Chyka P A, Butler A Y, Holliman B J, Herman M I
The University of Tennessee, Memphis 38163, USA.
Drug Saf. 2000 Feb;22(2):123-48. doi: 10.2165/00002018-200022020-00005.
As recognition of the role of free radicals and reactive toxins in the pathogenesis of disease, poisoning, and adverse drug reactions has evolved, interest in the use of acetylcysteine as a modulator of these effects has steadily increased in recent years. Acetylcysteine is commonly thought to serve as a glutathione precursor and consequently can increase or sustain intracellular glutathione which scavenges reactive oxygen species caused by toxins or subsequent tissue injury. At least 10 additional mechanisms of action for acetylcysteine have been demonstrated in various laboratory models, but a unifying framework of its actions is still to be proposed. This paper reviews the current experimental and therapeutic status of acetylcysteine for the treatment of poisonings and adverse drug reactions. Of the 45 potential uses of acetylcysteine that were identified for the treatment of poisonings or adverse drug reactions, 14 of the toxic effects have little support for its use while promising results have been demonstrated for 27 toxicities. Currently, treatment of acute paracetamol (acetaminophen) poisoning is the only widely accepted clinical indication for acetylcysteine as a treatment for poisoning or adverse drug reactions. In many clinical situations acetylcysteine is used empirically utilising modifications of dosage regimens employed for paracetamol poisoning. Often it is difficult to determine the benefit of therapy with acetylcysteine owing to the nature of the toxicity being treated, the use of other therapies, the presence of comorbid conditions, and the small number of patients studied. The diverse and positive nature of the investigations suggest that there is considerable promise in acetylcysteine as a research tool and pharmacological agent.
随着对自由基和反应性毒素在疾病、中毒及药物不良反应发病机制中作用的认识不断发展，近年来人们对使用乙酰半胱氨酸作为这些效应调节剂的兴趣稳步增加。乙酰半胱氨酸通常被认为是谷胱甘肽的前体，因此可以增加或维持细胞内谷胱甘肽水平，后者可清除由毒素或随后的组织损伤引起的活性氧。在各种实验室模型中已证实乙酰半胱氨酸至少还有10种其他作用机制，但仍有待提出其作用的统一框架。本文综述了乙酰半胱氨酸在治疗中毒和药物不良反应方面的当前实验和治疗现状。在已确定的用于治疗中毒或药物不良反应的45种乙酰半胱氨酸潜在用途中，14种毒性作用几乎没有使用依据，而27种毒性作用已显示出有前景的结果。目前，治疗急性对乙酰氨基酚（扑热息痛）中毒是乙酰半胱氨酸作为中毒或药物不良反应治疗唯一被广泛接受的临床适应证。在许多临床情况下，乙酰半胱氨酸是根据对乙酰氨基酚中毒所用剂量方案的修改经验性使用的。由于所治疗毒性的性质、其他治疗方法的使用、合并症的存在以及所研究患者数量较少，往往难以确定乙酰半胱氨酸治疗的益处。研究的多样性和积极性质表明，乙酰半胱氨酸作为一种研究工具和药物具有很大的前景。
