Infectious Disease III - Antifungals and Antivirals

Question 1

MOA of amphotericin B

Answer 1

binds to ergosterol, altering membrane permeability causing cell death

Question 2

spectrum of amphotericin B

Answer 2

broad spectrum - covers Mucor, yeasts, aspergillus and other molds

Question 3

dose of conventional amphotericin B should not exceed:

Answer 3

1.5 mg/kg/day

Question 4

typical dose of liposomal amphotericin B

Answer 4

3-6 mg/kg/day

Question 5

side effects of all amphotericin B formulations (though much less so with liposomal)

Answer 5

1) infusion related reactions - fever, rigors, malaise, HA
2) hypokalemia
3) hypomagnesemia
4) nephrotoxicity

Question 6

How are side effects/infusion reactions of amphotericin B mitigated?

Answer 6

pre-infusion with diphenhydramine and acetaminophen, fluids before and after

Question 7

Patients on which cardiac medication should have electrolytes very closely monitored in light of potential hypokalemia with amphotericin B?

Answer 7

digoxin

Question 8

MOA of flucytosine

Answer 8

converted to fluorouracil intracellularly and competes for uracil incorporation into DNA

Question 9

place in therapy of flucytosine

Answer 9

combination with amphotericin B in invasive candida or cryptococcal infections

Question 10

normal dosing of flucytosine

Answer 10

50-150 mg/kg/day PO in 4 divided doses

Question 11

CrCl cutoff for flucytosine renal adjustment

Answer 11

40 mL/min

frequency doubles (eg doses per day halve) at 20, 10 and below 10
dose after HD

Question 12

main side effect of flucytosine

Answer 12

myelosuppression (dose-related, results in neutropenia, anemia, thrombocytopenia)

others include increase SCr, BUN, bili, hypoglycemia, hypokalemia

Question 13

class side effects/properties of azole antifungals

Answer 13

increased LFTs, QT prolongation (except isavuconazonium)

all are moderate 3A4 inhibitors - various other inhibitions with each drug

Question 14

azoles MOA

Answer 14

decrease ergosterol synthesis and cell membrane formation

Question 15

itraconazole is contraindicated in patients with which disease state?

Answer 15

heart failure

Question 16

Due to its inhibition of _____ and ______ (enzymes/transporters), itraconazole should be used with caution with cardiac drugs, or other drugs that can prolong the QT interval.

Answer 16

CYP3A4 and Pgp

Question 17

other common side effects of itraconazole

Answer 17

HA, N/V, abd px, rash

Question 18

Which azoles require renal adjustment?

Answer 18

fluconazole, vori, posa

Question 19

Itraconazole has two different oral formulations. What is the difference between the two?

Answer 19

capsules and oral solution - oral solution is better absorbed and should be taken on an empty stomach, while capsules should be taken with food

Question 20

Which two azoles penetrate the CNS enough to be used in meningitis?

Answer 20

fluconazole and voriconazole

Question 21

Which two azoles cannot be used below CrCl/eGFR of 50? Why? Which is dosed based on CrCl? eGFR?

Answer 21

Voriconazole is dosed based on CrCl, posaconazole eGFR. The vehicle SBECD can accumulate below these renal cutoffs and worsen renal function.

Question 22

Voriconazole is a major substrate of which two CYP enzymes, explaining many of its drug interactions?

Answer 22

2C9 and 2C19

Question 23

Which azole is the drug of choice for aspergillosis?

Answer 23

voriconazole

Question 24

Which azole is most likely to cause CNS effects like hallucanations?

Answer 24

voriconazole

Question 25

Which azole should be filtered during IV administration due to possible particulates?

Answer 25

isavuconazonium

Question 26

Which azoles cover Mucor?

Answer 26

isavuconazole/azonium, posaconazole

Question 27

MOA of echinocandins

Answer 27

inhibit synthesis of beta 1,3 d-glucan component of fungal cell wall

Question 28

spectrum of echinocandins

Answer 28

really only cover candida spp well, including strains that are more resistant to azoles. some activity against aspergillus, but not a preferred drug.

Question 29

side effects of echinocandins

Answer 29

histamine-mediated symptoms (rash, pruritis, facial swelling, hypotension), increased LFTs and SCr, K/Mg abnormalities

Question 30

Which echinocandins require renal dose adjustment?

Answer 30

hehe none (:

Question 31

What are the warnings associated with voriconazole?

Answer 31

photosensitivity, visual disturbances (optic neuritis), liver damage