COX-2抑制剂的药理研究进展

环氧合酶 - 2 (COX - 2 )抑制剂是NSAIDs中最近问世的一个新类型 ,COX - 2抑制剂能特异性地抑制COX - 2 ,抑制与炎症相关的PG产生 ,不良反应比传统NSAIDs轻得多 ,因而受到广泛的关注。其中塞来昔布 (celecoxib ,西乐葆 )和罗非昔布 (rofecoxib ,万洛 )等新一代COX - 2抑制剂已在临床广泛应用于镇痛、关节炎和类风湿关节炎等治疗。本文对COX - 2抑制剂的药理等研究进展作一介绍。1　对胃肠道的作用与传统NSAIDs相比 ,COX - 2抑制剂不影响胃血流量 ,不影响胃粘膜中COX - 1mRNA的表达 ,不阻断COX- 1产生PG而维持正常的胃肠…     

美国FDA就环氧化酶-2抑制剂和非甾体类抗炎药物作出重要决定

2005年4月7日,美国食品和药品管理局(FDA)就选择性环氧化酶-2(COX-2)抑制剂、处方和非处方非选择性非甾体类抗炎药物(Non-Steroidal Anti-Inflammatory Drugs,NSAIDs)的上市销售作出一系列重要决定,要求这类药物的生产厂商修改其标签和说明书,增加一个带框的警告,以向消费者提供更多与使用这类药物相关的心血管和胃肠道不良反应风险的可能性以及对消费者在药品安全使用方面进行指导的详尽信息。     

从复旦大学附属华山医院用药情况浅谈非甾体类抗炎药使用特点和趋势

目的:从复旦大学附属华山医院门诊用药情况分析各类非甾体类抗炎药(NSAIDs)的用药特点和趋势。方法:根据2000~2004年华山医院门诊药房所用的NSAIDs的品种、数量和金额,回顾性地分析比较DDDs、日均费用(DDDc)和金额。结果:5年中NSAIDs年处方总金额在80~120万元间波动上升,DDDc逐年上升。DDDs排位较前的为美洛昔康、双氯芬酸钠缓释制剂和布洛芬缓释制剂。2000年后品种数增加,新一代NSAIDs环氧化酶-2选择性抑制剂被引入临床使用。结论:NSAIDs长期使用都存在一定风险,传统NSAIDs的改良剂型以及安全性更可靠的NSAIDs是研究方向。     

环氧化酶-2在恶性肿瘤细胞凋亡与增殖中的作用

流行病学研究表明 ,长期服用非甾体类抗炎药 (non -steroidanti-inflammatorydrugs,NSAIDs)可减少结直肠癌、食管癌、胃癌和胰腺癌等消化道肿瘤的危险性[1 ,2]。环氧化酶(cyclooxygenase ,COX) ,尤其是COX -2 ,有望成为抗癌药物的新靶点。COX -2参与肿瘤的发生发展 ,包括抑制凋     

环氧化酶-2选择性抑制剂的研究与开发

综述环氧化酶-2选择性抑制剂的分子基础及其构效关系。甾体抗炎药的有效治疗作用源于对环氧化酶-2的抑制作用，其副作用则是由于对环氧化酶-1的抑制作用所致，因此寻找高效环氧化酶-2选择性抑制剂成为甾体抗炎药的研究热点。     

昔布类高选择性环氧化酶-2抑制剂

综述国内外文献介绍高选择性环氧化酶-2抑制剂--昔布类药物的新进展.昔布类高选择性环氧化酶-2抑制剂研究进展十分迅速,它对环氧化酶-2的选择性高,在治疗骨关节炎和类风湿性关节炎、关节痛、术后疼痛和肿瘤方面展现了良好的治疗前景.     

西乐葆治疗膝骨关节炎43例临床分析

膝骨关节炎 (OA)又称退行性关节炎 ,是常见的一种慢性关节疾病 ,多见于老年人。膝OA虽无法根治 ,但合理的治疗可以减轻患者的疼痛 ,改善关节功能 ,提高生活质量。传统的非甾体抗炎药 (NSAIDs)往往引起胃肠道不良反应 ,严重者可并发胃溃疡、出血、穿孔等。塞来昔布 (西乐葆 )是环氧化酶 - 2 (COX - 2 )的特异性抑制剂 ,对膝OA有良好的治疗作用 ,且胃肠道不良反应少。本组分析西乐葆治疗 4 3例骨关节炎患者的疗效、安全性现将结果报道如下。资料与方法　 4 3例患者 ,男 2 0例 ,女 2 3例 ,年龄 4 1～ 85岁 ,平均年龄 6 1 18± 9 2 3岁 ,…     

高选择性环氧化酶—2抑制剂的进展与评价

目的 :介绍高选择性环氧化酶 - 2抑制剂———昔布类药物进展 ,并评价其临床疗效 ,以供临床参考。方法 :查阅国内、外近期相关文献进行分析、评价。结果与结论 :昔布类高选择性环氧化酶 - 2抑制剂进展十分迅速 ,对环氧化酶 - 2的选择性高 ,在治疗骨关节炎和类风湿性关节炎、关节痛、术后疼痛和肿瘤上展现了良好的治疗前景     

一类新型的抗炎镇痛药物——一氧化氮供体型非甾体抗炎药一类新型的抗炎镇痛药物——一氧化氮供体型非甾体抗炎药

传统的非甾体抗炎药(NSAIDs)和环氧化酶-2(COX-2)选择性抑制剂临床应用极为广泛，但严重的胃肠道和新近发现的心血管不良反应限制了它们进一步的应用。一氧化氮(NO)供体型NSAIDs (NO-NSAIDs)的研发是近年来减少NSAIDs和COX-2选择性抑制剂不良反应的重要策略，此类药物既具有NSAIDs的抗炎、镇痛作用，又具有NO介导的胃肠道和心血管保护作用。本文简要介绍NO-NSAIDs的化学，重点综述NO-NSAIDs的药理特点、作用机制以及一些潜在的治疗应用。     

环氧化酶-2及其抑制剂的研究进展

本文综述了近年关于环氧化酶-2及及其抑制剂研究进展的国内外文献,侧重于环氧化酶-2及其抑制剂的药理学新进展和不良反应的内容.     

选择性环氧合酶-2抑制剂的研究现状及进展

非甾体抗炎药（NSAIDs）是临床上应用非常广泛的一类药物，但严重的不良反应使其应用受到很大限制。研究已经发现，NSAIDs对炎症的有效治疗源干其对环氧合酶-2（COX-2）的抑制作用。综述了选择性COX-2抑制剂作用的分子基础、构效关系及其目前研究开发的现状和最新进展。     

Computer aided drug design approaches to develop cyclooxygenase based novel anti-inflammatory and anti-cancer drugs

Cyclooxygenases (COXs), the enzymes involved in the formation of prostaglandins from polyunsaturated fatty acids such as arachidonic acid, exist in two forms--the constitutive COX-1 that is cytoprotective and responsible for the production of prostaglandins and COX-2 which is induced by cytokines, mitogens and endotoxins in inflammatory cells and responsible for the increased levels of prostaglandins during inflammation. As a result COX-2 has become the natural target for the development of anti-inflammatory and anti-cancer drugs. While the conventional NSAIDs with gastric side effects inhibit both COX-1 and COX-2, the newly developed drugs for inflammation with no gastric side effects selectively block the COX-2 enzyme. NSAIDs, nonselective non-aspirin NSAIDs and COX-2 selective inhibitors, are being widely used for various arthritis and pain syndromes. Selective inhibitors of COX-2, however, convey a small but definite risk of myocardial infarction and stroke; the extent of which varies depending on the COX-2 specificity. In view of the gastric side effects of conventional NSAIDs and the recent market withdrawal of rofecoxib and valdecoxib due to their adverse cardiovascular side effects there is need to develop alternative anti-inflammatory agents with reduced gastric and cardiovascular problems. The present study reviews various Computer Aided Drug Design (CADD) approaches to develop Cyclooxygenase based anti-inflammatory and anti-cancer drugs.     

COX-2 selective inhibitors and bone

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely prescribed medications for relief of pain and inflammation. Recent animal studies using models of fracture healing and bone ingrowth suggest that NSAIDs (both non-selective NSAIDs and selective COX-2 inhibitors) adversely affect these bone-related processes. The dose and time-relationships of these medications and their resulting effects on bone have not yet been fully elucidated. Furthermore, whether COX-2 inhibitors and non-selective NSAIDs lead to clinically relevant adverse effects on bone healing in humans is unknown.     

Anti-inflammatory and side effects of cyclooxygenase inhibitors

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly used drugs in inflammatory diseases, since they are effective in management of pain, fever, redness, edema arising as a consequence of inflammatory mediator release. Studies have shown that both therapeutic and side effects of NSAIDs are dependent on cyclooxygenase (COX) inhibition. COX isoforms have been named constitutive (COX-1) and inducible (COX-2). COX-1 catalyzes formation of cytoprotective prostaglandins in thrombocytes, vascular endothelium, stomach mucosa, kidneys, pancreas, Langerhans islets, seminal vesicles, and brain. Induction of COX-2 by various growth factors, proinflammatory agents, endotoxins, mitogens, and tumor agents indicates that this isoform may have a role in induction of pathological processes, such as inflammation. It is well known that therapy with COX inhibitors is associated with a number of side effects including gastrointestinal erosions, and renal and hepatic insufficiency. Such critical adverse reactions are mostly dependent on COX-1 inhibition. As a result of research focused on reduction of the adverse effects of NSAIDs, selective COX-2 inhibitors, such as celecoxib and rofecoxib have been developed. However, many data demonstrate that mechanisms of action of these drugs are multidirectional and complex. These drugs or their derivatives, which belong to the same group, have distinct pharmacological effects, side effects and potencies which implies that there may be more than two, five or even tens of COX isoforms.     

NSAID-induced gastrointestinal damage and the design of GI-sparing NSAIDs

NSAIDs are among the most widely used medications, but the side effects of these drugs frequently include gastrointestinal (GI) ulceration and bleeding. COX-2 inhibitors were designed that were claimed to be devoid of ulcer-promoting effects; however, this promise has been unfulfilled, and there are concerns about the cardiovascular safety of COX-2 inhibitors. Several novel approaches to developing GI-sparing NSAIDs have been used, with promising preclinical and clinical results. Selective inhibition of terminal PG synthases, and NSAIDs modified to slowly release gastroprotective gaseous mediators (ie, nitric oxide or hydrogen sulfide) may offer renewed hope for developing anti-inflammatory therapies with greatly reduced GI toxicity.     

Nimesulide is a selective COX-2 inhibitory, atypical non-steroidal anti-inflammatory drug

In this review it is shown that nimesulide, a selective cyclooxigenase-2 (COX-2) inhibitor, is different from other selective COX-2 inhibitors and classical non-steroidal anti-inflammatory drugs (NSAIDs). The anti-inflammatory effect mechanism of nimesulide (inhibition of inflammatory mediators) is similar to other classic NSAIDs, but the protective effect of nimesulide on classic NSAID-induced ulcers elucidates the difference between nimesulide and these other drugs. It is known that the selective COX-2 inhibitor nimesulide prevents NSAID-induced ulcers, while celecoxib and rofecoxib, which are more selective to COX-2, failed to prevent these ulcers. Nimesulide produces gastro-protective effects via a completely different mechanism. In addition, while selective COX-2 inhibitors increase the risk for cardiovascular diseases, nimesulide does not exert significant cardiotoxicity. This data suggests that gastrointestinal side effects of classic NSAIDs cannot be related to the COX-1 inhibition alone and also suggest that nimesulide is an atypical NSAID, which is different from both non-selective and selective COX-2 inhibitors.     

Arylpyridazinones as selective cyclooxygenase-2 inhibitors

Selective cyclooxygenase-2 (COX-2) inhibitors now represent a new generation of anti-inflammatory drugs with reduced gastrointestinal side effects compared to current non-steroidal anti-inflammatory drugs (NSAIDs). The present patent claims selective COX-2 inhibitors based on the pyridazinone template in the tricyclic class, which was derived from DuP-697.     

The role of COX-2 in acute pain and the use of selective COX-2 inhibitors for acute pain relief

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the mainstay of therapy for the management of acute pain. Cyclooxygenase (COX) enzyme is of particular interest because it is the major target of NSAIDs. Although NSAIDs are remarkably effective in the management of pain and inflammation, their use is limited by several adverse effects including gastrointestinal bleeding and ulceration, impaired renal function, and inhibition of platelet aggregation. Discovery of a second cyclooxygenase, COX-2, led to the hypothesis that NSAID side effects could be decreased, as the inhibition of COX-2 is more directly implicated in ameliorating inflammation while the inhibition of COX-1 is related to adverse effects in the GI tract. This stimulated the development of selective COX-2 inhibitors (coxibs) that are better tolerated than nonselective NSAIDs but comparable in analgesic efficacy. This article provides an overview on the therapeutic use of selective COX-2 inhibitors for relief of acute pain, largely based on clinical trials in patients undergoing the surgical removal of impacted third molars, with focus on analgesic efficacy and the potential safety associated with their use compared to dual COX-1/COX-2 inhibitors.