Flashcards in Anti-Fungal Therapy Deck (36)
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?
which are the polyene antibiotics that interfere with production of cell membrane?
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
voriconazole (vfend)-2nd gen triazole
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
dose related inhibition of CYP450 responsible for testosterone creation and cortisol formation
what will impact absorption of ketoconazole?
what is the go-to first systemic antifungal of choice
what are advantages of diflucan?
IV/PO formations are available
hepatotoxicity is not present
what are disadvantages of fluconazole?
fungistatic not fungicidal
resistance is increasing
what is spectrum of fluconazole?
which fungi are not covered under fluconazole?
aspergillus and other molds
what is the primary source of resistance against antifungals (esp. fluconazole)?
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?
what drug levels decrease fluconazole?
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?
osmotic diarrhea esp at high doses (long term compliance is difficult)
what are side effects of voriconazole?
visual disturbances (returns to normal afterwards)
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
what is the biggest side effect problem with amphotericin B?
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)
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
1. decreased uptake
2. altered 5FU metabolism
what are indicated uses of flucytosine?
in combo with ampotericin B or fluconazole to treat
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