Antifungals Flashcards
What antifungal class does amphotericin B belong to?
polyene antifungal
How does amphotericin B achieve its cidal activity?
binds to ergosterol to form pores
What is the DOC for most systemic antifungal infections?
amphotericin B
Does amphotericin B have CNS activity?
No
If a patient is receiving an amphotericin B infusion, what immediate side effects would you expect to see?
Shake and bake sxs
does the presence of acute side effects during amphotericin B infusion warrant a dose change?
no, you can lower the rate
how long is the course of tx for amphotericin B?
6wks to 4 months
describe the long-term side effects of amphotericin b…
extremely nephrotoxic
elevated BUN and serum creatinine (azotemia)
What is flucytosine converted to in the body, and what does it act against?
converted to 5-F-U, acts against DNA/RNA synthesis
What is the DOC for cryptococcus infections?
Flucytosine + amphotericin B
Flucytosine acts against cryptococcus neoformans. What else is it active against?
candida, aspergillus fumigatus, sporotrichum
What is a serious side effect of flucytosine?
depression of bone marrow
What labs could be elevated during flucytosine tx? Are they concerning? Why?
ALT, AST elevation
Reversible upon discontinuation of drug
What do Azole drugs inhibit? does this lead to static or cidal activity?
inhibit ergosterol
static
describe the tissue distribution of ketoconazole
widely distributed
describe the spectrum of ketoconazole…
broad spectrum antifungal
what does ketoconazole inhibit, leading to what adverse effects?
P450 inhibitor, has many drug interactions
what are 2 major adverse effects of ketoconazole?
- gynecomastia and impotence due to inhibited adrenal and testicular fx
- prolonged QT
What contraindicates the administration of ketoconazole?
acute or chronic hepatic disease
under what circumstances should oral ketoconazole administration be considered?
only when no other antifungal therapy can be used
does fluconazole have good CNS penetration?
yes
Which azole antifungal makes a good suppressive or prophylactic therapy for HIV/AIDS patients?
fluconazole
which CYP does fluconazole inhibit, and should that concern you?
CYP2C9. not concerning due to limited nature of CYP2C9 activity compared to ketoconazole’s CYP450 activity
Can amphotericin B be administered w/ aminoglycosides? why?
with caution due to synergistic nephrotoxicity
when giving fluconazole for suppresive therapy, describe the duration of tx.
lifelong or until CD4 count elevates
what is the most common side effect of fluconazole?
headache
what is the DOC for aspergillus infection?
Voriconazole + ampho B
“VORacious AMPHOtite for asparagus”
voriconazole + ampho B is the DOC for aspergillosis. what else does voriconazole treat?
esophageal candidiasis
salvage tx of scedosporium and fusarium sp.
Voriconazole is metabolized greatest by CYP2C19. But Voriconazole also inhibits P450s. explain how it can still be metabolized by P450 enzymes…
CYP2C19 has the greatest action against voriconazole, least inhibited by voriconazole
What is a major adverse effect of voriconazole?
Can cause reversible visual impairment
Describe the spectrum of itraconazole
similar spectrum to ketoconazole and fluconazole but with greater activity against aspergillus
what are the adverse reactions of itraconazole?
GI upset, NV…
CYP3A4 inhibition
Describe the bioavailability of itraconazole as capsules…
40-55% on empty stomach, 90-100% w/ meal or cola
describe the bioavailability of itraconazole as an oral solution
55% w/ meal, and 72% under fasting conditions
What 3 species of
fungus does isavuconazonium tx?
aspergillus, mucor, rhizopus
Does isavuconazonium have drug interations?
yes, substrate for and moderate 3A4 inhibition
What 2 adverse effects can occur w/ isavuconazonium administration…
Nephro
decrease QT
When is isavuconazonium contraindicated?
pt. c family hx of short QT syndrome
describe the sprectrum of posaconazole…
tx of aspergillus and candida
does posaconazole interact w/ other drugs?
yes–3A4 substrate and inhibitor
what antibiotic can echinocandins be compared to?
these drugs are the “fungal PCN”
why is caspofungin known as a “penicillin of antifungals”
because it is cidal and inhibits cell wall synthesis
does caspofungin come w/ drug interactions or nephrotoxicity?
no
when should you consider caspofungin in refractory patients?
for invasive aspergillosis w/ azole/ampho b resistant fungi
what side effects should you educate pts on w/ caspofungin administration?
elevated AST/ALT, histamine release/flushing, HA, Chills, GI
how do echino candins work?
inhibit cell wall synthesis of b(1,3)-D-glucan
What are the topical antifungals?
grisofulvin, terbinafine, nystatin
What diseases do topical antifungals like griseofulvin, terbinafine and nystatin treat?
dermatophytosis, onychomycosis
what is the DOC for onychomycosis and why?
griseofulvin–binds to keratin
what are major adverse effects of griseofulvin?
Disulfiram-like effects, ohotosensitivity, GI sxs, headache, CNS
what contraindicates the use of griseofulvin?
acute intermittent porphyria
hepatocellular failure
pregnancy, men 6 months prior to fathering child
what is the moa of terbinafine?
inhibits ergosterol synthesis by inhibiting squalene epoxidase
where does terbinafine tend to concentrate?
the nail
what other drug can nystatin be compared to and why?
ampho b, both polyenes
what is the most common use for nystatin?
candidal infx
nystatin is not absorbed where?
GI tract, skin, or mucous membranes
Because nystatin has poor GI and skin absorption, what can it be used for?
PO adminstration for GI and skin candida infx
which antifungals are cidal?
ampho b
nystatin
terbinafine
caspofungin
