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Dewormers - Long term studies?


Debbie Meier

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Does anyone know if there has been any long term studies done on the effect of ivermectin in low doses on the eyes of dogs that have shown a intolerance when given higher dosages?

 

Here's the deal, with our ACD's we used Ivermectin in the a small heartworm dosage, we have done the same with the Border Collies. Each year we have used a higher dosage of ivermectin one time each year as an actual dewormer, would be simular to the mange dosage, we have had no ill effects on the ACD's, our vet suggested that if we had a dog that showed an intollerance that we should remove the dog from our program. The lack of any reaction made me feel comfortable using Ivermectin in the small heartworm dosage. A few months back without thinking I administered the higher dosage to two of our border collies (out of two different females), both exhibited blindness but recovered within 36 hours. Note to self, don't do that again.... I was doing some reading and there was one article that indicated that toxicity will actually cause scarring of the eyes.

 

So here is my question, even though we don't see any effects at the low dosage that are deemed "safe" could we still be causing damage using ivermectin or even the other forms of wormers that work in the same way by effecting the neotransmitters? Some of the articles I've read talked about the dogs that had reactions as having an inability to block the dewormer from their brains, so my thought is even low doses would get through. I guess I'm wondering if over the long term could these little doses each month cause small amounts of scarring to eyes increasing the dogs chances of having visual problems as they get older?

 

Any thoughts?

 

Deb

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Since all heartworm meds are in the same class of drugs, those dogs with the ABCB1-1 Delta (MDR1-1 Delta) mutation would be showing signs of long term effects (our canary in the coal mine). The normal gene limits drug uptake into the central nervous system. If your dogs do not have the mutation, they are not susceptible to increased risk of toxicity from these drugs.

 

Ivermectin is toxic at higher doses and this level is not a fixed amount but a range dependent upon individual dogs body chemistry (published range for "ABCB1 normal" dogs: 1.1 - 18 mg/lb).

 

BTW Heartgard was introduced in 1987.

 

The ABCB1-1Delta mutation is not responsible for subchronic neurotoxicity seen in dogs of non-collie breeds following macrocyclic lactone treatment for generalized demodicosis.

 

Bissonnette S, Paradis M, Daneau I, Silversides DW.

Vet Dermatol. 2009 Feb;20(1):60-6.

 

P-glycoprotein (P-gp), encoded by the multiple drug resistance gene ABCB1 (also known as MDR1), is an integral component of the blood brain barrier crucial in limiting drug uptake into the central nervous system. Altered expression or function of P-gp, as seen in dogs of the collie lineage homozygous for the nt228(del4) mutation of the ABCB1 gene (ABCB1-1Delta), can result in potentially fatal neurotoxicosis, especially following administration of systemic macrocyclic lactones (SML). Occasionally, dogs from unrelated breeds develop subchronic signs of neurotoxicity when receiving SML to treat generalized demodicosis. It is possible that these dogs are heterozygous carriers of the ABCB1-1Delta mutation, resulting in decreased P-gp activity and central neurotoxicosis. Cheek swabs were collected from 28 dogs with generalized demodicosis that had shown subchronic signs of neurotoxicity following daily oral administration of ivermectin or other SML. Ten of these animals received concurrent systemic treatment with other confirmed or putative P-gp substrates. After DNA extraction, the relevant portion of the ABCB1 gene was amplified by polymerase chain reaction, and sequenced. Twenty-seven dogs were homozygous normal while one dog was heterozygous for the ABCB1-1Delta mutation. Therefore, with the exception of one dog, the observed neurotoxicity could not be attributed to the ABCB1-1Delta mutation. Possible explanations for the adverse reactions observed include pharmacological interactions (administration of SML with other P-gp substrates or inhibitors), excessively high doses, polymorphisms in P-gp expression, uncharacterized mutations in the ABCB1 gene or in another gene, or phenomena unrelated to the SML-P-gp interaction.

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