Lecture 6-7 - Anti-fungals (Cooke) Flashcards
natural (derived from other fungi) anti-fungal drugs
amphotericin B
griseofulvin
synthetic anti-fungal drugs
azoles
allylamines
flucytosine
(only going over most commons)
derived from Penicillium mold and MOA disrupts mitosis
griseofulvin
topical griseofulvin is old treatment for
dermatophytosis (have better drugs with less SE now)
if giving griseofulvin orally should it be given with or w/o food
with a fatty meal
*azoles are used more commonly now
SE of griseofulvin
BM Suppression
teratogenic (not safe for pregos)
V/D
anorexia
derived from streptomyces
amphotericin B
MOA amphotericin B
binds sterols (cholesterols specific to fungi wall)
route of admin for amphotericin B
almost always IV, however there is a SC protocol for use PRN
amphotericin B oral absorption
POOR
Amphotericin B is __ toxic
nephrotoxic, must monitor renal values and give IVF
liposome form can reduce toxicity
CS of acute amphotericin B toxicity
vomiting
myalgia
fever
anaphylaxis
this is why give IV injection SLOWLY and D/C if there are any SE
amphotericin B spectrum
most fungi, some resistance is emerging
amphotericin B has poor penetration of
bone, brain/CSF, eye
what can you dilute amphotericin with
sterile H2O or D5W, NOT saline bc will precipitate
should always check renal values before, give IVF before and after administered
2 reasons would use SC route for amphotericin
cheaper
may reduce nephrotoxicity
benefits to amphotericin lipid complex drug
taken up by macs to the site of inflamm/fungus
greatest concentrations in liver, spleen, and lung = decreaed renal accumulation/toxicity
still need to monitor renal values and hydrate patient
benefit to liposome encapsulated AmB
small size, high concentration in CSF and kidneys (good for renal asper)
fluorinated pyrimidine
flucytosine
MOA flucytosine
interferes w DNA
absorption and penetration abilities of flucytosine
good oral absorption
penetrates CSF/BBB
Flucytosine can be used to tx
cryptococcus
candidiasis
flucystosine is synergistic with
amphotercin B
combo used for CNS dz/very sick p
cutaneous SE of flucytosine reported in dogs
drug eruptions
CBC SE of flucytosine reported in cats
thrombocytopenia
flucystosine __ toxic
nephrotoxic
most common antifungals used in vet med
azoles; imidazoles (ketoconazole) and triazoles (itra, flucon, posocon, voricon)
MOA azoles
inhibit cytochrome P450 and inhibit ergosterol synthesis (disrupts cell membrane syn), can’t transport ATP = growth inhibition
***fungiSTATIC
azoles are metabolized by the
liver (cytochrome P450) = drug interactions!
azoles require __ for absorptions
acid
can use antinausea drug for SE but not a PPI/H2 bc need the acid!
ketoconazole orally should be given with
fatty meal no antacids (need acid)
penetration of ketoconazole
poor penetration of brain/eye
topical ketoconazole can be used to tx
candida, malassezia
oral can tx blasto but not asper, cryptococcus, sporothrix
SE ketoconazole
nausea vomiting anorexia hepatotoxicity cortisol suppression (old school tx for cushing's)
ketoconazole is __ toxic
hepatotoxic (ALT, AST, ALP will go up, esp if ALT over ALP) = d/c drug
oral itraconazole capsules should be given with __ meal and liquid with a __ meal
fatty meal, acidic environment
fasted
distribution/penetration of itraconazole
no CNS
minimal urine excretion
SE itraconazole
less toxic than keto same SE (nausea, vomit, inapp, hepatotoxic, cutaneous drug reaction)
spectrum of itraconazole
broad;
histo, blasto, crypto, coccidioides, aspergillus
fluconazole oral bioavailability and distribution
high oral bioavailability
water soluble = wide distribution including BRAIN/EYE
renal excretion of active drug also makes it good for fungal UTI (ie DM p)
cryptococcus in the eye/CNS drug of choice
fluconazole
fluconazole derivative that is more potent than flu and itraconazole
voriconazole
itraconazole analoge that is as good or better than flu or itra for candida, crypto, asper, blasto, histo but is very very expensive
posaconazole
too expensive for vet med, 1 vial (100ml) = $1400 :0
topical azoles
clotrimazole and enilconazole
primary treatment for nasal aspergillus
clotrimazole
SE of topical clotrimazole
irritation
erythema
aspiration pneumonia
airway obstruction (larynx swelling)
non-responsive candida cystitis and renal aspergillosis possible treatment option
clotrimazole via infusion
SE caustic
allylamine that inhibits ergosterol synthesis
terbinafine; similar to azoles but acts at different spot in ergosterol synth pathway
most common tx for dermatophytosis
terbinafine
oral bioavailability of terbinafine
good!
3 anti-fungals that have good oral bioavailability
terbinafine
fluconazole
flucytosine
SE terbinafine
V/D
hepatotoxic
pancytopenia
__ seems to have some efficacy for treating pythium
terbinafine
__ is an agricultural fungicide that inhibits RNA polymerase that may be effective against plant pathogen oomycetes
mefenoxam
seems to be good but NOT available for use in animals yet (case report of pythium being tx with itra + terbinafine + mefenoxam)
terbinafine seems to be synergistic with
azoles
lowest concentration of drgu that inhibits growth of the organism cultured in vitro (not in vivo) (NOT the concentration required to KILL the organism)
MIC; minimum inhibitory concentration
when to consider sensitivity testing for fungal dz
systemic aspergillosis
non-responsive infection
minimal financial constraints
first and second choice for blastomycosis, histoplasmosis, and systemic aspergillosis
itraconazole
amphotericin B
first and second choice for cryptococcosis of CNS
Fluconazole
itraconazole
first and second choice for coccidioidomycosis
itraconazole
fluconazole
first and second choice for nasal aspergillosis
topical clotrimazole
topical enilconazole
first and second choice for sporothrix
itraconazole
terbinafine
