Stahlein

Question 1

difference in cell membranes of fungal and human cells

Answer 1

fungal cells have ergosterol
human cells have cholesterol

Question 2

why do we target ergosterol synthesis?

Answer 2

antifungal drugs target ergosterol and its biosynthesis to selectively affect fungal cells without harming human cells

Question 3

which enzyme do allylamines (terbinafine) inhibit

Answer 3

squaline epoxidase

Question 4

which enzyme do azoles inhibit

Answer 4

CYP450 14-alpha demethylase

Question 5

amphotericin B class and MOA

Answer 5

polyenes
binds ergosterol and forms pores in membrane

Question 6

amphotericin B selectivity

Answer 6

binds ergosterol better than cholesterol

Question 7

amphotericin B toxicities

Answer 7

infusion related toxicities
renal damage

Question 8

reversible amphotericin B toxicity

Answer 8

reduced renal perfusion

Question 9

irreversible amphotericin B toxicity

Answer 9

renal tubular injury

Question 10

Answer 10

amphotericin B
polyenes
binds ergosterol and forms pores in membrane

Question 11

nystatin MOA and class

Answer 11

polyene
binds ergosterol and forms pores in membrane

Question 12

nystatin dosage form

Answer 12

topical

Question 13

terbinafine MOA and class

Answer 13

allylamines
inhibit squaline epoxidase to disrupt ergosterol synthesis

Question 14

terbinafine selectivity

Answer 14

selective for fungal enzyme over mammalian

Question 15

Answer 15

terbinafine
inhibits squaline epoxidase

Question 16

azoles MOA

Answer 16

inhibition of 14-alpha demethylase by nitrogen binding iron in CYP450
inhibits conversion of lanosterol to ergosterol

Question 17

azole structure

Answer 17

Question 18

Answer 18

ketoconazole
dioxy ring and azole ring

Question 19

Answer 19

itraconazole
triazole (3Ns)

Question 20

Answer 20

fluconazole
2Fs and OH
2 triazoles

Question 21

Answer 21

voriconazole
one F
triazole

Question 22

Answer 22

posconazole
furan ring

Question 23

Answer 23

isavuconazole
prodrug
has sulfur group

Question 24

Answer 24

osteoconazole
3 Fs

Question 25

caspofungin, micafungin, anidulafungin, rezafungin MOA and class

Answer 25

echinocandins inhibit synthesis of beta 1-3 glucan cell wall component

Question 26

echinocandins selectivity

Answer 26

no enzyme in mammalian cells like beta glucan

Question 27

Answer 27

echinocandins inhibit synthesis of beta 1-3 glucan synthesis

Question 28

rezafungin considerations

Answer 28

once weekly IV injection long half life BIG structure

Question 29

Answer 29

rezafungin

Question 30

ibrexafungerp MOA

Answer 30

small molecule inhibitor of glucan synthase enzyme

Question 31

Answer 31

ibrexafungerp small molecule inhibitor of glucan synthase enzyme

Question 32

flucytosine class and MOA

Answer 32

antimetabolite inhibits thymidylate synthase which interferes with protein synthesis

Question 33

flucytosine selectivity

Answer 33

metabolized in fungal cells to 5-FU by cytosine deaminase which we lack

Question 34

Answer 34

flucytosine inhibits thymidylate synthase which interferes with protein synthesis

Question 35

tavaborole MOA

Answer 35

inhibits leucyl transfer RNA synthase (LeuRS) which inhibits protein synthesis

Question 36

Answer 36

tavaborole inhibits leucyl transfer RNA synthase (LeuRS) which inhibits protein synthesis

Question 37

amphotericin B and flucytosine toxicity consideration

Answer 37

both have renal tox but when used in combo we can use lower doses of amphotericin B

Question 38

how does amphotericin B help flucytosine concentrations

Answer 38

amphotericin B creates pores in membrane which allows more flucytosine in

Question 39

which antifungal has CYP450 interactions

Answer 39

azoles! - inhibitors and substrates

Question 40

how do CYP3A4 interactions work with azoles

Answer 40

increase concentrations of other drugs CYP inducers would decrease azole concentrations

Question 41

which drug is a potent CYP3A4 inhibitor

Answer 41

ketoconazole increases half life of cyclosporine and triazolam

Question 42

which drug is a 2C19 substrate

Answer 42

voriconazole

Question 43

what does the azole functional group do

Answer 43

nitrogen binds with iron to prevent formation of the intermediate

Question 44

what reaction does thymidylate synthase catalyze

Answer 44

dUMP to fDUMP

Question 45

how does flucytosine decrease DNA synthesis

Answer 45

inhibits thymidylate synthase so dTMP can not be formed