Ladies and gentlemen Welcome back to the website! I’m Dr. Dawson, and today we are talking about a specific mutation in dogs called the mdr1 mutation. The biggest thing about this specific mutation, the reason it gets so much press, and why I’m talking about it is that it has to do with heartworm prevention in dogs, so I just want to talk about it. This article might get a little bit long because I plan on talking about it more in depth than some of my other articles because, really, to understand it and all the context behind it, you really need to have a little bit more background than maybe some of the other topics that I’ve talked about.
I also want to shout out one of my subscribers, and if I pronounce your name wrong, please don’t crucify me, but feel free to correct me in the comments. Denny RN, uh, who has a collie, was mentioning this in one of my other articles, my apical article, which you can find up here, where they had an experience with heartworm prevention in their mixed breed dog, possibly a collie, possibly an australian shepherd dog, and so I did already have this article planned, but it gave me a little bit more food for thought, and I decided I’m gonna move it up a little bit in my schedule and The mdr-1 gene is a specific protein and gene that has been known to cause ivermectin susceptibility in colonies, Australian shepherds, and a few others. Now, we’ll get into a lot more detail about this, but the short version is that this protein causes dogs to be extremely susceptible to the toxic effects of ivermectin. It’s a little strange that a gene originally discovered in cancers has anything to do with ivermectin toxicity and anti-parasiticide, but I think you’ll find this interesting in the literature.
This protein has actually been somewhat renamed to multi-drug efflux transporter, so it’s a little bit of a longer, maybe less understandable name, but essentially what it’s saying is that it will pump out drugs out of a cell by transporting Down here at the bottom you’ll see cytoplasm that’s inside of a cell and then it goes outside of the cell and so this specific protein’s job is to pump things out that don’t belong in the cell and it specifically is looking for specific toxins or other things where they don’t belong and pumping them out to where the body can handle them so for example, ivermectin is toxic to the nervous system but hybermectin is not. Humans, cats, rabbits, mice, and rats everything else there’s some specific variations on how it works and several different copies and blah blah blah not important basically this specific protein is found in most or all mammals with the exception of some specific breeds of dogs that have a mutation which is basically a change abnormal change in the genetic code that causes this protein to be severely shortened so instead of it being say 2 000 units amino acids long it’s cut down to like 1 10 of that size so 200 now you have a bunch of protein that you actually need for the protein to function normally and so this mutation causes the protein to not function at all not that it doesn’t function just worse it just doesn’t function and some of these that we usually talk about are collies and australian shepherds and i’ll go through a whole list here in a minute but with ivermectin specifically as this is probably the most well-known drug interaction it ivermectin typically in a normal dog in a normal human in a normal mammal has very very safe safety margins and what this means is you can give an extremely high dose over therapeutic before you start to see toxic effects so in the case of dogs typically we can do 200 times normal dose in a normal dog and we will still see almost no side effects or very occasional side effects but with dogs with this mdr1 mutation the protein the protein is not functioning as a normal pump to keep drugs out of where they’re supposed to be so ivermectin works as basically a neurotoxin so for the case of heartworms and other parasites it basically causes a complete breakdown of their neuronal function and prevents them from being able to move causing paralysis and actually and eventually death so in mammals their bodies are more advanced and they’re able to keep things out that aren’t supposed to be there but in a dog with an mdr1 mutation we have an issue that we run into and basically the pump is not doing its job and so even a low dose of ivermectin may cause very toxic signs in a dog with an mdr1 mutation because the pump is not functional the other place where this is relevant is not just at the blood-brain barrier but it’s also affected at the level of the liver 95 of ivermectin is metabolized through the liver broken down and changed and then excreted but if we have this mdr1 pump that’s not pumping the drugs where they need to go it’s not only going to be at a lot higher concentration in the brain but it’s going to be there a lot longer because we no longer have normal liver function so what does this have to do with heartworm prevention So we know that heartworms are very susceptible to ivermectin, and so some of our heartworm preventions are actually ivermectins or other drugs in this class called macrocyclic lactones, which is a fancy term for drugs that are related to ivermectin.
One of the more common heartworm preventions that has ivermectin in it is Heartguard. The other one would be iverheart, and there are probably a few others, but we also know, and this is a little unfortunate, that a dog with an mdr1 mutation is at a higher risk when using not only ivermectin, but also the rest of our heartworm prevention drugs, including selamectin, milbamias, and oxime, so one of the problems that Denny r.n, the subscriber that I mentioned earlier Collies are kind of your poster child, but long- haired whippets shetland sheepdogs miniature australian shepherds McNabb, the Silken Windhound australian shepherds Denny rn said that their dog is most likely an australian shepherd or cauli or something in between they don’t really know so heartworm prevention is probably the most common drug that we worry about for the mdr-1 mutation but this protein also works on many other drugs other than heartworm prevention. Most of these breeds that appear to be affected come from a lineage where the breed most likely originated in Europe, but more specifically in Britain, and so this mutation most likely started there and has been kind of introduced and increased specifically in caulis because of some of the tv shows where there was some irresponsible breeding because the demand for the breed was so high after lassie and after you know some of these different films and it tends to be that when holland is affected, it tends to be that If you guys liked this more in-depth analysis of a specific disease and problem and maybe a little bit more long-form content that I have done in recent times, make sure you guys leave a comment down below saying that you liked it. hit the thumbs up and let me know because I’m just trying to figure out here how I want to really format my content because I want to make sure it’s watchable for you guys and that you also have the time to go through and watch it but that you also get all of the answers that you’re looking for, so if you guys still have questions or if you have any input on things that you would like to see changed, make sure you leave a comment down below, have a fantastic rest of your day, and we will see you guys in the next article.
Frequent Questions – 💬
❓ What is MDR1 in Aussie dogs?
MDR1 is the abbreviated name of a gene called Multi-Drug Resistance 1.
- A mutation of this gene causes sensitivity to Ivermectin and a number of other drugs.
- Dogs with the mutation will react to those drugs.
- Whether a dog reacts depends on the dosage of the drug.
❓ What is the MDR1 gene in collies?
Multidrug Resistance 1, also called MDR1, is an inherited condition affecting several breeds of dogs, especially herding dogs such as the border collie. The Mutation in the ABCB1 gene associated with MDR1 causes dysfunction of P-glycoprotein, which is responsible for removing certain drugs and toxins from the body.
❓ What are the symptoms of MDR1 in dogs?
Dogs with the mutated MDR1 gene have an alteration in the blood brain barrier affecting transport of drugs such as ivermectin. Exposure to these drugs may result in serious neurological symptoms, such as hypersalivation, ataxia, blindness, tremor, respiratory distress and even death.
❓ What drugs should be avoided with MDR1 in dogs?
Below is a list of drugs that should be generally avoided in dogs with an MDR1 status, or herding breeds or mixed breeds of unknown MDR1 status.
- Ivermectin.
- Selamectin.
- Milbemycin.
- Moxidectin.
- Loperamide.
- Acepromazine.
- Butorphanol.
- Vincristine.
References:
- “Veterinary Ophthalmology” by Kirk N. Gelatt, Gil Ben-Shlomo, et. al. – Wiley, 2021
- “Veterinary Toxicology: Basic and Clinical Principles” by Ramesh C Gupta – Elsevier Science, 2012
- “Kirk’s Current Veterinary Therapy XV” by John D. Bonagura, David C. Twedt – Elsevier Health Sciences, 2013
- “Infectious Diseases of the Dog and Cat” by Jane E. Sykes, Craig E. Greene – Elsevier Health Sciences, 2011
- “Blackwell’s Five-Minute Veterinary Consult: Canine and Feline” by Larry P. Tilley, Francis W. K. Smith, Jr., et. al. – Wiley, 2021
Lovely article filled with tons of informative content. Generally speaking would Pyrantel Pamoate in doses around 50 mg/mL be safe for an Australian Shepherd puppy as a roundworm and hookworm dewormer? Our current vet has little experience with the MDR1 mutation and recommends ivermectin. The other vet we went to for a second opinion recommends Pyrantal Pamoate.
Do you know if Imoxi (imidacloprid + moxidectin) Topical Solution safe for herding group dogs with the MDR1 Gene?\r I need to get Heartworm Preventative / Treatment for my Shetland Sheepdog. The veterinary clinic I take my dog to stop carrying Advantage Multi and is carrying Imoxi .I can not find information to see if Imoxi ingredients is safe for my 1 year old Shetland Sheepdog, I live in Texas.
Even in Florida or Texas, you should NOT use heartworm. My aussie’s mom got it and was paralyzed close to death. I have heard of aussies getting seizures. If they are allergic, they are allergic. One time my vet gave a new medication that had dual heartworm and fleas and ticks and my dog almost die. Sorry, no heartworm med for my aussie. He is 9 years old and super healthy because I keep him clean and do mot take him to dirty dog parks.