Macrocyclic Lactones

Introduction

This group of drugs are derived from Streptomyces species and are coded as 3-AV products. They are commonly known as avermectins and milbemycins. Drugs in use include; ivermectin, abamectin, doramectin, moxidectin, eprinomectin and selamectin.

Activity

• They have a wide spectrum of activity. They are endectocides; active against common nematodes at all developmental stages and against many arthropods.
• They are inactive against trematodes, cestodes and adult filarial worms. Though are active against migrating heart worm larvae and are used as heartworm prophylactics in cats and dogs.
• Their mode of action is by opening invertebrate specific glutamate-gated chloride channels on the post-synaptic membranes. This results in flaccid paralysis of the parasite.

Pharmacokinetics

• These drugs are excreted very slowly and so the plasma concentration curve has a very long tail.
• The initial peak will kill all adult worms and the residual "tail" is able to have a high enough concentration to ensure that infective larvae ingested, for a time after treatment, are incapable of establishing. This provides a period of protection against reinfection.
• Pour on products are available but these are unable to provide the initial adulticide peak but will provide a period of protection for an even greater period of time.
• These prolonged protection periods mean that these drugs are often used in prophylactic worm control programmes for cattle. They can be prophylactic and be given at spring turnout to prevent eggs and infective larvae accumulating on the pasture.

They can be metaphylactic and be given mid-season, thus protecting animals grazing on contaminated pastures.

• Due to this long tail on the plasma curve, the product remains in the animal's body longer than most. This means that its meat and milk withdrawal periods are longer than other anthelmintics. Eprinomectin is the exception is used in dairy cows as it isn't excreted in milk.

Safety

• These are on the whole safe drugs to use.
• But Collie type breeds of dogs, especially Rough Coated Collies can be fatal. This is because they can lack a efflux transporter protein that removes these drugs from the CNS. This means toxic concentrations are capable of accumulating.
• This can also occur when Ivermectin is used at the higher doses needed for some heartworm therapies.
• They are often in high concentrations in faeces, this means that bettles and other insects that use dung-pats for their development can be killed. This is currently a heated topic, especially in areas of a delicate ecosystem.