Antiparasitic Pharmacology

Question 1

List the 3 categories of parasites targeted by antiparasitics

Answer 1

endoparasites: nematode/cestode/trematode

ectoparasite: insect and ascarids

endectocides

Question 2

Compare a drug and a pesticide

Answer 2

Drugs have DIN numbers and can be used extralabelly

Pesticides have a PcP registration number and cannot be used extralabelly (controlled under the Pest control Product Act)

Question 3

List 3 categories of antiparasitics that target nematodes

Answer 3

imidazothiazoles/tetrahydropyrimidines

benzimidazole

Question 4

Give 1 example of a imidazothiazole

Answer 4

levamisole

Question 5

Give 1 example of a tetrahydropyrimidine

Answer 5

pyrantel

Question 6

What is the mechanism of imidazothiazoles and tetrahydropyrimidines

Answer 6

Nicotinic receptor agonists

AchE inhibitors

result in spastic paralysis of nematodes

concentration dependent

Question 7

How is levamisole administered

Answer 7

parental
PO
topical

Question 8

What is levamisole effective against? How is it commonly used/

Answer 8

mature and larvae of nematodes (ruminant endoparasites)

not effective against arrested larvae

used for ruminaants mainly

at a low dose it is an appetite stimulate

Question 9

What animal is levamisole not used for

Answer 9

horses

narrow therapeutic index

Question 10

compare the consequences of nicotinic and muscarinic overstimulation

Answer 10

Nicotinic - excess SNS
- muscle tremor
- tachycardia
- mydriasis

Muscarinic - excess PSNS (DUMBBELLS)
- diarrhea
- urination
- miosis
- bradycardia
- bronchorrhea
- emesis
- lacarimation
- lethargy
- salivation

Question 11

Explain how the pharmacokinetics of pyrantel are related to its efficacy and safety margins

Answer 11

It has poor absorbtion in the GI

It acts on worms IN the GI but has poor efficacy for worms in tissue

good safety profile because it isn’t well absorbed

Question 12

What is the brand name of pyrantel?

Answer 12

strongid

Question 13

What is the mechanism of action of benzimidazoles

Answer 13

tubulin/microtubule disruption
- it has a higher affinity for nematode microtubules (vs mammalian)

Question 14

What are the pharmocokinetics of benzimidazoles

Answer 14

Absorb:
- water insoluble therefore it is poorly absorbed in the GI

Distribute:
- Stays in GI
- long transit time in the GI
- it is time dependent!

Metabolism
- it is metabolized to sulfoxide metabolites (oxfendazole) which are active and absorbed and sulfone metabolites which are less active but still absorbed better than fendbenzole

Question 15

Give 1 example of a benzimidazole

Answer 15

fendbendazole

Question 16

What is fendbenzadole mainly used for

Answer 16

ascarid treatment in horses because it kills the worms slowly therefore not causing impaction colic

Question 17

What antiparasitics are used to control tapeworms? Provide an example

Answer 17

anti-cestode drugs
- praziquantil

Question 18

What is the mechanism of anti-cestode drugs

Answer 18

They alter Ca homeostasis causing spastic paralysis

Question 19

How are anti-cestode drugs administered and what are their notable pharmacokinetic properties

Answer 19

Po
topical
IM
SC

well absorbed in the GI
poor PO bioavailability due to high first pass effect

Question 20

What is praziquantel used for mainly

Answer 20

E. locularis in dogs (which is zoonotic)

Question 21

What type of anti-parasitics are used to treat flukes

Answer 21

anti trematode drugs

Question 22

What type of antiparasitics are used to treat coccidia

Answer 22

coccidiostats

Question 23

List 3 types of antiparasitics that target ectoparasites?

Answer 23

pyrethrins/pyrethroids

isoxazolines

organophosphates and carbamates

Question 24

What is the mechanism of action of pyrethrins/pyrethroids?

Answer 24

volage gated NA channels

causes Na influx into the cell that stimulated Ca release = NT release from the presynaptic neuron

Question 25

What are pyrethroids

Answer 25

synthetic pyrethrins

Question 26

Can you use K9 Advantix extralabelly? What is a primary contraindication for its use? What is its active ingredient?

Answer 26

No extralabel use = pesticide Cats = toxic pyrethrin

Question 27

What animal is most susceptible to pyrethrin/pyrethroid toxicosis and why?

Answer 27

Cats because they are poor at glucuronidation Can be toxic to dogs but it would need a much higher dose

Question 28

What are the 3 mainfestations of pyrethrin/pyrethroid toxicity

Answer 28

mild toxic = no treatment needed - hypersalivation - twitching - hyperesthesia allergy - topical - pruritis/alopecia/urticaria/hyperemia severe toxic - v+ - tremor/ataxia - blind/seizure - death

Question 29

What is the mechanism of action of isoxazolines

Answer 29

GABA gated Cl channel antagonist

Question 30

How is isoxazolines administered? What are they used for?

Answer 30

PO flea tick demodex sarcoptes

Question 31

What is the primary adverse effect of isoxazolines? What animals are they contraindicated for?

Answer 31

seizures not for animals with a history of seizure disorders - epileptic

Question 32

List 3 types of isoxazolines

Answer 32

surolaner fluralaner alfoxolaners

Question 33

What animals are most susceptible to organophosphate and carbamate toxicity?

Answer 33

cats fish birds

Question 34

What animals are most prone to organophosphate and carbamate toxicity?

Answer 34

dogs - most exposed

Question 35

How are organophosphates and carbamates used in ectoparasite prevention?

Answer 35

flea/tick collars not used anymore because of toxicity

Question 36

What is the mechanism of action of organophosphates and carbamates?

Answer 36

inhibit AchE organophosphates = irreversible inhibition carbamates = reversible inhibition

Question 37

What are the clinical effects of organophosphate and carbamate toxicity

Answer 37

muscarinic overstimulation (DUMBBELLS) nicotinic overstimulation (SNS) CNS effects death due to respiratory failure - excess respiratory secretions - bronchiolar contraction - intercostal muscle paralysis

Question 38

What is intermediate syndrome? What animals are most prone to this?

Answer 38

chronic exposure or exposure to highly lipophilic organophosphates/carbamates - along with the development of Ach tolerance (downregulation of muscarinic receptors) - result in overstimulation of nicotinic receptors common in cats

Question 39

What are the clinical signs of organophosphate and carbamate toxicity in large animals

Answer 39

Similar to small animals bloat delayed polyneuropathy (weakness/ataxia)

Question 40

Provide 2 examples of endectocides

Answer 40

macrolytic lactones milbemycin

Question 41

What is one type of macrolytic lactone? What is an example of a drug in that class?

Answer 41

avermectin ex ivermectin

Question 42

Where do avermectin antiparasitics come from? What are their mechanism of action

Answer 42

from Strep avermectinius They bind ligand gated Cl channels and increase their activity causing flaccid paralysis They target the GABA receptors on the somatic muscles of insects

Question 43

What are the pharmacokinetics of ivermectin? How is it administered?

Answer 43

it is lipophilic and potent PO/topical/parenteral can treat endo and ecto parasites

Question 44

Where does milbemycin come from? What is the mechanism of action of milbemycin

Answer 44

from Strep cyaneogriseus (same as avermectins) They bind ligand gated Cl channels and increase their activity causing flaccid paralysis They target the GABA receptors on the somatic muscles of insects

Question 45

What are the pharmacokinetics of milbemycin?

Answer 45

Absorb - good absorption in GI Distribution - Good distribution in tissues (high Vd) - distributes to fat (lipophilic) Metabolism - slow - enterohepatic recycling Excretion - bile = long duration of action

Question 46

Give 1 example of a milbemycin antiparasitic

Answer 46

moxidectin

Question 47

Why might treatment failure occur when using antiparasitics

Answer 47

lots of resistance! - it develops very fast it may be poorly integrated into management protocols poor understanding of the drug/disease (given at the wrong time/route)

Question 48

List 5 common sites of action that antiparasitics commonly act on

Answer 48

nicotinic receptors/AchE voltage gated Na channels tubulin/microtubules ligand gated Cl channels Ca2+

Question 49

What are nictoinic receptors?

Answer 49

non selective cation channels (K/Na/Ca)

Question 50

Where are nicotinic receptors located in mammals, nematodes, and insects respectively?

Answer 50

mammals = CNS/muscle/SNS and PSNS ganglia nematode = neuron/muscle insect = CNS

Question 51

List 2 natural sources of nicotinic receptor antagonists

Answer 51

alpha neurotoxins from some snakes - neuromuscular blocker leading to asphyxiation and death curare = plant extract - Ach receptor antagonist

Question 52

List the main disease affecting nicotinic receptors? How can you test for it?

Answer 52

myasthenia gravis autoimmune destruction of Ach receptors can cause megaesophagus Test: tensilon test - administer edrophonium (short acting AchE inhibitor) - if given to an animal with myesthenia gravis it will temporarily regain strength

Question 53

What is the mechanism of voltage gated Na channels and their antiparasitic function

Answer 53

excess Na causes over-depolarization and cell death

Question 54

How do tubulin and microtubules impact antiparasitic function

Answer 54

they form the cell cytoskeleton = important

Question 55

How do ligand gated Cl channels impact antiparasitic function

Answer 55

They act on GABA and glutamate channels The GABAa channel is a Cl channel - activation causes hyperpolarization