Eisenkraft Arik, Falk Avshalom
NBC Protection Division, IMOD, Israel.
Israel Defense Forces Medical Corps, Israel.
Toxicol Rep. 2016 Jan 18;3:202-210. doi: 10.1016/j.toxrep.2015.12.007. eCollection 2016.
Organophosphates (OPs) are cholinesterase inhibitors that lead to a characteristic toxidrome of hypersecretion, miosis, dyspnea, respiratory insufficiency, convulsions and, without proper and early antidotal treatment, death. Most of these compounds are highly lipophilic. Sulfur mustard is a toxic lipophilic alkylating agent, exerting its damage through alkylation of cellular macromolecules (e.g., DNA, proteins) and intense activation of pro-inflammatory pathways. Currently approved antidotes against OPs include the peripheral anticholinergic drug atropine and an oxime that reactivates the inhibited cholinesterase. Benzodiazepines are used to stop organophosphate-induced seizures. Despite these approved drugs, efforts have been made to introduce other medical countermeasures in order to attenuate both the short-term and long-term clinical effects following exposure. Currently, there is no antidote against sulfur mustard poisoning. Intravenous lipid emulsions are used as a source of calories in parenteral nutrition. In recent years, efficacy of lipid emulsions has been shown in the treatment of poisoning by fat-soluble compounds in animal models as well as clinically in humans. In this review we discuss the usefulness of intravenous lipid emulsions as an adjunct to the in-hospital treatment of chemical warfare agent poisoning.
有机磷酸酯(OPs)是胆碱酯酶抑制剂,可导致分泌亢进、瞳孔缩小、呼吸困难、呼吸功能不全、惊厥等典型中毒症状,若未进行适当的早期解毒治疗,可导致死亡。这些化合物大多具有高度亲脂性。硫芥是一种有毒的亲脂性烷基化剂,通过对细胞大分子(如DNA、蛋白质)进行烷基化并强烈激活促炎途径来造成损害。目前批准用于对抗OPs的解毒剂包括外周抗胆碱能药物阿托品和一种可使被抑制的胆碱酯酶重新激活的肟。苯二氮䓬类药物用于终止有机磷酸酯引起的惊厥。尽管有这些已获批准的药物,但人们仍在努力引入其他医学对策,以减轻接触后的短期和长期临床影响。目前,尚无针对硫芥中毒的解毒剂。静脉脂质乳剂在肠外营养中用作热量来源。近年来,脂质乳剂在动物模型以及人类临床中毒治疗中已显示出对脂溶性化合物中毒的治疗效果。在本综述中,我们讨论了静脉脂质乳剂作为化学战剂中毒院内治疗辅助手段的实用性。