选择性环氧化酶2抑制剂的不良反应  

Adverse reactions of selective cyclooxygenase-2 ( COX-2) inhibitors

作　　者：严旭琳[1] 欧阳颖[2] 

机构地区：[1]泸州医学院临床医学院儿科,646000 [2]四川省医学科学院四川省人民医院儿科

出　　处：《药物不良反应杂志》2012年第2期93-97,共5页Adverse Drug Reactions Journal

摘　　要：选择性环氧化酶2(COX-2)抑制剂是治疗类风湿关节炎和骨关节炎的一类新型非甾体抗炎药(NSAIDs)。选择性COX-2抑制剂分为倾向性COX-2抑制剂(美洛昔康、尼美舒利和双氯芬酸等)和特异性COX-2抑制剂(塞来昔布、罗非昔布、伐地考昔、依托考昔等),前者对COX-2的抑制作用明显大于对COX-1的抑制作用,但在抑制COX-2的同时也会部分抑制COX-1,后者仅对COX-2有强烈抑制作用。选择性COX-2抑制剂的主要不良反应为消化道溃疡、穿孔或出血,肾功能损伤,凝血功能障碍,以及血栓形成等。其机制与选择性COX-2抑制剂能同时抑制COX-1和COX-2,减弱其对消化道黏膜的保护作用、使肾小球滤过率下降而加重钠钾潴留、抑制细胞色素P4502C9酶活性而降低华法林代谢率以及影响血栓素A2和前列腺素I2的平衡等有关。同时服用选择性COX-2抑制剂与质子泵抑制剂可降低消化道不良反应的发生率;高血压病患者或有水钠潴留倾向者服用选择性COX-2抑制剂时,应定期监测血药浓度及肾功能,调整降压药剂量,避免多种NSAIDs同时应用;选择性COX-2抑制剂与小剂量阿司匹林联合应用可防治心血管不良反应。一旦出现不良反应,应立即停药并对症治疗。Selective cyclooxygenase-2 （COX-2） inhibitors are a new type of non-steroidal anti-inflammatory drugs （ NSAIDs）, which are used in treatment of rheumatoid arthritis and osteoarthritis. Selective COX-2 inhibitors are divided into relatively selective COX-2 inhibitors （ meloxicam, nimesulide and diclofenac acid, and others ） and highly selective COX-2 inhibitors （ celecoxib, rofecoxib, valdeeoxib, etoricoxib, and other）. The inhibitory effect of the former against COX-2 is significantly stronger than that against COX-1, but also partially inhibits COX-1 at the same time, while the latter only has strong inhibitory effect on COX-2 inhibitor. The main adverse reactions of selective COX-2 inhibitors are gastrointestinal ulcers, perforation or bleeding, damage to renal function, coagulation disorders and thrombosis. The factors associated with the mechanisms are as follows： the COX-2 inhibitors inhibit both COX-1 and COX-2 at the same time and weaken the protective effects on the gastrointestinal mucosa; the COX-2 inhibitors decrease glomerular filtration rate and increase retention of sodium and potassium; the COX-2 inhibitors inhibit CYP2C9＇s activity and decrease warfarin＇s metabolic rate; the COX-2 inhibitors affect the balance between thromboxane A2 （TxA2） and prostaglandin I2 （PGI2）. Proton pump inhibitors should be taken with the selective COX-2 inhibitors in order to decrease the incidence of gastrointestinal adverse reactions. For the patients with hypertension or sodium retention tendencies, plasma concentration and renal function should be monitored regularly, dose of antihypertensive drugs should be adjusted and coadministration of multiple NSAIDs at the same time should be avoided. Selective COX-2 inhibitors in combination with low-dose aspirin may prevent and cure cardiovascular adverse reactions. If adverse reactions induced by selective COX-2 inhibitors are confirmed, the drug should be discontinued and the symptomatic treatment should be given.

关 键 词：环氧化酶2抑制剂 消化性溃疡出血 肾疾病 血栓栓塞 

分 类 号：R971[医药卫生—药品]