DRUG SENSITIVITY

An allergic reaction to drugs is no stranger to man or beast, and it has long been recognised that Rough Collies are particularly sensitive to a range of sedatives, tranquillisers and anaesthetics, although there are those in the veterinary profession who continue to pour scorn on such claims.

Early in the 1980s a new class of anti-parasitic preparations for large animals, based on the active ingredient ivermectin, became available for general veterinary use and although not licensed for use on dogs veterinary practitioners were not slow in discovering its usefulness when treating persistent cases of parasitic infestations, so that it quickly became the drug of choice especially when mange was diagnosed.

Shortly after Ivermectin’s introduction to the veterinary armoury rumours began to circulate about its adverse side-effects when administered to Rough Collies. When a well known Italian breeder lost four of her valuable Rough Collies after an Ivermectin based drug was administered as a wide spectrum anti-parasitic preventative to her kennel suspicions became facts which were widely circulated by breeders throughout the world. However the veterinary profession as a whole remained sceptical despite Merck Sharp and Dohme Ltd [MSD], who manufactured the drug used in the Italian case, issuing the following advice — ‘Ivermectin is known to have an adverse effect on certain breeds of dog’ — in three letters written to the editor of ‘The Veterinary Record’. But this did not prevent further tragic incidences of use, and at least one more serious breeding kennel lost several valuable animals before MSD agreed to print a more detailed warning on the offending drug’s packaging.

GENETIC BREAKTHROUGH

As the number of breeds reporting adverse reactions increased and additional drugs, several of which were licensed for canine use, were added to the list of suspect preparations two groups of veterinary scientists began investigating the origin of this apparent problem, and early observations showed affected dogs had an elevated concentration of the offending substance in their central nervous system. When this fact was linked to the discover that genetically modified laboratory mice, being used in quite independent research into the necessity of the Multi Drug Resistance-1 [MDR-1] gene, quickly died when treated with an ‘Ivermectin’ based spray for a mite infestation, the American based team, headed by Dr Katrina Mealey and Dr Mark Neff, gained the necessary breakthrough in isolate the cause of this problem.


Having perfected a DNA test to prove their theories swabs were collected from a wide selection of apparently unrelated breeds, mostly pastoral and hounds that were resident in several countries, which had reported some incidence of drug sensitivity. Once analysed the results revealed a pre-existing mutation of the MDR-1 gene in the wider Collie family, possibly dated early to mid nineteenth century, confirming what many Collie enthusiasts had long suspected. The DNA test perfected by the research team is now available in both America and Europe which can only assist veterinarians in their choice of treatment options, this of greatest assistance in deciding the treatment of more serious conditions such as cancer and heart disease.

PROBLEM DRUGS

A large number of drugs are known to be controlled by the MDR-1 gene in man although there is insufficient data available to be specific about the way these drugs may affect dogs carrying the double mutant (-/-) MDR-1 gene. It is now recognised that more than fifty substances are known, suspected, or have the potential to cause problems with these dogs and this list is still being extended almost daily. The drugs listed below, in alphabetical order, are used to treat a wide spectrum of canine ailments including cancer, heart disease and pain relief, in addition to anti-parasitic and anti-histamines preparations which sparked off the original research, all fall into one of the above categories, and should therefore not be administered to any Rough Collie without first ascertaining its genetic status.

IMPORTANT NOTICE — Each of the listed preparations may be sold under a variety of trade names therefore Collie owners are strongly advised to check the list of active ingredients, supplied with all drugs, against this list, whether the drugs are purchased over the counter or prescribed by your vet, before administering to any Collie.

In view of the ever lengthening list of drugs known, suspected, or having the potential to cause problems those owners who have had their animals DNA tested for Drug Sensitivity should supply copies of official results to their veterinary practice and ensure that they record this information against the appropriate animal.

If your veterinary practice appears vague about this genetic abnormality we suggest that you provide them with a link to this page which supplies an overview of the problem in addition to providing links to appropriate up to date scientific material.

Acepromazine

Aldosterone

Amitriptyline

Antiemetics

Buprenorphine

Butorphanol

Chinidin

Cimeditine  

Cortisol

Cyclosporin A

Dexamethasone

Digoxin

Diltiazem

Domperidone

Doxorubicin

Doxycycline

Ebastine

Erythromycin

Estradiol

Etoposide

Fentanyl

Fexofenadine

Grepafloxacin

Hydrocortisone

Ivermectin

Itraconazole

Ketoconazole

Loperamide

Losartan

Methylprednisolone

Metoclopramide

Metronidazole

Milbemycin

Mitoxantrone

Morphine

Moxidectin

Ondansetron

Paclitaxe

Phenothiazines

Phenytoin

Quinidine

Ranitidine

Rifampin

Rifamicin

Selamectin

Sparfloxacin

Tacrolimus

Tetracycline

Verapamil

Vinblastine

Vincristine

WARNING — recently a number of broad spectrum anti-parasitic preparations, using one or other of the above substances, have been licensed for canine use. The drug companies manufacturing these preparations claim that the drug has been modified making it safe to use on breeds known to carry the MDR-1 mutation. Neither the Rough Collie Breed Council nor its Member Clubs have any way of verifying these claims and therefore urge extreme caution; only ever considering these products after careful consultation with and under the direct supervision of your veterinary advisor after ascertaining that they are fully conversant with the ramifications of this genetic condition.

ONGOING RESEARCH

The American research team’s findings were published as recently as 2004, and the DNA test not made widely available until 2007 so the significance of the MDR-1 mutation has yet to be fully evaluated, and there are those who believe that this is far in excess of currently accepted knowledge. The European scientific team working in Germany are still actively investigating the effects of abnormalities in the Multi Drug Resistance gene complex, together with its production of P-glycoprotein, on humans and it is believed that their finding will also apply to the canine species, but time is required before speculative theory can be translated into irrefutable fact. Until this happens breeders are urged to DNA test all breeding stock, taking the results into consideration when choosing a suitable mate, and owners are encouraged to insist that their veterinary advisors not only add their pet’s genetic MDR-1 status to their medical records, but to also fully research the problem before treating any Collie related animal.

In February 2011 the Rough Collie Breed Council, supported by the Smooth Collie Club of GB, English Shetland Sheepdog Club, Border Collies and the Australian Shepherd Dog of UK, hosted its first ever health seminar on MDR-1 and its significance to susceptible breeds at the Kennel Club Building, Stoneleigh Park.

Opened by Mr David Crapper, who was then the Rough Collie Breed Council Chairman and Rough Collie Health Coordinator, the 60+ delegates, representing all susceptible breeds and most Collie Breed Clubs, were each presented with a folder which included a specially prepared booklet relating the current known ramifications of the MDR-1 gene expressions together with a brief history and recent case studies.

Believing Rough Collie breeders might like to supply copies in their puppy packs as well as owners wanting a copy either for their own records or to give to their veterinary practice the RCBC now makes this 8 page booklet available for download here

NOTE - The Rough Collie Breed Council, on behalf of its Member Clubs, would like to assure all Collie owners that even those graded double negative [-/-] after a DNA test regularly live long happy healthy lives. The side effects of this drug sensitivity not surfacing until one of the problem drugs are administered to your collie for an unrelated health condition, the solution is to avoid these drugs which is perfectly possible

Related Internal Links



 

 

 

Useful external links

Breed distribution and history of Canine MDR 1 (pdf document)

Multi drug sensitivity

Multi drug resistance in Collies

Ivermectin sensitivity in Collie lineage

Collie bloodlines

MDR1 gene story and its significance