Multiple centrally acting antidotes protect against severe organophosphate toxicity

Academic Emergency Medicine : Official Journal of the Society for Academic Emergency Medicine
Marco L A SivilottiEric W Dickson

Abstract

Accumulation of acetylcholine in the central nervous system is believed to account for the rapid lethality of organophosphate pesticides and chemical nerve agents. Diazepam is known to supplement atropine therapy, but its specific mechanism of action is uncertain. To test four centrally acting agents for early antidotal efficacy in severe dichlorvos poisoning in the murine model. The up-and-down method was used to dose four candidate antidotes: diazepam, xylazine, morphine, and ketamine. Antidotes were administered subcutaneously to unsedated adult Sprague-Dawley rats who were pretreated with 3 mg/kg intraperitoneal glycopyrrolate. All animals received 20 mg/kg of dichlorvos subcutaneously 5 minutes later. A blinded observer adjudicated the outcomes of 10-minute mortality and survival time. All animals pretreated with either no antidote (8/8 deaths) or glycopyrrolate alone (8/8) died within 10 minutes of dichlorvos injection. Pretreatment with diazepam (3/9 deaths), or xylazine (3/9), decreased lethality substantially (Fisher p = 0.007; median effective doses, 0.12 mg/kg and 3.0 mg/kg, respectively). Intermediate doses of morphine (3.1 to 5.5 mg/kg) resulted in survival, but higher doses did not, presumably because of excessive...Continue Reading

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Citations

Jun 10, 2010·Journal of Medical Toxicology : Official Journal of the American College of Medical Toxicology·Christopher Rosenbaum, Steven B Bird
Jun 30, 2009·Journal of Emergencies, Trauma, and Shock·Praveen Aggarwal, Nayer Jamshed
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Jun 4, 2016·Annals of the New York Academy of Sciences·Steven B BirdTejvir S Khurana
Dec 20, 2016·Basic & Clinical Pharmacology & Toxicology·Ranko ŠkrbićMaja Vulović

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