Antifungals Flashcards
tell me some basics about fungi
eukaryotic, many dimorphic, mechanism injury usually cell disruption and death
3 basic grouping software body systems fungi affect
systemic, superficial, or eye
what route are antigun gals usually delivered and why
topical due to adverse effects
give 4 anti fungal targets and the class that target each
cell wall: echinocandins
cell membrane: polyenes, azoles, allylamines
nucleic acid synthesis: flucytosine
(not red) nuclear division: griseofulvin
give 3 principles of anti fungal therapy
often occur in immunosuppressed patients or patients on prolonged antimicrobial therapy; long term therapy often needed; often severe systemic side effects so use topical if needed
mechanism of action of amphotericin B (a polyene)
bind to ergosterol in cell membrane, create channels in membrane, alter permeability to allow leakage of contents
what is a macrocyclic polyene
have a ring with a lot of atoms
give key pharmacokinetics of amphotericin
concentration-dependent, fungicidal, persistent anti fungal effect which allows intermittent treatment, minimal GI absorption so needs IV or local administration
Amphotericin B has action against Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, Candida spp. and Aspergillus which are all organisms that cause _____ mycosis
systemic
amphotericin has a dose-related adverse effect of
nephrotoxicity: toxic to renal epithelial cells, esp. id distal convoluted tubule, renal vasoconstriction (ischemia, decreased GFR), worsened by sodium depletion
different formulations of amphotericin B require
different dosing regimens (and unfortunately the only affordable one is the colloidal dispersion which is nephrotoxic)
the topical polyene natamycin is treatment of choice for
Fusarium keratomycosis in horses
how should the polyene natamycin NOT be delivered
systemically bc it is expensive and toxic. topical
the polyene nystatin should NOT be administered…
systemically. it is toxic. give topically
nystatin is a topical anti fungal that can’t be absorbed from GI tract. what is it used to treat and how is it delivered
PO! oral and intestinal candidiasis is treated “topically”
MOA for -azoles
inhibit synthesis of ergosterol (inhibit cytochrome P450 enzyme), fungistatic (impaired ability of cell membrane to act as a barrier, and affects activity of membrane-bound enzymes)
which has fewer adverse effects and less effect on mammalian sterol synthesis, triazoles or imidazoles
triazoles safer. can use systemically. imidazole only topical.
potency, drug interactions, and toxicity or -azoles are all related to what
affinity or specificity of P450
drug interactions with -azoles are caused by what
inhibition of P-glycoprotein efflux pumps
give 5 main adverse effects of ketoconazole
inhibit mammalian P450, so drug interactions; inhibit testosterone and cortisol synthesis, hepatotoxicity, anorexia and vomiting, teratogenic so don’t use in pregnant animals
ketoconazole is soluble in what? what is the implication
soluble in acid, so best absorption GI after a meal
is ketoconazole protein bound? why does this matter
over 98% protein bound, so does not penetrate CSF, ocular fluid, or seminal fluid
name the 2 important triazoles
itraconazole and fluconazole
name the 3 important imidazoles
ketoconazole, clotrimazole, miconazole
main indication for itraconazole
first line tx for non life threatening systemic mycoses that don’t involve the CNS
is itraconazole specific for fungal P450
yes, it is a cytochrome P450 inhibitor, but very specific for fungal P450
when should you reduce dose of fluconazole
renal failure patients
describe activity of fluconazole: distribution, what it crosses
widely distributed through body, crosses BBB, so is used as firstling treatment for systemic mycoses with ocular or CNS involvement
miconazole is usually used for what 2 things
treat keratomycosis and dermatophysis topically; combine with chlorhex for Malassezia treatment topically
clotrimazole is usually combined and used to treat what
combine with steroid and antibiotic treatment of otitis in dogs, give topical only
enilconazole is given how? to treat what?
topical. very effective against dermatophytes: topical treatment of dermatophytes in dogs and horses, and fungal sinusitis in horses
MOA of terbinafine, an allylamine? include if fungicidal or fungistatic
fungicidal. inhibit ergosterol synthesis and is very selective for fungal P450 enzyme (so don’t have P450-assoc adverse interactions)
what is terbinafine used to treat
dermatophytes and Malassezia species
describe MOA of flucytosine, including how it is taken into cell
enters cell by cytosine permeate, converted into 5-fluorouracil, then incorporated into RNA disrupting protein synthesis or converted into 5FdUMP which inhibits DNA synthesis
in flucytosine, changes in fungal permeability or deaminase activity lead to what
resistance
use of flucytosine
adjunct therapy with amphotericin B for candidiasis or cryptococcus. combo allows decreased amphotericin B dose. amphotericin B increases fungal membrane permeability to flucytosine
give adverse effects of Na or K iodide
iodize, abortion/infertility (careful if pregnant)
what is lime sulfur (calcium polysulfide) used for dermatophysis topical
dermatophysis topical
what are two topical, whole-body treatments for dermatophysis
chhlorhex and miconazole since or enilconazole rinse
chlorine dioxide fas can be used to treat what in horses
white line disease
