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