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What is Moa of Amphotericin B?
binds ergosterol, cell membrane steroid of fungi
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What is chemistry of Amphotericin B?
- produced by Strep nodosus
- polyene macrolid
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What is the pk of Amphotericin B?
- poor GI absorption: IV administration
- broad spectrum, poor CSF access
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What are the adverse effects of Ampohtericin B?
- immediate: reactions r/t infusion..fever, chills, muscle spasms, hypotension
- delayed: slower reactions, renal damge (pre & post NS bolus), liver FX ABN
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What are the uses of Amphotericin B?
- reduce fungal burden of nasty bugs
- intrathhecal therapy suboptimal
- systemic candidemia
- aspergillus
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What is the Moa of Flucytosine?
- inhibits DNA & RNA synthesis within the fungal cells
- works in Synergism (Ampho B & Itraconazole)
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What is chemistry of Flucytosine?
- pyrimidine analog
- related to fluorouralcil (anti-neoplastic agent used in chemo)
- potent antifungal
- narrow spectrum of activity (neoformans, Candida)
- used as a combo agent
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What is pk of Flucytosine?
- oral, well absorbed including CSF
- toxicity in AIDS & renal insufficiency
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What are the adverse effects of Flucytosine?
- bone marrow toxicity
- toxic enterocolitis
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What is the Moa of Azoles?
reduces ergosterol synthesis by inhibition of fungal cytochrome P450 enzymes
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What is the chemistry of Azoles?
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What is the pk of Azoles?
variations in absorption, serum concentrations, elimination, mode of admin
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What are adverse effects of Azoles?
- minor GI upset
- liver enzyme abnormality
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What is the use for Azoles?
- broad spectrum
- treats Amphotericin resistant P boydii (fungs in soil, sewage, farm animals)
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Which class of Azoles causes drug reactions and why?
Imidazoles d/t poor selectivity in reacting with CP450
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What is the Moa of Echinocandins?
act on fungal wall & inhibit B-glucan
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What is the chemistry of Echinocandins?
- large peptides linked to long-chain fatty acids
- active against candida & aspergillus
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What are 3 types of Echinocandins?
caspofungin, micafungin, andidulafungin
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What is the pk of Echinocandins?
adjust dose if severe liver insufficiency
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What are adverse effects of Echinocandins?
- minor GI & flushing
- Micafungin can increase levels of Nifedipine (Ca2+ channel blocker)/Cyclosporin
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What are uses of Echinocandins?
- Casponfungin - disseminated & mucocutaneous candida
- Micafungin - mucocutaneous candidiasis, prophylaxis in bone marrow transplant patients
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What is Moa of Allylamine (Terbinafine)?
- fungicidal - inhibits fungal enzyme epoxidase
- interferes with ergosterol synthesis
- highly lipophilic
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What is Terbinafine (Lamisil)?
synthetic allylamine
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What is Terbinafine (Allylamine) used to treat?
onychymycosis/dermatophytosis
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What are the adverse effects of Terbinafine (Allylamine)?
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What baseline labs should you get before using Terbinafine?
baseline LFT's & CC (can be 2-3'x above normal before d/c)
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What is the chemistry of Nystatin?
polyene macrolide (like Ampho B)
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How is Nystatin adminstered?
only topical d/t toxicity
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What does Nystatin treat?
candida infections & thrush
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What other topical antifungals are used?
- topical azoles
- topical allylamines (terbinafine)
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What antifungal is used to treat mucocutaneous infections?
Griseofulvin
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What is Griseofulvin derived from?
penicillium
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What is Moa of Griseofulvin?
unknown
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What is Griseofulvin used to treat?
mucotaneous infection (dermatophytosis- skin, nail, & hair infections)
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