exam 5 - MCMP Antifungal

Question 1

what makes fungi cell membranes unique

Answer 1

chitin layer and amphoteric layer that has ergosterol

Question 2

What enzyme converts squalene to squalene epoxide

Answer 2

squalene epoxidase

Question 3

what drug inhibits squalene epoxidase

Answer 3

terbinafine

Question 4

what enzyme converts lanosterol

Answer 4

CYP 450, 14-a-demethylase

Question 5

what drug inhibits CYP 450 14-a-demethylase

Answer 5

azoles

Question 6

what class is amphotericin and nyastatin

Answer 6

polyenes

Question 7

moa of amph and nystatin

Answer 7

bind to ergosterol to form pores in cell membranes and draw them from membranes

Question 8

specificity of amph and nystatin

Answer 8

binds to more selectivity to ergosterol than cholesterol

Question 9

terbinafine class

Answer 9

allylamines

Question 10

moa terbinafine

Answer 10

inhibits squalene epoxidase to disrupt ergosterol synthesis and squalene build-up

Question 11

specificity of terbinafine

Answer 11

2,500 fold selectivity for fungal enzyme

Question 12

what are the azoles

Answer 12

ketoconazole
itraconazole
fluconazole
voriconazole
isaconazole

Question 13

moa of azoles

Answer 13

inhibit 14-a-demethylase to prevent ergosterol synthesis

Question 14

specificity of azoles

Answer 14

fungal enzyme more sensitive to inhibition

Question 15

how is oteseconazole specific

Answer 15

specific for 14-a-demethylase

Question 16

what are the echinocandina

Answer 16

caspofungin
micafungin
anidulafungin

Question 17

moa of echinocandins

Answer 17

inhibits B(1,3) glucan synthesis (cell wall)

Question 18

specificity of echinocandins

Answer 18

humans lack B-glucan

Question 19

what makes rezafungin unique

Answer 19

once weekly w/ long half-life

Question 20

ibrexafungerp moa

Answer 20

inhibits glucan synthase to deplete 1,3 B-D-glucan

Question 21

specificity of ibrexafungerp

Answer 21

selective for glucan synthase enzyme

Question 22

flucytosine class

Answer 22

pyrimidine analog (metabolite)

Question 23

moa of flucytosine

Answer 23

inhibits thymidylate synthase and interferes w/ protein synthesis

Question 24

specificity of flucytosine

Answer 24

humans cannot convert flucytosine to active metabolite

Question 25

inhibition of thymidylate synthase steps

Answer 25

flucytosine --> 5-FU --> 5-FdUMP

Question 26

inhibition of protein synthesis (flucytosine) steps

Answer 26

thymidylate trapped as inactive form and can't react w/ dUMP

Question 27

tavaborole moa

Answer 27

inhibits leucyl transfer RNA synthetase to inhibit protein synthesis

Question 28

tavaborole specificity

Answer 28

LeuRA only in fungal cells

Question 29

how does ampho cause toxicity

Answer 29

binds to cholesterol and cause toxicity (fever, vomiting, HA, hypotension)

Question 30

what is the major AE of amphotericin

Answer 30

renal damage

Question 31

what is the major AE of flucytosine

Answer 31

renal damage

Question 32

why are amph and flucytosine used together and what should be monitored

Answer 32

resistance kidney function

Question 33

describe the relationship between azoles and cyps

Answer 33

azoles are metabolized by and inhibit CYPs

Question 34

how can cyp inducers affect azoles

Answer 34

can decrease azole levels

Question 35

what drug has major DDIs w/ azoles

Answer 35

rifampin

Question 36

what is voriconazole metabolized by

Answer 36

2C19 > 3A4 > 2C9