Anthelmintics Flashcards
What are the 5 main classes of anthelmintics?
Group 1 - Benzimidazoles Group 2 - Levamisoles Group 3 - Macrocyclic lactones Group 4 - Amino acetonitrile derivatives Group 5 - Multi-actives
Which group is aka ‘white drenches’?
Benzimidazoles
Which group is aka ‘yellow drenches’?
Levamisoles
Which group is aka ‘clear drenches’?
Macrocyclic lactones
Which group is aka ‘orange drenches’?
Amino acetonitrile derivatives
Which group is aka ‘purple drenches’?
Multi-actives
What is the primary action of benzimidazoles?
Bind tubulin to prevent microtubule formation, starves the parasite, killing it.
Acts for 6-24hrs.
What are other actions of benzimidazole?
- Inhibits mitochondrual fumarate reductase
- Reduces glucose transport
- Uncoupling of oxidative phosphorylation
What is the spectrum of activity of benzimidazoles?
Broad spectrum. Effective against all 3 types of helminth, larvae and eggs.
Are there any side effects to benzimidazoles?
Well tolerated, characteristically free of side effects.
Describe the pharmacokinetics of benzimidazoles
- Oral administration
- Limited absorption from GIT (<1% oral dose in plasma)
- Efficacy increased if gut transit time decreased
Describe the mechanism of action of the levamisoles
- Ganglion stimulant, nicotinic agonist
- Paralyses helminth by sustained muscle contraction, loses ability to hold onto site in body, passed in faeces, coughing
Are there any side effects associated with levamisoles?
- Reflect nicotinic stimulation of animal
- Safety margin, 4-12 x therapeutic dose
What is the spectrum of activity of levamisoles?
Nematodes.
Describe the pharmacokinetics of the levamisoles
- Highly water soluble and is absorbed and excreted rapidly
- >24hrs, <1% initial dose left in tissues
Describe the mechanism of action of the macrocyclic lactones
- Stimulate glutamate-gated chloride channels in nerve and muscle cells
- Cl- influx, hyperpolaristation of post-synaptic cell, interfering with neurotransmission
- Results in flaccid paralysis
What is the spectrum of activity of macrocyclic lactones?
Nematodes and ectoparasites
Describe the pharmacokinetics of macrocyclic lactones
Given topically, v lipid soluble, long half life
Are there any side effects associated with macrocyclic lactones?
- Generally safe and well tolerated
- Exceptions are in mdr 1 deficient animals, drug enters CNS so are susceptible to effects
What is the nature of the selective toxicity of macrocyclic lactones?
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.
Give an example of a drug in the amino acetonitrile derivative group
Monepantel
What is the mechanism of action of monepantel?
Targets nematode specific subunit of nicotinic ACh receptor
Are there any side effects associated with monepantel?
None reported
What is the spectrum of activity of monepantel?
Nematodes
Describe the pharmacokinetics of monepantel
Readily absorbed and oxidised to a sulfone metabolite which is excreted in urine and bile.
Name 4 other anthelmintic classes
Praziquantel
Salicylanides
Clorsulon
Cyclooctadepsipeptides
Give an example of drug belonging to the multi-actives group
Derquantel
What is the mechanism of action of derquantel?
Nicotinic antagonist
What is the spectrum of activity of derquantel?
Sheep nematodes
Are there any safety issues associated with the use of derquantel?
- 4.5 x therapeutic dose causes dullness, depression, incoordination, weakness, decreased GI motility, abnormal breathing pattern, recumbancy, death
Describe the mechanism of action of praziquantel
- Tetanic contraction of parasite musculature
- Rapid vacuolisation of syncitial tegument
- Releases intracellular Ca, muscle contraction, water drawn in, parasite ruptures and bursts
What is the spectrum of activity of praziquantel?
Cestodes and trematodes
Describe the pharmacokinetics of praziquantel
Widely absorbed and distributed
Describe the mechanism of action of the salicyclanides
- Creates proton ionophore
- Influx of H+, decrease pH, uncoupling of oxidative phosphorylation
What is the spectrum of activity of the salicyclanides?
Trematodes
Describe the pharmacokinetics of salicyclanides
- Readily absorbed from GIT
- Highly bound by plasma proteins
Are there any risks associated with salicylanides?
No direct effect on mammalian cells
Describe the mechanism of action of clorsulon
- Inhibits 3-phosphoglycerate kinase and phosphoglyceromutase
- Blocks glycolytic pathway
What is the spectrum of activity of clorsulon?
Adult F. hepatica
Describe the mechanism of action of the cylclooctadepsipeptides
- Inhibits release of ACh from pre-synaptic neurone
- Flaccid paralysis and death
What is the spectrum of activity of the cyclooctadepsipeptides?
Adult nematodes
What are the 5 routes of administration used for anthelmintics?
- Drench
- Bolus
- Pour on
- Injectable
- Oral
What will a good worming strategy include?
- Testing (FEC)
- Reporting lack of efficacy
- Grazing management
- Weighing animals to administer right dose
- Avoiding unnecessary treatment
