The ABCB1 gene, previously known as the MDR1 gene, codes for P-glycoprotein, which is a transmembrane ATPase that transports small molecules out of the cell in an energy dependent process. This P-glycoprotein is also an important component of the blood–brain barrier where it serves to protect the central nervous system from exposure to some drugs. A mutation in the ABCB1 gene has been described; dogs that are homozygous or heterozygous for the ABCB1 gene mutation have an increased sensitivity to certain drugs used for sedation, including acepromazine, morphine, butorphanol and fentanyl.

Collies show the highest frequency of the mutation, with approximately 75% of dogs from this group carrying at least one copy of the mutant gene. Other breeds that frequently carry the mutation include the Australian Shepherd, Shetland Sheepdog and Old English Sheepdog.

Recommendations for sedation

Recommendations are largely empirical because there are limited data on the effect of the mutation on the pharmacodynamics and kinetics of sedative and opioid analgesic drugs.

If appropriate, preferentially use an alpha-2 agonist for sedation. If acepromazine is included in the sedative protocol, use the low end of the dose range (5 µg (micrograms)/kg i.v or 10 µg/kg i.m.).

When selecting an opioid for incorporation in the protocol avoid butorphanol, morphine and fentanyl, and use methadone at the low end of the dose range (0.1–0.2 mg/kg i.v., i.m.).

References

Deshpande D, Hill KE, Mealey KL, Chambers JP and Gieseg MA (2016) The effect of the Canine ABCB-1 D  mutation on sedation after intravenous administration of acepromazine.Journal of Veterinary Internal Medicine 30, 636–641