非甾体类抗炎药对肾功能损害的探讨

非甾体类抗炎药具有解热、镇痛、抗炎抗风湿的作用,少数药物还有抑制血小板聚集、防止血栓形成等作用。药物作用与甾体类抗炎药相似,但是本类药物在化学结构与甾体类抗炎药物不同,故称为非甾体类抗炎药。本类药物主要作用机制为抑制前列腺素的合成,由于药物的选择性低和本类药物对肾脏的直接毒性,长期大量使用会导致肾功能损害。临床应用此类药物应合理使用密切观察,一旦发生肾功能损害,立即停药及时治疗,避免和减少不良反应的发生。     

抗类风湿性关节炎的药物介绍

概述抗类风湿性关节炎(RA)的药物.选择性环氧化酶 Ⅱ(COX Ⅱ)抑制药(如美洛昔康等),抗炎镇痛效果与传统非甾体抗炎药(NSAID)相似,但对胃肠道损害明显减轻;新的免疫调节药(如来氟米特等)在临床治疗中取得较好疗效;新的生物制剂(如重组可溶性肿瘤坏死因子受体融合蛋白等)对RA患者疗效较好,且无严重不良反应.     

浅谈非甾体类抗炎药对胃黏膜的损伤及防治

非甾体类抗炎药(NSAIDs)问世后,在临床上已广泛应用,其抗炎、止痛和解热作用显著,其对胃黏膜的损害也相当常见,本文通过对非甾体类抗炎药(NSAIDs)作用机制的探讨,从而采取有效的措施,在治疗疾病的同时,避免或减少其不良反应的发生。     

艾瑞昔布治疗退行性膝关节炎的临床效果及对患者疼痛症状的影响

<正>退行性膝关节炎属于门诊常见、多发的关节疼痛疾病,主要的临床特征为起病缓慢,治疗时间长,主要的发病人群为中老年女性患者,是一种慢性进行性骨关节疾病[1]。最有效的治疗方法为口服消炎止痛药物[2]。艾瑞昔布为非甾体抗炎药,通过抑制环氧酶(COX)发挥镇痛作用。非甾体抗炎药(NSAIDs)的主要作用为解热、镇痛,同时还具有抗炎、抗风湿的作用,其治疗疗效较好,在临床上取得较为广泛的应用,此类药物的缺陷在于不良反应较多,主要出现不良反应的部位为胃肠道,同时还会出现肾损害、肝损害、心血管损害、变态反应等不良     

国家食品药品监督管理局密切关注非甾体类抗炎药物的安全性问题

近日,美国食品药品监督管理局(FDA)综合现有的研究数据认为,非甾体抗炎药存在潜在的心血管和消化道出血风险,要求这些药品生产厂家在其说明书中提出警示。国家食品药品监督管理局已经注意到了此事,并在密切关注在我国生产、销售和使用的所有非甾体类抗炎药物的安全性问题。非甾体抗炎药(NSAIDs)是一类具有抗炎、解热和镇痛作用的药物,在临床上广泛用于骨关节炎、类风湿性关节炎和多种免疫功能紊乱的炎症性疾病及各种疼痛(如牙痛、头痛、痛经及肌肉痛)症状的缓解,是全世界范围内使用最广泛的一类药物。在我国非甾体抗炎药的临床用量很大,…     

从罗非昔布事件谈非甾体抗炎药物的安全性

非甾体抗炎药(NSAIDs)从诞生之日起一直作为临床解热镇痛的主要药物。在近10年来,不同化学结构和剂型的新型NSAIDs大量涌现,极大地丰富了临床医生用药选择,但随之而来的一些严重不良反应,如消化道出血、肝肾损害、心血管毒性等不良事件,也不断出现。     

非甾体抗炎药的临床应用及不良反应

目的：探讨非甾体抗炎药的临床应用及不良反应。方法：对50例发生非甾体抗炎药的不良反应的病例资料进行回顾性分析。结果：非甾体抗炎药的不良反应包括胃肠道反应,肝、肾以及血液系统损害等。结论：随着非甾体抗炎药的广泛应用,其不良反应发生的情况较为多见,在使用过程中,临床医生应严加关注,确保用药安全,以减少药物对机体的副作用。     

非甾体抗炎药对胃肠黏膜的损伤及防治

随着非甾体抗炎药(NSAIDs)在临床的广泛应用,其对胃肠道黏膜的损害已受到越来越多的关注。本文通过综述有关文献资料,总结非甾体抗炎药对胃肠黏膜的影响,提出有效的预防和治疗措施。     

口服非甾体抗炎药物的利用分析

目的：了解非甾体抗炎药的用药特点及变化趋势，并进行临床利用评价。方法：采用用药频度(DDDs)排序、金额排序、序号比的比较，对华中科技大学同济医学院附属同济医院2000年1月～2002年12月3 a中口服非甾体抗炎药的利用进行分析。结果：3 a中用药频度排序前5位的药物(阿司匹林、氯唑沙宗、布洛芬、奥沙普嗪、吲哚美辛等)基本不变，表明传统非甾体抗炎药在临床中发挥了重要作用，此外第2代高选择性非甾体抗炎药的问世，揭开了镇痛抗炎治疗的新篇章，显示了良好应用前景。结论：非甾体抗炎药正向着高效、长效、低毒的方向发展。     

非甾体抗炎药的研发近况

2005年4月7日美国FDA发表了非甾体类抗炎药有增加心血管不良事件和胃肠道出血的潜在风险的声明;我国国家食品药品监督管理局随之也表示,将对这类药品的安全性问题予以"密切关注". 非甾体抗炎药(NSAIDs)其结构与作用机制均不同于肾上腺皮质激素类药,但具有解热、镇痛、抗炎等功效,所以称之为非甾体抗炎药.NSAIDs在临床上广泛用于治疗骨关节炎、类风湿性关节炎和多种免疫功能紊乱的炎症性疾病,及各种疼痛症状的缓解,是全世界范围内使用最广泛的一类药物.     

Assessment and prevention of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs

Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for analgesic, anti-inflammatory and, in the case of aspirin, for anti-thrombotic actions. The serious gastrointestinal side-effects associated with these drugs are of concern and pose a significant obstacle to their use. This review discusses the pathogenic mechanisms by which the conventional acidic NSAIDs induce gastrointestinal toxicity, with particular emphasis on non-prostaglandin effects. Methods of assessment of NSAID-induced enteropathy are reviewed, with particular emphasis on the use of functional measurement of NSAID-induced changes in the gastrointestinal tract. The advances in our knowledge of the pathogenesis of these effects have resulted in the development of a range of novel NSAIDs. Where functional assessment of the effects of NSAIDs has been employed, it appears to be more useful as an indicator of early-stage changes rather than a predictor of the effects of long-term NSAID exposure. Successful pharmaceutical strategies now offer considerable promise for reducing the severity of NSAID damage to the gastrointestinal tract. The utility of intestinal permeability measurements for selection and assessment of these strategies is discussed.     

The pharmacological profile of ML3000: A new pyrrolizine derivative inhibiting the enzymes cyclo-oxygenase and 5-lipoxygenase

Since the discovery of aspirin about one century ago, many non-steroidal anti-inflammatory drugs (NSAIDs) have been used for the treatment of inflammatory states and pain. While the NSAIDs are generally safe and effective, common side effects frequently limit therapy. Typical mechanism-based side effects are gastrointestinal (GI)-related, ranging from GI upset and intolerance to ulceration and bleeding after long-term therapy. In order to overcome these side effects several strategies have been followed, among them the development of selective COX-2 inhibitors. Our strategy to find compounds that are active on the one hand and tolerated by the GI tract on the other hand, is based on the shunt to leukotrienes. This theory is founded upon the fact that NSAIDs, while inhibiting the cyclooxygenase branch of the arachidonic acid cascade, are able to increase the 5-lipoxygenase (5-LOX) branch of arachidonic acid metabolism. This shunt to the 5-LOX side leads to the increase in chemotactic LTB₄ and vasoconstrictive peptidoleukotrienes, the contributory effects of which to gastrointestinal disorders are widely accepted. Therefore, the design of anti-inflammatory compounds with 5-LOX inhibitory effects seems reasonable. With the compound ML3000, this theory has gained further evidence. ML3000 is an anti-inflammatory compound with potent activity in various animal experiments that represent models for acute and chronic inflammation, pain, fever and asthma. It is a balanced inhibitor of the enzymes 5-LOX and COX-1/2 in the submicromolar range. The compound demonstrates excellent gastrointestinal tolerance in various animal species. The preclinical profile of ML3000, which is currently in Phase III clinical development, is presented in this publication.     

NSAID injury to the gastrointestinal tract: evidence that NSAIDs interact with phospholipids to weaken the hydrophobic surface barrier and induce the formation of unstable pores in membranes

In this review, we have discussed our current understanding of the barrier properties that are in place to protect the upper gastrointestinal mucosa from luminal acid, and the pathogenic mechanism by which nonsteroidal anti-inflammatory drugs (NSAIDs) induce injury to the gastrointestinal tract. The changes in our view of the importance of NSAID-induced cyclo-oxygenase (COX) inhibition on the pathogenesis and prevention of NSAID-induced gastrointestinal injury is presented. The focus of this paper has been placed on the effects of NSAIDs on the mucosal surface, and specifically the effect of these powerful drugs in inducing changes in the hydrophobicity, fluidity, biomechanical and permeability properties of extracellular and membrane phospholipids. Lastly, recent evidence is presented that salicylic acid and related NSAIDs may alter the stability of membranes, inducing the formation of unstable pores that may lead to back-diffusion of luminal acid and membrane rupture. This understanding of the interaction of NSAIDs with membrane phospholipids may prove valuable in the design of novel NSAID formulations with reduced gastrointestinal side-effects.     

Dual COX-inhibitors: the answer is NO?

Nitric oxide (NO) releasing non-steroidal anti-inflammatory drugs (NSAIDs) are a new class of anti-inflammatory agents obtained by adding an NO releasing moiety to existing NSAIDs. They have also christened as COX inhibiting NO-donating drugs (CINOD). Preclinical and clinical studies suggest that CINOD inhibit COX-1 and COX-2 activities while cause less adverse effects on gastrointestinal tract in comparison to conventional NSAIDs and coxibs and reduce systemic blood pressure. A different class of NO-donating drugs has been obtained by coupling NO to aspirin. These NO-releasing aspirins are new chemical entities that maintain and possibly expands the pharmacological properties of aspirin, but spare the gastrointestinal mucosa. Animal studies have shown that CINOD and NO-aspirins maintain gastric mucosal blood flow and reduce leukocyte-endothelial cell adherence.     

Hydrogels of dextran containing nonsteroidal anti-inflammatory drugs as pendant agents

The oral administration of nonsteroidal anti-inflammatory drugs (NSAIDs) is often associated with upper gastrointestinal tract side effects. To reduce these effects and improve the therapeutic efficacy, NSAIDs are often formulated as controlled release systems. We have prepared a new formulation consisting of dextran hydrogels containing NSAIDs as pendant agents, through ultraviolet irradiation of solutions of dextran functionalized with methacrylic groups in the presence of the drug derivatized in the same way. Release studies of different drugs from this system, carried out in media simulating the gastrointestinal tract, have demonstrated that the amount of released drug is strictly related to the concentration of the polymer in the solution submitted to irradiation as well as to its derivatization degree. Our obtained data confirm that the system is able to realize a colon-specific drug delivery.     

Gastrointestinal effects of COX-2 inhibitors

The developing popularity of non-steroidal anti-inflammatory drugs (NSAIDs) over the last 100 years has been paralleled by an increase in associated complications, particularly affecting the gastrointestinal (GI) tract [1]. Over this period, there have been several attempts to develop less toxic NSAIDs, most of which have been unsuccessful. Since the discovery that the enzyme cyclooxygenase (COX) exists as two isoforms, the largely constitutive COX-1 and the mainly inducible COX-2, much interest has centred on the development of drugs capable of selectively inhibiting COX-2. Early studies that investigated specific COX-2 inhibitors (with no effect on the COX-1 isoform over the whole range of concentrations achieved in clinical usage) are encouraging, as they demonstrate that these drugs have fewer effects on gastroduodenal mucosa than standard NSAIDs given at equivalent doses. Further clinical experience with these agents outside trial settings and additional studies to assess the role of COX-2 when induced in the GI tract are needed, before such agents can be safely recommended for widespread prescribing.     

Gastrointestinal effects of COX-2 inhibitors

The developing popularity of non-steroidal anti-inflammatory drugs (NSAIDs) over the last 100 years has been paralleled by an increase in associated complications, particularly affecting the gastrointestinal (GI) tract [1]. Over this period, there have been several attempts to develop less toxic NSAIDs, most of which have been unsuccessful. Since the discovery that the enzyme cyclooxygenase (COX) exists as two isoforms, the largely constitutive COX-1 and the mainly inducible COX-2, much interest has centred on the development of drugs capable of selectively inhibiting COX-2. Early studies that investigated specific COX-2 inhibitors (with no effect on the COX-1 isoform over the whole range of concentrations achieved in clinical usage) are encouraging, as they demonstrate that these drugs have fewer effects on gastroduodenal mucosa than standard NSAIDs given at equivalent doses. Further clinical experience with these agents outside trial settings and additional studies to assess the role of COX-2 when induced in the GI tract are needed, before such agents can be safely recommended for widespread prescribing.     

非甾体抗炎药致胃肠道黏膜损伤的研究进展

随着非甾体抗炎药(NSAIDs)在临床的广泛应用,其对胃肠道黏膜的损害已受到越来越多的关注。笔者就NSAIDs胃肠道黏膜损害的发病机制、临床表现和防治等做一综述。     

非甾体抗炎药的胃肠损害及其预防

非甾体抗炎药（NSAIDs）在临床上广泛用于风湿性疾病及心血管疾病的治疗。NSAIDs的常见不良反应为胃肠道不适、恶心，严重不良反应有消化性溃疡、胃肠道出血或穿孔。胃肠损伤发生的原因是由于NSAIDs抑制了环氧酶（COX）系统而阻断了前列腺素的合成，因此干扰了正常黏膜保护机制导致局部受损。NSAIDs致胃肠道损伤的危险因素为高龄、有消化性溃疡或出血史。预防NSAIDs所致胃肠损伤的措施有：应用预防溃疡的药物，选择新一代高选择性COX-2抑制剂，根据患者情况应用抗幽门螺杆菌疗法，依据患者相关的危险因素采用不同的治疗方案。     

Section Review: Pulmonary-Allergy,Dermatological, Gastrointestinal & Arthritis: Development of NSAIDs with reduced gastrointestinal and renal toxicity

While nonsteroidal anti-inflammatory drugs remain among the most widely used medications, their use continues to be associated with significant toxicity, particularly in the gastrointestinal tract and kidney. As more is learned about the pathogenesis of these adverse effects, several strategies have been taken to develop NSAIDs that are less toxic. Many such strategies have failed to have significant impact on the frequency and/or severity of NSAID-related adverse effects. However, recently, two new approaches have been taken which show great promise. Selective inhibitors of the inducible isoform of prostaglandin synthase are reported to spare the gastrointestinal tract. As we know little about the possible physiological role of this isoform of prostaglandin synthase, there are some concerns about the true potential for these compounds. A second approach is the linking of standard NSAIDs to a nitric oxide-releasing moiety. Studies in experimental models are extremely encouraging, demonstrating that these compounds retain the desired effects of the NSAID, but do not produce injury in the gastrointestinal tract or kidney.