非甾体抗炎药物的临床药理进展

<正> 从19世纪末水杨酸类使用于临床开始,非甾体抗炎药(NSAIDs)的研究已有近百年的历史,但对于该类药物的现代临床药理学的研究仅仅是近20年内的事情。随着研究的不断深入,有关NSAIDs的临床及亚细胞生化作用正在不断地被揭示,并有力地推动着新型NSAIDs的发展。     

非甾体抗炎药物分析方法进展

根据近几年的文献,综合介绍非甾体抗炎药物所采用的主要分析方法,包括容量法,紫外分光光度法,高效液相色谱法以及其他方法。     

非甾体抗炎药在慢性疼痛治疗中的应用

美国疼痛学会在1995年提出将疼痛列为第5大生命体征。2001年亚太地区疼痛论坛提出"消除疼痛"是患者的基本权利。2002年8月第10届国际疼痛学会(IASP),与会专家达成基本共识,即慢性疼痛是一种疾病。     

非甾体抗炎药物的作用机制及进展

阿司匹林于1898年上市以来,已一个多世纪。至今非甾体抗炎药(NSAIDS)已增至百余个品种,成为全球最畅销的药物。NSAIDS疗效明确,耐受性好,但其胃肠道反应限制了NSAIDS的进一步应用。近年来,国内外学者对NSAIDS的作用机制进行了大量研究,得出产生不良反应是由于NSAIDS非选择性的抑制了环氧合酶(COX)的两个亚型：COX-1、COX-2,从而使非甾体抗炎药得到了更进一步的发展。     

非甾体抗炎药物的进展

目的：对非甾体抗炎药物的发展进行介绍。方法：通过对国内外文献的分析，概述了非甾体抗炎药作用机制及主要的研究进展。结果：新型非甾体抗炎药和传统相比，具有疗效好、不良反应小的特点。结论：新型非甾体抗炎药通过结构的改变，降低药物的不良反应，为临床应用提供了更好的选择，同时也为此类药物的发展提供了一个良好的研究方向。     

非甾体抗炎药的进展

非甾体抗炎药(NSAIDS)能有效地减轻急性关节炎的症状,主要通过抑制炎症组织中环氧酶(COX)活性,使前列腺素(PG)合成减少而发挥作用,由于COX介导的PG也是一种正常的生理物质,尤其对胃和肾等组织器官具保护作用.因此NSAIDS在起到抗炎作用的同时,常产生一些不良反应.     

美国FDA建议限制使用COX-2抑制剂和非甾体抗炎药物

2004年12月23日，美国食品药品管理局(FDA)发出消息，对包括选择性COX-2抑制剂在内的非甾体抗炎药(NSAIDs)的使用提出建议。同时声明，此项建议只是暂时性的，直到获得更多的研究数据和进一步的评价结果。FDA发布警告是基于近期公布的一些临床研究数据。     

对FDA要求修改非甾体抗炎药说明书的思考

为保证患者的安全,美国FDA发布使用COX-2抑制剂及非甾体抗炎药(NSAID)的声明,要求修改所有NSAID(包括COX-2抑制剂)的说明书,增加该类药物可增加心血管及胃肠道事件风险的黑框警告.这个声明基于3个长期服用COX-2抑制剂的随机对照双盲试验(RCT)出现了远期心血管事件.COX-2抑制剂以外的NSAID从未做过长期心血管安全性随机对照双盲试验,然而一些药物流行病的回顾性分析中出现了心血管事件增多的提示.监测药物上市后不良反应是保证病人用药安全性的主要手段.通过近期对NSAID不良反应的讨论.目的是提高医药人员对不良反应监测重要性的认识并积极参与不良反应监测工作.     

2005～2007年我国非甾体抗炎药市场应用分析

目的：以骨骼肌肉系统使用非甾体抗炎药物为例,分析该类药物在2005～2007年的销售数量、销售金额及生产厂家风云榜。方法：采用药物分类累加的方法统计2005～2007年非甾体抗炎药的销售数量和金额排序,并对前10位药品销售数量和金额对比,及前10位厂家对比。结果：双氯芬酸稳居销售榜首,美洛昔康、布洛芬等药物位居其后。结论：新一代的非甾体抗炎药已经占据主要市场,各类药物各有特色,但是仍需注意其消化系统及心血管系统的不良反应。     

非甾体类抗炎药与心血管疾病的研究进展

非甾体类抗炎药（NSAIDs）是当今广泛应用的一类药物。目前许多证据表明选择性的环氧化酶-2（COX-2）抑制剂具有不良心血管作用，包括增加心肌梗死、中风、心衰和高血压的危险，对有心血管病史或高心血管疾病危险者上述不良作用可能最为明显。对上述病人，仅在没有可替代的药物时使用COX-2抑制剂，并使用最小的剂量和必需的最短的时间。普通的非选择性的环氧化酶（COX）抑制剂其心血管安全性也有待更多的证据。因此，使用NSAIDs时要注意权衡利弊。     

A Receptor-Grounded Approach to Teaching Nonsteroidal Antiinflammatory Drug Chemistry and Structure-Activity Relationships

Objective

To describe a receptor-based approach to promote learning about nonsteroidal anti-inflammatory drug (NSAID) chemistry, structure-activity relationships, and therapeutic decision-making.

Design

Three lessons on cyclooxygenase (COX) and NSAID chemistry, and NSAID therapeutic utility, were developed using text-based resources and primary medicinal chemistry and pharmacy practice literature. Learning tools were developed to assist students in content mastery.

Assessment

Student learning was evaluated via performance on quizzes and examinations that measured understanding of COX and NSAID chemistry, and the application of that knowledge to therapeutic problem solving.

Conclusion

Student performance on NSAID-focused quizzes and examinations documented the success of this approach.     

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。     

环氧酶选择性抑制剂筛选模型的建立

目的　建立COX1和COX2活性检测模型,为COX2选择性抑制剂的筛选及抗炎作用机制研究提供可靠方法。方法　COX1抑制剂筛选模型用新生小公牛主动脉内皮细胞为酶源,6-keto-PGF_1α的含量变化评价化合物对COX1的抑制作用。COX2抑制剂筛选模型用激活的小鼠腹腔巨噬细胞,PGE₂含量变化评价化合物对COX2的抑制作用。结果　Indomethacin可显著地抑制COX1的活性, Meloxicam可显著地抑制COX2的活性, 其对COX2的选择性抑制作用高于前者。结论　COX1和COX2抑制剂筛选模型可用于COX2选择性抑制剂的筛选和机制研究。     

Pharmacokinetic Analysis of the Enantiomeric Inversion of Chiral Nonsteroidal Antiinflammatory Drugs

Equations describing plasma concentration–time courses of the individual enantiomers of chiral 2-arylpropionic acid nonsteroidal antiinflammatory drugs were derived from a general model. The model assumes first-order absorption and elimination of the enantiomers with presystemic and/or systemic R-to-S enantiomeric inversion. Utilizing reported pharmacokinetic parameters, plasma concentrations of the enantiomers of ibuprofen (IB) were simulated. In the case of presystemic inversion, S:R plasma concentration ratios remained constant after an initial rise; the ratio progressively increased with time, however, when systemic inversion was assumed. Under the assumption of simultaneous systemic and presystemic inversion, the increase in the ratio in the postabsorptive phase was preceded by a steeper increase during absorption. Furthermore, it was shown that purturbation of IB absorption from the gastrointestinal tract may serve as an important discriminative measure for identification of the inversion site. For systemic and presystemic inversions, negative and positive sigmoidal relationships, respectively, were observed between the S:R concentration ratio 5 hr after drug administration and the time to reach the maximum plasma concentration. The applicability of the model to previously reported IB data is discussed.     

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。     

Non-steroidal Anti-inflammatory Drugs and the Risk of Pneumonia Complications: A Systematic Review

There have been concerns regarding the safety of nonsteroidal antiinflammatory drugs (NSAIDs) in patients with respiratory infections. However, to date, the quality of the evidence has not been systematically assessed. The purpose of this systematic review was to evaluate the role of NSAIDs on pneumonia complications. OVID MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Database of Abstracts of Reviews of Effects, and Google Scholar were searched. Studies that examined pneumonia complications in patients who had taken NSAIDs before onset of symptoms were identified. Quality assessment was conducted using the Risk of Bias in Non-randomized Studies – of Interventions (ROBINS-I) assessment tool, which was adapted to include biases that were pertinent to this question. The search strategy identified 1721 potential studies through the 5 primary databases and searching reference lists. Of these, 10 studies met the inclusion criteria, including 5 nested case-control studies, 2 population-based case-control studies, and 3 cohort studies. In total, 59,724 adults were included from 4 of the studies (range = 57–59,250) and 1217 children from 5 studies (range = 148–540). All studies demonstrated a positive association; in adults (odds ratio/risk ratio range = 1.8–8.1) and children (odds ratio/risk ratio range = 1.9–6.8). Studies were limited by moderate or serious risk of confounding bias, exposure misclassification, and protopathic biases and sparse data bias. The results of this review demonstrate that published studies on the effect of NSAIDs use and risk of pneumonia complications are subject to a number of biases. These results should not be extrapolated as evidence of harm for NSAIDs, including ibuprofen, in respiratory ailments but highlight the need for more methodologically robust studies to evaluate this potential relationship.     

非甾体抗炎药环氧化酶/5-脂氧化酶双重抑制剂的研究进展

非甾体抗炎药具有解热、镇痛、抗炎和抗风湿等作用。现有的非甾体抗炎药大多存在胃肠道不良反应或心脏病发作和心肌梗死等方面的副作用,而环氧化酶/5-脂氧化酶双重抑制剂不仅具有较强的解热、镇痛、抗炎和抗风湿等作用,而且未发现有心脏病发作、心肌梗死和胃肠道损伤的危险,因此环氧化酶/5-脂氧化酶双重抑制剂已成为研究新一代非甾体抗炎药的途径。     

Naproxen disposition in patients with alcoholic cirrhosis

Summary Chronic liver disease is known to alter the absorption and disposition of many drugs. To assess the influence of chronic alcoholic liver disease on the disposition of naproxen, we administered the drug both as a single dose and to steady state to 10 individuals with alcoholic cirrhosis and to 10 healthy controls. Plasma and serum samples collected after naproxen dosing were assayed for both total and (following equilibrium dialysis) unbound drug concentration. Clearance calculated based on both total and unbound naproxen concentration revealed no change in total plasma clearance of the drug at steady state but a marked reduction of approximately 60% in clearance based on unbound drug. Naproxen volume of distribution changed only minimally. Because clearance based on unbound drug concentration at a given dosing rate determines the plasma or blood free drug concentration, this concentration may increase significantly in patients with alcoholic liver disease given usual doses of naproxen. Unbound drug concentration is thought to determine the pharmacologic effect of a drug. We therefore recommend that naproxen dosing be reduced by at least half in patients with chronic alcoholic liver disease. In the absence of data to the contrary, this recommendation can be extended to individuals with other forms of hepatic disease.