Anthelmintics

Most parasitic nematode infections, including Teladorsagia and Haemonchus, are currently controlled using anthelmintic drugs. There are several different classes of anthelmintic, the three major ones being the benzimidazoles, tetrahydropyrimidines/imidazothiazoles and macrocyclic lactones. Here, we give a brief overview of these drugs and explain their basic mechanisms.

Benzimidazoles (BZ – WHITE)

Examples: Albendazole, Fenbendazole, Oxfendazole

Benzimidazoles target a protein called tubulin, which has a major role in maintaining cell structure. The destruction of cell structure results in the death of the worm. Importantly, the drug is selectively toxic to worms, because even though tubulin is found in all cells (worm and mammalian), the drug binds more strongly to the worm tubulin.

Tetrahydropyrimidines/imidazothiazoles (LEV – YELLOW)

Examples: Levamisole

The tetrahydropyrimidines/imidazothiazoles act on the nervous system of the parasite. Muscle cell surfaces contain ion channels which control the chemical composition inside the cell. This drug class binds to a receptor on a particular type of ion channel. This causes paralysis of the worm muscle and results in worm expulsion. The drugs affect the worm but not the host because they are uniquely shaped for binding to worm receptor only.

Macrocyclic lactones (ML – CLEAR)

Examples: Ivermectin, Moxidectin, Doramectin

The macrocyclic lactones include Ivermectin, perhaps the most well known of this class of drug, as it is used to treat onchocerciasis (river blindness) in humans. Ivermectin binds to and disrupts a different type of ion channel in the worm cells, causing paralysis and inhibiting feeding and reproduction. Much like the earlier two classes of drug, the macrocyclic lactones also have a selective effect on worms because the specific ion channel is absent in the mammalian hosts.

Amino-acetonitrile derivates (AADs – ORANGE)

Example: Monepantel

These are the latest drugs developed to treat parasitic worms. Monepantel is the only licensed compound and it only available for use in sheep. The AADs also disrupt the normal function of ion channels but target a different receptor. This results in many effects including muscle paralysis and ultimately death. The target of the AADs in Haemonchus is a receptor that is specific to worms and not found in mammals.

Spiroindoles (SI – PURPLE)

Example: Derquantel

Derquantel is a paraherquamide derivate drug and is used in conjunction with the macrocyclic lactone Abamectin. It targets the same ion channels as the tetrahydropyrimidines/imidazothiazoles but through a different pathway.  The drug causes paralysis of the worm and results in worm expulsion.

Together, these anthelmintics represent the current arsenal available against parasitic worm infections. In the UK, farmers rely most heavily on the first three classes, but resistance to these drugs is now widespread.

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