Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats.

Toxicology of avermectins and milbemycins (macrocylic lactones) and the role of P-glycoprotein in dogs and cats.
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DOI:
10.1016/j.cvsm.2011.12.005
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发表时间:
2012-03
影响因子:
1.9
通讯作者:
Eubig, Paul A.
Eubig, Paul A.
中科院分区:
农林科学2区
文献类型:
--
作者:
Merola, Valentina M.;Eubig, Paul A.

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大环内酯是一种能够杀死多种节肢动物和线虫的杀寄生虫剂。伊维菌素对标示的适应症有很高的安全边际,已成为世界上最畅销的抗寄生虫药。1某些品种的犬和这些品种的混合犬在ABCB 1基因(以前的MDR 1基因)中存在缺陷,导致缺乏功能性P-糖蛋白(P-gp),这导致ML在中枢神经系统(CNS)中蓄积,暴露时不良反应的风险较高。中毒时,中枢神经系统体征如共济失调、嗜睡、昏迷、震颤、癫痫发作、瞳孔散大和失明占优势。一般而言,最大限量具有较长的半衰期,因此,当发生过量时,接触会导致长期患病。ML中毒没有特定的解毒剂,因此治疗的最重要部分是良好的支持性护理。
The macrocyclic lactones (MLs) are parasiticides able to kill a wide variety of arthropods and nematodes. They have a high margin of safety for labeled indications, and ivermectin has become the best selling antiparasitic in the world. 1 Dogs of certain breeds and mixtures of those breeds have a defect in the ABCB1 gene (formerly MDR1 gene) that results in a lack of functional P-glycoprotein (P-gp), which leads to accumulation of the MLs in the central nervous system (CNS) and a higher risk of adverse effects when exposed. With toxicosis, CNS signs such as ataxia, lethargy, coma, tremors, seizures, mydriasis, and blindness predominate. In general, the MLs have a long half-life and therefore exposure results in a long duration of illness when overdoses occur. There is no specific antidote for ML toxicosis so the most important part of treatment is good supportive care.
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