anti-fungals Flashcards
drugs used for subcutaneous and systemic mycoses (SEVERE INFEC)
amphotericin B
flucytosine
azoles
echinocandins
amphotericin B
polyene - fungicidal
binds ergosterol - forms pores in cell membranes
leakage of intracellular ions and macromolecules = cell death
antifungal with broadest spectrum
amphotericin B
amphotericin B administration
IV (poor GI absorption)
low CSF penetration - intrathecal therapy for meningeal dz
initial induction tx to rapidly reduce fungal burden
amphotericin B
amphotericin AE
infusion related toxicity - muscle spasms. fever/chills. hypotension. attenuate by dec influsion rate or decreasing daily dose (occurs as pt is receiving infusion)
pre-medication with antihistamines, glucocorticoids, antipyretics, meperidine to minimize AE
Slower toxicity:
binds cholesterol and forms pores in mammalian cell membranes = renal toxicity
renal impairment and azotemia - in almost all pt
dec GFR
renal tubular acidosis - Mg and K wasting
attenuate renal damage with Sodium loading
LFTs
hypochromic normocytic anemia
seizures - d/t intrathecal administration
preferred tx for deep fungal infections during pregnancy
amphotericin
what is amphotericin usually administered with
IV saline (sodium)- to reduce renal damage
what is recommended to monitor with pt taking amphotericin
renal function liver function serum electrolytes (Mg and K) blood counts Hgb
amphotericin B lipid formulations
reduce nephrotoxicity - reduces exposure to nephron
1) liposomal amphotericin B
2) amphotericin B lipid complex
3) amphotericin B colloidal dispersion
Flucytosine
synthetic pyrimidine antimetabolite
taken by fungal cells via cytosine permease - converted intracellularly to 5’FU - 5-FdUMP = inhibits thymidylate synthetase = blocking dTMP synthesis
5-FUTP = inhibits protein synthesis
mammalian cells don’t have enzyme, can’t convert parent drug to active metabolite
flucytosine + ______ gives synergistic effect
flucytosine + amphotericin B
when to use flyucytosine
in serious infections by candida and/or cryptococcus
Flucytosine AE
result of 5’FU
BM toxicity
Azoles
imidazoles and triazoles
imidazoles
ketoconazole
miconazole
clotrimazole
triazoles
itraconazole
fluconazole
voriconazole
posaconazole
azoles MOA
14-alpha demethylase = catalyses conversion of lanosterol to ergosterol - inhibits enzyme
makes membrane leaky, inc permeability
azoles AE
minor GI upset
Ketoconazole
inhibits mammalian P450
can dec testosterone as a consequence = gynecomastia, dec libido, dec potency in men
high doses may inhibit steroid synth and dec cortisol elvels
ketoconazole use
rarely used for systemic b/c of AE. used for superficial
CYP3A4 inhibitor = potentiate toxicities of warfarin, cyclopsorine etc
best absorbed at low pH (antacids, H2 blockers, PPIs interfere)
poor penetration in CSF
fluconazole
oral/IV
moderate inhibitor of CYP3A4
strong inhibitor of CYP2C9 = can inc levels of phenytoin, zidovudine, warfarin
DOC in esophageal/oropharyngeal, vulvovaginal, urianry candidiasis
fluconazole
DOC for candidemia
fluconazole