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Collie and ivermectin, what to know.

I decided to treat this topic as it is well-known especially among breeders, less among common owners, that some Collies, due to a genetic mutation of the MDR-1 gene, are intolerant to ivermectin, an antiparasitic that can cause intoxications and bring them even to death.

The phenomenon of ivermectin toxicity in the Colie was first described in 1983.
Contrary to what we could think, the mutation of this gene does not only affect Collies in all his various breeds (Scots, Border, Rough ...). Nowadays there are several breeds in which said mutation was detected.
Among the most common:
  • Collie
  • Australian Shepherd
  • Bobtail
  • Shetland Shepherd
  • German shepherd
  • Swiss shepherd
 
IVERMECTIN
Ivermectin is the active ingredient used in various medicines for the prevention and treatment of various parasites including Dirofilaria.
Treatments based on this substance can be given by mouth, by injection and applied to the skin as a spot-on with different doses.
For example: IVOMEC, GUARDIAN, CARDOTEK...
It is an active ingredient considered as safe and with a low risk of collateral effects by veterinarians. Let's consider the specific case.
 
MUTATION OF THE MDR-1 GENE
MDR-1 is a very important gene that encodes a protein, the P-glycoprotein responsible for the distribution of ivermectin (but not only) inside the body. When the MDR-1 gene changes, the produced p-glycoprotein is altered and can't perform its function:  the active ingredient transmitted by it is abnormally distributed, with consequent cases of toxicity, in particular as regards the central nervous sytem. The intoxication of the animal will happen quickly in case of massive dose of medicine, as for the therapy of dogs with Dirofilaria, bringing the animal to death; in case of smaller dosages, a prompt admission can save him.
 
Each gene is composed by two alleles: if they are identical, we speak of homozygosis, if they are different we talk about heterozygosis.
This mutation is autosomal recessive: therefore, a dog with homozygous mutated MDR-1 will have a higher sensitivity to ivermectin and will show symptoms much more serious than a heterozygous subject who, instead, having one healthy and one mutated allele, will be only moderately sensitive and the seriousness of his symptoms will be minor or sometimes null in the case of very low doses.
This defect then passes to the offspring, starting from even apparently healthy subjects but who are actually carriers.
 
Contrary to what we commonly believe, it is not only the dreaded ivermectin that may give problems to the dogs affected by this mutation: to date there are more than 20 molecules identified as dangerous and among them there are also common antibiotics, antiparasitics, antifungal, antiemetic, antacids, steroids and many medicines commonly used in veterinary anesthesia (doxorubicin, vincristine, vinblastine, doxycycline, erythromycin, itraconazole, ketaconazole, rifampicin, tetracycline, cyclosporine, tacrolimus, domperidone, ranitidine, butorphanol, ivermectin, morphine, moxidectin, phenothiazines, selamectin only to name a few among the most common).
The seriousness of the symptoms will obviously always be connected with the dose taken and with the degree of genetic defect (sick or carrier).
 
SYMPTOMS OF POISONING
Symptoms related to cerebral accumulation of ivermectin appear in 4-12 hours after exposure to the medicine in case of use of massive doses and in about 48-96 hours in the case of administration of smaller doses.
You will notice:
  • Dilated pupils with greater sensitivity to light
  • Digestive problems, lack of appetite and abundant salivation
  • Lethargy: drowsiness up to a real difficulty for the animal to stand up
  • Motor problems: the animal has difficulty in moving, stumbles, falls, staggers and can appear as disoriented and does not respond to your call
  • Respiratory problems: the animal will have a shallow, gasping breathing, which can cause him loss of consciousness, fainting. He may have epileptic fits that in case of lack of treatment will lead him to coma and death.
 
TREATMENT
Being a genetic disorder, treatment will only be palliative and will help to control the most dangerous symptoms, waiting for the animal to dispose of intoxication.
In any case, should you notice a symptom among those mentioned above in a genetically at-risk subject, it is important to contact immediately a veterinarian.
 
Dogs affected by mutation are apparently healthy and have normal physiological and haematological parameters; fortunately today it is possible to diagnose mutation with a specific genetic test through which you can establish with certainty if the dog is healthy, mutated heterozygous, that is with only one of the two mutated alleles, or mutated homozygous, that's to say with both mutated alleles.
The test is useful to identify the genotype of the reproducers intended for coupling and thus reduce the onset of this mutation. Considering the large number of potentially toxic medicines and the seriousness of symptoms that may occur following the intake of one of these molecules, in order to safeguard the health of our dog is very important to know if the MDR1 gene is changed or not. Therapies or anesthesia that may become necessary during the life of your dog will be calibrated according to the possible mutation of the MDR1 gene.
 
I hope I have been clear enough: it's difficult to simplify genetic concepts. Leave your comment, should you have other questions. I will be available.
I'll be back soon with my next article!
 

Eleonora Bosoni  

Dr. in Veterinary Medicine

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