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Some dog breeds are more sensitive to certain drugs compared to other breeds. For example, Australian Shepherds, Collies and Longhaired Whippets? are more sensitive to antiparasitic and anticancer drugs. The problem is due to a mutation in the multidrug resistance gene (MDR1). The product of MDR1 gene, P-glycoprotein, is an important component of the blood-brain barrier that is responsible for pumping many drugs out of the brain. Dogs with mutant MDR1 gene cannot remove some drugs out of the brain as normal dogs would, which may result in abnormal neurological signs. The result may be an illness requiring an extended hospital stay or even death of the dog.
In addition to its expression in the blood-brain barrier, P-glycoprotein expression occurs also in the intestinal tract, liver, and kidney. In these organs, the absence of P-glycoprotein will alter the pharmacokinetic properties of drugs identified as P-glycoprotein substrates, resulting in enhance oral bioavailability and/or reducing drug elimination through the liver, kidney, and gut. In consequence, plasma concentrations will increase and adverse drug reactivity may occur. Drugs that have been documented, or are strongly suspected to cause problems in dogs with MDR1 mutation:
- Acepromazine (tranquilizer)
- Butorphanol (pain control)
- Cyclosporin (immunosuppression drug)
- Digoxin (heart drug)
- Doxorubicin (anticancer drug)
- Ivermectin (antiparasitic drug)
- Loperamide (Imodium?, antidiarrheal drug)
- Moxidectin
- Vinblastine (anticancer drug)
- Vincristine (anticancer drug)
Biochemical studies have shown that mutant MDR1 gene has the potential to act on over 50 different drugs. The following drugs may potentially cause problems when given to dogs that have the mutation:
- Domperidone
- Etoposide
- Mitoxantrone
- Morphine
- Ondansetron
- Paclitaxel
- Quinidine
- Rifampicin
DNA Test
Dogs affected with multidrug sensitivity typically display neurological symptoms after drug admission such as hypersalivation, ataxia, blindness, tremor, depression, coma, respiratory compromose, and death. Carriers of the mutant gene may display mild neurological manifestations. DNA-based test for the detection of the gene responsible for multidrug sensitivity became available. Since this test directly targets the mutant gene, it is 100% accurate and provides breeders with definitive information on the genetic status of their animals. Instead of avoiding drugs as ivermectin in known susceptible breeds, veterinarians can now determine if a dog is normal, in which case the drug can be administered, or dog is affected, in which case an alternative treatment can be given. Breeders can use this information to detect carriers and eliminate this disease from their breeding lines. |
