MDR1 (or Multi-Drug Resistant protein gene)
The MDR1 gene protects the brain by ensuring that any harmful chemical are transported AWAY from the brain. In some dogs who are members of the herding varieties such as Collies and Australian Shepherds, a mutation in this gene causes extreme reactions to various drugs including Ivermectin (found in some heart worm medication), Loperamide (found in things like Imodium for diarrhoea) and several others including pesticidal treatments. The mutation causes the gene to be defective and makes it difficult for the dog to remove these drugs from the brain, leading to a build up of toxins. As a result, the dog may experience problems of a neurological nature such as seizures, incoordination, or even death.
All our characteristics are derived by our genes – a copy of which we get from our mother and one from our father. Dogs that have two copies of the mutation will display a sensitivity to these types of drugs. It is also worth noting that they will pass on one copy of the mutation to any potential offspring so it is important that dogs are tested before entering a breeding programme.
Dogs that only have one copy of the genetic mutation may still react to these drugs if they are administered at high doses and they also have a 50% chance of passing on the mutation to their puppies too.
Breeds affected by the MDR1 mutation (frequency %) |
|
| Breed | Approximate Frequency |
| Australian Shepherd | 50% |
| Australian Shepherd, Mini | 50% |
| Border Collie | < 5% |
| Rough Collie | 70 % |
| English Shepherd | 15 % |
| German Shepherd | 10 % |
| Herding Breed Cross | 10 % |
| Long-haired Whippet | 65 % |
| McNab | 30 % |
| Mixed Breed | 5 % |
| Old English Sheepdog | 5 % |
| Shetland Sheepdog | 15 % |
| Silken Windhound | 30 % |
The drugs fall into 3 categories – class A, B and C:
CLASS A
DO NOT USE in dogs with MDR1 defect.
An affected dog (-/-) carries two MDR1 gene mutations, having received one from each of its parents. It will also pass on a mutant MDR1 gene to its offspring.
MDR1-affected dogs are likely to experience drug toxicity following normal doses of the drugs listed here:
Anti-Parasitic drugs:
Ivermectine substances: Diapec®, Ecomectin®, Equimax®,Eqvalan®, Ivomec®, Noromectin®, Paramectin®, Qualimec®, Sumex® & Virbamec®
Doramectine substances: Dectomax®
Moxidectine substances: Cydectin® & Equest®
Loperamide substances (anti-diarrhoea): Immodium®
Metronidazole (Flagyl ® – general antibiotic
CLASS B
Toxic reactions have been known to occur so only use under the close supervision of your vet
Cancer treatments (Cytostatics): Vinblastine, Doxorubicine, Paclitaxel, Docetaxel, Methotrexat & Vincristine
Glucocortisoids (steroids commonly used to treat auto-immune diseases): Dexamethason
Immuno-suppressants: Cyclosporine A
Heart glycosides: Digoxine & Methyldigoxine
Antiarrhythmics (heart problems): Verapamil, Diltiazem & Chinidine
Pain control: Morphine & Butorphenol
Anti-emetics (sickness/vomiting): Ondansetron, Domperidon andMetoclopramide
Antibiotics: Sparfloxacin, Grepafloxicin & Erythromycin
Antihistamines: Ebastin, (although safe for most dogs, Piriton should be queried when dealing with MDR1 positive dogs)
Tranquillisers & pre-anaesthetic agents: Aceptomazine (ACP) & Butorphenol
Other drugs: Etoposide, Mitoxantrone, Ondanestron, Paclitaxel, Rifampicin
CLASS C
Can be used safely providing the correct dosage is given.
Stronghold®, Advocate® & Milbemax® can be used only in the recommended application and dosage.
The importance of knowing your Collie’s MDR1 status cannot be over-emphasised, as you never know when he or she may require surgery and/or drug treatment. If your dog is known to be affected, you will at least be in a position to inform your vet of the dangers of certain drugs, by printing off the information.
There are several laboratories offering DNA tests for MDR1 – Laboklin Laboratories of Manchester (UK branch of the Laboklin Company of Bad Kissingen, Germany).
UK lab: http://www.laboklin.co.uk/
Germany lab: http://www.laboklin.de/
Animal Genetics is another lab that does this test. There are clinics with reduced rates throughout the year. You can find out more by contacting Pastoral Breeds Health Foundation http://www.pbhf-dog.com/
www.animalgenetics.eu/Canine/Genetic_Disease/MDR1.asp
The test is carried out using simple buccal (cheek) swabs, which you can easily do yourself.
Testing is also available in the US where you can simply send for a kit to take a cheek swab and sent it off to the lab: http://www.horsetesting.com/Canine/Canine-sample-kit.asp – I understand that the cost is in the region of $55
Hi Kerry
My 2Year old Border Collie has shown sensitivity to some medications so we’ve avoided certain meds. Since talking to you at lastnights first aid class in Inverness i’ve looked into this on the internet and alot of alarm bells seemed to ring . My poor wee mite struggles with meds and wee have often been looked at as if Im crazy when I mention the effects and his presentation when at the vets. I’ve a second dog whos a rescue and seems alot more robust so I’m begining to shake off the feeling that i must but a dog mum with Munchousens by proxy. Im now looking into getting him tested for his future safety.
Hi Fiona,
Nice to hear from you 🙂 A lot of dogs do have varying levels of sensitivity and as you know, I try to avoid chemicals as much as I can – they are sometimes the only way but if I can find a safe and natural alternative, I admit I do tend to take this route. Regards the flea/tick repellent we were discussing, you could try using a mixture of grapefruit essential oil dropped into almond oil as the carrier fluid. I mix the two together, shake in a spray bottle and spray onto a grooming mit then smooth down the sides of my dogs coats, under their chins and on the heads and necks as this is where ticks/fleas mostly like to hang out. They do not like either citrus or almond so this mixture works well for my boys and may be worth a try if the meds are causing your BC trouble xx
Kerry,
I have 2 Aussies and one is n/n and the other is m/m. Same mother different father.
I educated my vet about the MDR1 gene, she had never encountered any collies with this mutation. However I know and will always let whoever goes near my dog know. I am in U.S. and used the cheek swab method I got from the University of Washington.
Brilliant! Well done Kim. It always amazes me how much information slips through the net and it takes fab people like yourself to educate those who are supposed to be “in the know”. Im sure the conversation you had with your vet will have sparked them to look into it for themselves and will no doubt save many a life in the future. Im really proud of you xx
I saw you use grapefruit oil for fleas. I just want to point out grapefruit is also a glycoprotein inhibitor and not recommended for mdr1 dogs. This may be newer info, but want to get that out there. I am trying to discover now if it is just grapefruit or all citrus, as orange oil is very effective.
that’s very interesting .. you’ll have to let me know what you find out 😉 thanks for getting in touch
My Pyrenean sheepdog had bad reactions to almost every drug ever prescribed for her. Also anesthesia, she always took 3-4 days to recover from an operation. I believe that requiring 3 lots of anesthesia in 4 weeks led to her pancreatitis and kidney failure and death.
I have a 7yr old border collie, fit, healthy and working horses until I retired and we moved to Yorkshire. Shortly after moving, he started collapsing on exercise and was found to have a problem with the messages getting through from the brain to tell his heart to beat. His heart was going into Arrythmia and actually stopping. He is on corvental d to speed his heart rate up, apparently with no major side effects. Crazy dog out going manic as usual until 5 months ago he majorly collapsed without the warning signs I have learned to look for and turned out it was acute liver failure, unknown source but all his levels were off the scale and he wasn’t expected to survive. Glad to say he has bounced back yet again, due partly to my new regime. I home cook for him, use 4 seasons wormer and white vinegar as a flea preventative. Boosters are due so I am having a Titer test done in the hope he has enough immunity and will take it from there. I have a couple of concerns, hopefully someone will know the answers. Firstly, leptospirosis, vaccination doesn’t appear to last so am I right in thinking he will need this? Also I don’t think the four seasons guards against lungworm, so has anyone got any advice on how to protect him please?
Ooooh this one is a can of worms to answer Judith.
In all honesty vaccinations are a mine field and depending on your personal beliefs, dog’s history, drug understanding and lifestyle, what fits one dog doesn’t necessarily seem appropriate for another. With the lepto, it is primarily useful to dogs who are in and out of bodies of water such as drains, canals, ponds etc where rats may be found. Unless this applies to your dog then it’s probably not something I would look at personally but, again, it is very much something you have to make your own peace with and choose when you have all the facts. What I will say is that any vaccination in dogs who are NOT fit is not a good idea so depending on how fit he is currently, and certainly with a heart problem, I’m not sure that I’d be going down that route if I were you. Lungworm, although a real “thing”, is perhaps not as prevalent as some drug manufacturers would have us believe so don’t worry yourself into grey hairs about it. I would speak to your vet about which products protect against lung worm that have no contraindication for MDR1 collies, just to be on the safe side (I am assuming since you have commented on this particular blog that your dog is MDR1 positive?).
I’m sorry I cant be more definitive but it really is a divisive subject and one we all unfortunately have to make for ourselves
Best wishes and good luck with your information hunt!
Kerry
I jus want to let people know how important I think this is. My beautiful smooth coat Border Collie ( or could have been a McNab collie) came from a sheep farm in the Antelope Valley . He was almost sixteen and developed diarrhea. He was given Flagyl , which he had when he was much younger. He did not do well. His diarrhea was not even affected until I switched his hard kibble to soft, canned food. After a couple of rounds of Flagyl he started walking in circles. They told me to give him anti-nausea Ned’s. Nothing worked. his stools improved, but walked in circles and kept losing weight. He was a great dog, but I do not recommend these drugs, use only as a last resort. Better yet, get your dogs tested for the genetic issue.
I’m so sorry to read that … poor love
My 10 yr old rough collie passed away due to the anesthesia from a routine vet procedure. I did consult my vet of the anesthesia concern i had and he dismissed my concerns as he had never encountered these issues. I did the routine blood work as well that they suggest you do. My collie deteriorated rapidly I had walked him to the vets on Friday morning for a cyst removal on his tail this procedure was performed at 10am I picked him up in the afternoon He was not able to walk after the procedure nor drink water or eat they insisted he would get better once the anesthesia wore off. He never got better was lifeless Thru ought the evening the next morning he seemed worse I called rhe vet at 9am he passed about 10 minutes later before I could get him to the vets. I than researched online every scenario I could find and found the documentation on the mdr gene and will now have my youngest collie tested to avoid this tragedy. I can’t stress enough that you need to also be sure to find a doctor that will listen to you I went to a small town vet that was very uneducated in this condition in collies he was also very offish when I requested a list of the drugs that my dog was given he admitted he used a different anesthesia that my dog had been given in the past etc and had to give my dog more dosages due to the fact he was waking up during the procedure. I think there is a lack of education with this genetic condition with collies. And you can’t always trust that the vet will know. My advise is to have all collies tested to avoid these tragedies:-(
Im so sorry to read your tragic story. I can only agree with you entirely that knowing your dog’s MDR1 status BEFORE administering any drugs is a must … if I could turn back the clock for you, I would x
[…] Be mindful that along with the fact this habit is more than a little “icky” if the dog eats from a source where the host animal has recently been wormed, not only will your dog be consuming the worms that are ejected but also the drug that was given to the host animal to treat it. For dogs in the herding varieties, if they have a condition known as MDR1, this can be incredibly dangerous as the drugs used to worm animals can, in some cases, prove fatal to dogs with this condition. (check out our blog on MDR1 if you have a dog who may fall into this category such as Border Collies, Shelties, Old English Sheep Dogs etc: MDR1 blog) […]
[…] Please bare in mind that not all dogs (dependant upon their history or medication they may be on, or their specific breed) may be safe to use Piriton. Some dogs who fall into the herding varieties such as Border Collies, Shelties, Old English Sheepdogs etc could have a genetic defect called MDR1. If they do, then administering a drug such as Piriton can be incredibly dangerous and should be avoided at all costs. If you do not know if your pastoral breed dog is MDR1 positive or not, a simple cheek swab sent off to a genetic lab for DNA testing can put your mind at rest one way or the other. Here’s our blog on MDR1 just in case you want to read more about this mutation: MDR1 blog […]
Please help, my collie has scabies and when I rescued him I was told MDR1. My vet has to,d me to use conventional spot in treatment advocate. He has never had any drugs and is 9 years old as he has always been so well, but a fox with Mange has been visiting my garden and now I have Hague problem, what would you suggest. I am so worried about using this spot on. I also have anther untested rescue collie mix who now has it.
I wouldn’t use Advocate on any dog who has tested positive for MDR1. Has the vet suggested this for treatment of the scabies or for future preventative measures?
I think that it is also important that people take note of what it means when they get the test and are told that their dog will be ok becuase he/she is ‘only a carrier’!
Because the MDR1 genetic mutation is dominant then a heterozygous dog (one mutant one normal gene) may well still get drug toxicity reactions.
My dog is a ‘carrier’ (no such thing really for this condition) and he was completely wiped out by a normal flea/worm tablet (Nexguard Spectra with Milbemycin Oxime) and could not stand for an hour or so.
I got the test because of this episode and because he is prone to diarrhoea and I wanted to know if he could be given Loperamide.
The genetic testing company gave me the carrier result and stated that he was healthy and only had be careful who he was mated with. This is worse than having no test because if I’d followed this advice I’d have been getting loperamide for him and that would have been disastrous.Thank you for the information
Andrew thank you so much for commenting and sharing your experience. Very very important to know the seriousness of a “carrier” diagnosis and yes you are quite right, the outcome could well have been absolutely tragic.
Best wishes
Kerry