MDR1 gene mutation and drug sensitivity in dogs

Dogs with a mutation of the MDR1 gene (also called the ABCB1 gene) are susceptible to toxicity fromMDR1 gene mutation and drug sensitivity in dogs various types of drugs because they produce a defective protein pump, called P-glycoprotein.  The defective protein pump prevents certain drugs from being removed from the cell.  The increased amount of drug inside the cell can have negative effects on the function of the cell.  Dogs obtain one set of genes from both parents.  As a result, a dog that has a mutation of the MDR1 gene can have either one or two mutated versions of the gene.  A dog that has 2 sets of mutated genes is called homozygous (mutant/mutant) for the mutated gene. A dog that has only one set of the gene in the mutated form is called heterozygous (mutant/normal) for the mutated gene. A dog that is homozygous for the mutated MDR1 gene because it obtain a mutated form of the gene from both parents will be more susceptible to certain drugs than a dog that is heterozygous for the MDR1 gene mutation and only received a mutated form of the gene from one parent.

Medications dogs with the MDR1 gene mutation are known to be sensitive to

There are a number of different types of drugs that are known to cause problems in dogs that carry the MDR1 gene mutation.  Use of these drugs in dogs with the MDR1 mutation should be at lower doses than commonly recommended.  Specific recommended dose reductions vary, but tend to be greater in homozygous mutants (30-50% reductions) compared to heterozygous mutants (25% reductions).  Some of the more common drugs of concern include:

Ivermectin is one of the most common drugs associated with toxicity in animals with the MDR1 gene mutation.  It can cause neurological signs such as increased salivation, loss of balance, blindness, coma and death.  Fortunately, this occurs only when doses of ivermectin are used at high doses such as those used to treat mange, which are about 50 times greater than the dose used in heartworm preventatives.  Therefore, the doses of drug used in commercial heartworm preventatives are low enough to be used safely in dogs with the MDR1 gene mutation.  Other anti-parasitic agents selamectin, milbemycin, and moxidectin are similar to ivermectin and can cause neurological toxicity in dogs with the MDR1 mutation.

Loperamide (Imodium) is an over-the-counter anti-diarrhea medication that can cause neurological toxicity and should be avoided in dogs with the MDR1 mutation.

Acepromazine is a sedative that tends to cause greater and longer duration of sedation in dogs with the MDR1 mutation.  Butorphanol is another sedative agent that causes

Certain chemotherapy agents are known to cause greater side effects of decreased white blood cell counts and intestinal side effects such as lack of appetite, vomiting and diarrhea in dogs with the MDR1 mutation.  These include vincristine, vinblastine and doxorubicin, and likely mitoxantrone, etoposide, and paclitaxel.

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Dr Stephen Atwater

Stephen W. Atwater, DVM, MS, Diplomate ACVIM (oncology) is a board-certified veterinary oncology specialist. His professional interests include utilizing emerging therapies for difficult to treat cancers.

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