MDR1: Multi-drug Resistance #1
*Important Medical Information For All Collie Owners*
MDR1 and Why It's So Important For Collie Owners
-by Dawn Renfrew
It has long been known that some collies are sensitive to the drug "invermectin" and related drugs. Invermectin is commonly used in dogs as a heartworm preventative, as well as (at higher concentrations) a treatment for mange. But more recently, it has been revealed that these sensitivities extend far beyond invermectin and its relatives to encompass a growing number of drugs used for a variety of therapies, including anti-cancer, anti-diarrhoeal, cardiac, immunosuppressive, antibiotics, pain killers and more. Please note that the drugs themselves are not problematic - in fact they are very effective in their indicated usages with most breeds of dogs and with some Collies. The problem lies with the sensitivities that many Collies have (and members of related breeds to a lesser extent) resulting from a mutation of the MDR1 gene. When sensitive Collies are given the (listed) drugs, death can result, so it is VERY important for ALL Collie owners to know the MDR1 status of their dogs.
Here is a backgrounder to what is going on. A molecule called P-glycoprotein, found in the brain and other organs, functions to transport certain drugs out of the brain (and other organs) to prevent their build-up. The MDR1 gene (for Multiple Drug Resistance #1) codes for this molecule and the "Normal" form of the gene makes a perfectly functioning molecule. But there is also a "Mutant" form of the gene which makes a defective P-glycoprotein molecule that does not work properly and thus allows the drugs to build up in the brain and cause death (neurotoxicity). Collies have a very high incidence of the Mutant forms of the gene. (Breeds that are related to Collies have varying incidences of the gene, probably corresponding to the relatedness of the breeds). Like humans, every Collie individual has 2 copies of each gene, one from each parent. So when the status of the gene (MDR1 status) is reported, the form of each copy is noted. Thus you get Collies that are Normal/Normal, Mutant/Normal and Mutant/Mutant. In theory, due to the way this gene is inherited, Collies have a 75% change of having at least one copy of the mutant gene (making hem Mutant/Normal or Mutant/Mutant) and a 25% chance of having two copies of the mutant gene (making them Mutant/Mutant). Mutant/Mutant Collies will definitely be adversely affected by the listed drugs, Mutant/Normal Collies "may" be adversely affected and only Normal/Normal Collies will be unaffected. Due (likely) to the long-term breeding history of Collies, ther are actually fewer Normal/Normal Collies 20% of the population in North America) and more Mutant/Mutant Collies (33% of the population) than expected from genetic inheritance probability.
This research is being pioneered at Washington State University (WSU) Veterinary Clinical Pharmacology Laboratory by Dr. Katrian Mealey and at the University of California Davis Veterinary Genetics Laboratory by Dr. Mark Neff. More extensive information is available at the WSU website (www.vetmed.wsu.edu/depts-VCPL/). The American Working Collie Association (AWCA) website (www.awca.net) also has additional information and lists references to scientific papers.
Now if all this seems alarming, there IS good news! Recently the MDR1 gene was identified and a simple test was developed so you can determine your Collie's MDR1 status. The test can be done at home, it is inexpensive and can be done by anyone. Test kits can be ordered from the WSU lab (US $60) through the links provided at the WSU or AWCA websites. It takes 1-2 weeks to get the kit, which consists of instructions and 2 extra long sterile cotton swabs. All you do is twiddle the swab between your Collie's cheek and gum for about 30 seconds, to collect epithelial (skin) cells, put the swab back in the package and mail it back to the lab. In about two weeks they send you the results (with an explanation). The kids and analysis are also now available in Canada (Cdn $75) from HealthGene in Ontario (www.healthgene.com).
Not all vets know about this genetic information or the testing so it is a good idea to print off copies of your dog's results for the vet as well as for yourself. The AWCA website also has a nice summary of information for vets under "technical summary for veterinarians" that can also be printed and given to them along with a page listing the drugs to avoid that you can personalize with your Collie's MDR1 status.
The list of drugs that should be avoided if you have Mutant/Normal or Mutant/Mutant Collies is given on both the WSU and the AWCA websites. As research continues, the list of drugs grows, so it is important to periodically check the websites and update your records. Now you might think it best to just avoid all of the listed drugs regardless of your Collie's MDR1 status but remember that these are effective and safe drugs for Normal/Normal Collies and if you have one of these lucky Collies you wouldn't want to deny it the use of a good therapy. Currently the drugs to avoid using with Mutant/Normal and Mutant/Mutant dogs are:
Anti-parasitic agents: invermectin, milbemycin oxime, selecamecin, moxidectin, abamectin
Gastrointestinal agents: loperamide (over-the-counter anti-diarrhoeal such as Imodium AD, some forms of Kaopectate and PeptoBismol).
Anti-cancer agents: doxorubicin, vincristine, vinblastine, vinca alkaloids
Immunosuppressive agents: cyclosporin, cyclosporin A, tacrolimus
Cardiac agents: digoxin, quinidine
Antibiotics: erythromycin, grepafloxacin
Steroids: dexamethasonem hydrocortisone
Pain Control: butorphanol
and possibly also:
A very useful, extensive list of North American trade and brand names these drugs go under is given at www.busteralert.org.
In a nutshell:
Please have your Collie tested for MDR1 status ASAP. You never know when it may need a pain killer, tranquilizer or anti-cancer treatment.
Make sure your vet is aware of your Collie's MDR1 status and which drugs to avoid.
Always check the drug list before your Collie is given any medication.
Remember that Mutant/Normal and Mutant/Mutant Collie are NOT unhealthy or "bad" dogs. There are just some drugs they cannot tolerate.
Remember that the listed drugs are NOT "bad drugs". They just cannot be used for all Collies.