Codeine: Time to Say "No"
Codeine: Time to Say "No"
复制标题
DOI：
10.1542/peds.2016-2396
复制
发表时间：
2016-10-01
期刊：
影响因子：
8
通讯作者：
Cote, Charles J.
中科院分区：
文献类型：
--
作者：
Tobias, Joseph D.;Green, Thomas P.;Cote, Charles J.
几十年来，可待因一直作为止痛剂和镇咳药用于儿科患者。可待因是一种前体药物，其内在药理活性很低，必须在肝脏中代谢为吗啡，这是可待因镇痛作用的原因。然而，有相当大的遗传变异的活性，负责肝酶，CYP2D6，因此，个别患者对可待因的反应从没有影响到高敏感性。药物监测记录了儿童接受可待因后意外呼吸抑制和死亡的发生，其中许多人被证明是超快速代谢者。有记录或疑似阻塞性睡眠呼吸暂停的患者似乎特别危险，因为阿片类药物敏感性，加剧了该组快速代谢者的危险。近日，多个组织及规管机构，包括世界生组织、美国食物及药物管理局及欧洲药物管理局，均就可待因对儿童的不良影响发出严厉警告。这些组织和其他组织已经或正在考虑宣布可待因作为儿童镇痛药或止咳药的禁忌症。额外的临床研究必须扩展对口服阿片类和非阿片类替代品的风险和益处的理解，有效的药物治疗急性和慢性疼痛。
Codeine has been prescribed to pediatric patients for many decades as both an analgesic and an antitussive agent. Codeine is a prodrug with little inherent pharmacologic activity and must be metabolized in the liver into morphine, which is responsible for codeine's analgesic effects. However, there is substantial genetic variability in the activity of the responsible hepatic enzyme, CYP2D6, and, as a consequence, individual patient response to codeine varies from no effect to high sensitivity. Drug surveillance has documented the occurrence of unanticipated respiratory depression and death after receiving codeine in children, many of whom have been shown to be ultrarapid metabolizers. Patients with documented or suspected obstructive sleep apnea appear to be at particular risk because of opioid sensitivity, compounding the danger among rapid metabolizers in this group. Recently, various organizations and regulatory bodies, including the World Health Organization, the US Food and Drug Administration, and the European Medicines Agency, have promulgated stern warnings regarding the occurrence of adverse effects of codeine in children. These and other groups have or are considering a declaration of a contraindication for the use of codeine for children as either an analgesic or an antitussive. Additional clinical research must extend the understanding of the risks and benefits of both opioid and nonopioid alternatives for orally administered, effective agents for acute and chronic pain.