Lab 1 - nematode pharmacology

Question 1

Name the “big three” antiparasitic agents for treating nematode infections.

Answer 1

Macrocyclic lactones

Benzimidazoles

Nicotinic agonists

Question 2

What is the mode of action of the macrocyclic lactones?

Answer 2

Bind glutamate-gated chloride ion channels, opening them and eventually causing paralysis in the parasite.

Question 3

Avermectins and Milbemycins belong to which major class of antiparasitic drugs?

Answer 3

Macrocyclic lactones

Question 4

List the species and/or breeds that may experience toxicity from Ivermectin.

Answer 4

Collies, when used at doses higher than for heartworm prevention.

Turtles

Question 5

Why are certain species of dog vulnerable to Ivermectin toxicity?

Answer 5

GABA-gated chloride ion channels in mammals are found in the CNS. In normal animals, the drug is pumped out of the blood-brain-barrier by permeability glycoprotein (P-gp).

Collies and some other dog breeds have a mutant P-gp that allows neurotoxicity to occur.

Question 6

List the helminths against which macrocyclic lactones have no effect.

Answer 6

Cestodes

Trematodes

Question 7

In which clade might you find glutamate-gated chloride channels?

Answer 7

Only in the protostome invertebrate phyla.

This is why you can treat mammals with Ivermectin and only see toxic effects in their parasitic nematodes.

Question 8

What is the mode of action of the benzimidazoles?

Answer 8

Binds beta-tubulin, preventing microtubule formation and treadmilling. This in turn prevents cell division.

Question 9

Why are benzimidazoles not toxic (for the most part) in mammals?

Answer 9

Benzimidazoles have a higher affinity for nematode beta tubulin than mammalian beta tubulin.

Question 10

Fenbendazole, Oxfendazole, Albendazole, and Febantel are examples of what major class of antiparasitic drug?

Answer 10

Benzimidazoles

Question 11

Which benzimidazoles can have teratogenic effects on a fetus?

Answer 11

Albendazole

Oxfendazole

Question 12

Febantel is a pro-drug (i.e. metabolized into drug components) for which two benzimidazoles?

Answer 12

Fenbendazole

Oxfendazole

Question 13

Against which other organisms does fenbendazole have activity?

Answer 13

Protozoa

Flatworms

Question 14

Against which other organisms does Albendazole have activity?

Answer 14

Protozoa

Flatworms

Question 15

What is the action of Nicotinic Agonist drugs?

Answer 15

Activates nicotinic ACh receptors, opening ion channels and causing muscle contraction, leading to paralysis in the worm.

Question 16

Levamisole, Pyrantel, and Morantel are examples of which major class of antiparasitic drug?

Answer 16

Nicotinic Agonists

Question 17

In which species is Levamisole used?

Answer 17

Ruminants

Pigs

Question 18

In which species is Pyrantel used?

Answer 18

Dog

Cat

Horse

Pig

Question 19

In which species is Morantel used?

Answer 19

Ruminant

Question 20

Against which nematode are the Nicotinic Agonists ineffective?

Answer 20

Trichuris (whip worms)

Question 21

Nicotinic Agonists may have some activity against which other helminths?

Answer 21

Cestodes in horses (?)

Question 22

Name the “three little drugs” used in treating nematode infections.

Answer 22

Emodepside

Piperazine

Dichlorvos

Question 23

What is the mode of action of Emodepside?

Answer 23

Agonist of presynaptic latrophilin receptor (which is a GPRC), which causes increased release of inhibitory neuropeptides.

The net result is paralysis

Question 24

Emodepside is used for nematode treatment in which species?

How is it administered?

Answer 24

Cats

Topical

Question 25

What are the effects of overdosing with Emodepside?

Answer 25

Tremors

Can also cause vomiting and salivation if application site is licked

Question 26

What is the mode of action of Piperazine?

Answer 26

GABA receptor agonist.

Hyperpolarizes muscles, resulting in paralysis.

Question 27

What are the primary uses of Piperazine, and in which species is it used?

Answer 27

Primarily kills ascarids.

Mostly used in pigs. Some OTC products for dogs and cats.

Question 28

What is the mode of action of Dichlorvos?

Answer 28

Organophosphate. Inhibits ACh-esterase. Causes of a buildup of ACh in the nematode.

Question 29

In which species is Dichlorvos used?

Answer 29

Only in pigs.