MULTI DRUG RESISTANCE GENE   (MDR-1)

Herding breeds as well as several others are adversely affected by some drugs that cannot

be pumped out of the brain properly.  Washington State University identified the gene and have

done extensive studies with published results.


You can also have your puppy tested for the presence of the MDR1 gene through WSU.

1 copy of a mutant (bad) gene is known as a carrier

2 copies of a mutant gene is called affected

Puppies acquire 1 gene from each parent, and I never breed 2 carriers together; therefor, there may be an occasional

carrier, there will never be an affected.

Bottomline:  ALL should be treated as if they were affected and Avoid All the Drugs Listed

Dogs that are tested completely clear are still known to have reactions just as one that is not clear.


See the links below to go to the WSU site to read the documents as well as the

Drug List to Avoid.  I have attached 1 of the documents below.

You will also find this information in the packets I give out with the puppies at pick up.

PLEASE TAKE THE LIST FROM YOUR PACKET ON YOUR VET VISITS

Vets are aware of the problem, but in the daily rush can easily forget

The most problematic times are the drugs used during surgeries (ie:  spay/neuter)

and some precriptions (ie: Ivermectrin)


LINKS:


https://vcpl.vetmed.wsu.edu/docs/librariesprovider17/default-document-library/vcplflier.pdf


https://vcpl.vetmed.wsu.edu/problem-drugs



Problem Drugs


Many different drugs and drug classes have been reported to cause problems in dogs with the MDR1 mutation. The VCPL continues to work to

 identify drugs that may be dangerous to dogs with the MDR1 mutation and to determine alternative drugs and doses for these dogs.

Drugs that have been documented to cause problems in dogs with the MDR1 mutation include:

Ivermectin (antiparasitic agent)- While the dose of ivermectin used to prevent heartworm infection is SAFE in dogs with the mutation (6 micrograms per kilogram), higher doses, such as those used for treating mange (300-600 micrograms per kilogram) will cause neurological toxicity in

 dogs that are homozygous for the MDR1 mutation (MDR1 mutant/mutant) and can cause toxicity in dogs that are heterozygous for the 

mutation (MDR1 mutant/normal).

Selamectin, milbemycin, and moxidectin (antaparasitic agents)- Similar to ivermectin, these drugs are safe in dogs with the mutation if used for heartworm prevention at the manufacturer’s recommended dose. Higher doses (generally 10-20 times higher than the heartworm prevention dose) have been documented to cause neurological toxicity in dogs with the MDR1 mutation.

Loperamide (ImodiumTM; antidiarrheal agent)- At doses used to treat diarrhea, this drug will cause neurological toxicity in dogs with the MDR1 mutation. This drug should be avoided in all dogs with the MDR1 mutation.

Acepromazine (tranquilizer and pre-anesthetic agent)- Based on collaborative research, the VCPL has determined that dose reductions are

 required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.

Butorphanol (analgesic and pre-anesthetic agent)- Dose reduction required for dogs MDR1 mutant/mutant and MDR1 mutant/normal.

Chemotherapy Agents (Vincristine, Vinblastine, Doxorubicin, Paclitaxel)- Based on collaborative research, the VCPL has determined that dose reductions are required for dogs MDR1 mutant/mutant and MDR1 mutant/normal in order to avoid SEVERE toxicity.

Apomorphine - this drug is used to induce vomiting in dogs that have ingested poisons/toxins. It can cause central nervous system 

depression in dogs with the MDR1 mutation at standard doses.

************************************************************************************************************************************************

Drugs that are known to be pumped out of the brain by the protein that the MDR1 gene is responsible for producing but appear to be safely tolerated by dogs with the MDR1 mutation:

problem-drugs

Cyclosporin (immunosuppressive agent)- While we know that cyclosporin is pumped by P-glycoprotein (the protein encoded by the MDR1 gene), we have not documented any increased sensitivity to this drug in dogs with the MDR1 mutation compared to “normal” dogs. Therefore, we do not recommend altering the dose of cyclosporin for dogs with the MDR1 mutation, but we do recommend therapeutic drug monitoring.

Digoxin (cardiac drug)- While we know that digoxin is pumped by P-glycoprotein (the protein encoded by the MDR1 gene), we have not documented any increased sensitivity to this drug in dogs with the MDR1 mutation compared to “normal” dogs. Therefore, we do not recommend altering the dose of digoxin for dogs with the MDR1 mutation, but do recommend therapeutic drug monitoring.

Doxycycline (antibacterial drug)- While we know that doxycycline is pumped by P-glycoprotein (the protein encoded by the MDR1 gene), we have not documented any increased sensitivity to this drug in dogs with the MDR1 mutation compared to “normal” dogs. Therefore, we do not recommend altering the dose of doxycycline for dogs with the MDR1 mutation.

Drugs that are known to be transported by the human or rodent forms of the protein encoded by the MDR1 gene but appear to be tolerated by dogs with the MDR1 mutation:

Morphine, buprenorphine, fentanyl (opioid analgesics or pain medications)- We suspect that these drugs are pumped by P-glycoprotein (the protein encoded by the MDR1 gene) in dogs because they have been reported to be pumped by P-glycoprotein in people, but we are not aware of any reports of toxicity caused by these drugs in dogs with the MDR1 mutation. We do not have specific dose recommendations for these drugs for dogs with the MDR1 mutation.

The following drugs have been reported to be pumped by P-glycoprotein (the protein encoded by the MDR1) in humans, but there is currently no data stating whether they are or are not pumped by canine P-glycoprotein. Therefore we suggest using caution when administering these drugs to dogs with the MDR1 mutation.

Domperidone

Etoposide

Mitoxantrone

Ondansetron

Rifampicin

There are many other drugs that have been shown to be pumped by human P-glycoprotein (the protein encoded by the MDR1 gene), 

but data is not yet available with regard to their effect in dogs with the MDR1 mutation.



0