PHARMACOLOGY - Anthelmintics Flashcards
What are the five main classes of anthelmintic drugs used in veterinary medicine?
Benzimidazoles
Levamisoles
Macrocyclic lactones
Amino-acetonitrile derivatives
Multi-actives
What is the spectrum of activity for Benzimidazoles?
Effective against all helminths (nematodes, cestodes, tapeworms) including the adult, larvae and egg stages
What is the mechanism of action for Benzimidazoles?
Benzimidazoles bind to helminth tubulin preventing microtubule formation and thus starving the parasite
Describe the nature of selective toxicity of Benzimidazoles
Benzimidazoles have a higher affinity for helminth tubulin than for mammalian tubulin and bind irreversibly to the helminth tubulin
Why should Benzimidazoles not be used for pregnant patients?
Benzimidazoles have been proven to be teratogenic meaning they can cause congenital disease in developing embryos
What is the spectrum of activity for Levamisoles?
Effective against adult nematodes
What is the mechanism of action for Levamisoles?
Levamisoles act as a nicotinic agonist, stimulating the ganglia of nicotinic acetylcholine receptors leading to sustained muscle contraction and paralysis of the nematode. The nematode can no longer attach to the gut wall and is eventually excreted in the faeces
Describe the nature of toxicity of Levamisoles
Levamisoles have a higher affinity for nematode nicotinic acetylcholine receptors than for mammalian nicotinic acetylcholine receptors
(T/F) Levamisoles have a large therapeutic index
FALSE. Levamisoles have a narrow therapeutic index
What is important to keep in mind when administering Levamisoles to small animal patients?
Small animals are more tolerant to oral administration of Levamisoles than of parenteral administration
Tetrahydropyramidines are derivatives of which drug class?
Tetrahydropyramidines are Levamisole derivatives
How do tetrahydropyramidines differ from Levamisoles?
Tetrahydropyramidines differ in their pharmacokinetics. These drugs are not well-absorbed from the gastrointestinal tract and are very quickly metabolised
What is the spectrum of activity for Macrocyclic lactones?
Macrocylic lactones are endectocides meaning they are effective against nematodes and ectoparasites
What is the mechanism of action for Macrocyclic lactones?
Macrocyclic lactones stimulate glutamate-gated chloride channels in invertebrate nerve and muscle cells resulting in flaccid paralysis of the nematode
Describe the nature of selective toxicity of Macrocyclic lactones
Macrocyclic lactones target glutamate-gated chloride channels which only exist in nematodes and ectoparasites
Give a specific example of an amino-acetonitrile derivative
Monepantel
What is the spectrum of activity for Monepantel?
Effective against adult nematodes
What is the mechanism of action for Monepantel?
Monepantel targets a nematode specific subunit of the nicotinic acetylcholine receptor, triggering flaccid paralysis
Give a specific example of a Multi-active anthelmintic
Derquantel
What is the spectrum of activity for Derquantel?
Sheep adult nematodes
Why should Derquantel only be used for sheep nematodes?
Because Derquantel has had adverse effects on small animals and horses
What is the mechanism of action for Derquantel?
Derquantel acts as a nicotinic antagonist, inhibiting the actions of the nicotinic acetylcholine receptors leading to flaccid paralysis of the nematode
Which drug can be used in combination with Derquantel to have an effect against both nematodes, cestodes and trematodes?
Praziquantel
What is the spectrum of activity for Praziquantel?
Effective against adult cestodes and trematodes, unreliable against larval stages
What is the mechanism of action for Praziquantel?
Praziquantel causes the rapid release of Ca2+ ions from intracellular stores causing tetanic contraction of the helminth musculature leading to paralysis
What is the spectrum of activity for Salicylanides and Nitroxynil?
Effective against adult trematodes
What is the mechanism of action for Salicylanides and Nitroxynil?
Salicylanides and Nitroxynil form a proton ionophore in the cell membranes of the trematodes, causing an influx of H+ ions leading to the uncoupling of oxidative phosphorylation. This prevents the trematode from producing energy, eventually killing the trematode
Why are Salicylanides and Nitroxynil only effective against adult trematodes?
Because these drugs are highly plasma protein bound so can only affect the parasites that are feeding on the blood, i.e. the adult trematodes
Why do Salicylanides and Nitroxynil doses need to be repeated at a three week interval?
These drugs only target adult trematodes so repeated dosing of these drugs is required at a three week interval to kill any immature trematodes not killed by the previous dose
Give an example of a salicylanide anthelmintic
Clorsulon
What is the spectrum of activity for Clorsulon?
Effective against adult Fasciola hepatica (F. hepatica)
(T/F) Clorsulon is highly plasma protein bound
TRUE
Give a specific example of a Cyclooctadepsipeptide drug
Emodepside
What is the spectrum of activity for Emodepside?
Effective against adult nematodes
What is the mechanism of action for Emodepside?
Emodepside acts as a nicotinic antagonist, inhibiting the actions of the nicotinic acetylcholine receptors leading to flaccid paralysis of the nematode
