Acepromazine - Drug Reaction in Herding Dogs

Drug Reaction in Herding Dogs

For over 20 years herding dogs have died from negative reactions to acepromazine that were rooted in genetic mutations. This reveals a lack of understanding about Acepromazine, and other drugs with potentially toxic side effects. Scientists isolated the problem: the Multi Drug Resistant 1 (MDR1) gene. In addition, more than 30 potentially toxic drugs have been identified, and a lab test has been developed to identify dogs with the abnormal MDR1 gene. We now recognize 3 different factors that contribute to drug toxicity especially common in herding dogs: a genetic mutation, drugs that inactivate normal cell pumps, and substances that inactivate cell enzymes so they cannot break down drugs.

Cell enzymes (CYP3A), In addition to having proteins on the membrane that remove drugs from the cell, most cells have enzymes that break down drugs and inactivate them. Cytochrome P 450 (CYP 450) is a family of enzymes that inactivates about 60% of drugs used in pets. One of the CYP 450 family—CYP3A—can be blocked or inactivated by ketoconazole and by grapefruit juice. With CYP3A inactivated, drugs reach toxic concentrations within cells.

Dogs can have both the defective MDR1 gene and have inactivated CYP3A enzymes. These dogs are very likely to develop toxicity with certain drugs.

Breeds with MDR1 gene

Herding dogs:Australian Shepherd, Border Collie, Collie, English Shepherd, German Shepherd, Old English Sheepdog and Sighthounds

Drugs that become toxic if not pumped out by P-glycoproteins

Many different drugs are normally pumped from cells by P-glycoproteins: anticancer drugs, antiparasitics, antibiotics, cardiac drugs, immunosuppressants, opioids, steroid hormones, and miscellaneous drugs. Acepromazine can become toxic in dogs with the MDR1 mutation.

The anxiolytic drugs like Acepromazine can lead to hearing loss and other serious side effects.