Multi-drug Sensitivities in Dogs

A number of dog breeds are more prone to serious side effects from certain drugs than other breeds. For example, Collies can have severe adverse reactions to the antiparasitic drug, ivermectin.
The cause of this sensitivity is a DNA sequence change (mutation) in the dog’s multi-drug resistance gene, known as the MDR1 gene. The function of this gene is to prevent dangerous drugs from entering the CSF. Dogs with the mutated MDR1 gene have an alteration in the blood brain barrier affecting transport of drugs such as ivermectin. Exposure to these drugs may result in serious neurological signs, such as hypersalivation, ataxia, blindness, tremor, respiratory distress and even death.
As well as protecting the brain, the MDR1 gene plays a vital role in drug elimination. Dogs that have a
mutated MDR1 gene can have reduced drug elimination compared to others, resulting in elevated plasma drug levels and an increased tendency for toxicity.
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)

Approximately 75% of Collies in Australia have the mutated MDR1 gene. The mutation has also been found in Shetland Sheepdogs (Shelties), Old English Sheepdogs, German Shepherd Dogs, Long-haired Whippets and a variety of mixed breed dogs.

You can test your dog for multidrug sensitivity and prevent serious adverse drug reactions.

Washington State University
Gribbles Molecular Science and Gribbles Veterinary Pathology


Research: Health Implications in Early Spay and Neuter in Dogs

Recent results from research funded by the AKC Canine Health Foundation have the potential to significantly impact recommendations for spaying and neutering dogs in the United States. Most dogs in the United States are spayed or neutered, and for years the procedures have been completed prior to maturity. The study, published in the prominent, open access journal PLOS One, suggests that veterinarians should be more cautious about the age at which they spay and neuter in order to protect the overall health of dogs.

A team of researchers led by Dr. Benjamin L. Hart at the University of California, Davis has completed  the most detailed study performed to date that evaluates incidence of cancer diagnoses and joint problems in one breed — Golden Retrievers — by neuter status: early (before 12 months old), late (12 months or older), and intact. Consistent with previous studies on the topic, the results showed increased likelihood of hemangiosarcoma, lymphoma, mast cell tumors, and canine cruciate ligament (CCL) rupture in neutered dogs.

The most profound observations were in hip dysplasia in male dogs when comparing early and late-neutering. The risk of development of hip dysplasia doubles, and disease occurs at a younger age in the early-neuter group compared to both the intact and late-neuter group. No occurrence of CCL disease was observed in intact male or intact female dogs, or in late-neutered females. In early-neutered dogs, the incidence of CCL was 5.1 percent in males and 7.7 percent in females, suggesting that neutering prior to sexual maturity significantly increases a dog’s risk of developing CCL disease. With respect to cancer, cases of lymphoma were 3-fold greater in the early-neutered males. Interestingly, incidence of mast cell tumors (male and female dogs) and hemangiosarcoma (female dogs only) were highest in the late-neuter group.

“Dr. Hart’s landmark study is the first to provide evidence for when to spay or neuter dogs. For years the veterinary community has been aware that early-spay and neuter may impact orthopedic health in dogs. Through a very detailed analysis and inclusion of body condition score as a risk factor, Dr. Hart was able to show that timing of spay and neuter does indeed have health implications,” said Dr. Shila Nordone, Chief Scientific Officer for the AKC Canine Health Foundation.

“CCL disease is painful, debilitating, and costs dog owners $1 billion annually to treat. The AKC Canine Health Foundation is committed to funding research, like Dr. Hart’s study, that can lead to evidence-based health recommendations. Armed with prudent guidelines for when to spay and neuter dogs we will have a significant impact on the quality of life for dogs,” continued Dr. Nordone.

Importantly, the task at hand is now to determine if the observations in this study are indeed true across all breeds and mixed breeds of dogs. Dr. Hart is interested in continuing his work by studying Labrador Retrievers, German Shepherd Dogs, and Dachshunds. Additionally, gaps in knowledge continue to exist concerning the complex relationship between sex hormones and cancer.

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