Part 5: Antifungal Agents

Question 1

t/f fungal cells are more structurally similar to our own cells than bacteria

Answer 1

true

Question 2

t/f there are fewer drugable targets for fungi than bacteria

Answer 2

t

Question 3

what is a unique part of the fungal cell wall that is often a drug target?

Answer 3

ergosterol

Question 4

what do our cells contain in the cell walls instead of ergosterol?

Answer 4

cholesterol

Question 5

what 2 enzymes are specific to fungi?

Answer 5

those involved in cytosine metabolism (cytosine permase and cytosine deaminase)

Question 6

ergosterol is important to the ____ of the cell wall

Answer 6

structure

Question 7

what are 2 drugs that bind to ergosterol?

Answer 7

amphotericin B and nystatin

Question 8

what is the MOA of drugs liike amphotericin B and nystatin?

Answer 8

bind to ergosterol, the the molecules of drug associate together to make pores in the fungal membrane so it ruptures

Question 9

at high concentrations, amphotericin B and nystatin are _____

Answer 9

fungicidal

Question 10

t/f there are significant ADRs associated with amphotericin and nystatin and with the development of new antifungals, they are not used very much

Answer 10

t

Question 11

ampho B and nystatin are reserved for treating ___

Answer 11

specific topical infections

Question 12

nystatin is still commonly used for treating what type of infection?

Answer 12

oral thrush

Question 13

azole antifungals are a class of drugs that inhibit _____ which are required for making ergosterol

Answer 13

fungal CYP450

Question 14

inhibition of fungal CYP enzymes reduces the amount of ____ in the fungal cell membrane

Answer 14

ergosterol

Question 15

give 3 examples of azole antifungals?

Answer 15

clotrimazole, ketoconazole, fluconazole

Question 16

at high concentrations, azoles are ___

Answer 16

fungicidal

Question 17

t/f azoles have some affinity for human CYP 450

Answer 17

true

Question 18

which azole in particular has some affinity for human CYP 450?

Answer 18

ketoconazole

Question 19

why is ketoconazole not used clinically very often?

Answer 19

inhibits human cyp as well, resulting in drug interaction s

Question 20

for vaginal yeast infections, a combination of ___ and __ antifungals may be used to increase concentration and quicken recovery time

Answer 20

systemic and topical

Question 21

CanesOral is a combination of a single oral dose of ___ and a topical _____ cream

Answer 21

fluconazole; clotrimazole

Question 22

which azole is used for systemic fungal infections?

Answer 22

fluconazole

Question 23

patients with what conditions are more susceptible to developing systemic fungal infections?

Answer 23

immunocompromised: cancer, HIV

Question 24

what is the function of cytosine permase?

Answer 24

found in bacterial and fungal cells and facillitates entry of cytosine into cells

Question 25

what is the function of cytosine deaminase?

Answer 25

specific to fungal cells and converts cytosine into uracil (used in DNA and RNA synthesis)

Question 26

t/f flucytosine is not an active cytotoxic drug

Answer 26

t

Question 27

the structure of flucytosine is structurally similar to that of ___and ___

Answer 27

uracil and cytosine

Question 28

flucytosine enters fungal cells by ___ and is metabolized inside the cell by

Answer 28

cytosine permease facilitated transport ; cytosine deaminase

Question 29

when flucytosine is metabolized by deaminase, it thinks its making uracil, but its actually making ___

Answer 29

5-fluorouracil

Question 30

5-fluorouracil is a ____ compound

Answer 30

antimetabolite

Question 31

5-fluorouracil is commonly used in the treatment of ___

Answer 31

cancer

Question 32

MOA of 5-fluorouracil

Answer 32

inhibits thymidylate synthase (another enzyme importnat to nucleotide synthesis in eukaryotic cells) so DNA cannot be made.

Question 33

5-fluorouracil metabolites alos get incorporated into ____ and _____, which alters the structure and function of these molecules

Answer 33

RNA and DNA

Question 34

5- fluorouracil causes ____ and ____ synthesis to be impaired and the fungal cell dies

Answer 34

RNA and DNA

Question 35

what makes flucytosine specific to fungal cells?

Answer 35

only taken up by cells expressing cytosine permease and only metabolized by cytosine deaminase

Question 36

what causes resistance to flucytosine?

Answer 36

mutations in the enzymes (cytosine permease and deaminase) or in the process that creates 5-fluorouracil

Question 37

flucytosine is commonly used in combination with other antifungals like ___ for the treatment of systemic fungal infection s

Answer 37

ampho B

Question 38

what is the benefit of coadministering ampho B and flucytosine?

Answer 38

ampho B increases the amount of flucytosine that is taken into fungal cells and reduces resistance