MDR1 drug hypersensitivity in dogs - Toutoupourlechien

Does your dog belong to a breed related to the Collie? There is then a risk that he suffers from MDR1 drug hypersensitivity

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What is MDR1 drug hypersensitivity?

MDR1 drug hypersensitivity is the result of a mutation in a gene that makes certain drug molecules neurotoxic for several breeds of dogs related to Collies.

The MDR1 gene (for Multi Drug Resistance) - now also called ABCB1 - is responsible for the synthesis of a protein expressed in the endothelial cells that line the blood capillaries of the brain. These proteins are essential components of the blood-brain barrier whose role is to protect the integrity of the central nervous system by opposing in particular the entry of drug molecules into the brain.These same proteins are also present in the liver or kidneys to promote the elimination of substances toxic to the dog's body through urine and bile.

When there is a mutation in the MDR1 gene, these proteins are no longer made correctly and this leads, in dogs carrying this mutation, to an increase in the passage of toxins through the blood-brain barrier and a accumulation of these in the brain.

What are the risks in case of MDR1 drug hypersensitivity?

In dogs suffering from this anomaly, the administration of certain drugs leads to neurotoxicity and the appearance:

  • central nervous system disorders such as locomotor disorders (ataxia, paresis or paralysis), tremors or convulsions that can lead to coma or even death of the animal by respiratory depression,
  • eye disorders such as abnormal dilation of the pupils (mydriasis) or loss of vision,
  • digestive disorders which may include vomiting and anorexia.

There is no antidote and the treatment is based on medical resuscitation. Unfortunately, there are still many cases of death in the event of drug poisoning.

What drugs and dog breeds are involved?

The main breeds of dog at risk in France include the Collie, the Australian Shepherd, the Miniature Australian Shepherd, the Shetland Sheepdog, the Berger Blanc Suisse, the Border Collie, the Collie with long hair and short hair, the German Shepherd as well as the Bobtail. Of course, dogs resulting from crosses with the breeds mentioned above also present an increased risk of drug sensitivity.

Within these breeds, the dogs most at risk of developing intoxication following the ingestion of drugs are dogs homozygous for the MDR1 gene mutation.In other words, dogs with two mutated copies of the gene in their genome are at the highest risk. However, dogs that only have one copy of the mutated gene, also called heterozygous for the mutated gene, are also at risk and therefore it is important to take the same precautions for dogs that are heterozygous as for dogs that are homozygous for the gene. mutated.

The drug molecules that must absolutely be avoided in sensitive dogs are:

  • ivermectin, a molecule used in certain antiparasitic products, and molecules close to ivermectin such as doramectin, abamectin, moxidectin and milbemycin,
  • loperamides, molecules used in certain anti-diarrheal drugs,
  • emodepside, another molecule used in certain anti-parasitic products.

There are also other molecules with which precautions must be taken, such as:

  • of molecules used in drugs to treat gastroenterological disorders (cimetidine, ranitidine, domperidone, ondansetron),
  • of molecules used in cardiac drugs (digoxin, digitoxin, quinidine, diltiazem, verapamil),
  • of active ingredients used in oncology (doxorubicin, vinblastine, vincristine, actinomycin D and mitoxantrone)
  • of molecules active on the immune system (ciclosporin A and tacrolimus),
  • dexamethasone, estradiol, morphine and phenytoin.

How do I know my dog is suffering from this drug hypersensitivity?

In breeds at risk, there is a genetic test to detect a dog carrying the mutation and thus know if he is at risk. In the absence of having done the DNA test, all dogs of the breeds at risk must be presumed carriers of the mutation.

In these dogs even more than in other animals, it is therefore recommended never to administer medication to them without the advice of a veterinarian. This includes pest control products available without a prescription.

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