Anthelmintics Flashcards
Describe the Benzimidazoles.
Tend to be insoluble in water - white drenches, administered orally, poor absorption from GI tract, food enhances absorption, plasma levels increased if retained in rumen rather than abomasum. The metabolism is variable but in general most of the drug is excreted unchanged in the faeces, and some in urine. There is a withdrawal periods so BDZ should not be used in lactating animals.
What is the key to Anthelmintic efficacy and safety?
The anthelmintic must target a receptor site on the parasite. The receptor site must be unique to the parasite OR The parasite receptor site must be far more sensitive to the anthelmintic than the host animal receptor site. Pharmacodynamics and parasite location are key to anthelmintic activity.
What is the Mechanism of action of the Benzimidazoles?
These drugs bind to nematode tubulin and prevent the formation of microtubules. Microtubules are essential for protein assembly, energy metabolism, mitosis, tubulin is also important for mammals but BDZs have a much lower affinity for mammalian tubulin. duration of exposure is critical so the drug is delivered to rumen vs abomasum.
Describe the Spectrum of activity of Bendimidazoles?
1-BZ. broad and often affects on adult and larval stages. Horses - GI round worms, lung worms. Ruminants - GI worms, lung worms, inhibited larvae of ostertagia more difficult to treat. Dogs and cats - taenia, lung worm, GI round worm. Triclabendazole effective against mature and immature fluke but not nematodes. Albendazole some efficacy against adult stages.
What are Pro-benzimidazoles?
Febantel, netobimin, thiophanate, converted to fenbendazole, albendazole and lobendazole. Giving the pro drug form makes them more soluble - they then require conversion to the active form in the liver. Febantel is converted to fenbendazole which is then metabolised to oxfendazole.
Describe the Macrocyclic lactones
made up of avermectins and milbemycins. They are all derived from streptomyces species of fungi.They are quite lipid soluble.
What are the pharmacokinetics of the avermectins?
They undergo hepatic metabolism and faecal excretion - some in the urine. Half life and distributions are often dependent on the route of administration and the species. Eprinomectin is largely excreted unchanged. Low milk/plasma co-efficient meaning that the drug is partitioned away from the milk so no withdrawal periods are required. Selamectin - large amounts are partitioned into the sebaceous glands providing a reservoir.
What are the mechanisms of action of the milbemycins and avermectins?
Milbemycin - potentiate the effect of glutamate at chloride channels in the parasite. Avermectins - also by acting on glutamate gated chloride channels in the parasite. Both may have effects on other chloride channels such as GABA gated. This leads to paralysis of the parasite. These receptor sites are absent or only present in the CNS of the host. as these anthelmintics do not penetrate the BBB they are selective for the parasite.
What is the difference in route of administration between the benzimidazoles and the Macrocylic lactones?
Unlike the benzimidazoles, the macrocylic lactones are lipid soluble and can be given by a range of routes, eg oral, s/c, pour on, spot on, and they prevent reinfection for a period of time after treatment.
What are the side effects of the Macrocyclic lactones
Toxicity is related to the binding of the anthelmintic to the GABA related neurons which are restricted to the CNS in the host. In general this group of agents do not cross the BBB but there are some individual breed sensitivities. This may be related to inefficiency of certain P-glycoproteins responsible for exclusion of the avermectins/milbemycins from the CNS.
What is Selamectin?
An avermectin (macrocylic lactones) applied topically in dogs and cats. It treats adult GI nematodes, heart worm prevention, fleas treatment and prevention, sarcoptic mange mite infection, ear mites, lice.
What is Moxidectin?
A milbemycin. Applied as a spot on also - will cover all the same things as selamectin but also larval as well as mature GI nematodes and demodectic mange mite. This improved spectrum is probably a reflection of increased lipid solubility and tissue persistence.
Describe Levimisole (an imidazothiazole)
Levamisole is the L isomer of DL tetramisole. It has all the original efficacy, reduced toxicity. The dose was able to be halved. It is rapidly absorbed from the GI tract. It is also available in injectable and pour on forms. It has equal efficacy irrespective of route.
Describe the mechanism of action of the Imidazothiozoles.
They are rapidly metabolised and eliminated in both the urine and faeces. They act on the nervous system of the parasite, at the acetylcholine/nicotinic receptors in the ganglia. The parasite then gets a contracted paralysis which is reversible. The parasite loses its hold on the host. Due to mechanism not ovicidal but adults and larvae affected. Max concentration not duration of exposure is key.
What are the spectrum of activity and uses as well as adverse side effects of the Imidazothiozoles ?
They are broad spectrum - treat GI nematodes, lung worm, not efficacious against flukes and tape worms. Designated 2-LV. Toxicity reflects activity at nicotinic receptors. Also suggestion of muscarinic stimulation. Salivation, lacrimation, tremors etc. Similar to organophosphate poisoning. Atropine may help provide symptomatic relief.
