Blue Buffalo. or Taste of Wild? update on Bud

We're way off original topic.

There has been a large amount of opinion and supposition here and the information is anecdotal and really not very valuable as related to specific seizure patients.

Seizure is a difficult disease, it is not always easily understood and treated.

Only rarely are seizures CAUSED by specific drugs, toxins, etc. I've never seen an unadulterated diet CAUSE a seizure. That being said, there are many drugs, disease states, diets, nutritional supplements, life styles, environmental influences that can change the seizure threshhold in any individual, and managing them can aid in controlling seizures.

If you are one who has had success eliminating or reducing seizures by utilizing these methods, GREAT. It isn't always that easy, and doesn't always work.

I'll let this be the last word and close this now.

Doug, DVM

rockhillmanor wrote:
If you would have read my post on dosing procedures it is very easy to be giving more than needed which would increase the buildup more so in any dog prone to problems having a mutation or not.

Based upon the data I've linked, one would need to exceed 5-10 pills of the prescribed Milbemycin oxime in order for a MDR1 affected dog to reach toxic levels. "Build up" will not occur if pills are given monthly; complete elimination (below detection limits) occurs within 1 week after dosing; therefore, multiple pills (5-10) would need to be given within a week in order to reach toxic levels. Neither of these scenarios sound "very easy" to me.

Most of the toxicosis cases I have read (I've read many) either involved off label use of livestock meds at too high of doses, the dogs consumed the meds on their own either directly (got into the meds) or indirectly (consumed livestock manure after livestock was dewormed), or use of these meds (at higher doses) for treating mange in MDR1 affected dogs. I've also read the pharmacokinetic studies on these drugs to learn the uptake, excretion, and environmental survivability after excretion (UV degradation is fast).

I don't use website heresay whenever researching information regarding my dogs health or passing on info. I use clinical reports. Reading clinical reports will glaze over the eyes of most people and they won't even take the time to read them and many can not understand the verbiage used. For that reason I don't always feel the need to post all the links. I'm offering help to the OP not you. Your need to slam all the time is getting old. Not to mention I did reference a link that you approved of.

If you would have read my post on dosing procedures it is very easy to be giving more than needed which would increase the buildup more so in any dog prone to problems having a mutation or not.

The OP's dog was also tested heartworm positive and went thru the 'treatment' for heartworms. Depending on what they choose for the treatment that could also have a contributing factor with a breed that may or may not have the mutation.

There is evidence that seizures in some dogs can be prevented. Sometimes we need to sit back and look at the whole picture before making decisions. JMHO

Treatment of MDR1 Mutant Dogs with Macrocyclic Lactones

Milbemycin oxime

is, apart from other indications, an effective heartworm preventative at a minimum recommended oral dose of 0.5 mg/kg at monthly intervals (Interceptor®, Milbemax®). When doses of 0.5-2.5 mg/kg milbemycin oxime were orally applied to ivermectin-sensitive Collies, no clinical signs of neurotoxicosis were observed. Therefore, this compound can be safely used for heartworm prevention in MDR1(-/-) dogs. At higher concentrations of 5-10 mg/kg, as well as at daily dosing protocols of 0.5-2.8 mg/kg, which are normally well tolerated in dogs, milbemycin oxime provoked neurological toxicity in MDR1 mutant dogs including ataxia, salivation and depression.

You also have to consider the risk vs the payback. Heartworms can kill a dog and the treatment can too. So a few seizures (if any) are better than the malady.

IMO Kennel cough can be skipped (unless you board your dogs) as the treatment is antibiotics.

I prefer to go to published scientific studies for information on health issues as opposed to websites that are not peered reviewed for accuracy of the content or ones that are simply repeating internet myths.

This link has the full article. There may be a link between the MDR1 mutation and how effective anti epileptic drugs are at managing the disease. The researchers did not find evidence that the mutated body function that makes these dogs more sensitive to drugs was involved with altering how effective anti epileptic drugs are for these dogs.


Association between ABCB1 (MDR1 mutation) Genotype and Seizure Outcome in Collies with Epilepsy

Abstract

Background
Medically refractory seizures are an important problem in both humans and dogs with epilepsy. Altered expression of ABCB1, the gene encoding for p-glycoprotein (PGP), has been proposed to play a role in drug-resistant epilepsy.

Hypothesis
Heterogeneity of the ABCB1 gene is associated with seizure outcome in dogs with epilepsy.

Animals
Twenty-nine Collies with epilepsy being treated with antiepileptic drugs (AEDs).

Methods
Prospective and retrospective cohort study. Dogs were classified as having a good outcome (?1 seizure/month, no cluster seizures) or a poor outcome (>1 seizure/month, with or without cluster seizures) based on owner-completed questionnaire. Serum AED concentrations were measured, and ABCB1 genotyping was performed on buccal tissue samples. Association analyses were performed for genotype and seizure outcome, number of AEDs administered, serum AED concentrations, and incidence of adverse effects.

Results
Fourteen dogs of 29 (48%) were homozygous for the ABCB1-1? mutation (M/M), 11 dogs (38%) were heterozygous (M/N), and 4 dogs (14%) had the wild-type genotype (N/N). Dogs with the M/M genotype were significantly more likely to have fewer seizures and have less AED-related sedation than M/N or N/N dogs (P = .003 and P = .001, respectively). Serum phenobarbital and bromide concentrations did not differ between groups, but the M/N and N/N groups received a larger number of AEDs than the M/M group (P = .014).

Conclusions and Clinical Importance
ABCB1 genotype is associated with seizure outcome in Collies with epilepsy. This cannot be attributed to differences in PGP function, but might be because of intrinsic variations in seizure severity among phenotypes.

Evaluation of the safety of spinosad and milbemycin 5-oxime orally administered to Collies with the MDR1 gene mutation
Objective—To determine whether signs of avermectin (AVM)-milbemycin (MB) toxicosis would be evident in AVM-MB–sensitive Collies after treatment with an experimental formulation of spinosad alone or spinosad combined with MB 5-oxime (MBO) at doses up to 5 and 10 times the MBO maximum label dose.

Animals—20 adult Collies homozygous or heterozygous for the MDR1 gene mutation that had signs of toxicosis after oral administration of ivermectin.

Procedures—On the basis of AVM-MB sensitivity score, each dog was assigned in a randomized block design to 1 of 5 treatment groups (control group, 300 mg of spinosad/kg [5 times maximum label dose], 180 mg of spinosad/kg with 3 mg of MBO/kg [3 times maximum MBO label dose], 300 mg of spinosad/kg with 5 mg of MBO/kg, and 300 mg of spinosad/kg with 10 mg of MBO/kg). Treatments were administered orally as a sequence of single doses during 5 consecutive days. After a 28-day washout period, treatment sequences were repeated. Posttreatment observation and scoring by blinded observers were conducted to specifically include neurologic abnormalities typical of AVM-MB toxicosis, such as signs of depression, ataxia, mydriasis, and hypersalivation.

Results—No signs of AVM-MB toxicosis were attributed to treatment in any dog during the study.

Conclusions and Clinical Relevance—Results indicated that oral administration of spinosad at 300 mg/kg alone or in combination with MBO at doses up to 10 mg/kg did not cause signs of AVM-MB toxicosis in AVM-MB–sensitive dogs with the MDR1 gene mutation.

rockhillmanor wrote:

NO!! I really doubt the dosing of an avermectin at the preventive dose has anything to do with his seizures.

The OP stated they are using Sentinel that is milbemycin Oxime based.

IMHO when there is ongoing research on collies having a mutation related to the use of milbemycin oxime that can cause seizures. It would seem real prudent to stop using that heart worm med that has it as an ingredient.

It would be nice if you would read the information about the MDR1 mutation provided by those doing the research.

Ivermectin (antiparasitic agent)- While the dose of ivermectin used to prevent heartworm infection is SAFE in dogs with the mutation (6 micrograms per kilogram), higher doses, such as those used for treating mange (300-600 micrograms per kilogram) will cause neurological toxicity in dogs that are homozygous for the MDR1 mutation (MDR1 mutant/mutant) and can cause toxicity in dogs that are heterozygous for the mutation (MDR1 mutant/normal).


Selamectin, milbemycin, and moxidectin (antaparasitic agents)- Similar to ivermectin, these drugs are safe in dogs with the mutation if used for heartworm prevention at the manufacturer’s recommended dose. Higher doses (generally 10-20 times higher than the heartworm prevention dose) have been documented to cause neurological toxicity in dogs with the MDR1 mutation.

source: WA State Veterinary Clinical Pharmacology Lab: MDR1 Problem Drugs

This information very clearly states that the doses used for heartworm preventative are SAFE. If you have them, please provide links to research studies (not website posted hearsay) that offer contradictory data indicating that these drugs (used at the heartworm preventative doses) trigger neurological toxicity caused symptoms in dogs with the MDR1 mutation.

NO!! I really doubt the dosing of an avermectin at the preventive dose has anything to do with his seizures.

The OP stated they are using Sentinel that is milbemycin Oxime based.

IMHO when there is ongoing research on 'some' collies having a mutation related to the use of milbemycin oxime that can cause seizures. It would seem real prudent to stop using that heart worm med that has it as an ingredient.

Which came first the chicken or the egg? Is he seizure prone or induced by the ingredient known to CAUSE them in collies having the mutation?

Either way if it's a known problem in the breed I owned, I sure would change to a different one to eliminate at least one of the possible causes.

NOT all heart worm meds use all the SAME ingredients or are safe for all dogs. Nor do you know which ones your dog might have a reaction to until he does.

Ivermectin-Based Treatment Options:
Selamectin-Based Treatment Options:
Moxidectin-Based Treatment Options:
Milbemycin Oxime-Based Treatment Options:

Lists of which product uses what
http://www.petcarerx.com/article/heartworm-medication-dog-heartworm-prevention-meds/218
http://www.drsfostersmith.com/pic/article.cfm?articleid=580

I gave Sentinel and had 2 dogs on life support almost lost them both.
I gave HeartGuard Plus to a Great Dane that reduced him to a drooling stupor. All given at the recommended dose. Had to do with the specific 'different' added ingredients.

IMHO like in the case of Sentinel and others where you are also treating for fleas etc. Throwing in all the other preventative ingredients in with the heartwormt treatment just compounds the problems with some dogs.