Antifungals Flashcards
amphotericin B MOA
cidal
interacts with ergosterol in fungal membrane, results in pore formation that increases permeability which leads to cell death
DOC for most systemic fungal infections
Amphotericin B
amphotericin B infusion toxicites
chills, fevers, muscle spasms, vomiting, headache
amphotericin B cumulative toxicities
powerful nephrotoxic agent (azotemia, BUN and crea)
can lead to irreversible kidney damage
MOA for flucytosine
metabolic antagonism of fungal DNA and RNA
converted to 5-fluorouracil which interferes with synthesis
DOC for cryptococcus infections
Flucytosine + Amp B (synergistic)
Does flucytosine penetrate CNS?
Yes
All flu drugs are good CNS penetrators
toxicities of flucytosine
depression of bone marrow, GI disturbances, elevation of AST or ALT
MOA for “azole” antifungals
static
inhibits synthesis of ergosterol and eventually inhibition of fungal growth
spectrum for ketoconazole
broad spectrum, good for topical infections
ketoconazole toxicities
inhibitor of P450 system, gynecomastia and impotence, prolonged QT
ketoconazole contraindications
acute or chronic hepatic disease
fluconazole penetration
penetrates well into other bodily fluids, particularly CSF
Fluconazole in HIV patients?
good for suppressive and/or prophylactic therapy in HIV patients
Toxicities of fluconazole
potent inhibitor of CYP2C9, but less drug interactions than other azoles, headache (due to CNS penetration)
DOC for aspergillus
voriconazole + amp B
voriconazole penetration
moderate CSF penetration
voriconazole toxicities
is both metabolized and inhibits P450s (metabolized in reverse order), visual impairment that is reversible
spectrum of itraconazole
similar to ketoconazole but has greater activity against aspergillus
toxicities of itraconazole
potent inhibitor of CYP3A4, GI effects, N/V/D, abd pain
bioavailability of itraconazole
capsules: better absorption with meal or soda
oral solution: better absorbed on empty stomach
spectrum of isavuconazonium
mucormycosis and invasive aspergillosis
toxicities of isavuconazonium
CYP3A4, nephrotoxicity, dose dependent decrease in QT interval
spectrum for posaconazole
aspergillus and candida
toxicities of posaconazole
CYP3A4, other toxicities are not well known due to the drug being very new
MOA of echinocandins
inhibits synthesis of B(1,3)-D-glucan, which is a major fungal cell wall component
what makes caspofungin a good drug?
lack of nephrotoxicity and few drug interactions
caspofungin for aspergillosis?
yes, in refractory patients that are resistant to azoles or amp B
griseofulvin MOA
static
binds to microtubules of certain fungi and destroys mitotic spindle structure
DOC for onychomycosis
griseofulvin
route for griseofulvin
ORAL only
what is griseofulvin mostly used for
dermatophytosis infections of skin, hair, nails
griseofulvin toxicities
headache, disulfuram-like effects, photosensitivity
griseofulvin contraindications
acute intermittent porphyria, hepatocellular failure, pregnancy and men 6 months prior to fathering a child
terbinafine MOA
cidal
interferes with sterol biosynthesis, squalene monooxygenase
route for terbinafine
oral or topical
spectrum for nystatin
primarily used for candida infections
what are the two polyene antibiotics we learned
amp B and nystatin
