吗啡对P2Y12受体拮抗剂药代及药效动力学的影响

Effect of morphine on pharmacokinetics and pharmacodynamics of P2Y12 receptor antagonists

吗啡联合P2Y12受体拮抗剂常用于急性心肌梗死患者的治疗。P2Y12受体拮抗剂能快速、强效抑制血小板活性,并降低再发栓塞风险,吗啡为心绞痛治疗的常规用药。既往有研究指出,吗啡能降低急性冠脉综合征患者氯吡格雷的血药浓度、减弱其抗血小板作用,并可能导致较差的预后。基于健康受试者和急性心肌梗死患者的随机试验也证实,吗啡与新型P2Y12受体拮抗剂替格瑞洛与普拉格雷同样存在类似的药物相互作用。尽管心肌梗死患者的治疗中仍存在吗啡合用P2Y12受体拮抗剂,然而,目前综述两药物相互作用的报道较少。因此,该文基于既往实验性、观察性和随机临床研究,概述吗啡与P2Y12受体拮抗剂之间的药物相互作用。

P2Y12 receptor antagonists and morphine are often recommended in patients with acute myocardial infarction.P2Y12 receptor antagonists can rapidly and potently reduce the platelet activity and prevent future thrombotic events. Meanwhile,combined morphine is used to relieve symptoms of angina. A number of studies have confirmed that morphine can decrease plasma concentrations of clopidogrel and impair its antiplatelet activity,which may lead to poor response in clopidogreltreated patients with acute coronary syndrome. The randomized trials in healthy volunteers and patients with acute myocardial infarction also confirmed the similar drug-drug interaction between morphine and ticagrelor or prasugrel. Although the P2Y12 receptor antagonists combined with morphine are still used for myocardial infarction patients,there are few report on the objective evaluation of this drug interaction. This review,based on the findings of experimental as well as observational and randomized clinical studies,summarizes completely the drug interactions between oral P2Y12 receptor antagonists and morphine.