Seizure or not

My Sheltie has had 3 separate seizures, all after taking 1-2 doses of Previcox. Previcox was prescribed in Nov. 2011 at his senior exam to use as needed for arthritis in his hind hips. He is 13 yrs old and has had his hind legs slip out a number of times. I used the Previcox for the 1st time in Feb. He had diarrhea prior to this for a few days & a call to the vet had him on a bland rice & chicken diet. He seemed stiff walking so I gave him the 1/2 tablet dose of Previcox. Within 12 hrs. he had a seizure (laid on side, legs stiff paddling, foaming at mouth) for about 30 seconds then got up and walked around seeming fine within 5 min.  About 8 hrs. later he had another seizure & I called the vet & took him in. Due to the Diarrhea the vet figured he was having stomach cramps, gave me metronidazole for the diarrhea & loperamide for the cramps. All was fine. On Mar. 31 his hind legs seemed to be slipping more than usual, a friend was taking care of him for the weekend. We gave her the Previcox to give if needed. She gave him a dose on Sat. & all seemed well. She gave him a 2nd dose on Sun. & 2 hours later he had a seizure similar to the one in Feb. I called the vet, they said it could be cramps since she gave him the med with just alittle food. She didn't give him anymore doses and he was fine through the week. I took our dog to the vet that Thur to see if he should be on something regularly for his hips and was told to give him the Previcox daily. On Fri. I gave him 1 dose, all seemed well. On Sat. gave 2nd dose. Within 2 hours he had a seizure followed by another 45 min later. We took him to the vet urgent care and he was put on phenobarbitol to stop the seizures. They kept him 24 hrs and he is now on phenobarbitol to prevent additional seizures. Since all 3 times of seizures were linked to happening after a dose of previcox, I think the previcox caused the seizures. The vets aren't linking that. He is wiped out & and can't stand from the phenobarbitol. I agree to keep him on it for a few days but I am feeling the Previcox is the cause of the seizures & not sure that I want him to stay on the phenobarbitol for long term. Any input??

[Ghilly]

Have you had your dog tested to see if he has the MSR1 gene mutation?  Collies and breeds that were developed using the Collie have a sensitivity to many drugs because of this gene mutation.  In short, it allows drugs that would normally not cross the blood brain barrier to cross, causing all kinds of problems from reactions to seizures to toxicities to death.  

It has been discovered that more than 80% of the collies in the USA have the mutation, so it stands to reason that breeds that were developed using the collie have a good chance of having the mutation as well.  Shelties are as close as you can get to collies without actually BEING collies, so I would have your dog tested before trying to dose him again with this drug.

I have to sign off now because I have to be in work in 20 minutes, but when I get home late tonight I will post with information on how p-glycoprotein works and why there are now more than 20 (that we know of) drugs that are toxic to dogs that have the mdr1 gene mutation.

Ghilly

[Ghilly]

There is a gene present in animals (humans, too) called the MDR1 gene.  MDR stands for multi-drug resistance.  This gene is responsible for encoding a protein called p-glycoprotein.  The job of p-glycoprotein is to remove drugs and certain toxins from the brain.  Dogs who have the MDR1 mutation cannot process these drugs correctly and remove them from their brains.  This results in a buildup of neurotoxins that cause neurological symptoms ranging from seizures to coma and death.  

There are several breeds of dogs who are prone to having the MDR1 gene mutation.  The breed that is most heavily affected is the Collie.  In the United States, 3 out of 4 Collies have the mutation.  There are other breeds that are affected but the Collie is affected the worst.  Other breeds that are affected are Old English Sheepdogs, Shelties, German Shepherds, Border Collies, Australian Shepherds, longhaired Whippets, and two breeds that are not very well known, the Silken Windhound and the McNab.  

Two drugs that are very popular for use in dogs that should never be prescribed to dogs with the mutation are Ivermectin and loperamide (Immodium).  Heartgard, a very popular heartworm preventative, contains ivermectin.   Even milbemycin, selamectin and moxidectin, other ingredients used in heartworm preventatives that are allegedly safe in MDR1 dogs, are ONLY safe if given in the exact dosages prescribed.  Even with the "safe" drugs, too high of a dose can be dangerous in a dog with the gene mutation.  

There are many drugs that are pumped out by the human version of p-glycoprotein, but it is not yet known how many of these drugs will adversely affect dogs with the MDR1 mutation.  It's entirely possible that adverse reactions to MANY medications in Collie-based breeds are a result of the MDR1 gene mutation, but only further research will tell.  Whenever seizure activity is chronicled in a Collie-bred dog, however, I am suspicious that the dog is a MDR1 mutation dog and the seizure activity the result of the neurotoxicity resulting from the drug crossing the blood brain barrier and not being removed because of a defective p-glycoprotein.

Ghilly

[Ghilly]

I just wanted to apologize for the typo in my first post.  I had accidentally written mSr1 instead of mDr1 and didn't notice it until this morning.  I hope it didn't confuse anyone.

Ghilly