drug sensitivity of Colley-like breeds(Australian Shepherd)

Sheepdog, Berger Blanc Suisse, Longhaired Whippet,  McNab,  Old English Sheepdog,  Silken Windhound , Wäller, Border Collie
Australian Shepherd

Colley, Australian Shepherd, Miniature Australian Shepherd, English Shepherd, Shetland Sheepdog, White Swiss Shepherd, Longhaired Whippet, McNab, Old English Sheepdog, Silken Windhound, Wäller, Border Collie A little genetics:
Mutations in DNA are frequent and are an evolutionary factor that allows them life to develop. For example, the color in dogs is due to a genetic mutation. Unfortunately, some mutations can induce serious diseases such as familial nephropathy in Cocker's disease (kidney disease causing death before the age of 2 years), or cerebellar ataxia at the Staffordshire American Terrier (degeneration of the nervous system).
Others, finally, without affecting the function of the mutated gene, are called silent.

The blood-brain barrier:
The MDR1 gene, abbreviated to Multi-Drug Resistance synthesizes a protein that is strongly expressed in the endothelial cells that line the cerebral capillaries on the blood flow side. They are the most important essential components of this barrier.

This protein, Glycoprotein-P, protects the integrity of the Central Nervous System (SNC) by opposing the penetration of many drugs in the brain.
Glycoprotein-P has expressed in other areas of the body: the intestinal mucosa or it helps to reduce the absorption of xenobiotics from the gastrointestinal tract, the liver or the kidneys, promoting the elimination of endogenous and exogenous toxic substances through urine and bile.

The MDR1 mutation, which my dog?
The mutation consists of a sequence Truncated DNA (some basic information about the DNA strand is missing) making it impossible to synthesize the protein. it follows, in dogs carrying mutation, an increase in the absorption by the CNS of a number of chemical molecules leading to an increase in their adverse effects characteristic of an overdose:
mydriasis (abnormal dilation of the pupil), nervous disorders, digestive disorders, coma and sometimes death if the concentration becomes too high.
And a little history:
A mutation has occurred in the MDR1 gene around the middle of the 18th century in a dog of shepherd belonging to the family of dogs that will give birth later to the Colley.

This mutation renders the MDR1 gene non-functional. Over time, the mutation spread to these sheepdogs and now concerns eleven breeds: Colley (long hair and long hair short), Australian Shepherd (and miniature), Shetland, White Swiss Shepherd, English Shepherd, Bobtail, Longhaired Whippet, McNab, Silken Windhound, Wäller and, to a lesser extent, the Border Collie.

The mutation having appeared in the Colley, it is in this race that we find the most a large number of dogs concerned by this one. 8 Colleys on 10 is sensitive, or in a position to do so, to certain molecules chemical.

Consequences for our dogs:
The mutation does not disrupt or alter in any way the lives of our dogs: Their well-being, their health, their longevity is preserved. It is the arrival on the market of a new type of deworming in the late 1980s, ivermectin, which, causing fatal accidents in Colleys, scientists warned. The MDR1 mutation will be highlighted by Professor Mealey and the work carried out by the University of Washington laboratory in 2001.

The P-glycoprotein synthesized by the MDR1 gene exerts its actions on a wide range of molecules with very diversified structures: anti-cancer agents, immunosuppressants, antiparasitic agents, cardiac drugs, antibiotics, opioid analgesics, etc....

While many will never be given to our dogs, others will be given the active ingredients of some dewormers, for example, are dangerous for dogs affected by MDR1 and must be avoided at all costs.

Reactions:
Dogs that are homozygous for the MDR1 genetic mutation (generally noted as MDR1 (-/-) meaning that they have inherited 2 mutated copies of the MDR1 gene from their parents) quickly show the effects of an adverse reaction to drug substances
that interact with P-glycoprotein at levels that do not cause an adverse reaction in normal MDR1 dogs (+/+). Chemical molecules accumulate in the CNS and can express their neurotoxicity.
The reactions will depend on the dose given to the dog, the type of chemical molecule and the how it was delivered: enteral route (administration through the digestive tract, again called per os), or parenteral route (intravenous, subcutaneous, intramuscular injection).

Reactions can be numerous: nervous signs (prostration, ataxia, mydriasis...), paresis (partial loss of motor skills) or paralysis, digestive signs (vomiting, nausea, hypersalivation...), pallor, dilated pupils, convulsions, then coma, even death.

It is imperative to avoid it:
Ivermectin (antiparasitic agent) and related molecules: Doramectin, abamectin, moxidectin, milbemycin. Ivermectin is fatal to mutate homozygous dogs (-/-) and dangerous for heterozygous dogs for the mutation (+/-). Loperamide (antidiarrheal agent): 

Imodium and Liberal Emodepside (pest control agent): Profender

Concerning anesthesia:
The increased sensitivity of the dogs affected by MDR1 requires the use of gas anesthetics, which are under the permanent control of the practitioner and can be measured very finely. Refuse any injection anesthesia.

And in the event of an accident:
This is a veterinary emergency. It should be consulted immediately. There is no antidote effective with ivermectins. The treatment is based on repeated administration of activated charcoal, assisted nutrition, appropriate rehydration, sometimes (in case of coma) mechanical ventilation is necessary (source Genindexe). As for loperamide, naloxone is an antidote.

Prevention:
An oral or blood sample sent by mail to one of the 2 laboratories offering the screening will make it possible to determine its MDR1 profile. The result is known about two weeks later. We can only advise you to do so.
If your dog is MDR1 (+/-) or (-/-):
Finally, precautions must be observed with other molecules: antiemetics (Motilium, Primera, Primperid, Emeprid...), light tranquilizers (Vétranquil).


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