Multidrug Resistance 1 (MDR1) drug sensitivity is the result of a genetic variant that can place dogs at risk of severe or life-threatening complications after taking particular medications at specific doses.
Treatment focuses on prevention by avoiding or lowering the dosages of drugs that may cause side effects in dogs who have this genetic variant.
Genetic testing is the most helpful tool for diagnosing MDR1 drug sensitivity.
MDR1 drug sensitivity occurs when dogs inherit a genetic variant in their ABCB1 gene (formerly known as the MDR1 gene). This variant causes a change in a protein called P-glycoprotein (P-gp).
Under normal conditions, the protein helps eliminate drugs after administration and helps keep specific substances — including some drugs and toxins — out of the brain and other organs.
However, when P-gp is not functioning correctly, these drugs and toxins can build up or even cross into the brain, causing severe and sometimes fatal reactions.
The MDR1 variant is most commonly found in herding breeds, including, but not limited to the following:
Collies
Australian Shepherds
American Shepherds
German Shepherds
Shetland Sheepdogs
Old English Sheepdogs
The most common signs of drug toxicity in dogs with MDR1 drug sensitivity include:
Vomiting
Weakness
Uncoordinated movement
Tremors
Seizures
Blindness
Death
P-gp affects the absorption, elimination and distribution of many drugs, but only a few of these drugs can cause severe toxicity in animals with the MDR1 variant.
For example, medications commonly used in heartworm preventatives, such as ivermectin, can cause toxicity if given in high dosages. However, heartworm preventatives are still safe for MDR1 drug-sensitive dogs to take at low, FDA-approved dosages.
Other medications that should be used with caution and at reduced doses include sedatives like acepromazine and butorphanol, anti-cancer medications and more. One drug that should be avoided entirely is an anti-diarrheal medication called loperamide (sold under the brand name Imodium).
Certain medications, when used in combination with each other, can increase the total concentration of individual drugs and introduce more risk of an adverse reaction — even in dogs without the genetic variant. Examples include ketoconazole, cyclosporine and spinosad (Comfortis).
Speak with your veterinarian before changing any drug dosages or discontinuing their use.
A variant that causes MDR1 drug sensitivity is identified by genetic testing. However, an initial diagnosis often occurs in young dogs after they have an adverse reaction to a particular drug.
There is no cure or antidote for MDR1 drug sensitivity. Treatment involves decreasing drug doses to avoid adverse reactions or choosing alternate drugs altogether. Dogs with adverse drug reactions are treated based on their symptoms and supportive care.
It is important to know that not all drug sensitivities are due to the MDR1 variant, and you should talk to your veterinarian about other concerns regarding drug sensitivity.
With proper consideration of drug interactions and dosages, MDR1 drug-sensitive dogs can live normal lives without incident.
Severe and potentially life-threatening consequences can occur if drugs are taken at incorrect dosages, if they are used in certain combinations with other drugs or if at-risk dogs are unintentionally exposed to problem drugs (e.g. ivermectin used to deworm horses).
The ABCB1 gene encodes P-glycoprotein, determining its base-level functionality. A dog may be severely affected by drug sensitivity if they inherit two copies of the ABCB1 variant, giving them only an abnormal P-gp. Dogs can still experience drug toxicity even with just one copy of the variant, but the effects are generally less severe.
Because MDR1 drug sensitivity can be easily managed after it is identified, the elimination of all dogs with this variant from a breeding program is not recommended.
Dr. Jenna Dockweiler with her Welsh Springer Spaniel, Mason. Photo: Jassen Photography.Dr. Jenna Dockweiler, M.S., D.V.M., D.A.C.T., C.C.R.T., C.V.A.T., is a veterinary geneticist at Embark Veterinary, Inc. She graduated from Kansas State University’s College of Veterinary Medicine in 2014, and then completed a small animal rotating internship at Wheat Ridge Animal Hospital in 2015. In 2017, she finished a comparative theriogenology residency at Cornell University's College of Veterinary Medicine and also became a diplomate of the American College of Theriogenologists. She practiced small animal theriogenology and general practice for four years prior to joining Embark. In her spare time, Dr. Dockweiler enjoys photography, hiking and competing in performance events and conformation with her Welsh Springer Spaniels, named Mason and Minnow.
This health topic was developed as part of a collaboration between the Cornell Richard P. Riney Canine Health Center and Embark Veterinary, Inc. You can learn more about the hereditary risks of other canine health conditions by exploring our genetics articles.
Dr. Aly Cohen and her Pomeranian Mishka. Photo provided.Dr. Aly Cohen is an extension veterinarian for the Cornell Richard P. Riney Canine Health Center and a clinical instructor for Cornell’s Maddie’s Shelter Medicine Program. She also serves as the contract veterinarian for the Ross Park Zoo in Binghamton, New York. Dr. Cohen graduated from the Ross University School of Veterinary Medicine, and her veterinary interests include surgery and emergency medicine. She has two Pomeranians named Mishka and Java.
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