions
14 alpha demethylase inhibitor that is prodrug
isavuconazonium sulfate
squalene epoxidase inhibitors
naftifine
butenafine
terbinafine
squalene epoxidase inhibitor SAR
allyl amines with napthalene group to mimic squalene
caspofungin MoA
inhibits cell wall biosynthesis
1,3-beta-D-glucan synthase
flucytosine MoA
converted to 5-FUMP and/or 5-FdUMP which inhibits protein/DNA synthesis
flucytosine use
in conjunction with amphotericin B
flucytosine side effects
GI due to gut flora also being affected
Griseofulvin MoA
binds tubulin to prevent mitosis
griseofulvin use
skin and nail infections because it gets taken into keratin
oral
