Anthelmintics

Question 1

What are the 5 main classes of anthelmintics?

Answer 1

Group 1 - Benzimidazoles
Group 2 - Levamisoles
Group 3 - Macrocyclic lactones
Group 4 - Amino acetonitrile derivatives
Group 5 - Multi-actives

Question 2

Which group is aka ‘white drenches’?

Answer 2

Benzimidazoles

Question 3

Which group is aka ‘yellow drenches’?

Answer 3

Levamisoles

Question 4

Which group is aka ‘clear drenches’?

Answer 4

Macrocyclic lactones

Question 5

Which group is aka ‘orange drenches’?

Answer 5

Amino acetonitrile derivatives

Question 6

Which group is aka ‘purple drenches’?

Answer 6

Multi-actives

Question 7

What is the primary action of benzimidazoles?

Answer 7

Bind tubulin to prevent microtubule formation, starves the parasite, killing it.
Acts for 6-24hrs.

Question 8

What are other actions of benzimidazole?

Answer 8

1. Inhibits mitochondrual fumarate reductase
2. Reduces glucose transport
3. Uncoupling of oxidative phosphorylation

Question 9

What is the spectrum of activity of benzimidazoles?

Answer 9

Broad spectrum. Effective against all 3 types of helminth, larvae and eggs.

Question 10

Are there any side effects to benzimidazoles?

Answer 10

Well tolerated, characteristically free of side effects.

Question 11

Describe the pharmacokinetics of benzimidazoles

Answer 11

• Oral administration
• Limited absorption from GIT (<1% oral dose in plasma)
• Efficacy increased if gut transit time decreased

Question 12

Describe the mechanism of action of the levamisoles

Answer 12

• Ganglion stimulant, nicotinic agonist
• Paralyses helminth by sustained muscle contraction, loses ability to hold onto site in body, passed in faeces, coughing

Question 13

Are there any side effects associated with levamisoles?

Answer 13

• Reflect nicotinic stimulation of animal

- Safety margin, 4-12 x therapeutic dose

Question 14

What is the spectrum of activity of levamisoles?

Answer 14

Nematodes.

Question 15

Describe the pharmacokinetics of the levamisoles

Answer 15

• Highly water soluble and is absorbed and excreted rapidly

- >24hrs, <1% initial dose left in tissues

Question 16

Describe the mechanism of action of the macrocyclic lactones

Answer 16

• Stimulate glutamate-gated chloride channels in nerve and muscle cells
• Cl- influx, hyperpolaristation of post-synaptic cell, interfering with neurotransmission
• Results in flaccid paralysis

Question 17

What is the spectrum of activity of macrocyclic lactones?

Answer 17

Nematodes and ectoparasites

Question 18

Describe the pharmacokinetics of macrocyclic lactones

Answer 18

Given topically, v lipid soluble, long half life

Question 19

Are there any side effects associated with macrocyclic lactones?

Answer 19

• Generally safe and well tolerated

- Exceptions are in mdr 1 deficient animals, drug enters CNS so are susceptible to effects

Question 20

What is the nature of the selective toxicity of macrocyclic lactones?

Answer 20

Mammalian glutamate receptors are in CNS. ML lipid soluble so can cross into CNS. P-glycoprotein pump extrudes drug immediately from CNS, stopping drug accumulating and having effect on host.

Question 21

Give an example of a drug in the amino acetonitrile derivative group

Answer 21

Monepantel

Question 22

What is the mechanism of action of monepantel?

Answer 22

Targets nematode specific subunit of nicotinic ACh receptor

Question 23

Are there any side effects associated with monepantel?

Answer 23

None reported

Question 24

What is the spectrum of activity of monepantel?

Answer 24

Nematodes

Question 25

Describe the pharmacokinetics of monepantel

Answer 25

Readily absorbed and oxidised to a sulfone metabolite which is excreted in urine and bile.

Question 26

Name 4 other anthelmintic classes

Answer 26

Praziquantel Salicylanides Clorsulon Cyclooctadepsipeptides

Question 27

Give an example of drug belonging to the multi-actives group

Answer 27

Derquantel

Question 28

What is the mechanism of action of derquantel?

Answer 28

Nicotinic antagonist

Question 29

What is the spectrum of activity of derquantel?

Answer 29

Sheep nematodes

Question 30

Are there any safety issues associated with the use of derquantel?

Answer 30

- 4.5 x therapeutic dose causes dullness, depression, incoordination, weakness, decreased GI motility, abnormal breathing pattern, recumbancy, death

Question 31

Describe the mechanism of action of praziquantel

Answer 31

- Tetanic contraction of parasite musculature - Rapid vacuolisation of syncitial tegument - Releases intracellular Ca, muscle contraction, water drawn in, parasite ruptures and bursts

Question 32

What is the spectrum of activity of praziquantel?

Answer 32

Cestodes and trematodes

Question 33

Describe the pharmacokinetics of praziquantel

Answer 33

Widely absorbed and distributed

Question 34

Describe the mechanism of action of the salicyclanides

Answer 34

- Creates proton ionophore | - Influx of H+, decrease pH, uncoupling of oxidative phosphorylation

Question 35

What is the spectrum of activity of the salicyclanides?

Answer 35

Trematodes

Question 36

Describe the pharmacokinetics of salicyclanides

Answer 36

- Readily absorbed from GIT | - Highly bound by plasma proteins

Question 37

Are there any risks associated with salicylanides?

Answer 37

No direct effect on mammalian cells

Question 38

Describe the mechanism of action of clorsulon

Answer 38

- Inhibits 3-phosphoglycerate kinase and phosphoglyceromutase - Blocks glycolytic pathway

Question 39

What is the spectrum of activity of clorsulon?

Answer 39

Adult F. hepatica

Question 40

Describe the mechanism of action of the cylclooctadepsipeptides

Answer 40

- Inhibits release of ACh from pre-synaptic neurone | - Flaccid paralysis and death

Question 41

What is the spectrum of activity of the cyclooctadepsipeptides?

Answer 41

Adult nematodes

Question 42

What are the 5 routes of administration used for anthelmintics?

Answer 42

1. Drench 2. Bolus 3. Pour on 4. Injectable 5. Oral

Question 43

What will a good worming strategy include?

Answer 43

- Testing (FEC) - Reporting lack of efficacy - Grazing management - Weighing animals to administer right dose - Avoiding unnecessary treatment