Ivermectin toxicity

From Dog

Toxicity due to ivermectin is a relatively common syndrome in dogs, due an autosomal recessive trait (MDR-1) gene has been identified that causes a defect in the p-glycoprotein multidrug transporter to the blood brain barrier. This allows for the ivermectin pass into the brain at low dosages thus causing toxicity.

This trait may also cause toxicity from other related drugs and should also be avoided or used in lower doses in susceptible breeds. Toxicity can also occur from a one-time injection or from daily dosing.

Several breeds are more likely to be affected by avermectins including collie[1] and collie crosses[2]. The Huntaway, Old English Sheepdog, Australian Shepherds[3], and Shetland Sheepdog have also been mentioned as susceptible breeds. This increased susceptibility is due to a difference in the blood-brain barrier in these breeds. Younger animals also appear more susceptible to intoxication.

The most important aspect of intoxication with avermectins is the prolonged recovery time (weeks to months).

Clinical signs

Clinical signs are usually dose related and do not occur immediately. Often symptoms begin approximately 1-4 hours post ingestion and can range from mild ataxia, vocalization, disorientation, dementia, whole body tremors, dilated pupils, apparent blindness, circling, head pressing, slowed heart rate, hypothermia, coma, and death.

Diagnosis

Routine baseline diagnostics to include a complete blood count, biochemical profile and urinalysis are generally within normal limits. Abnormalities in blood gas analysis may be seen in association with respiratory depression, which is slower and more shallow breathing.

A temporary return to consciousness or alertness after the administration of physostigmine (a medication) supports, but does not confirm, a diagnosis of ivermectin toxicity.

Ivermectin sensitivity testing (the presence MDR-1 mutant gene) is available at Washington State University College of Veterinary Medicine. They use a cheek brush sample for analysis.

Treatment

Treatment is largely supportive and symptomatic, as there are no specific reversal agents available to treat ivermectin toxicity. However, if an accidental exposure was recent (with 4 to 6 hours), induction of vomiting may be recommended, gastric lavage and activated charcoal to minimize drug absorption.

Supportive treatment: IV fluids and parenteral nutrition (feeding tube or IV nutrition) are given to maintain hydration and meet caloric needs. To prevent decubital ulcers (bed sores), soft bedding (mattress) is provided, the pet is turned every few hours, and any sores that form are treated. If anaphylaxis occurs, appropriate treatment is given. Seizures and hyperthermia are controlled as necessary.

Specific treatment: Physostigmine may be administered in severe poisoning cases.

References

  1. Hopper K et al (2002) Ivermectin toxicity in 17 collies. J Vet Intern Med 16(1):89-94
  2. Sartor LL et al (2004) Loperamide toxicity in a collie with the MDR1 mutation associated with ivermectin sensitivity. J Vet Intern Med 18(1):117-118
  3. Nelson OL et al (2003) Ivermectin toxicity in an Australian Shepherd dog with the MDR1 mutation associated with ivermectin sensitivity in Collies. J Vet Intern Med 17(3):354-356