Drug Sensitivity Testing in Dogs (MDR1)

  Many dogs, especially herding dogs and herding cross breeds, carry an abnormality in the multidrug resistance gene (MDR1).  This makes them very sensitive and reactive to certain drugs.  Such drug reactions can cause serious neurologic disease and even death.

 
Collies and Australian shepherds are very commonly affected but English Shepherds, herding cross breeds, German Shepherds, Long-Haired Whippets, Shelties, McNabs, Old English Sheepdogs, Border Collies, Silken Windhounds, and mixed breed dogs may also be affected.  Since herding breeds and their crosses are so over-represented with this problem, and commonly have white feet, you can remember it as “white feet, don’t treat”.
P-glycoprotein 1 (permeability glycoprotein) is the multidrug resistance protein.  It sits in membranes in many areas of the body, like the intestinal tract, kidneys, liver, adrenal glands, and nervous system.  MDR1’s job is to pump things out of the cells and regulate what things get into the brain and nervous system.  When animals have a mutation of the MDR1 gene, drugs and toxins can accumulate in unexpected and dangerous levels.  Dogs can have 0, 1 or 2 copies of the gene.  One copy of the gene may result in sensitivity and mild reactions to a given drug; two copies would lead to more severe reactions.

The drugs implicated include a broad range of medications.  The antidiarrheal medication imodium, the antibiotic erythromycin, and antiparasitic drugs such as ivermectin, milbemycin, selamectin, moxidectin, and emodepside [Profender] may cause neurologic toxicity.  Some medications will have an increased sensitivity.   These drugs include the sedative acepromazine, the pain medication butorphanol, and the chemotherapy agents doxorubicin, vincristine, and vinblastine.

The signs of toxicities may vary and will have an onset of 24-48 hours post administration.  Animals most commonly show excessive sedation, salivation, vomiting, and a slow heart rate.  They may also have dilated pupils, tremors, a wobbly gait, and disorientation.  There is no antidote or specific treatment.  Patients have to be supported until the medications can completely wear off.  This may involve many days, or even weeks, of hospitalization including fluids, nutritional support and sometimes a ventilator.  The diagnosis is based on medication exposure and suspicion.

Thanks to the discovery of the mutation of the multidrug resistant gene and the establishment of testing by the Washington State University College of Veterinary Medicine (my school), we can predict these drug sensitivities.  The American Animal Hospital Association and the American Veterinary Medical Association together offer a set of Canine and Feline Preventive Healthcare Guidelines. They recommend that dog owners use genetic testing—like the MDR1 test —as part of an overall healthcare plan for their pets.  The Lien Animal Clinic recommends testing all dogs with potential herding ancestry and considers testing mixed breed dogs. Testing at our clinic involves taking a cheek swab or a blood sample and submitting it to the WSU laboratory.  

Timothy R Kraabel, DVM, DABVP (Canine/Feline Practice)

Outreach Chairman, American Board of VeterinaryPractitioners