非甾体类抗炎药与环氧化酶异构体

非甾体类抗炎药与环氧化酶异构体杨岫岩董怡１９７１年，Ｖａｎｅ等提出环氧化酶（ＣＯＸ）理论，解释了非甾体类抗炎药（ＮＳＡＩＤｓ）的作用机制。Ｏ′Ｂａｎｉｏｎ等于１９９１年发现ＣＯＸ存在不同的异构体［１］，从而提出了ＣＯＸ异构体的新理论。这个理论揭示了各...     

老年人非甾体抗炎药相关性胃十二指肠损伤的防治

非甾体类抗炎药（non-steroidal anti-inflammatory drugs,NSAIDs）是目前应用最广泛的药物之一。主要用于缓解各种疼痛、治疗类风湿性关节炎、骨性关节炎等风湿性疾病。还有越来越多的人长期服用低剂量阿司匹林预防心脑血管疾病。此外,NSAIDs已被初步证实可降低结肠癌及早老性痴呆等的发病率,这使NSAIDs的使用呈现上升趋势。     

非甾体类抗炎药胃十二指肠损害的处理

关键内容非甾体类抗炎药（ＮＳＡＩＤｓ）通过多种途径损伤胃肠粘膜, 主要是通过抑制环氧合酶（ＣＯＸ）干扰前列腺素（ＰＧＳ）的 合成。ＮＳＡＩＤ溃疡常为“无痛”性,可以消化道出血或穿 孔为首发症状。一旦发现ＮＳＡＩＤ溃疡,对可以停用ＮＳＡＩＤｓ者应予常规 抑酸剂治疗;如患者需继续服用ＮＳＡＩＤｓ,则需用常规剂 量或倍量质子泵抑制剂（ＰＰＩ）治疗。对具有发生症状性ＮＳＡＩＤ溃疡高危因素的患者,应常规 给予抗溃疡药物预防治疗。预防药物可选用ＰＧＳ类似物, 如米索前列醇或ＰＰＩ。Ｈ＿２受体桔抗剂（Ｈ＿２ＲＡ）、…     

尽力减少非甾体类抗炎药对胃十二指肠的副作用

阿司匹林问世已届百年，这是一种多年来常用的镇痛解热药。５０年代初保泰松问世后，非甾体类抗炎药（ＮＳＡＩＤ）逐渐应用于临床治疗风湿病和骨关节炎等。１９６０年以来，许多新型结构和剂型的ＮＳＡＩＤ相继合成，至今已有５０多种在世界市场上销售，例如吲哚美辛、舒...     

非甾体抗炎药的胃肠黏膜损害

非甾体抗炎药(NSAIDs)包括阿斯匹林是临床最常用的一类药物,本类药对胃肠黏膜屏障的损害进而引致胃肠道不良反应的报告不断增多,已成为医师和患者共同关心的课     

非甾体类抗炎药临床应用调查

目的 了解目前国内非甾体类抗炎药(NSAID)的临床应用情况.方法 对我国上海、北京、天津、沈阳及广州5个城市约50家医院消化科、风湿/骨科、心内外科、神经内科及全科医师进行问卷调查,获得有效问卷575份.结果 54.7%的医师会选择使用环氧合酶(COX)-2选择性抑制剂;传统NSAID中,选择处方洛索洛芬、双氯芬酸、美洛昔康的医师比例分别为22.6%、23.3%、14.6%;选择处方常规剂量的非肠溶阿司匹林、小剂量非肠溶阿司匹林、常规剂量肠溶阿司匹林、小剂量肠溶阿司匹林及其他剂型的医师比例分别为17.0%,14.7%,36.8%、28.5%及3.0%;在分别处方阿司匹林、传统NSAID及COX-2时,不同的预防性用药频率(不、偶尔、经常、通常及仅在高风险患者中使用)中,选择"偶尔"使用药物预防NSAID相关胃肠道损伤的医师比例分别为41.1%、40.7%及45.1%,同时处方比例最高的药物分别为Hz受体阻滞剂及质子泵抑制剂;处方NSAID前37.1%的临床医师会检查患者的幽门螺杆菌,76.3%的医师会实施幽门螺杆菌根除治疗.结论 最常使用的传统NSAID是双氯芬酸;最常使用的阿司匹林剂型为肠溶型阿司匹林;临床医师均多为"偶尔"处方药物预防三类NSAID相关胃肠道损伤,且最常使用的药物均为抑酸剂;仅有较少比例的临床医师在处方NSAID前会检查患者的幽f J螺杆菌.     

非甾体类抗炎药与心血管事件风险的研究进展

非甾体类抗炎药是一类广泛用于消炎、镇痛的药物,根据对环氧化酶的选择性不同分为三类,研究发现其对心血管事件有一定的影响。环氧化酶-1选择性抑制剂对心血管疾病有二级预防作用,但一级预防作用尚存争议。大多环氧化酶-2选择性抑制剂增加心血管事件风险,部分尚存争议。非选择性抑制剂大多增加心血管事件风险,少部分则几乎无影响。现拟对非甾体类消炎药与心血管事件风险的研究进展做一综述。     

非甾体类抗炎药与消化道肿瘤

非甾体类抗炎药(NSAID)对抑制实验动物的结肠癌、胃癌和食管癌有效,多数的流行病学调查也得到类似结论.消化道肿瘤组织中COX-2表达增加,因此COX抑制剂可能通过减少花生四烯酸代谢产物产生、减少免疫抑制性前列腺素的合成、抑制血管形成等途径抑制肿瘤.但NSAID也可以在完全缺乏COX活性的细胞中发挥抗增殖作用,因此激活对转录因子核因子кB的抑制以及抑制包括依赖CAMP的蛋白激酶在内的大量酶类等也可能是其抗肿瘤的作用方式.     

非甾体类抗炎药物相关性小肠疾病

非甾体类抗炎药(NSAID)是临床上应用最为广泛的抗炎药物之一，主要用于治疗风湿、类风湿性关节炎、骨关节疾病，以及对血管疾病的预防。据估计每天全世界约有3000万人在服用，因此该类药物引起的副作用不容忽视，尤其是胃肠道的不良反应最为突出。NSAID对胃十二指肠黏膜损伤和引起医源性上消化道溃疡的副作用已经非常肯定，并得到临床广泛重视。     

非甾体类抗炎药相关性肠病

非甾体类抗炎药(NSAIDs)是临床上应用最为广泛的抗炎药物之一. 近来也用于预防心血管疾病以及骨关节、肌肉疼痛. 但是在长期大量使用的时候, 常引起胃十二指肠黏膜损害. 随着临床诊疗手段的不断发展, 发现NSAIDs引起的肠黏膜损害日益增多. 本文就NSAIDs相关性肠病发病机制及防治等作一综述.     

Meta-analysis: cardiovascular events associated with nonsteroidal anti-inflammatory drugs

Purpose

We performed a meta-analysis of randomized controlled trials to assess the effect of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) on cardiovascular events in trials of joint disease and Alzheimer’s disease.

Methods

We performed comprehensive searches of MEDLINE, EMBASE, CINAHL and Cochrane databases from 1966 to July 2005, and references of identified articles and reviews. We included randomized placebo-controlled trials of at least 6 weeks duration that evaluated nonselective NSAIDs in trials of joint disease or Alzheimer’s disease, and reported at least one cardiovascular event or death. The outcome measured was the composite of death, myocardial infarction or cerebrovascular accident, with the pooled results reported as odds ratios (OR). Subgroup analyses evaluated the difference between trials of joint disease and Alzheimer’s disease, and for naproxen and non-naproxen NSAIDs.

Results

Pooled data from 13 trials with 7718 participants showed that nonselective NSAIDs had no significant effect on cardiovascular events (OR 1.3; 95% confidence interval [CI], 0.8 to 2.1). No significant effect was seen for joint disease trials (OR 0.6; 95% CI, 0.2 to 1.7) or Alzheimer disease trials (OR 1.6; 95% CI, 0.9 to 2.7). There was no significant difference in results for naproxen and non-naproxen NSAIDs.

Conclusion

Nonselective NSAIDs have no significant effect on cardiovascular events or death in trials of joint disease and Alzheimer disease, but a small adverse effect could not be excluded. An indication for risk was present in trials of Alzheimer’s disease but not in joint disease trials. There was no significant adverse or cardioprotective effect of naproxen.     

非甾体类抗炎药物与消化性溃疡出血的关系

目的探讨非甾体类抗炎药物(NSAIDs)诱发消化性溃疡出血的临床流行病学特点。方法回顾分析1991~2004年我院诊治的消化性溃疡出血的临床资料,并用电脑数据库处理分析。结果在694例消化性溃疡并出血患者中,26.80%近期内有服用NSAIDs史。服用NSAIDs组与未服用NSAIDs组比较,服用NSAIDs组前驱症状(腹痛、消化不良等)发生率较低(30.65%比61.42%P<0.01);平均年龄较大[(44.16±13.25)岁比(35.23±11.49)岁,P<0.05];女性比例相对较多(26.34%比15.55%,P<0.01);胃溃疡比例较高(28.50%比20.67%,P<0.01);外科手术率无明显差别(P>0.05);结论NSAIDs是诱发消化性溃疡出血的一常见原因,应加强对NSAIDs胃肠毒副作用的防治。     

非甾体消炎药及阿司匹林相关消化性溃疡出血住院患者的实时调查

目的 分析非甾体消炎药(NSAIDs)及阿司匹林相关消化性溃疡出血患者的临床特点及其预后.方法 由同一调查者对2004年8月至2005年12月在北京大学第三医院消化科住院的所有消化性溃疡出血患者进行实时问卷调查.问卷内容包括人口学资料、NSAIDs及阿司匹林用药情况、临床表现、实验室及内镜检查、治疗、费用及预后等.通过单因素及多因素loistic回归分析确定与止血治疗无效相关的危险因素.结果 有NSAIDs及阿司匹林服药史的消化性溃疡出血患者共51例(设为NSAIDs组),占同期147例住院的消化性溃疡出血患者的34.7%,其余为非NSAIDs组.与非NSAIDs组比较,NSAIDs组平均年龄较大、急性起病者多见(P=0.014),腹痛症状少(61.5%比27.5%,P＜0.001),患冠心病(10.4%比17.6%,P＜0.001)、高血压(10.4%比39.2%,P＜0.001)及糖尿病(4.2%比19.6%,P=0.005)者多见,重度贫血多见(7.3%比23.5%,P=0.008),接受输血治疗者多见(24.0%比41.2%,P=0.025),再出血者多见(9.4%比15.7%,P=0.034);住院总费用及治疗费高于非NSAIDs组(P=0.089及P=0.063).既往溃疡病史为NSAIDs组止血治疗失败的危险因素(P＜0.05).结论 与非NSAIDs组相比,NSAIDs及阿司匹林相关消化性溃疡出血患者较少有腹痛症状,起病急,出血重,止血治疗效果差,治疗所需费用较高,特别是既往有溃疡病史的患者.临床医生在应用NSAIDs及阿司匹林前应注意相关高危因素.

Abstract：

Objective To investigate the clinical characteristic and prognosis of nonsteroidal antiinflammatory drugs( NSAIDs)and aspirin associated peptic ulcer bleeding. Method All patients with peptic ulcer bleeding were studied by the same researcher after admission and discharge. Results Fifty-one cases with NSAIDs and aspirin medication of the total peptic ulcer bleeding patients ( 147 cases) were included (34. 7% ). Compared with patients not associated with NSAIDs and aspirin medication, they are older [(41.2 ± 1. 9 ) years vs ( 59.4 ± 2. 2 ) years, P ＜ 0. 001], more commonly associated with hypertension ( 10. 4% vs 39. 2% ,P ＜0. 001 ), coronary heart disease ( 10. 4% vs 17.6% ,P ＜0. 001 ) ,diabetes (4. 2%vs 19. 6%, P = 0. 005 ); and had more severe anemia (7. 3% vs 23. 5%, P = 0. 008 ). Fewer patients in NSAIDs group had epigastric pain (61.5% vs 27.5%, P ＜ 0. 001 ), while there was more re-bleeding (9.4% vs 15.7%, P = 0.034). In all bleeding patients, factors associated with re-bleeding, surgical intervention and death included NSAIDs and aspirin medication, and low platelet count. In patients with NSAIDs and aspirin medication, re-bleeding was associated with previous ulcer history ( P ＜ 0. 05 ).Conclusion Peptic ulcer bleeding patients with NSAIDs and aspirin medication were more severe ill, and less likely to present with epigastric pain.     

非甾体消炎药对大鼠小肠黏膜机械屏障功能的影响

目的 探讨非甾体消炎药对大鼠小肠黏膜机械屏障功能的影响.方法 雄性SD大鼠32只,分为模型组和对照组,模型组予双氯芬酸灌胃,2次/d,每次7.5 mg/kg,对照组使用相同剂最的生理盐水灌胃,分别按造模后1 d和5 d时相点分为2个亚组(每组8只).进行胃及小肠大体损伤评分、小肠黏膜病理组织损伤评分,采用Carl Zeiss Imaging Systems图像分析系统进行绒毛高度、黏膜厚度、黏膜截面积定量分析,观察透射电镜下肠黏膜超微结构变化.结果 模型组胃黏膜的损伤评分与对照组的差异无统计学意义.模型组第1天小肠黏膜可见散在红斑、糜烂和溃疡,溃疡沿肠系膜侧分布;第5天小肠黏膜可见出血、穿孔和窦道形成,其大体损伤评分均高于对照组(P＜0.05).模型组第1天和第5大Chiu氏病理评分分别为3.5分和5.0分,与对照组相比差异有统计学意义(P＜0.05).造模第1天大鼠空、回肠绒毛高度分别为(126.9±32.0)μm和(118.6±22.9)μm,较对照组显著降低(P＜O.05);而空、回肠黏膜厚度、黏膜截面积和对照组相比差异无统计学意义,但有下降趋势;第5大大鼠空、回肠绒毛高度[(73.4±25.4)μm和(109.3±17.6)μm]显著降低、黏膜厚度[(123.8±51.6)μm和(165.7±37.4)μm]变薄、黏膜截而积[(2.48±1.01)mm2和(3.27±0.76)mm2]变小,与对照组相比差异均有统计学意义(P＜0.05).透射电镜下见模型组第1天大鼠小肠黏膜微绒毛水肿、排列紊乱,线粒体肿胀,部分峪减少,内质网出现不同程度扩张,细胞问连接开始出现部分增宽;第5天小肠黏膜上皮微绒毛脱落更为明显,细胞连接断裂破坏严重.结论 双氯芬酸可导致大鼠小肠黏膜屏障功能受损.绒毛变短、黏膜厚度变薄、微绒毛脱落和细胞间紧密连接增宽可能是其形态学基础.     

甲硝唑、雷贝拉唑预防非甾体类抗炎药所致小肠黏膜损伤的实验研究

目的 利用短期口服小剂量双氯芬酸建立大鼠非甾体类抗炎药(NSAID)小肠黏膜损伤模型,观察甲硝唑、雷贝拉唑对NSAID所致小肠黏膜损伤的预防作用.方法 将64只大鼠随机抽签分为空白组、模型组、甲硝唑组和雷贝拉唑组,每组16只.再将各组动物进一步分为T1(急性期)和T2(亚急性期)亚组,每组8只.甲硝唑组和雷贝拉唑组大鼠在造模前1 d分别给予甲硝唑50 mg/kg或雷贝拉唑15 mg/kg灌胃1次.次日,空白组以1 ml蒸馏水灌胃每天2次;模型组给予双氯芬酸7.5 mg/kg每天2次;甲硝唑组给予双氯芬酸7.5 mg/kg和甲硝唑50 mg/kg,每天2次;雷贝拉唑组给予双氯芬酸7.5 mg/kg和雷贝拉唑15 mg/kg,每天2次.各组的T1亚组灌胃1 d后处死,T2亚组灌胃5 d后处死.结果 小剂量双氯芬酸能引起小肠黏膜显著出血性损伤,小肠黏膜可见大量红斑、糜烂、溃疡,局部肠腔可见囊样扩张.模型组的T1、T2亚组损伤均较空白组严重(P＜0.05),且T2组损伤明显大于T1组(P＜0.05).甲硝唑和雷贝拉唑组的T1,T2亚组的损伤均小于模型组(均P＜0.05).模型组T1亚组的血清一氧化氮含量明显低于空白组(P＜0.05),T2亚组则明显高于空白组(P＜0.05).模型组与甲硝唑组、雷贝拉唑组之间一氧化氮含量比较差异无统计学意义(P＞0.05).结论 短期小剂量口服双氯芬酸后,即可引起小肠黏膜损伤.并随时间呈进行性加重; 血清一氧化氮含量在小肠黏膜损伤后呈现先降低,后升高趋势.甲硝唑、雷贝拉唑对NSAID诱发的小肠黏膜损伤具有一定的预防作用.     

Mechanisms,prevention and clinical implications of nonsteroidal anti-inflammatory drug-enteropathy

This article reviews the latest developments in understanding the pathogenesis, detection and treatment of small intestinal damage and bleeding caused by nonsteroidal anti-inflammatory drugs (NSAIDs). With improvements in the detection of NSAID-induced damage in the small intestine, it is now clear that this injury and the associated bleeding occurs more frequently than that occurring in the stomach and duodenum, and can also be regarded as more dangerous. However, there are no proven-effective therapies for NSAID-enteropathy, and detection remains a challenge, particularly because of the poor correlation between tissue injury and symptoms. Moreover, recent studies suggest that commonly used drugs for protecting the upper gastrointestinal tract (i.e., proton pump inhibitors) can significantly worsen NSAID-induced damage in the small intestine. The pathogenesis of NSAID-enteropathy is complex, but studies in animal models are shedding light on the key factors that contribute to ulceration and bleeding, and are providing clues to the development of effective therapies and prevention strategies. Novel NSAIDs that do not cause small intestinal damage in animal models offer hope for a solution to this serious adverse effect of one of the most widely used classes of drugs.     

非甾体抗炎药相关性溃疡并出血的临床特点

目的 研究非甾体抗炎药(NSAIDs)相关性胃十二指肠溃疡并出血的临床特点。方法 调查我院1997年1月-2001年12月间因胃十二指肠溃疡并出血收住院治疗患者的临床资料,根据人院前1周内有无服用NSAIDs史将患者分为2组,对2组病人的临床资料进行分析比较。结果 本研究共纳入446例患者,其中服药组86例,未服药组360例。2组病人在性别、出血方式、既往消化性溃疡史、胃及十二指肠溃疡的具体部位、糜烂,以及是否需要内镜治疗等方面的差异无显著性。但是服药组患者的年龄较未服药组更高,血红蛋白在服药组下降更明显(P＝0.004);胃溃疡和复合溃疡、多发溃疡在服药组更多见(P＜0．001),而未服药组幽门螺杆菌(Hp)的感染率较服药组更高,分别为72．5％和53.4％(P＝0.001)。进一步的研究发现,患者年龄和Hp感染状态对NSAIDs相关溃疡并出血的临床特点无明显影响。结论 应加强对NSAIDs相关性胃十二指肠溃疡并出血临床特点的认识,尽量减少NSAIDs的不良反应。     

Vasospastic angina induced by nonsteroidal anti-inflammatory drugs

We report two cases of vasospastic angina associated with anaphylactic reaction caused by nonsteroidal antiinflammatory drugs (NSAIDs). Both patients exhibited anaphylactic manifestations, such as general rash and urticaria, along with angina pectoris with electrocardiographic ST-segment elevations after suppository administration of diclofenac sodium or indomethacin, the most commonly used NSAIDs. Although these patients had normal coronary arteriograms, intracoronary administration of ergonovine or acetylcholine provoked diffuse coronary artery spasms accompanied by chest pain and ischemic ST-segment changes. It is therefore suggested that an allergic mechanism may be involved as a causative factor of the coronary artery spasm induced by NSAIDs.     

非甾体抗炎药相关性溃疡并出血的临床分析

目的 探讨非甾体抗炎药相关性溃疡并出血的临床及内镜特点。方法 对196例消化性溃疡并出血病人的临床资料进行回顾性分析，根据出血前1周内是否服用NSAIDs分为NSAIDs组(55例)和非NSAIDs组(141例)，并进行分析比较。结果 NSAIDs组与非NSAIDs组在年龄、溃疡类型、溃疡数目、临床症状及Hp感染等方面均有显著差异。结论 加强对非甾体抗炎药相关性溃疡并出血的认识，并采取相应措施，以减少非甾体抗炎药对胃肠道产生的毒副作用。