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Ivermectin Sensitivity- Overview

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Ivermectin Sensitivity is a hypersensitivity to the drug Ivermectin. In affected dogs the drug and other toxins cannot be removed from the brain and surrounding tissue. This results in the accumulation of toxins and can lead to adverse neurological affects. Ivermectin is a commonly used heartworm prevention drug. A mutation in the multi-drug resistance gene (MDR1) in dogs prevents the production of a transport protein (P-Glycoprotein), which removes the drug and toxins from the brain and tissues. The resulting accumulation from this failure to detoxify the brain and tissues often results in severe neurological affects such as hyper-salivation, ataxia, blindness, coma, respiratory arrest and death. Unfortunately this sensitivity is not only restricted to Ivermectin, but many other preventative canine drugs. It is essential that owners be aware if their dog is Ivermectin sensitive as many affected dogs require as little as 1/200th of the dose required to cause toxicity in healthy dogs. Ivermectin sensitivity has an extreme degree of severity as it can cause immediate death.

Genetic Testing

Ivermectin sensitivity is an autosomal recessive disease meaning the dog will only be affected when two copies of the recessive gene variant are present. These will have been inherited from both parents. A direct gene test can detect whether a dog is clear, carrier or is affected by the disease.

Genetic test interpretation

Not Detected

This dog does not have the gene variant and will never produce affected offspring. This dog would not be expected to experience unexpected adverse drug reactions to normal doses of ivermectin, loperamide (Imodium), and some anticancer drugs.

Carrier

This dog has one copy of the gene variant. It is not affected, however, it will pass the gene variant onto its offspring 50% of the time. This dog will not experience toxicity after normal doses of loperamide (Imodium), some anticancer drugs, and high doses of ivermectin (greater than 50 micrograms per kilogram).

Affected

This dog has two copies of the gene variant.  It will be affected and will pass one copy of the gene variant onto its offspring 100% of the time. This dog would be expected to experience toxicity after normal doses of loperamide (Imodium), some anticancer drugs, and high doses of ivermectin (greater than 50 micrograms per kilogram).           

Breeds Affected  

Frequency 

Australian Shepherd

50%

Australian Shepherd, Mini       

50%

Border Collie              

<5%

Collie

70%

English Shepherd

15%

German Shepherd           

10%

Herding Breed Cross          

10%

Long-haired Whippet          

65%

McNab                  

30%

Mixed Breed              

5%

Old English Sheepdog         

5%

Shetland Sheepdog           

15%

Silken Windhound           

30%

A number of drugs have been shown to cause problems in dogs with a mutated MDR1 gene. These include:

  • Acepromazine (tranquilliser)
  • Butorphanol (analgesic)
  • Cyclosporin (immunosuppressant)
  • Digoxin (cardiac inotrope)
  • Doxorubicin (antineoplastic)
  • Ivermectin (antiparasitic)
  • Loperamide (antidiarrhoeal)
  • Vinblastine (antineoplastic)
  • Vincristine (antineoplastic)

(Please note that this is not a complete list of drugs that may affect dogs with the MDR1 gene mutation)

References:
1. Mealey KL et al. Ivermectin sensitivity in Collies is associated with a deletion mutation of the MDR1 gene. Pharmacogenetics 2001 11 (8):727-733.
2. Mealey KL et al. Increased toxicity of p-glycoprotein-substrate chemotherapeutic agents in dogs with the MDR1 deletion mutation associated with Ivermectin sensitivity. J Am Vet Med Assoc 2003 223 (10): 1453-1455.

 

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