Brusch Anna M, Clarke Russell C, Platt Peter R, Phillips Elizabeth J
Department of Clinical Immunology, Fremantle Hospital, Fremantle, WA, Australia; Sir Charles Gairdner Hospital, Perth, WA, Australia.
Br J Clin Pharmacol. 2014 Jul;78(1):14-23. doi: 10.1111/bcp.12290.
Neuromuscular blocking agents (NMBAs) are the most commonly implicated drugs in IgE-mediated anaphylaxis during anaesthesia that can lead to perioperative morbidity and mortality. The rate of NMBA anaphylaxis shows marked geographical variation in patients who have had no known prior exposure to NMBAs, suggesting that there may be external or environmental factors that contribute to the underlying aetiology and pathophysiology of reactions. Substituted ammonium ions are shared among NMBAs and are therefore thought to be the main allergenic determinant of this class of drugs. Substituted ammonium ions are found in a wide variety of chemical structures, including prescription medications, over-the-counter medications and common household chemicals, such as the quaternary ammonium disinfectants. Epidemiological studies have shown parallels in the consumption of pholcodine, a nonprescription antitussive drug which contains a tertiary ammonium ion, and the incidence of NMBA anaphylaxis. This link has prompted the withdrawal of pholcodine in some countries, with an ensuing fall in the observed rate of NMBA anaphylaxis. While such observations are compelling in their suggestion of a relationship between pholcodine exposure and NMBA hypersensitivity, important questions remain regarding the mechanisms by which pholcodine is able to sensitize against NMBAs and whether there are other, as yet unidentified, agents that can elicit similar hypersensitivity reactions. This review aims to explore the evidence linking pholcodine exposure to NMBA hypersensitivity and discuss the implications for our understanding of the pathophysiology of these reactions.
神经肌肉阻滞剂（NMBAs）是麻醉期间IgE介导的过敏反应中最常涉及的药物，可导致围手术期发病和死亡。在既往无已知NMBAs暴露史的患者中，NMBAs过敏反应发生率存在显著的地域差异，这表明可能存在外部或环境因素导致这些反应的潜在病因和病理生理过程。NMBAs中存在取代铵离子，因此被认为是这类药物的主要过敏原决定因素。取代铵离子存在于多种化学结构中，包括处方药、非处方药和常见家用化学品，如季铵消毒剂。流行病学研究表明，含有叔铵离子的非处方止咳药福尔可定的消费量与NMBAs过敏反应发生率之间存在相似之处。这一关联促使一些国家停用福尔可定，随后观察到的NMBAs过敏反应发生率有所下降。虽然这些观察结果有力地表明了福尔可定暴露与NMBAs超敏反应之间的关系，但关于福尔可定能够使机体对NMBAs致敏的机制以及是否存在其他尚未确定的可引发类似超敏反应药物的问题仍然存在。本综述旨在探讨将福尔可定暴露与NMBAs超敏反应联系起来的证据，并讨论其对我们理解这些反应病理生理学的意义。
