MDR1 Gene and What it means….
In recent years, it has been brought to the attention of the veterinary community and (breeding communities) that many of the herding breeds of dogs have a genetic predisposition to adverse drug reactions to a variety of different drugs. It has long been known that the collie breeds (Rough Collies, Smooth Collies, and Border Collies) and many of the sight hounds have been genetically predisposed to this, however, more recently some of the other breeds have become noted for it as well. Though it’s not terribly common in the German Shepherd breed, it is common enough to make note of it here, I think.
These drug sensitivities result from a mutation in the multi drug-resistant gene (MDR 1 gene). The problem first came to light back in 1983 when several collies died from ivermectin poisoning. Since then, more drug sensitivities, as well as more “sensitive” breeds have been discovered.
| Breeds affected by the MDR1 mutation (frequency %) | |
|---|---|
| Breed | Approximate Frequency |
| Australian Shepherd | 50% |
| Australian Shepherd, Mini | 50% |
| Border Collie | 5% |
| 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 MDR1 gene is responsible for ensuring that the body’s natural P-glycoprotein’s function normally by protecting the body from toxins. It does this by acting as a transport to move substances from one cell to another. P–Glycoproteins are normally extensively distributed in the blood barriers as well as a few other major organs. In MDR1 affected dogs, the function of the P–glycoprotein is compromised so therefore the blood brain barrier is compromised. If toxins leak across the blood brain barrier, they entered the central nervous system causing reactions such as excessive salivation, ataxia, seizures, blindness, respiratory problems, or even death.
DNA testing is now available through Washington State University. There are three possible results of testing – clear, carriers, and affected. Dogs that are….
“Clear” (+/+) for MDR1 – should not exhibit any drug sensitivities and pass on only healthy genes to their offspring.
“Carriers” (+/-) of the MDR1 – may experience some drug sensitivity & can pass on either a healthy or a defective gene to their offspring.
“Affected” (-/-) by MDR1 – will have drug sensitivities and will display toxic reactions to a wide range of drugs.
Testing for the MDR1 gene mutation allows us to not only make sure that we don’t inadvertently give a medication to a dog that can not handle that drug, but it also allows us to make sure that when breeding, we are not perpetuating a problem in the breed.
There are many drugs that should be avoided in MDR1 affected dogs. There are some other drugs that are known to be pumped out of the brain by the MDR1 gene but also appear to be fairly well tolerated by dogs with MDR1 mutations.
Avoid Medications: Some of the medications or drugs that should be strictly avoided in MDR1 affected dogs include:
Acepromazine (tranquilizer and pre-anesthetic agent)
Butorphanol (analgesic and pre-anesthetic agent)
Erythromycin
Ivermectin (antiparasitic agent)
Loperamide (ImodiumTM; antidiarrheal agent)
Selamectin, milbemycin, and moxidectin (anti-parasitic agents)
Vincristine, Vinblastine, Doxorubicin (chemotherapy agents)
Domperidone
Etoposide
Mitoxantrone
Ondansetron
Paclitaxel
Rifampicin
Tolerated Medications: Some of the drugs that are known to be fairly well tolerated in dogs with in the ER one mutations include:
Cyclosporin (immunosuppressive agent)
Digoxin (cardiac drug)
Doxycycline (antibacterial drug)
Generally Safe Medications: Here are a few of the drugs that are pumped out by the protein produced by the MDR1 gene, but appear to be safely tolerated in dogs with the MDR1 mutation:
Morphine
Buprenorphine
Fentanyl (opioid analgesics or pain medications)
Here is another table I found showing three classes of drug compounds which includes some drugs NOT approved for dogs:
Class A includes substances that have been proven to pass through the blood-brain barrier in MDR1-affected dogs and cause problems
Class B lists substances which have shown interactions in animal tests
Class C substances can be given without problems, even to affected dogs:
If you desire to get your dog tested and discover that he is affected (-/-), you will at least be in a position to inform your vet of the dangers of certain drugs to ensure the best care for your pet.
| Class A | DO NOT USE in dogs with MDR1 affected dogs (-/-) — they 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® & Quest® Anti-diarrheal: Loperamide substances (Immodium®)General antibiotic: Metronidazole (Flagyl ®) |
| 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 Glucocorticoids: Dexamethason Immuno-suppressants: Cyclosporine Heart glycosides: Digoxine & Methyldigoxine Anti-arrhythmics (heart meds): Verapamil, Diltiazem & Chinidine Pain control: Morphine & Butorphenol Anti-emetics (sickness/vomiting): Ondansetron, Domperidon and Metoclopramide Antibiotics: Sparfloxacin, Grepafloxicin & Erythromycin Antihistamines: Ebastin Tranquilizers & pre-anesthetic agents: Acepromazine (ACE) & Butorphenol Other drugs: Etoposide, Mitoxantrone, Ondanestron, Paclitaxel, Rifampicin |
| Class C | Can be used safely providing the correct dosage is given. | Morphine Buprenorphine Fentanyl (opioid analgesics or pain medications) |
References: Veterinary Clinical Pharmacology Laboratory, Washington State University