Anthelmintics

Question 1

What is an anthelmintic agent?

Answer 1

Expel parasitic worms from the body by stunning or killing the parasites

Question 2

What do helminths require?

Answer 2

A feeding site
A working GI tract
Neuromuscular coordination
Homeostasis

Question 3

What are the different preparations of anthelmintic agents?

Answer 3

Oral preparations
Slow release bolus
Pro drug
Injections

Question 4

What are the 3 mechanisms of action of anthelmintic agents?

Answer 4

Affect microtubular function
Cause helminth paralysis
Affect energy-generating systems

Question 5

What are the 5 classification groups of anthelmintic agents?

Answer 5

Benzimidazoles
Levamisole
Macrocyclic lactone
Amino-acetonitrile derivatives 
Spiroindoles

Question 6

What are the properties of an ideal anthelmintic?

Answer 6

Selective toxicity - wide therapeutic index
Broad spectrum of activity
Cost effective
Drug resistance not likely
Efficacy and potency

Question 7

What is benzimidazoles mechanism of action?

Answer 7

Compromises beta-tubulin cytoskeleton

Glucose uptake is microtubule dependent - causes starvation

Question 8

What spectrum of activity are benzimidazoles?

Answer 8

Wide

Mostly nematodes

Question 9

What is a pro-drug?

Answer 9

Inactive compound that is metabolised in the body to make it biologically active

Question 10

What is an example of a pro-drug?

Answer 10

Febantel

Question 11

What factors affect benzimidazoles efficacy?

Answer 11

Diet - fibre
GI flow rate
Parasite infection
Ruminant oesophageal groove closure

Question 12

What neurotransmitters do helminths use?

Answer 12

Cholinergic (ACh) - excitation

GABAergic - inhibition

Question 13

What is levamisole’s mechanism of action?

Answer 13

Prolonged activation of excitatory nicotinic ACh receptors - Nicotinic receptor agonists
Spastic muscle paralysis

Question 14

What are the two groups of levamisoles?

Answer 14

Imidazothiazoles and tetrahydropyrimidines

Question 15

What are the two semisynthetic derivatives of macrocyclic lactones?

Answer 15

Avermectins

Milbemycins

Question 16

What is the mechanism of action of avermectins?

Answer 16

Activate the glutamate-gated chloride channels - targets neuromuscular junction
Causes flaccid paralysis/starvation

Question 17

What toxicity can be caused by avermectin?

Answer 17

MDR1 gene in collies

Question 18

What is the difference between milbemycin and avermectin?

Answer 18

Milbemycin has a longer half life
Also effects ticks and fleas
Given in combination with praziquantel

Question 19

What is the mechanism of action of amino-acetonitrile derivatives?

Answer 19

Activate the nematode specific ACh receptor

Causes irreversible paralysis

Question 20

What are amino-acetonitrile derivatives active against?

Answer 20

Adults and maturing larvae

Triple resistant nematodes

Question 21

What is the mechanism of action of spiroindoles?

Answer 21

Block cholinergic neuromuscular transmission

Flaccid paralysis

Question 22

What are spiroindoles used to treat?

Answer 22

Broad range of adult/immature nematodes in sheep

Question 23

What anthelmintic is used to treat tapeworms?

Answer 23

Praziquantel

Question 24

What is the mechanism of action of praziquantel?

Answer 24

Increases the permeability of cell membranes to Ca2+

Sustained muscle contraction and tegmental disruption

Question 25

What are the main trematodal agents?

Answer 25

Triclabendazole - fasciola hepatica

Question 26

What is anthelmintic resistance?

Answer 26

The ability of parasites to survive treatments at the reccomended dose rate

Question 27

What is the clinical definition of resistance?

Answer 27

95% or less reduction in a faecal egg count test

Question 28

What is triple resistance?

Answer 28

Resistance to the 3 different anthelmintic agents 1 - BZ 2 - LV 3 - ML

Question 29

What human factors contribute to resistance?

Answer 29

Under dosing Unnecessary dosing Misdiagnosis - inappropriate drugs

Question 30

What helminth factors contribute to resistance?

Answer 30

Molecular changes Modified activity of parasitic enzymatic systems Changes to receptors Amplification of target genes

Question 31

What causes benzimidazole resistance?

Answer 31

Cross resistance due to altered beta-tubulin

Question 32

What causes Levamisole resistance?

Answer 32

Modified nicotinic ACh receptors - altered drug binding

Question 33

What causes Macrocyclic lactone resistance?

Answer 33

Alterations in multiple genes

Question 34

How to minimise resistance?

Answer 34

Cycle through classes Combination products Correct dosing and product

Question 35

What is an example of a combination product?

Answer 35

Abamectin and derquantel

Question 36

What is an example of a parasite that has a vaccination?

Answer 36

Dictyocaulus viviparus

Question 37

What are some alternative options to anthelmintics?

Answer 37

Use genetically resistant host species Nematophagous fungi Vaccination