Antifungals

Question 1

tell me some basics about fungi

Answer 1

eukaryotic, many dimorphic, mechanism injury usually cell disruption and death

Question 2

3 basic grouping software body systems fungi affect

Answer 2

systemic, superficial, or eye

Question 3

what route are antigun gals usually delivered and why

Answer 3

topical due to adverse effects

Question 4

give 4 anti fungal targets and the class that target each

Answer 4

cell wall: echinocandins
cell membrane: polyenes, azoles, allylamines
nucleic acid synthesis: flucytosine
(not red) nuclear division: griseofulvin

Question 5

give 3 principles of anti fungal therapy

Answer 5

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

Question 6

mechanism of action of amphotericin B (a polyene)

Answer 6

bind to ergosterol in cell membrane, create channels in membrane, alter permeability to allow leakage of contents

Question 7

what is a macrocyclic polyene

Answer 7

have a ring with a lot of atoms

Question 8

give key pharmacokinetics of amphotericin

Answer 8

concentration-dependent, fungicidal, persistent anti fungal effect which allows intermittent treatment, minimal GI absorption so needs IV or local administration

Question 9

Amphotericin B has action against Histoplasma capsulatum, Cryptococcus neoformans, Coccidioides immitis, Blastomyces dermatitidis, Candida spp. and Aspergillus which are all organisms that cause _____ mycosis

Answer 9

systemic

Question 10

amphotericin has a dose-related adverse effect of

Answer 10

nephrotoxicity: toxic to renal epithelial cells, esp. id distal convoluted tubule, renal vasoconstriction (ischemia, decreased GFR), worsened by sodium depletion

Question 11

different formulations of amphotericin B require

Answer 11

different dosing regimens (and unfortunately the only affordable one is the colloidal dispersion which is nephrotoxic)

Question 12

the topical polyene natamycin is treatment of choice for

Answer 12

Fusarium keratomycosis in horses

Question 13

how should the polyene natamycin NOT be delivered

Answer 13

systemically bc it is expensive and toxic. topical

Question 14

the polyene nystatin should NOT be administered…

Answer 14

systemically. it is toxic. give topically

Question 15

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

Answer 15

PO! oral and intestinal candidiasis is treated “topically”

Question 16

MOA for -azoles

Answer 16

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)

Question 17

which has fewer adverse effects and less effect on mammalian sterol synthesis, triazoles or imidazoles

Answer 17

triazoles safer. can use systemically. imidazole only topical.

Question 18

potency, drug interactions, and toxicity or -azoles are all related to what

Answer 18

affinity or specificity of P450

Question 19

drug interactions with -azoles are caused by what

Answer 19

inhibition of P-glycoprotein efflux pumps

Question 20

give 5 main adverse effects of ketoconazole

Answer 20

inhibit mammalian P450, so drug interactions; inhibit testosterone and cortisol synthesis, hepatotoxicity, anorexia and vomiting, teratogenic so don’t use in pregnant animals

Question 21

ketoconazole is soluble in what? what is the implication

Answer 21

soluble in acid, so best absorption GI after a meal

Question 22

is ketoconazole protein bound? why does this matter

Answer 22

over 98% protein bound, so does not penetrate CSF, ocular fluid, or seminal fluid

Question 23

name the 2 important triazoles

Answer 23

itraconazole and fluconazole

Question 24

name the 3 important imidazoles

Answer 24

ketoconazole, clotrimazole, miconazole

Question 25

main indication for itraconazole

Answer 25

first line tx for non life threatening systemic mycoses that don’t involve the CNS

Question 26

is itraconazole specific for fungal P450

Answer 26

yes, it is a cytochrome P450 inhibitor, but very specific for fungal P450

Question 27

when should you reduce dose of fluconazole

Answer 27

renal failure patients

Question 28

describe activity of fluconazole: distribution, what it crosses

Answer 28

widely distributed through body, crosses BBB, so is used as firstling treatment for systemic mycoses with ocular or CNS involvement

Question 29

miconazole is usually used for what 2 things

Answer 29

treat keratomycosis and dermatophysis topically; combine with chlorhex for Malassezia treatment topically

Question 30

clotrimazole is usually combined and used to treat what

Answer 30

combine with steroid and antibiotic treatment of otitis in dogs, give topical only

Question 31

enilconazole is given how? to treat what?

Answer 31

topical. very effective against dermatophytes: topical treatment of dermatophytes in dogs and horses, and fungal sinusitis in horses

Question 32

MOA of terbinafine, an allylamine? include if fungicidal or fungistatic

Answer 32

fungicidal. inhibit ergosterol synthesis and is very selective for fungal P450 enzyme (so don’t have P450-assoc adverse interactions)

Question 33

what is terbinafine used to treat

Answer 33

dermatophytes and Malassezia species

Question 34

describe MOA of flucytosine, including how it is taken into cell

Answer 34

enters cell by cytosine permeate, converted into 5-fluorouracil, then incorporated into RNA disrupting protein synthesis or converted into 5FdUMP which inhibits DNA synthesis

Question 35

in flucytosine, changes in fungal permeability or deaminase activity lead to what

Answer 35

resistance

Question 36

use of flucytosine

Answer 36

adjunct therapy with amphotericin B for candidiasis or cryptococcus. combo allows decreased amphotericin B dose. amphotericin B increases fungal membrane permeability to flucytosine

Question 37

give adverse effects of Na or K iodide

Answer 37

iodize, abortion/infertility (careful if pregnant)

Question 38

what is lime sulfur (calcium polysulfide) used for dermatophysis topical

Answer 38

dermatophysis topical

Question 39

what are two topical, whole-body treatments for dermatophysis

Answer 39

chhlorhex and miconazole since or enilconazole rinse

Question 40

chlorine dioxide fas can be used to treat what in horses

Answer 40

white line disease