Antifungal Flashcards
Cryptococcosis
Ampho + flucytosine
Chronic suppression - fluconazole
Chromoblastomycosis
Flucytosine only
Flucytosine Uses
Primary for chromoblastomycosis
Secondary for urinary candida
Septra Uses
Primary for pneumosyctis pneumonia
Amphotericin B
MOA - binds to steroids in membranes (higher affinity for ergosterol rather than cholesterol, but interatction with cholesterol accounts for SE
- Oral – n/v/d
-IV - n/v/d and chills/fever, nephrotroxicty
-IT - Unique CNS related tox - HA, n/v, rediculitis, paresis, visual impairment
Pregnancy B
Nephrotoxicity - biggest limiting factor
- can be minimized by loading with Na
- nephrotox is due to increased permeability in kidney - can be irreversible if total dose is greater than 4 g
Other ampho preps have better SE, but more $$$
Flucytosine
MOA - 5FU - cytosine deaminase – inhibits fungal thymidylate synthase
Resistance is common
Must adjust for renal, esp if given with ampho
SE
- BM – lethal
- Enterocolitis with sever diarrhea - esp if combo with ampho
- CNS
- Pregnancy C
Uses - Monotx for chromoblastomycosis, urinary candidia
- Combotx with ampho for cryptococcus
- -esp for meningitis in HIV
Azoles Notes
MOA - Inhibit 14-alpha-lanosterol demethylase – enzyme needed for ergosterol synthesis
- concentration dependent activity
Broad antifungal activity
Resistance - little resistance except for zygomycetes (can only be treated with posaconazole)
Not completely selective for fungi over man
Many drug interactions - CYPs
Teratogenic - voriconazole is worst, but ampho is ok
Better tolerated than ampho/flucytosine
Oral ok
Itraconazole
Azole
Primary for histoplasmosis in HIV
Oral TX of onychomycosis
Powder capsule dependent on gastric acidity for absorption
- more available in empty stomach
Poor CNS or urine penetration
SE - n/v, SJS
Contraindicated in pts with ventricular dysfunction
IV has cylcodextrin which can accumulate in kidney
Fluconazole
Azole
Primary for chronic suppression of cryptococcal in HIV, systemic/vaginal candida, recurrent candida in HIV
Good CSF penetration - cryptococcal and coccidiodial meningitis
Single dose for yeast infections
PK - gastric acidity not important
- high urine concentration
- not metabolized by CYPs, but does inhibit them
SE - GI, SJS, QT, abnormal liver function
Voriconazole
Azole
Modified fluconazole similar in spectrum to itraconazole
Most important tx o aspergillis – better than ampho
Very active against fusarium; salvage tx for scedosporium or fusarium
PK - Like fluconazole – gastric acidity not important, good distribution
-metabolized by 2C19 – genetic polymporphisms in Asians - slow metabolizers = higher concentrations
Has cyclodextrin (like itraconazole) which can build up in kidney
SE - visual changes (transient) – blurred vision, photophobia, altered color image
- SJS
- Photosensitivity
Posaconazole
Azole
Similar SE to fluconazole
Must be taken with high fat meals
Use - only azole active against zygomycetes (ampho is best alternate)
- approved for fungal prophylaxis in HIV
- tx for refractory mycoses
Ketoconazole
Azole
Occasionally used as alt tx for candida
SE - dose dependent decrease in [testosterone and estrogen]
- results in oligospermia, gynecomastia, loss of libido
- High doses cause decrease in [corticosteroid]
Echinocandins
Capsofungin, micafungin, amidulafungin
MOA - block synthesis of beta-D-glucan (fungal cell wall component)
Clearance via hydrolysis and n-acetylation
Hepatic insufficiency increases AUC by 50%
Primary tx for ora/esophageal/systemic candida
-alternative for aspergillis
Micafungin - alternative for prophylaxis of invasive candida infections
Griseofulvin
MOA - binds to fungal microtubules - blocks mitosis and is fungistatic
- absorption requires micronized particles and given with high fat meals
- symptomatic relief in 48 hours
- keratophilic and binds to keratin
Terbinafine or itra/fluconazole preferred
SE - teratogenic, n/v/d, alltergy
DDI - disulfiram like effect (like metro)
-reduces efficacy of oral contraceptives
Terbinafine
Agent of choice for dermatophytic and sporotrichosis
MOA - interferes with ergosterol synthesis
-inhibits 2D6
Prego B
Faster onset than griseo and w/o disulfiram rxn
