Parasiticides TY

Question 1

Why do parasiticides that affect chloride channels do not affect mammals?

Answer 1

Mammals do not have glutamate gated chloride channels

Do not cross the BBB

Question 2

What are the two types of post synaptic cholinergic receptors?

Answer 2

Muscarinic and nicotinic

Question 3

What is the MOA of organophosphates?

Answer 3

Irreversible inhibition of acetylcholinesterase (enzyme that breaks down acetylcholine in the neural synapse)

Mimics acetylcholine and inactivates enzyme at post-synaptic membrane

Question 4

What are the signs of cholinesterase toxicity?

Answer 4

Acute: Rapid muscarinic signs, SLUD, Bradycardia, miosis; Nicotinic signs: Muscle stiffness, tremors, weakness; CNS signs; Death

Delayed: Not assoc w/ ACHe inhibition; OP ester induced delayed neuropathy; Onset 7-21 d

Chronic: like acute, rarely causes death

Question 5

What are some examples of cholinesterase inhibitors?

Answer 5

Carbamates- reversible inhibition

Organophosphates- IRREVERSIBLE inhibition

Question 6

What are the treatments for cholinesterase toxicity?

Answer 6

Atropine (muscarinic effects only)

2-PAM (prolidoxime)- frees AchE enzyme (OPP only)

Question 7

What class of drug does fipronil belong to and what is its MOA?

Answer 7

Phenylpyrazole;
GABA receptor antagonist (γ-aminobutyric acid)
Interferes with the passage of chloride in GABA regulated channels

Question 8

What species has a toxic reaction to fipronil?

Answer 8

Rabbits

Question 9

What ticks have shown resistance to fipronil?

Answer 9

5 spp of cattle ticks

Question 10

What is the MOA of metaflumazone?

Answer 10

Semicarbazone (Promeris)

Blocks influx of Na+ required to propagate a nerve impulse along axon/dendrite of neuron

Question 11

What is the MOA of amitraz?

Answer 11

Formamidine (Promeris, Preventic, Mitaban)
MAO-inhibitor
• a2 adrenergic activity, inhibits PG synthesis
• Can increase in plasma glucose by inhibiting insulin release via its alpha2-adrenergic activity

Question 12

What are the side effects/precautions to consider with amitraz?

Answer 12

Transient sedation (~24 h, up to 72h), pruritus, hypothermia, bradycardia, hypotension, hyperglycemia (DIABETICS), ataxia, VD, edema, erythema and rarely seizures have been reported; toy breeds may be more susceptible – use ½ dose

Drug is unstable and rapidly oxidizes on exposure to air and sunlight; more toxic

Do not use with deep pyodermas with drainage tracts

Question 13

What species have toxic reaction to amitraz?

Answer 13

Cats and rabbits

Question 14

How do you treat amitraz toxicity?

Answer 14

Yohimbine or atipamezole (a2 antagonists)

Counteracts a2 adrenergic activity

Question 15

What vehicle in amitraz is thought to contribute to its toxicity?

Answer 15

Xylene

Question 16

What medications are contraindicated with amitraz?

Answer 16

Other MAO inhibitors (selegiline)

TCA (amitriptyline, clomipramine)

Question 17

What are the 2 classes of insect growth regulators?

Answer 17

Juvenile hormone analogs

Chitin synthesis inhibitors

Question 18

List 3 examples of juvenile hormone analogs.

Answer 18

Pyriproxifen
Methoprene
Fenoxycarb

Question 19

What is the MOA of juvenile hormone analogs?

Answer 19

JHesterase normally breaks down JH –> molting
-Mimics JH so that molting does not progress
Also causes fleas to produce infertile eggs

Question 20

List 2 examples of chitin synthesis inhibitors.

Answer 20

Cyromazine

Lufenuron

Question 21

What is the MOA of cyromazine?

Answer 21

Does not technically inhibit chitin; increases stiffness of exoskeleton so that it can’t expand

Question 22

What is a draw back of lufenuron as a monotherapy?

Answer 22

Does not kill adult fleas

Question 23

Lufenuron has been proposed as a potential treatment/prevetative for what parasite?

Answer 23

Encephaltiozoon cuniculi in rabbits

Question 24

What are the AE of lufenuron?

Answer 24

VD, lethargy/depression, pruritus/urticaria, dyspnea, anorexia, reddened skin

Question 25

List 3 examples of neonicotinoids.

Answer 25

Imidacloprid Dinotefuran Nitenpyram

Question 26

What is the MOA of neonicotinoids?

Answer 26

Binds nicotinic AchR on postsynaptic neuron, blocks impulses > CNS impairment death

Question 27

What is the MOA specifically of dinotefuran?

Answer 27

Permanently binds to nicotinic AchR in the nerve synapse; Causes continuous nerve stimulation Kills by contact; ingestion by flea is not necessary

Question 28

How is nitenpyram excreted?

Answer 28

Unchanged in urine

Question 29

What are pyrethrins? Pyrethroids?

Answer 29

Pyrethrins- Naturally derived volatile oil extract of the chrysanthemum flower; contact poison Pyrethroids- synthetic, includes permethrin and deltamethrin

Question 30

What is the MOA of pyrethrins/pyrethroids?

Answer 30

Blocks Na+ channel in arthropod nerve cell membranes, causing paralysis and death

Question 31

What is commonly added to pyrethrins to increase parasitcide effect?

Answer 31

+ IGR: methoprene, pyriproxyfen + Piperonyl butoxide inhibits insect metabolic enzymes (P450 system) allowing a lower dose of primary insecticide to be used limiting metabolism of pyrethrins in insects

Question 32

What species have toxic reactions to pyrethrins?

Answer 32

Bees and fish

Question 33

Why are pyrethroids used over pyrethrins?

Answer 33

More stable and potent

Question 34

Which species has a toxic reaction to permethrin?

Answer 34

Cats

Question 35

Whicy pyrethroid has been reported to kill sandfly vectors with leishmania?

Answer 35

Deltamethrin (collar)

Question 36

What are the classes of macrocyclic lactones?

Answer 36

Avermectins: ivermectin, doramectin, selamectin Milbemycins: milbemycin, moxidectin

Question 37

What is the MOA of macrocyclic lactones?

Answer 37

GABA Cl- channel agonist | Enhances GABA release at pre-synaptic neurons

Question 38

What anatomical locations are p-glycoproteins located?

Answer 38

``` Apical intestinal epithelium Brain capillary endothelia Biliary canalicular cells Renal proximal tubular epithelia Placenta, testes ```

Question 39

What gene encodes P-glycoprotein?

Answer 39

ATP-Binding Cassette subfamily 1 (ABCB1) | formerly MDR1

Question 40

What mutation is well known in various herding breeds which causes p-glycoprotein issues?

Answer 40

Nt230 (del4) mutation

Question 41

What samples can be submitted to look for this mutation?

Answer 41

EDTA blood or check swab

Question 42

List the dog breeds have been reported to have predisposition to this mutation.

Answer 42

50% of Aussies are affected, 75% of Collies Shetland sheepdog, silken windhound, longhaired whippet, GSD, border collie, Old English sheepdog, English shepherd, McNab, WHWT, Samoyed

Question 43

What other medications can dogs with this mutation be sensitive to?

Answer 43

Other macrocyclic lactones (selamectin, milbemycin, moxidectin) Loperamide, CsA, digoxin, vinca alkaloids, doxorubicin

Question 44

What % of ivermectin is absorbed by ruminants?

Answer 44

25-33% (compared to 95% by simple stomachs) due to rumen inactivation

Question 45

What species should ivermectin be avoided?

Answer 45

Chelonians (turtiles) Indigo snakes Skinks

Question 46

What allergic reaction to ivermectin can be seen in horses?

Answer 46

Swelling/pruritus at ventral mid-line 24 hours after administration Reaction of dead Onchocerca microfilaria

Question 47

What species of birds can have adverse reactions to ivermectin?

Answer 47

Orange-cheeked waxbill, Finches, Budgerigars

Question 48

What medications are contraindicated with ivermectin?

Answer 48

Benzodiazepines, ketamine (reptiles), spinosad, ketoconazole, cyclosporine, erythromycin, spironolactone

Question 49

What are alternative treatments for dogs with ABCB1 mutation for treating demodex?

Answer 49

Isoxazolines! | Milbemycin, moxidectin

Question 50

What is the MOA of spinosad and spinetoram?

Answer 50

Nicotinic acetylcholine D-alpha R agonist causing involuntary muscle contractions and tremors Also opens chloride channels similarly to other macrocyclic lactones

Question 51

What two macrocyclic lactones are present in spinosad?

Answer 51

Spinosyn A and D

Question 52

Which tick is spinosad effective against?

Answer 52

Rhipicephalus sanguineous (Brown Dog Tick)

Question 53

How is indoxacarb activated?

Answer 53

Pro-insecticide-requires bio-activation Minimal mammalian vs rapid decarbomethoxylation by insects Rapid conversion of indoxacarb to N-decarbomethoxylated derivative (esterase and amidase activity) 40x potency of indoxacarb;

Question 54

What is the MOA of indoxacarb?

Answer 54

Block Na channels in nervous system of insects: mild tremors, feeding cessation, death in hours

Question 55

What are some agents that can be used as repellants?

Answer 55

Pyrethrin/permethrin, citronella, diethyltoluamide (DEET), ethohexadiol, dimethyl phthalate, butoxypropylene glycol, MGK-264, amitraz, Avon SkinSoSoft bath oil (fragrance is active ing)

Question 56

What is rotenone and what is its MOA?

Answer 56

Natural organic cmpd from root of Derris plant MOA: Inhibitor of mitochondrial respiratory enzymes Rinse or a shampoo for dogs/cats TOXIC TO FISH, SWINE: V/D, GI, coma TOXIC TO SNAKES

Question 57

What is the MOA of isoxazolines?

Answer 57

Inhibits specific binding of the γ-aminobutyric acid (GABA) receptor channel blocker Inhibits uptake of chloride ions, leads to excess neuronal stimulation and death