Anti-Fungal Pharm Flashcards
MOA amphotericin B
forms complex with ergosterol and disrupts plasma membrane permeability (forms pores)
what organisms does amphotericin B fight against
CC(yeasts), HBC(endemic mycoses), AA(pathogenic molds) - Candida albicans • Cryptococcus neoformans • Histoplasma capsulatum • Blastomyces dermatitidis • Coccidioides immitis • Aspergillus fumigatus • Agents of mucormycosis
resistance to amphotericin B
- decreased ergosterol
- modified ergosterol (less affinity for amphotericin B)
when to give IV amphotericin B
systemic infections for wide distributions
- fungal meningitis
when to give oral amphotericin B
fungi in GI lumen
adverse effects amphotericin B
- fever, chills, muscle spasms, vom, HA, hypotension
- renal damage
- anemia
- seizures
how to prevent adverse effects amphotericin B
premedication with corticosteroids, antipyretics, antihistamines, or meperidine
MOA flucytosine
flucytosine –> cytosine permease –> FdUMP and FUTP –> FdUMP inhibits DNA synthesis, FUTP inhibits RNA synthesis
what organisms does flucytosine fight against
- C. neoformans
- some candida
- dematiaceous molds that cause chromoblastomycosis
resistance to flucytosine
altered metabolism of flucytosine
how is flucytosine administered
oral only (in US) - widely distributes in body including CNS
adverse effects flucytosine
- bone marrow toxicity (anemia, leukopenia, thombocytopenia)
- derangement of liver enzymes
MOA of azoles
reduction of ergosterol synthesis by inhibiting fungal CYP450
what organisms do azoles fight against
broad spectrum
- many candida
- c. neoformans
- endemic mycoses
- dermatophytes
- aspergillus
resistance to azoles
upregulation of fungal CYP350
adverse effects azoles
- minor GI symptoms
- can cause abnormalities in liver enzymes
- some drug-drug interactions
adverse effects ketoconazole
greater propensity to inhibit mammalian cytochrome P450 and less selective for fungal P450 enzymes
- rarely used
adverse effects of sukassazole
somi’s dumb
what fungi does itraconazole specifically treat
- dimorphic fungi (histoplasma, blastomyces, sporothrix)
- aspergillus sp
- dermatophytes and onchomycosis
what is the azole choice for invasive aspergillosis
voriconazole
benefits of fluconazole
- high oral availability
- good CSF penetration
- drug interactions less common
- lease effect of all azoles on hepatic enzymes
azole choice of treatment for secondary prophylaxis of cryptococcal meningitis
fluconazole
most commonly used tx for mucocutaneous candidiasis
fluconazole
can fluconazole be used against aspergillosis
nope, no activity against it or other filamentous fungi
toxicities from voriconazole
- rash
- elevated hepatic enzymes
- visual disturbances
- photosensitivity dermatitis
what changes in dose of other drugs need to occur when prescribing voriconazole or posaconazole
there needs to be a dose reduction in meds metabolized by CYP3A4 because voriconazole and posaconazole inhibit mammalian CYP3A4
(cyclosporine, tacrolimus, statins)
broadest spectrum of all azoles
posaconazole
only azole with significant activity against mucormycosis
posaconazole
when is posaconazole used as prophylaxis
- during induction chemotherapy for leukemia
- in allogenic bone marrow transplant pts
MOA of echinocandins
inhibit synthesis of beta (1-3)-glucan at fungal cell wall by inhibiting glucan synthase
spectrum of activity for echinocandins
- candida
- aspergillus
- NO coverage C. neoformans or agents of zygomycosis/mucormycosis
what fungi does caspofungin (an echinocandin) specifically treat
- disseminated and mucocutaneous candidal infections
- empiric anti-fungal therapy during febrile neutropenia
- invasive aspergillosus
what fungi does micafungin (an echinocandin) specifically treat
- mucocutaneous candidiasis
- candidemia
- prophylaxis of candidal infections in bone marrow transplant pts
what fungi does anidulafungin (an echinocandin) specifically treat
- esophageal candidiasis and invasive candidiasis
how are each echinocandin administered and what is their half life
only parenteral administration (IV)
- caspofungin: 9-11 hours
- micafungin: 11-15 hours
- anidulafungin: 24-48 hours
adverse effects echinocandins
- well tolerated
- minor GI stuff
