MDR1 is a dominant gene .
1 copy = moderately affected
2 copies = strongly affected
Many Drugs are known to cause neurological signs related to the MDR1 mutation.
These are among the worst:
Acepromazine, butorphanol, doxorubicin, emodepside, erythromycin, ivermectin, loperamide, milbemycin, moxidectin, rifampin, selamectin, vinblastine and vincristine.
The MDR1 gene mutation can be fatal when affected Aussies are exposed to medications like Trifexis and Ivermectin for dogs (among many other medications).
MDR stands for multi-drug resistance and the mutation in the MDR1 gene prevents many breeds, including Australian Shepherds, from removing many drugs from the brain resulting in toxicity. The MDR1 mutation is believed to occur in approximately 50% of Australian Shepherds. Dogs with the MDR1 mutation can be 200 times more sensitive to the drugs than dogs that do not have this mutation.
Dogs with the mutation lack a protein (P-glycoprotein) which is responsible for pumping the drugs from the brain. When this process is interrupted the drugs build up and permeate the brain and neurological toxicity results.
Just because a dog tests negative does not mean it's safe.
All herding dogs, even those tested and cleared for the MDR1 gene mutation, can be at risk. How? The same problem caused by the MDR1 mutation can be triggered by several medications. The effect of the drugs may result in the same toxicity in healthy dogs as would occur with dogs who have tested positive for the MDR1 mutation. Of course, these drugs would affect dogs that have been cleared, those that are carriers, and those that are affected. So, no dog is completely safe.
So instead of the normal P-glycoprotein pumps not working because of the MDR1 mutation they are deactivated by the drugs. Either way the effect of neurotoxicity is the same.
The MDR1 Chart above shows the drugs broken down by the degree of risk they pose. This is not a complete list.
Im addition, grapefruit juice or extract should be avoided.