Loperamide Toxicity in a Collie with the MDR1 Mutation Associated with Ivermectin Sensitivity

A 3-year-old spayed female Collie was referred to the University of Wisconsin Veterinary Teaching Hospital (UWVTH) with a 2-day history of decreased appetite, vomiting, and diarrhea.The dog had been adopted from a Collie rescue agency 2 weeks before presentation, and previous historic information was not available.The referring veterinarian reported no abnormalities on physical examination and treated the dog with loperamide (0.14 mg/kg PO q12h).The dog presented to the referring veterinarian again the next morning.She had vomited once during the night and had developed profuse ptyalism.The veterinarian performed a diagnostic workup consisting of a CBC, serum biochemistry, venous blood gas analysis, and abdominal radiography.The only abnormalities detected were mild hypokalemia (3.4 mEq/L; reference range, 3.7-5.8mEq/L) and hyperglycemia (131 mg/dL; reference range, 60-110 mg/dL).Treatment consisted of subcutaneous fluid administration and loperamide at the dosage previously specified.Over the next several hours, ptyalism continued and the dog developed progressively more severe neurologic signs, including rear limb weakness, apparent difficulty holding up the head, vocalization, disorientation, and ataxia.That evening, the dog was taken to an emergency veterinary hospital, where she was treated with additional subcutaneous fluid and metoclopramide (0.3 mg/kg SC) and discharged.The next day, the dog's owners contacted the Collie rescue organization regarding their dog's medical condition and were advised to discontinue loperamide because of possible breed sensitivity to the drug.The dog was presented to the UWVTH that afternoon for evaluation of neurologic and gastrointestinal signs, but by the time of presentation the dog's neurologic status had begun to improve.On physical examination, the dog was normothermic (100.1ЊF) and had a normal heart rate.The dog was panting and vocalizing (whining), and ptyalism was noted.Neurologic examination identified disorientation, hyperexcitability, and hyperresponsiveness to noise.The dog was recumbent but able to walk when encouraged.