Immodium or other substrates for P-glycoprotein

This drug is commonly used to treat Diarrhoea in humans it should not be used to treat dogs especially Collies, it works by temporarily paralyzing the lower intestines in humans. In dogs however especially Collies it could well lead to coma followed by death. If you have given Immodium to your Collie print this out and take it with you to your Vet to help him care for your dog. 

The phenomenon of ivermectin toxicity in Collies was first described in 1983. Ivermectin causes neurologic toxicity in some, but not all Collies, at doses that are 1/200th of the dose required to cause toxicity in other dogs. Neurologic manifestations of ivermectin in susceptible dogs include, hypersalivation, ataxia, blindness, coma, respiratory compromise, and death.

Despite numerous investigations during the 1980?s and 1990?s, the cause of this peculiar breed susceptibility was not elucidated. Recently, a veterinarian at WSU discovered that the cause of ivermectin sensitivity in Collies is a deletion mutation in the MDR1 gene. The MDR1 gene encodes a large transmembrane protein, P-glycoprotein, that is an integral part of the blood-brain barrier. P-glycoprotein functions in a protective capacity to transport a variety of drug substrates, including ivermectin, from brain tissue back into capillaries. Other drugs that are substrates for P-glycoprotein include loperamide (Immodium?), digoxin, ondansetron, many chemotherapeutic drugs including vincristine, vinblastine, and doxorubicin, and other drugs. Collies have been documented to be susceptible to neurotoxicity induced by some of these drugs also.

A test is now available to determine if Collies are homozygous for the deletion mutation (i.e., display the ivermectin-sensitive phenotype), heterozygous for the deletion mutation (carriers) or homozygous for the normal gene sequence.

Ongoing research is directed at determining if other breeds that have been reported to be sensitive to ivermectin (Australian Shepherds, Shelties, Border Collies, and Old English Sheepdogs) have a similar mutation.

Text was copied from the WSU site without permission but an email was sent asking to reproduce the text and use the picture but no reply was forthcoming, it will of course be removed should the copyright owner object at a later date.

 

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