Infectious Disease III - Antifungals and Antivirals Flashcards
MOA of amphotericin B
binds to ergosterol, altering membrane permeability causing cell death
spectrum of amphotericin B
broad spectrum - covers Mucor, yeasts, aspergillus and other molds
dose of conventional amphotericin B should not exceed:
1.5 mg/kg/day
typical dose of liposomal amphotericin B
3-6 mg/kg/day
side effects of all amphotericin B formulations (though much less so with liposomal)
1) infusion related reactions - fever, rigors, malaise, HA
2) hypokalemia
3) hypomagnesemia
4) nephrotoxicity
How are side effects/infusion reactions of amphotericin B mitigated?
pre-infusion with diphenhydramine and acetaminophen, fluids before and after
Patients on which cardiac medication should have electrolytes very closely monitored in light of potential hypokalemia with amphotericin B?
digoxin
MOA of flucytosine
converted to fluorouracil intracellularly and competes for uracil incorporation into DNA
place in therapy of flucytosine
combination with amphotericin B in invasive candida or cryptococcal infections
normal dosing of flucytosine
50-150 mg/kg/day PO in 4 divided doses
CrCl cutoff for flucytosine renal adjustment
40 mL/min
frequency doubles (eg doses per day halve) at 20, 10 and below 10 dose after HD
main side effect of flucytosine
myelosuppression (dose-related, results in neutropenia, anemia, thrombocytopenia)
others include increase SCr, BUN, bili, hypoglycemia, hypokalemia
class side effects/properties of azole antifungals
increased LFTs, QT prolongation (except isavuconazonium)
all are moderate 3A4 inhibitors - various other inhibitions with each drug
azoles MOA
decrease ergosterol synthesis and cell membrane formation
itraconazole is contraindicated in patients with which disease state?
heart failure
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.
CYP3A4 and Pgp
other common side effects of itraconazole
HA, N/V, abd px, rash
Which azoles require renal adjustment?
fluconazole, vori, posa
Itraconazole has two different oral formulations. What is the difference between the two?
capsules and oral solution - oral solution is better absorbed and should be taken on an empty stomach, while capsules should be taken with food
Which two azoles penetrate the CNS enough to be used in meningitis?
fluconazole and voriconazole
Which two azoles cannot be used below CrCl/eGFR of 50? Why? Which is dosed based on CrCl? eGFR?
Voriconazole is dosed based on CrCl, posaconazole eGFR. The vehicle SBECD can accumulate below these renal cutoffs and worsen renal function.
Voriconazole is a major substrate of which two CYP enzymes, explaining many of its drug interactions?
2C9 and 2C19
Which azole is the drug of choice for aspergillosis?
voriconazole
Which azole is most likely to cause CNS effects like hallucanations?
voriconazole
Which azole should be filtered during IV administration due to possible particulates?
isavuconazonium
Which azoles cover Mucor?
isavuconazole/azonium, posaconazole
MOA of echinocandins
inhibit synthesis of beta 1,3 d-glucan component of fungal cell wall
spectrum of echinocandins
really only cover candida spp well, including strains that are more resistant to azoles. some activity against aspergillus, but not a preferred drug.
side effects of echinocandins
histamine-mediated symptoms (rash, pruritis, facial swelling, hypotension), increased LFTs and SCr, K/Mg abnormalities
Which echinocandins require renal dose adjustment?
hehe none (:
What are the warnings associated with voriconazole?
photosensitivity, visual disturbances (optic neuritis), liver damage
