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The flashcards below were created by user
vanousheh
on FreezingBlue Flashcards.
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What is the broadest spectrum antifungal?
Amphotericin B
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What is its mechanism of action?
Interacts c ergosterol to create membrane channels that cause loss of intracellular components
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What is the mechanism of resistance?
Organisms c less ergosterol in their membranes
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How is it administered?
Give IV for systemic infections
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What is its distribution?
- Large volume of distribution --> not removed by dialysis
- Board Q: Don't need to redose ampho after kidney dialysis (need to redose aminoglycosides)
- Poor CNS penetration
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What is its major toxicity?
Highly nephrotoxic
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What minor side effects can be seen c ampho injection?
Chills and fever
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What can be given to reduce these effects?
Meperidine__opioid analgesic
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In what cases is amphotericin B NOT the DOC?
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Systemic aspergillosis --> voriconazole
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Reminder: Aspergillus = septate hyphae, branching @ acute angles, immunosuppressed
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Cryptococcus --> amphotericin + flucytosine
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How long is Tx given?
From 6 wks to 3 or 4 months
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What is the mechanism of flucytosine?
Converted to 5-fluorouracil which inhibits thymidylate synthase and fungal DNA synthesis
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What are its pharmacokinetic properties?
Well absorbed orally, enters CSF (perfect for Cryptococcus)
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What are the adverse effects of flucytosine?
Depression of bone marrow, GI disturbance, hair loss
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What is the mechanism of ketoconazole?
Inhibits fungal lanosine 14 alpha-demethylase to prevent ergosterol synthesis
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What is its antifungal spectrum?
Wide, but still smaller than ampho
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What are its pharmacokinetics?
- Well absorbed after oral administration and bound to albumin
- Extensively metabolized by liver and partially secreted by kidney (not affected by renal disease)
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What causes its major adverse effects?
- Inhibition of human CYP3A4:
- Interactions c many Rx: warfarin, phenytoin (NOT digoxin)
- Inhibition of adrenal and testicular function (due to inhibition of cholesterol synthesis)
- Gynecomastia (also seen c cimetidine)
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How does fluconazole stand out from the other -azoles?
- Excellent CNS penetration
- NO interaction c P450
- No inhibition of testicular and adrenal steroidogenesis
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How is it administered?
IV and oral
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What Rx is almost identical to ketoconazole?
Itraconazole
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What is the DOC for invasive aspergillosis?
Voriconazole
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What are the adverse effects?
- Drug interactions like ketoconazole via inhibition of P450
- Visual impairment
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Which class of Rx are fungi unlikely to develop resistance to?
Echinocandins
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What is the echinocandin MOA?
Inhibit synthesis of beta (1,3)-D-glucan in the cell wall
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What makes them a good Rx choice?
Lack of nephrotoxicity
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What are the echinocandins?
Caspofungin, micafungin, anidulafungin
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How are they administered?
IV
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What is caspofungin often used for?
Invasive aspergillosis in refractory patients
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What are the caspofungin adverse effects?
- ? LFTs, histamine release, HA, chills, GI effects
- Boards: histamine release also seen in tubocurarine, opioids, vancomycin
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What is the MOA of griseofulvin?
Binds to microtubules and destroys mitotic spindle ? inhibits mitosis (fungistatic)
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When is it indicated?
Dermatophyte infections of skin, hair, and nails
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What are its pharmacokinetic properties?
- Oral or topical application
- Poor solubility and absorption from GI tract
- Accumulates in keratin
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What are its adverse effects?
- Disulfiram-like effects [BOOM]
- Reminder: cefamandole, cefoperazone
- Contraindicated in acute intermittent porphyria
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What is the nystatin MOA?
Similar to amphotericin B --> binds sterol and lyses cell
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When is nystatin often used?
Candidal infections
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How is it administered?
Orally and topically
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What are the pharmacokinetic properties?
- NOT absorbed from the GI tract
- Similar to vancomycin and aminoglycosides
- NOT absorbed from skin or mucous membranes
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What is the MOA of terbinafine (Lamisil)?
Interferes c fungal sterol synthesis
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How is it used?
Oral or topical application for dermatophytes and onychomycoses
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What are the pharmacokinetic properties?
Well abosrbed, widely distributed, accumulates in keratin
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What is the worst side effect of terbinafine?
Hepatic failure
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What are the other Rx often used topically?
- Miconazole nitrate: tinea pedis, vaginal candidiasis
- Clotrimazole (Lotrimine)
- Ciclopirox olamine
- Tolnaftate (Tinactin)
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