Why is ivermectin contraindicated or used with caution in Collies and other MDR1 mutation dogs?

Why is ivermectin contraindicated or used with caution in Collies and other MDR1 mutation dogs?

• A. It is completely safe in Collies
• B. It has no CNS toxicity risk in any breed
• C. MDR1 mutations have no effect on drug distribution
• D. MDR1 mutation leads to reduced P-glycoprotein function at the blood-brain barrier, increasing risk of CNS toxicity

Answer: (D)

Key idea: P-glycoprotein at the blood–brain barrier normally pumps ivermectin out of the brain, keeping CNS exposure low. In dogs with the MDR1 mutation, this transporter has reduced function, so ivermectin can enter the brain more readily. In Collies and other MDR1-mutant dogs, this means even standard doses carry a real risk of CNS toxicity, presenting as ataxia, tremors, weakness, hypersalivation, seizures, or depression, and in severe cases coma. Because of this mechanism, ivermectin is contraindicated or used with extreme caution in these breeds. The other statements ignore the role of the MDR1 mutation and P-glycoprotein in limiting CNS drug entry, which is why they’re not correct.

Key idea: P-glycoprotein at the blood–brain barrier normally pumps ivermectin out of the brain, keeping CNS exposure low. In dogs with the MDR1 mutation, this transporter has reduced function, so ivermectin can enter the brain more readily. In Collies and other MDR1-mutant dogs, this means even standard doses carry a real risk of CNS toxicity, presenting as ataxia, tremors, weakness, hypersalivation, seizures, or depression, and in severe cases coma. Because of this mechanism, ivermectin is contraindicated or used with extreme caution in these breeds. The other statements ignore the role of the MDR1 mutation and P-glycoprotein in limiting CNS drug entry, which is why they’re not correct.