Ivermectin Toxicity

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https://europepmc.org/article/med/7631491

The clinical signs of ivermectin toxicity were determined in 6 groups of 10 epileptic and 8 non-epileptic chickens for 72 h after dosing with sc injections of 5.0, 7.5, 10.0, 12.5 or 15.0 mg ivermectin/kg bw. At the 5.0 mg/kg dose, mild diarrhea developed 4 h post-dosing and lasted until the end of the 72-h monitoring period. With higher doses of ivermectin body weight, egg production and feed and water consumption were markedly reduced. Severe diarrhea, mydriasis, bradypnea, ataxia, sedation, coma and death occurred with the highest dose of ivermectin. No differences in the signs of ivermectin toxicity were observed between epileptic and non-epileptic chickens. To assess the efficacy of the antiGABAergic convulsants, methyl-beta carboline-carboxylate (beta-CCM), picrotoxin and pentylenetetrazol (PTZ), as antidotes for ivermectin toxicity, 8 epileptic and 6 non-epileptic chickens/treatment group were given dosages of each convulsant which previously induced convulsions in 50% (ED50) and again in 100% (ED100) of treated chickens. These convulsants were given 6 h after dosing with 15.0 mg ivermectin/kg. The ED100 dosages of picrotoxin and PTZ alleviated mydriasis and sedation, but did not reduce the diarrhea. The ED50 dose convulsants were not effective in reducing or alleviating ivermectin toxicity, nor was alleviation of any sign of ivermectin toxicity obtained with any dosage of beta-CCM. Although the dosages of these antiGABAergic convulsants used normally produced convulsions in epileptic and non-epileptic chickens, no convulsions were observed in chickens with ivermectin toxicity. (ABSTRACT TRUNCATED AT 250 WORDS)

Kim JS, Crichlow EC. Clinical signs of ivermectin toxicity and the efficacy of antigabaergic convulsants as antidotes for ivermectin poisoning in epileptic chickens. Veterinary and Human Toxicology. 1995 Apr;37(2):122-126. PMID: 7631491.

 

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https://www.researchgate.net/public...oxicity_events_of_ivermectin_in_chicks'_model

Ivermectin is a very safe drug; however, there are many studies on its toxic effects in different animals due to sensitivity, misuse, or accidental overdose. This study aimed to further characterize the neurotoxic effects of ivermectin in chicks and identify possible therapeutic strategies for use in cases of ivermectin toxicity. The LD₅₀ of ivermectin was determined by the Dixon method. The acute toxicity signs of ivermectin were induced at doses of 131.5,2629 and 394.5 mg/kg orally. The therapeutic effect of flumazenil on ivermectin poisoning was also studied. Administration of repeated doses of ivermectin for five consecutive days was recorded to measure the neurobehavioral within the open field and tonic immobility test. The oral LD₅₀ of ivermectin was 525.9mg/kg. The acute signs of poisoning on ivermectin-treated chicks were lethargy, ataxia, tremor, diarrhea, recumbency, and death. Flumazenil at a dose of 0.1mg/kg significantly reduced the toxicity signs induced by the ivermectin in chicks, especially tremor and ataxia, and prevented death. The administration of ivermectin at 26.3, 52.6, and 105.2 mg/kg doses led to a significant decrease in motor activity through a significant increase in the time of starting the movement and a decrease in the number of cross lines. We concluded that ivermectin has a neurotoxic effect in chicks when used in high doses; the results also indicate a potential clinical application of flumazenil for treatment side effects and toxicity of ivermectin, as well as ivermectin, has depressant effect in chicks represented by open-field activity.