Washington State University College of Veterinary Medicine
Originally found in http://www.vetmed.wsu.edu/depts-VCPL/.

Some dogs can have adverse reactions to drugs such as ivermectin, loperamide , Imodium® , and others. It was previously unknown why some individual dogs were sensitive and others were not. Advances in molecular biology at the Veterinary Clinical Pharmacology Laboratory at Washington State University's College of Veterinary Medicine have led to the discovery of the cause of multi-drug sensitivity in affected dogs. The problem is due to a mutation in the multi-drug resistance gene (mdr1). This gene encodes a protein, P-glycoprotein, that is responsible for pumping many drugs and other toxins out of the brain. Dogs with the mutant gene can not pump some drugs out of the brain as a normal dog would, which may result in abnormal neurologic signs. The result may be an illness requiring an extended hospital stay--or even death.

A test has recently been developed at Washington State University to screen for the presence of the mutant gene*. Instead of avoiding drugs such as ivermectin in known susceptible breeds, veterinarians can now determine if a dog is normal, in which case the drug can be administered or abnormal, in which case an alternative treatment can be given.

Affected Breeds

The only way to know if an individual dog has the mutant mdr1 gene is to have the dog tested. As more dogs are tested, more breeds will probably be added to the list of affected breeds: Australian Shepherds, Australian Cattle Dogs, Bearded Collies, Border Collies, Bullmastiffs , Collies, German Shepherds, Irish Water Spaniels Mastiffs, Old English Sheepdogs, Poodles, Shetland Sheepdogs, and Whippets. There are also reports of some PONS who react to meds.

Problem Drugs

There are many different types of drugs that have been reported to cause problems in dogs, ranging from over-the-counter antidiarrheal agents like Imodium® to antiparasitic and chemotherapy agents. It is likely this list will grow to include more drugs as our research progresses.

Drugs that have been documented, or are strongly suspected to cause problems in dogs with the mdr1 mutation:

Ivermectin (antiparasitic agent) Imodium (over-the-counter antidiarrheal agent) Loperamide (over-the-counter antidiarrheal agent) Doxorubicin (anticancer agent) Vincristine (anticancer agent) Vinblastine (anticancer agent) Cyclosporin (immunosuppressive agent) Digoxin (heart drug) Acepromazine (tranquilizer) Butorphanol (pain control) Potential Problem Drugs

The following drugs may potentially cause problems when given to dogs that have the mutation. Biochemical studies have shown that this gene has the potential to act on over 50 different drugs.

Potential Problem Drugs

The following drugs may potentially cause problems when given to dogs that have the mutation:

• Ondansetron
• Domperidone
• Paclitaxel
• Mitoxantrone
• Etoposide
• Rifampicin
• Quinidine
• Morphine

Approximately 3 of every 4 Collies in the United States have the mutant MDR1 gene. The frequency is about the same in France and Australia, so it is likely that most Collies worldwide have the mutation. The MDR1 mutation has also been found in Shetland Sheepdogs (Shelties). Australian Shepherds, Old English Sheepdogs, German Shepherds, Long-haired Whippets, Silken Windhounds, and a variety of mixed breed dogs. Isn't it time for extensive studies on Polish Lowland Sheepdogs ??