Anti-Fungal Therapy Flashcards
what has caused increased prevalence of systemic fungal infections?
overuse of antibiotics (esp. broad spectrum)
abx use has become a risk factor for getting systemic mycoses
what are superficial mycoses?
fungus that affects skin, hair and nails
what are subcutaneous mycoses?
fungus that affects the muscle, CT below the skin
what are systemic (invasive) mycoses?
involve internal organs,
primary and opportunistics
what are allergic mycoses?
fungus that affects the lungs or sinuses
pts may have chronic asthma, cystic fibrosis or sinusitis
what are fungal cell membranes made of?
ergosterol instead of cholesterol
-makes drug production specific to fungi that does not damage mammal cells
do fungi have cell walls?
yes
which are the polyene antibiotics that interfere with production of cell membrane?
amphotericin B
nystatin (typically topical)
which are the azole antifungals that interfere with production of cell membrane?
ketoconazole (nizoril)-imidazole-1st systemic antifungal that you could give orally itraconazole (sporanox)-triazole fluconazole (diflucan)-triazole voriconazole (vfend)-2nd gen triazole miconazole clotrimazole
what is the MOA of azoles?
inhibit activity of lanosterol 14alpha demethylase which inhibits production of ergosterol
- some cross reactivity is found with CYP450
- some steroidogenesis problems in mammalian cells
when are ketoconazole used?
yeasts and molds
poor absorption and strong side effects
>99% protein binding
cleared through kidney and liver
what are side effects of ketoconazole?
N/V worse with higher doses
hepatotoxicity
dose related inhibition of CYP450 responsible for testosterone creation and cortisol formation
what will impact absorption of ketoconazole?
gastric pH
what is the go-to first systemic antifungal of choice
fluconazole
what are advantages of diflucan?
well tolerated IV/PO formations are available favorable pharmacokinetics better bioavailability hepatotoxicity is not present
what are disadvantages of fluconazole?
fungistatic not fungicidal
resistance is increasing
narrow spectrum
drug interactions
what is spectrum of fluconazole?
C. albicans
Cryptococcus neoformans
which fungi are not covered under fluconazole?
C. krusei
C. glabrata
aspergillus and other molds
what is the primary source of resistance against antifungals (esp. fluconazole)?
genetic mutations
efflux pumps (pump drug out of the cell)
what are side effects of fluconazole?
N/V rash more likely with high doses
what drug levels will fluconazole increase?
phenytoin cyclosporin rifabutin warfarin zidovudine
what drug levels decrease fluconazole?
rifampin
what are indicated uses of fluconazole?
mucosal candidiasis (vulvovaginal) systemic fungal (IV) maintenance of cryptococcal meningitis -good CNS concentration
what are side effects of itraconazole?
taste disturbances
N/V
osmotic diarrhea esp at high doses (long term compliance is difficult)
what are side effects of voriconazole?
visual disturbances (returns to normal afterwards) IV> oral
what are target organisms for amphotericin B?
aspergillus terreus, scedosporium spp
most lethal fungal cell killer
what are main uses of voriconazole?
other candida spp
aspergillus
what is the biggest side effect problem with amphotericin B?
nephrotoxic
top 5 most nephrotoxic drugs
(renovascular and tubulovascular)
how would you counteract the nephrotoxicity of amphotericin B?
volume load and load up with Na and K
what is amphotericin B used for?
cryptococcal meningitis (2nd line after fluconazole)
mucomycosis
invasive fungal infection that is not responding to other agents
what is the MOA of flucytosine?
interferes with fungal DNA generation
what is main drawback of flucytosine?
rapid resistance develops when used as a monotherapy
- decreased uptake
- altered 5FU metabolism
what are indicated uses of flucytosine?
in combo with ampotericin B or fluconazole to treat
- candidiasis
- cryptococcosis
- ?aspergillosis
what are flucytosine side effects?
D/V, alterations in LFTs and anemia with long term use
what are MOAs of echinocandins, caspofungin and micafungin?
disrupt maintenance of cell wall
what are indications of echinocandins?
non albicans Candida or fluconazole resistant spp
Aspergillus
