Lecture 6-7 - Anti-fungals (Cooke)

Question 1

natural (derived from other fungi) anti-fungal drugs

Answer 1

amphotericin B

griseofulvin

Question 2

synthetic anti-fungal drugs

Answer 2

azoles
allylamines
flucytosine

(only going over most commons)

Question 3

derived from Penicillium mold and MOA disrupts mitosis

Answer 3

griseofulvin

Question 4

topical griseofulvin is old treatment for

Answer 4

dermatophytosis (have better drugs with less SE now)

Question 5

if giving griseofulvin orally should it be given with or w/o food

Answer 5

with a fatty meal

*azoles are used more commonly now

Question 6

SE of griseofulvin

Answer 6

BM Suppression
teratogenic (not safe for pregos)
V/D
anorexia

Question 7

derived from streptomyces

Answer 7

amphotericin B

Question 8

MOA amphotericin B

Answer 8

binds sterols (cholesterols specific to fungi wall)

Question 9

route of admin for amphotericin B

Answer 9

almost always IV, however there is a SC protocol for use PRN

Question 10

amphotericin B oral absorption

Answer 10

POOR

Question 11

Amphotericin B is __ toxic

Answer 11

nephrotoxic, must monitor renal values and give IVF

liposome form can reduce toxicity

Question 12

CS of acute amphotericin B toxicity

Answer 12

vomiting
myalgia
fever
anaphylaxis

this is why give IV injection SLOWLY and D/C if there are any SE

Question 13

amphotericin B spectrum

Answer 13

most fungi, some resistance is emerging

Question 14

amphotericin B has poor penetration of

Answer 14

bone, brain/CSF, eye

Question 15

what can you dilute amphotericin with

Answer 15

sterile H2O or D5W, NOT saline bc will precipitate

should always check renal values before, give IVF before and after administered

Question 16

2 reasons would use SC route for amphotericin

Answer 16

cheaper

may reduce nephrotoxicity

Question 17

benefits to amphotericin lipid complex drug

Answer 17

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

Question 18

benefit to liposome encapsulated AmB

Answer 18

small size, high concentration in CSF and kidneys (good for renal asper)

Question 19

fluorinated pyrimidine

Answer 19

flucytosine

Question 20

MOA flucytosine

Answer 20

interferes w DNA

Question 21

absorption and penetration abilities of flucytosine

Answer 21

good oral absorption

penetrates CSF/BBB

Question 22

Flucytosine can be used to tx

Answer 22

cryptococcus

candidiasis

Question 23

flucystosine is synergistic with

Answer 23

amphotercin B

combo used for CNS dz/very sick p

Question 24

cutaneous SE of flucytosine reported in dogs

Answer 24

drug eruptions

Question 25

CBC SE of flucytosine reported in cats

Answer 25

thrombocytopenia

Question 26

flucystosine __ toxic

Answer 26

nephrotoxic

Question 27

most common antifungals used in vet med

Answer 27

azoles; imidazoles (ketoconazole) and triazoles (itra, flucon, posocon, voricon)

Question 28

MOA azoles

Answer 28

inhibit cytochrome P450 and inhibit ergosterol synthesis (disrupts cell membrane syn), can't transport ATP = growth inhibition ***fungiSTATIC

Question 29

azoles are metabolized by the

Answer 29

liver (cytochrome P450) = drug interactions!

Question 30

azoles require __ for absorptions

Answer 30

acid can use antinausea drug for SE but not a PPI/H2 bc need the acid!

Question 31

ketoconazole orally should be given with

Answer 31

``` fatty meal no antacids (need acid) ```

Question 32

penetration of ketoconazole

Answer 32

poor penetration of brain/eye

Question 33

topical ketoconazole can be used to tx

Answer 33

candida, malassezia oral can tx blasto but not asper, cryptococcus, sporothrix

Question 34

SE ketoconazole

Answer 34

``` nausea vomiting anorexia hepatotoxicity cortisol suppression (old school tx for cushing's) ```

Question 35

ketoconazole is __ toxic

Answer 35

hepatotoxic (ALT, AST, ALP will go up, esp if ALT over ALP) = d/c drug

Question 36

oral itraconazole capsules should be given with __ meal and liquid with a __ meal

Answer 36

fatty meal, acidic environment fasted

Question 37

distribution/penetration of itraconazole

Answer 37

no CNS | minimal urine excretion

Question 38

SE itraconazole

Answer 38

``` less toxic than keto same SE (nausea, vomit, inapp, hepatotoxic, cutaneous drug reaction) ```

Question 39

spectrum of itraconazole

Answer 39

broad; | histo, blasto, crypto, coccidioides, aspergillus

Question 40

fluconazole oral bioavailability and distribution

Answer 40

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)

Question 41

cryptococcus in the eye/CNS drug of choice

Answer 41

fluconazole

Question 42

fluconazole derivative that is more potent than flu and itraconazole

Answer 42

voriconazole

Question 43

itraconazole analoge that is as good or better than flu or itra for candida, crypto, asper, blasto, histo but is very very expensive

Answer 43

posaconazole too expensive for vet med, 1 vial (100ml) = $1400 :0

Question 44

topical azoles

Answer 44

clotrimazole and enilconazole

Question 45

primary treatment for nasal aspergillus

Answer 45

clotrimazole

Question 46

SE of topical clotrimazole

Answer 46

irritation erythema aspiration pneumonia airway obstruction (larynx swelling)

Question 47

non-responsive candida cystitis and renal aspergillosis possible treatment option

Answer 47

clotrimazole via infusion | SE caustic

Question 48

allylamine that inhibits ergosterol synthesis

Answer 48

terbinafine; similar to azoles but acts at different spot in ergosterol synth pathway

Question 49

most common tx for dermatophytosis

Answer 49

terbinafine

Question 50

oral bioavailability of terbinafine

Answer 50

good!

Question 51

3 anti-fungals that have good oral bioavailability

Answer 51

terbinafine fluconazole flucytosine

Question 52

SE terbinafine

Answer 52

V/D hepatotoxic pancytopenia

Question 53

__ seems to have some efficacy for treating pythium

Answer 53

terbinafine

Question 54

__ is an agricultural fungicide that inhibits RNA polymerase that may be effective against plant pathogen oomycetes

Answer 54

mefenoxam seems to be good but NOT available for use in animals yet (case report of pythium being tx with itra + terbinafine + mefenoxam)

Question 55

terbinafine seems to be synergistic with

Answer 55

azoles

Question 56

lowest concentration of drgu that inhibits growth of the organism cultured in vitro (not in vivo) (NOT the concentration required to KILL the organism)

Answer 56

MIC; minimum inhibitory concentration

Question 57

when to consider sensitivity testing for fungal dz

Answer 57

systemic aspergillosis non-responsive infection minimal financial constraints

Question 58

first and second choice for blastomycosis, histoplasmosis, and systemic aspergillosis

Answer 58

itraconazole | amphotericin B

Question 59

first and second choice for cryptococcosis of CNS

Answer 59

Fluconazole | itraconazole

Question 60

first and second choice for coccidioidomycosis

Answer 60

itraconazole | fluconazole

Question 61

first and second choice for nasal aspergillosis

Answer 61

topical clotrimazole | topical enilconazole

Question 62

first and second choice for sporothrix

Answer 62

itraconazole | terbinafine