antihelminthics

Question 1

What is an anthelminthic?

Answer 1

kills worms (helminths)

Question 2

Parasiticide

Answer 2

Drug that kills parasites

Question 3

Pesticide

Answer 3

Drug usually used for external parasites/arthropods (Ectoparasiticide)
includes insecticides and acaricide (ticks/mites)

Question 4

Insecticide

Answer 4

kills insects

Question 5

Acaricide

Answer 5

kills ticks/mites

Question 6

3 major gorups of anthelminthics

Answer 6

1. Benzimidazoles (BZD) and pro-benzimidazoles
2. Nicotinic agonists
3. Macrocyclic Lactones (ML)

Question 7

Benzimidazoles and pro-benzimidazoles

Answer 7

Generic names in this group usually end in -azole

Fenbendazole
Albendazole
Febantel
Others: Oxibendazole, oxfendazole

Question 8

Benzimidazoles and pro-benzimidazoles mode of action

Answer 8

Prevents microtubule assembly
Interferes with cell internal structure and metabolism
Causes slow parasite death

Need to stay around for awhile to work
* Rumen and cecum act as reservoir for absorption in ruminants and horses, respectively (only 1 dose needed)
* Small animals usually need several doses

Question 9

Benzimidazoles and pro-benzimidazoles spectrum of action

Answer 9

Nematodes - primarily
* Adulticidal, larvicidal, and ovicidal activity

Trematodes and Cestodes - adulticidal ONLY IN RUMINANTS
(essentially in ruminant flukes and tapeworms)

Question 10

Benzimidazoles and pro-benzimidazoles administration

Answer 10

Oral only, not very water soluble

Question 11

Benzimidazoles and pro-benzimidazoles safety

Answer 11

Generally very safe
Exceptions: on the label, follow directions
* Albendazole: ruminants during early pregnancy (teratogenic)
* Febantel: dogs during pregnancy

Occasionally, toxicity with extra-label use in exotic species - check before use it

Question 12

Which Benzimidazoles and pro-benzimidazoles are used for which species?

Answer 12

Dogs - widely used
* Febantel, fenbendazole
* Albendazole not approved

Horses - widely used
* Fenbendazole

Ruminants - widely used
* Albendazole, fenbendazole

Pigs and poultry - widely used
* Fenbendazole

Question 13

nicotinic agonists families

Answer 13

Two families:
* Imidazothiazoles (levamisole)
* tetrahydropyrimidines (pyrantel, morantel)

Question 14

nicotonic agonists mode of action

Answer 14

They act selectively as agonists at nicotinic receptors on nematode muscle cells: depolarizing neuromuscular-blocking drugs
Contraction, and rapid spastic paralysis of worms

Question 15

nicotinic agonists administration

Answer 15

primarily oral

Question 16

nicotinic agonists spectrum of action

Answer 16

only work against adults
Lung worms adults and larval stages
Pyrantel and morantel not absorbed from the gut
* only work against worms in the lumen (adults)
* can use in puppies under 2 weeks

Question 17

nicotinic agonists safety

Answer 17

Safety margin of levamisole is lower than for other modern anthelmintics
Signs of toxicity related to the mode of action: it works in the host cells as well (block musc depolarization): salivation, tremors, ataxia, urination, defecation

Question 18

pyrantel against tapeworms in horses

Answer 18

use a double dose

Question 19

Macrocyclic Lactones

Answer 19

2 families: milbemycins and avermecins
products of soil fungus

Question 20

Macrocyclic Lactones mode of action

Answer 20

Bind to glutamate gated chloride channels leading to hyperpolarization of nerves and muscles
Multiple effects in muscles: paralysis of muscles, affects parasite reproduction
Some products have persistent activity, affected by formulation and administration route

Question 21

Macrocyclic Lactones Spectrum of action

Answer 21

Nematodes: adults, mucosal larvae, hypobiotic larvae (becuase it stays a long time, not that it actually kills them)
Arthropods: blood sucking and tissue dwelling. Varies depending on product and species

Question 22

Macrocyclic Lactones routes of administration

Answer 22

Oral
Injection
Topical, absorbed through skin

Question 23

Macrocyclic Lactones safety

Answer 23

In general, wide safety margin
Mammalian toxicity probably related to GABA synapses (neurotransmitter in CNS of vertebrates)
Macrolides generally don’t reach susceptible targets in vertebrate CNS because of the blood brain barrier
Toxicity related to CNS depression

Question 24

ivermectin in dogs

Answer 24

Macrocyclic Lactones
Approved dose OK for all dogs
Higher doses may cause problem in dogs, especially Collie type
* Do not use at higher doses in dogs Collie type breeding
* Sensitivity due to mutation affecting P-glycoprotein (part of BBB)
* Other breeds have mutation but at a very low frequency (70% in Collies, 5% in mixed breed dogs)

Other ML have higher safety margin in susceptible dogs

Question 25

Where are macrocyclic lactones used?

Answer 25

Where are they used? - Everywhere! * Horses * Cattle * Small ruminants * Dogs and cats * Many exotic animals * Humans * Fish

Question 26

Isoquinolines

Answer 26

**Praziquantel** and epsiprantel Used for **tapeworms** and some flukes in **small animals** and horses **No effect on nematodes** Only drugs approved for tapeworms in small animals Mode of action: unknown. It seems to affect permeability of calcium ions in the muscular membrane: tetanic contraction of muscles Safe and effective

Question 26

Isoquinolines

Answer 26

**Praziquantel** and epsiprantel Used for **tapeworms** and some flukes in **small animals** and horses **No effect on nematodes** Only drugs approved for tapeworms in small animals Mode of action: unknown. It seems to affect permeability of calcium ions in the muscular membrane: tetanic contraction of muscles Safe and effective

Question 27

What does Praziquantel treat?

Answer 27

tapeworms small animals

Question 28

Arsenicals

Answer 28

**Melarsomine** Used for **heartworm treatment** because nothing else works Most effective against adults Not effective against microfilariae or L3, early L4 Not for dogs in poor health (**many adverse reactions and side effects**) Mode of action unknown

Question 29

what is Melarsomine used to treat?

Answer 29

heartworms arsenical

Question 30

Emodepside

Answer 30

Cyclic octadepsipeptides Currently marketed for **cats** in US Stimulates specific neuromuscular receptor Spectrum: **only nematodes** | profender

Question 31

Clorsulon

Answer 31

Benzenesulfonamides For **bovine liver fluke (Fasciola spp.)** Sold in combination with ivermectin Inhibits fluke glycolytic enzymes

Question 32

Which of the following anthelminthics act on the neuromusc system? ivermectin febantel albendazole fenbendazole

Answer 32

ivermectin

Question 33

which can be used againt nematodes, cestodes, and trematodes in ruminants? macrocylic lactones benzimidazoles nicotinic isoquinolines

Answer 33

benzimidazoles

Question 34

Which can be used against cestodes in small animals? ivermectin fenbendazole pyrantel praziquatel

Answer 34

praziquatel

Question 35

T/F If 2 drugs have the same mechanism of action anthelminthic resistance to one means there is resistance to the other

Answer 35

true

Question 36

What is resistace?

Answer 36

**It used to work, now it doesn’t** Resistance is a **heritable characteristic** Results from **random mutation** always going on in a population * Assume little or no advantage in the absence of the drug (low frequency in population) **Drug use selects for resistant alleles** and increases their frequency in the population Resistance mechanisms vary

Question 37

What’s different about resistance in multicellular organisms?

Answer 37

SEX

Question 37

What’s different about resistance in multicellular organisms?

Answer 37

SEX

Question 38

contributing factors to anthelminthic resistance

Answer 38

Animals **eat where they defecate** Kept in **groups** Prevalent approach has been to deworm to prevent any possible problem from developing Widespread use of pour-ons in cattle **The more often the drug is used, the faster the resistance is developed** worse in **GRAZING animals**

Question 39

Refugia

Answer 39

**Pool of parasites not exposed to drug** These are parasites not exposed to the drug when you give it – not the resistant ones Goal is to **dilute resistant genes** in the parasite population: to delay anthelmintic resistance Increasing use of **targeted selective treatment** contributes to the increase of the refugia **Avoids exposing all parasites in animals to a drug** treatment Examples: * Herd of horses: only deworm individuals with high egg counts * Flock of sheep: only deworm anemic ones