MDR1 (Vitally important for anybody with a herding breed or herding cross!)

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MDR1 (Vitally important for anybody with a herding breed or herding cross!)

Post by Eleanor on Thu Feb 06, 2014 9:56 pm

P-glycoprotein 1, also known as Multiple Drug Resistance 1 (MDR1), is a gene responsible for pumping foreign substances out of various cells in order to protect the body. However, a mutation of this gene is causing dogs to suffer from adverse effects to pharmacological treatments and medicines, leading to sometimes fatal results. Antiparasitical and anticancer drugs, in particular, cause these reactions in affected dogs.  

This most commonly occurs in the herding breeds, which are genetically predisposed to the mutation and the subsequent drug reactions. The mutation has been linked in particular to Collies, since the discovery of MDR1 in the early 1980s, when dogs began to suffer from severe reactions to medicines such as Ivomec (however, the mutation is thought to have emerged as early as 1873 in Rough Collies).
The Washington State University College of Veterinary Medicine has compiled the most complete list of known affected breeds and their chances of carrying the mutated gene. Owners of herding breeds, particularly Collies, are strongly urged to get their dog(s) tested for MDR1 to determine whether or not they are affected and in need of alternative or altered treatment.

List of breeds known to be affected, as well as the estimated frequency of the mutation, as compiled by the Washington State University College of Veterinary Medicine:

Australian Shepherd – 50%
Australian Shepherd, Miniature – 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%

Drugs known to affect dogs with MDR1 (changes to medication depend on whether the dog is heterozygous or homozygous for the mutation):

Acepromazine – can cause prolonged sedation. In affected dogs, it is recommended that the dosage be decreased by anywhere from 25-50%.

Butorphanol – can also cause prolonged sedation. In affected dogs, it is recommended that the dosage be decreased by anywhere from 25-50%.

Emodepside – a de-wormer used in some countries for dogs. Has resulted in neurological toxicity with affected dogs.

Erythromycin – may cause neurological symptoms in affected dogs.

Ivermectin – an antiparasitic agent. The dosage needed to prevent heartworm is considered to be safe in affected dogs; however, higher doses are used to treat mange, which may (heterozygous) or will (homozygous) cause neurological toxicity.

Loperamide – an antidiarrheal agent. Should be avoided for any dog affected by MDR1, as the drug will cause neurological toxicity.

Selamectin (Stronghold), milbemycin (Milbemax), and moxidectin (Advocate) – Antiparasitical agents. Safe when used for heartworm prevention, provided the recommended dose is adhered to.  Higher doses have been known to cause neurological toxicity in affected dogs.
Vincristine, Vinblastine, Doxorubicin - chemotherapy agents. Affected dogs are thought to be more sensitive to these drugs.  Bone marrow suppression and gastrointestinal toxicity may occur. Affected dogs should have their dose reduced by anywhere from 25-50%. The dogs should also be monitored carefully for adverse effects.

If you have any of the breeds listed, please contact your vet to discuss having the test to determine whether or not your dog(s) are affected by MDR1. The test (blood sample or cheek cell swab) is very simple and is highly recommended for the breeds with a 50% frequency or higher; in breeds with lower frequency, it is still advisable to seek veterinary advice.

You can order a test kit from the Washington State University College of Veterinary Medicine website: https://apps.vetmed.wsu.edu/vcplkitrequests/kitrequest.aspx

Information sourced from the Washington State University College of Veterinary Medicine - http://www.vetmed.wsu.edu/depts-VCPL/index.aspx


Last edited by ECdogs on Thu Feb 06, 2014 10:03 pm; edited 1 time in total
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Eleanor

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Re: MDR1 (Vitally important for anybody with a herding breed or herding cross!)

Post by LyndaW on Thu Feb 06, 2014 10:01 pm

Good post Eleanor.
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Re: MDR1 (Vitally important for anybody with a herding breed or herding cross!)

Post by Eleanor on Thu Feb 06, 2014 10:07 pm

Thanks happy
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Re: MDR1 (Vitally important for anybody with a herding breed or herding cross!)

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