Part 5: Antifungal Agents Flashcards
t/f fungal cells are more structurally similar to our own cells than bacteria
true
t/f there are fewer drugable targets for fungi than bacteria
t
what is a unique part of the fungal cell wall that is often a drug target?
ergosterol
what do our cells contain in the cell walls instead of ergosterol?
cholesterol
what 2 enzymes are specific to fungi?
those involved in cytosine metabolism (cytosine permase and cytosine deaminase)
ergosterol is important to the ____ of the cell wall
structure
what are 2 drugs that bind to ergosterol?
amphotericin B and nystatin
what is the MOA of drugs liike amphotericin B and nystatin?
bind to ergosterol, the the molecules of drug associate together to make pores in the fungal membrane so it ruptures
at high concentrations, amphotericin B and nystatin are _____
fungicidal
t/f there are significant ADRs associated with amphotericin and nystatin and with the development of new antifungals, they are not used very much
t
ampho B and nystatin are reserved for treating ___
specific topical infections
nystatin is still commonly used for treating what type of infection?
oral thrush
azole antifungals are a class of drugs that inhibit _____ which are required for making ergosterol
fungal CYP450
inhibition of fungal CYP enzymes reduces the amount of ____ in the fungal cell membrane
ergosterol
give 3 examples of azole antifungals?
clotrimazole, ketoconazole, fluconazole
at high concentrations, azoles are ___
fungicidal
t/f azoles have some affinity for human CYP 450
true
which azole in particular has some affinity for human CYP 450?
ketoconazole
why is ketoconazole not used clinically very often?
inhibits human cyp as well, resulting in drug interaction s
for vaginal yeast infections, a combination of ___ and __ antifungals may be used to increase concentration and quicken recovery time
systemic and topical
CanesOral is a combination of a single oral dose of ___ and a topical _____ cream
fluconazole; clotrimazole
which azole is used for systemic fungal infections?
fluconazole
patients with what conditions are more susceptible to developing systemic fungal infections?
immunocompromised: cancer, HIV
what is the function of cytosine permase?
found in bacterial and fungal cells and facillitates entry of cytosine into cells
what is the function of cytosine deaminase?
specific to fungal cells and converts cytosine into uracil (used in DNA and RNA synthesis)
t/f flucytosine is not an active cytotoxic drug
t
the structure of flucytosine is structurally similar to that of ___and ___
uracil and cytosine
flucytosine enters fungal cells by ___ and is metabolized inside the cell by
cytosine permease facilitated transport ; cytosine deaminase
when flucytosine is metabolized by deaminase, it thinks its making uracil, but its actually making ___
5-fluorouracil
5-fluorouracil is a ____ compound
antimetabolite
5-fluorouracil is commonly used in the treatment of ___
cancer
MOA of 5-fluorouracil
inhibits thymidylate synthase (another enzyme importnat to nucleotide synthesis in eukaryotic cells) so DNA cannot be made.
5-fluorouracil metabolites alos get incorporated into ____ and _____, which alters the structure and function of these molecules
RNA and DNA
5- fluorouracil causes ____ and ____ synthesis to be impaired and the fungal cell dies
RNA and DNA
what makes flucytosine specific to fungal cells?
only taken up by cells expressing cytosine permease and only metabolized by cytosine deaminase
what causes resistance to flucytosine?
mutations in the enzymes (cytosine permease and deaminase) or in the process that creates 5-fluorouracil
flucytosine is commonly used in combination with other antifungals like ___ for the treatment of systemic fungal infection s
ampho B
what is the benefit of coadministering ampho B and flucytosine?
ampho B increases the amount of flucytosine that is taken into fungal cells and reduces resistance
