USE OF N-ACETYLCYSTEINE IN CLINICAL TOXICOLOGY
USE OF N-ACETYLCYSTEINE IN CLINICAL TOXICOLOGY
复制标题
DOI：
10.1016/0002-9343(91)90296-a
复制
发表时间：
1991-09-30
影响因子：
5.9
通讯作者：
MEREDITH, TJ
中科院分区：
文献类型：
--
作者：
FLANAGAN, RJ;MEREDITH, TJ
N-乙酰半胱氨酸在临床毒理学中的主要用途是治疗扑热息痛(扑热息痛)过量。对乙酰氨基酚的肝肾毒性是由一种通常由还原型谷胱甘肽解毒的反应性代谢物介导的。如果谷胱甘肽耗尽，与大分子的共价结合和/或硫醇酶的氧化可能导致细胞死亡。口服或静脉注射N-乙酰半胱氨酸或口服D，L-蛋氨酸在10小时内给药可减轻对乙酰氨基酚引起的肝肾损伤，但此后效果就不那么好了。在体内，N-乙酰半胱氨酸形成L-半胱氨酸、半胱氨酸、L-蛋氨酸、谷胱甘肽和混合二硫化物；L-蛋氨酸也形成半胱氨酸，从而产生谷胱甘肽和其他产物。对乙酰氨基酚中毒在昏迷或呕吐时或口服活性炭时禁忌口服N-乙酰半胱氨酸或蛋氨酸。口服N-乙酰半胱氨酸也可能导致恶心、呕吐和腹泻。在多达10%的患者中，在注射N-乙酰半胱氨酸(20小时静脉注射方案)15-60分钟后，可能会出现类过敏反应，包括血管水肿、支气管痉挛、潮红、低血压、恶心/呕吐、皮疹、心动过速和呼吸窘迫。在意外静脉注射过量后，N-乙酰半胱氨酸的不良反应类似，但更严重；已发生死亡事件。减少N-乙酰半胱氨酸的负荷量可能会降低不良反应的风险，同时保持疗效。长期服用N-乙酰半胱氨酸可能会为对乙酰氨基酚吸收或排出延迟的患者提供更好的保护。N-乙酰半胱氨酸也可能在治疗四氯化碳、氯仿、1，2-二氯丙烷和其他化合物的毒性方面发挥作用。N-乙酰半胱氨酸和其他药物在预防急性一氧化碳中毒的神经精神后遗症方面的可能性是未来研究的重要领域。
The major use of N-acetylcysteine in clinical toxicology is in the treatment of acetaminophen (paracetamol) overdosage. The hepatorenal toxicity of acetaminophen is mediated by a reactive metabolite normally detoxified by reduced glutathione. If glutathione is depleted, covalent binding to macromolecules and/or oxidation of thiol enzymes can lead to cell death. Oral or intravenous N-acetylcysteine or oral D,L-methionine mitigates acetaminophen-induced hepatorenal damage if given within 10 hours, but becomes less effective thereafter. In vivo, N-acetylcysteine forms L-cysteine, cystine, L-methionine, glutathione, and mixed disulfides; L-methionine also forms cysteine, thus giving rise to glutathione and other products.Oral therapy with N-acetylcysteine or methionine for acetaminophen poisoning is contraindicated in the presence of coma or vomiting, or if activated charcoal has been given by mouth. Nausea, vomiting, and diarrhea may also occur as a result of oral N-acetylcysteine administration. Anaphylactoid reactions including angio-edema, bronchospasm, flushing, hypotension, nausea/vomiting, rash, tachycardia, and respiratory distress may occur 15-60 minutes into N-acetylcysteine infusion (20 hour intravenous regimen) in up to 10% of patients. Following accidental intravenous overdosage, the adverse reactions of N-acetylcysteine are similar but more severe; fatalities have occurred. A reduction in the loading dose of N-acetylcysteine may reduce the risk of adverse reactions while maintaining efficacy. Administration of N-acetylcysteine for a longer period might provide enhanced protection for patients in whom acetaminophen absorption or elimination is delayed.N-acetylcysteine may also have a role in the treatment of toxicity from carbon tetrachloride, chloroform, 1,2-dichloropropane, and other compounds. The possible use of N-acetyl-cysteine and other agents in the prevention of the neuropsychiatric sequelae of acute carbon monoxide poisoning is an important area for future research.