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ML4000的合成及生物活性研究

目的:合成非甾体抗炎药ML4000并研究其生物活性。方法:ML4000以环氧合酶(COX)和5-脂氧合酶(5-LOX)双重抑制剂利克飞龙(licofelone,ML3000)为先导化合物,结构上链接了1个一氧化氮(NO)供体;通过灌胃给药,观察ML4000在动物体内的初步代谢、抗炎活性、胃肠道作用以及血清和胃黏膜NO水平。结果:ML4000经IR,MS,1H NMR,13C NMR以及元素分析等确证结构;大鼠灌胃ML4000(10 mg.kg-1)0.25 h后,即可测到ML4000代谢为ML3000;ML4000抗炎活性与ML3000相当;连续14 d灌胃(60mg.kg-1,qd),未见大鼠胃肠道出血;灌胃给药(60 mg.kg-1)1 h后大鼠血清和胃黏膜NO量显著增加。结论:合成的ML4000具有较强的抗炎作用,胃肠道耐受性好,并能够释放出NO。     

非甾体类抗炎药致上消化道出血的临床分析

目的探讨非甾体类抗炎药(NSAIDs)致上消化道出血的临床特点。方法对182例上消化道出血患者的临床资料进行回顾性分析,根据出血前1周内是否服用过NSAIDs,将患者分为NSAIDs组(43例)和非NSAIDs组(139例)。对比分析两组患者的临床资料。结果两组比较,NSAIDs组与非NSAIDs组在年龄、溃疡类型等方面差异有统计学意义。结论应加强对NSAIDs相关性上消化道出血临床特点的认识,以减少NSAIDs的不良反应。     

The effects of non-steroidal anti-inflammatory drugs on the disposition of methotrexate in patients with rheumatoid arthritis

We have studied the pharmacokinetics of methotrexate in patients with rheumatoid arthritis concurrently taking the most commonly used non-steroidal anti-inflammatory drugs (NSAIDs), aspirin, diclofenac, naproxen, indomethacin, and ibuprofen. The area under the curve, the total systemic clearance, the distribution volume, and the half-life of methotrexate in patients receiving concurrent NSAID therapy did not change significantly (at p <0.05). Concurrent treatment with NSAIDs resulted in increased inter-patient variability of methotrexate concentration, possibly as a result of biochemical interactions; however, it does not appear clinically relevant. The data suggest that the NSAIDs do not significantly affect the disposition of methotrexate, contrary to some of the earlier reports. © 1998 John Wiley & Sons, Ltd.     

非甾体抗炎药物在骨性关节炎中的应用

骨性关节炎是老年人中常见、多发的慢性进行性骨关节疾病,主要临床表现为缓慢发展的可使活动受限的关节疼痛、僵硬和肿胀,严重的能导致关节功能障碍.非甾体抗炎药物是目前治疗骨性关节炎等关节炎性疾病的最常用药物,作用机制为抑制环氧化酶活性、阻断该酶催化花生四烯酸转化为炎性物质前列腺素,从而发挥止痛、消炎作用.非甾体抗炎药物分为非选择性环氧化酶抑制剂和选择性环氧化酶-2抑制剂两类,应用广泛,但也存在多种不良反应,故选择用药时要严格掌握适应证,合理用药.     

非甾体抗炎药物在骨性关节炎中的应用

骨性关节炎是老年人中常见、多发的慢性进行性骨关节疾病,主要临床表现为缓慢发展的可使活动受限的关节疼痛、僵硬和肿胀,严重的能导致关节功能障碍。非甾体抗炎药物是目前治疗骨性关节炎等关节炎性疾病的最常用药物,作用机制为抑制环氧化酶活性、阻断该酶催化花生四烯酸转化为炎性物质前列腺素,从而发挥止痛、消炎作用。非甾体抗炎药物分为非选择性环氧化酶抑制剂和选择性环氧化酶-2抑制剂两类,应用广泛,但也存在多种不良反应,故选择用药时要严格掌握适应证,合理用药。     

非甾体类消炎药不良反应的相关研究

目的分析比较几种常用的非甾体类消炎药（布洛芬、双氯芬酸、美洛昔康）的不良反应。方法将160例骨关节炎、类风湿性关节炎患者随机分成3组,分别予以布洛芬、双氯芬酸、美洛昔康治疗6个月,观察比较其消化道、心血管系统不良反应及血象变化。结果布洛芬组患者消化道损害发生率显著高于美洛昔康组,有统计学意义;三组患者心血管事件的发生率无统计学差异,血象变化亦无统计学差异。结论选择性COX-2抑制剂的消化道损害显著低于非选择性的非甾体类消炎药,但其对于心血管事件的不良影响尚不明确,临床医师用药需谨慎。     

Renal and cardiovascular toxicity of non-steroidal anti-inflammatory drugs

Introduction. In addition to gastro-intestinal side effects, non-steroidal anti-inflammatory drugs (NSAIDs) have been associated with renal and cardiac complications. We review the mechanisms of NSAID-induced renal and cardiac toxicity and the epidemiological evidence regarding the magnitude of these problems. Methods. A Medline search was undertaken, using MESH and keyword terms, specified drug names, and renal/cardiac outcomes. The Cochrane Database was also searched. Results. Renal toxicity may manifest as acute or chronic failure and/or nephropathy, cardiac toxicity, as failure. For the most part, renal and cardiac side effects are consequences of interference by NSAIDs with prostaglandin-dependent processes, including homeostasis and vasodilitation/constrictor balance. Based on the epidemiological evidence, NSAID-induced vasomotor renal failure is fairly uncommon, and is usually identified and treated promptly. Factors increasing the risk include old age, pre-existing renal failure, and NSAIDs with long half-lives. In patients with existing cardiac disease, NSAIDs increase the risk of failure and may account for up to 19% of failure-related hospital admissions. The risk of renal and cardiac toxicity may be highest early in the course of treatment. NSAIDs may increase mean arterial pressure by around 5 mm Hg, an amount clinically significant in those with hypertension. Conclusions. NSAIDs may produce clinically significant renal and cardiac toxicity. Some of the factors increasing susceptibility may be identified easily, thereby permitting prescribers to either choose alternatives or look for evidence of harm in those most at risk.     

固相萃取-液相色谱法测定水环境中4种非甾体抗炎药物

目的建立专属、灵敏的固相萃取-液相色谱分析方法,测定水环境中4种非甾体抗炎药(酮洛芬、美洛昔康、双氯芬酸、布洛芬)的质量浓度。方法采用固相萃取技术进行样品前处理,用HPLC法测定。色谱柱:C18(200mm×4.6mm,5μm);流动相:乙腈-20mmol.L-1乙酸铵(60∶40),冰乙酸调pH至3.5;流速:1.0mL·min-1;检测波长:263nm。结果各目标分析物在0.5～50.0mg·mL-1范围内线性关系良好,定量下限均为0.5mg·mL-1。精密度(RSD)范围为0.6%～2.0%,萃取回收率大于78.0%,样品溶液在12h内稳定性良好。结论该法简单、灵敏、准确,可用于水环境中多种非甾体抗炎药的分析。     

非水毛细管电泳法分离分析非甾体抗炎药物

目的建立一种非水毛细管电泳法(NACE)分离非甾体抗炎药物,并对奥沙普秦肠溶片进行定量分析。方法以含醋酸铵15mmol/L的甲醇-乙腈(3∶7)混合液为电泳缓冲液,运行电压20kV,柱温20℃,进样压力2.5kPa,进样时间10 s,UV检测波长200nm;内标法(内标:布洛芬)定量奥沙普秦肠溶片。结果NACE能有效分离布洛芬、萘普生、奥沙普秦、舒林酸和双氯芬酸钠五种非甾体抗炎药物。奥沙普秦与布洛芬的峰面积比对奥沙普秦浓度C(μg/mL)的线性回归方程为Y=0.0434C-7.1×10-3(R=0.999 9,n=9),线性范围0.8~80μg/mL,加样回收率99.05%~101.48%,日内、日间精密度分别为0.54%~0.83%,0.55%~0.92%。结论NACE用于奥沙普秦等非甾体抗炎药物的分离分析,选择性高,重现性好,准确,快速,可作为该类药物及其制剂的质量控制手段。     

山茶油对非甾体抗炎药经皮渗透的促进作用

目的考察山茶油对5种非甾体抗炎药体外经皮渗透的促进作用及其与药物油水分配系数的关系。方法采用两室扩散池装置,以离体大鼠腹部皮肤为渗透屏障,用预处理皮肤法考察山茶油的促渗透作用;用HPLC法测定非甾体抗炎药不同时间在接受池药物浓度,计算累积渗透量及其他渗透动力学参数;用摇瓶法测定药物正辛醇介质分配系数以拟合其与山茶油促渗活性关系。结果山茶油可有效促进非甾体抗炎药的经皮渗透率(除双氯芬酸钠外),尤其对氟比洛芬,促渗效果最明显(P<0.01),其增渗倍数达到3.51;山茶油的促渗活性与非甾体抗炎药的正辛醇介质分配系数呈类似抛物线关系。结论山茶油作为一种低毒、无刺激性的渗透促进剂,能够有效提高药物的经皮渗透效果,具有良好的开发应用前景。     

非甾体抗炎药致重症药疹文献汇总分析

目的：以临床实例出发探讨非甾体抗炎药致重症药疹的特点和关联性,为临床用药安全提供参考。方法：通过检索1970-2017年国内外期刊数据库公开报道的非甾体抗炎药致重症药疹的病例,提取文献中患者年龄、性别、致ADR药物、重症药疹类型等信息进行统计和分析。结果：非甾体抗炎药致重症药疹文献49篇,共计病例49例。其中单一用药致重症药疹病例有27例,联合用药22例;49例非甾体抗炎药致重症药疹中发生率最高为对乙酰氨基酚,其次为吡罗昔康、布洛芬、依托考昔;非甾体抗炎药致重症药疹平均潜伏期为（7.88±10.42）d,其中致药物超敏反应综合征潜伏期最长,可长达（36.50±14.20）d;大部分患者停药后好转,1例因中毒性表皮坏死松解征死亡。结论：非甾体抗炎药致重症药疹具有潜在的危险性,临床应用时应提高警惕,以减少重症药疹给患者带来的危害。     

幽门螺杆菌感染与非甾体类抗炎药相关性初探

目的 探讨幽门螺杆菌感染与非甾体类抗炎药的关系。方法 将本院2004年1月至2005年12月期间收治的88例连续服用非甾体类抗炎药治疗4～12周的患者行胃镜及病理组织学检查，经检查将88例患者分为幽门螺杆菌感染组和非感染组，分析非甾体类抗炎药与幽门螺杆菌感染的关系。结果 幽门螺杆菌感染组36例，非甾体类抗炎药相关性胃病发生率16．67％（6／36），非幽门螺杆菌感染组52例，非甾体类抗炎药相关性胃病发生率19．23％（10／52）。结论 幽门螺杆菌感染并不加剧非甾体类抗炎药相关性胃病的发生。     

Comparative efficacy and safety of intravenous non-steroidal anti-inflammatory drugs in two animal models of pain

In this study, the antinociceptive activity of five non-steroidal anti-inflammatory drugs (NSAIDs) was determined in two animal models of different pain intensity and compared with their capacity to produce motor incoordination and death. Intravenous clonixine, diclofenac, dipyrone (metamizole), ketorolac, and piroxicam produced dose-dependent antinociception in the acetylcholine-induced writhing test with ED₅₀ values ranging from 14 (clonixine) to 205 (dipyrone) μmol/kg. The behavioral responses in the 55°C hot plate assay were also inhibited in a dosedependent manner, but significantly higher doses were required to display antinociceptive activity, the ED₅₀ values ranging from 116 (clonixine) to 2, 263 (dipyrone) μmol/kg. In the writhing test, the antinociceptive effects of NSAIDs were present at doses far below those producing toxic effects. In contrast, their ED₅₀ values against a more intense nociceptive stimulus approached those producing lethal effects so that the therapeutic ratios were very small, ranging from 1.3 (diclofenac) to 3.0 (dipyrone). The antinociceptive activity of the reference drug morphine is striking, since both types of nociceptive responses were eliminated at doses substantially lower than those producing death (therapeutic ratios of 502 and 121). Morphine exhibited the highest antinociceptive efficacy, followed by dipyrone, ketorolac, clonixine, and piroxicam. Diclofenac showed a more limited efficacy. These findings imply potential risks for patients treated iv with this class of drugs and suggest caution in the use of high doses of NSAIDs. Future development of injectable NSAID formulations should include a detailed analysis of adverse reactions following iv administration of high doses. © 1995 Wiley-Liss, Inc.     

An update on the efficacy of non-steroidal anti-inflammatory drugs in Alzheimer's disease

Several epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD), especially for patients carrying one or more ?4 allele of the apolipoprotein E. The biological mechanism of this protection is not completely understood and may involve inhibition of COX activity, inhibition of β-amyloid_1-42 (Aβ42) production and aggregation, inhibition of β-secretase activity, activation of PPAR-γ or stimulation of neurotrophin synthesis. Unfortunately, long-term, placebo-controlled clinical trials with both non-selective and COX-2 selective NSAIDs in AD patients produced negative results. A secondary prevention study with rofecoxib in patients with mild cognitive impairment and a primary prevention study with naproxen and celecoxib in elderly subjects with a family history of AD were also negative. All these failures have diminished the hope that NSAIDs could be beneficial in the treatment of AD. It is hypothesized that the chronic use of NSAIDs may be beneficial only in the normal brain by inhibiting the production of Aβ42. Once the Aβ deposition process has started, NSAIDs are no longer effective and may even be detrimental because of their inhibiting activity on activated microglia of the AD brain, which mediates Aβ clearance and activates compensatory hippocampal neurogenesis.     

非甾体抗炎药治疗我国中老年骨关节炎疗效和安全性的网状Meta分析

目的 系统评价不同非甾体抗炎药(NSAIDs)治疗中国中老年骨关节炎(OA)患者的疗效和安全性.方法 检索PubMed、Cochrane Library、CNKI、WanFang Data和VIP数据库,搜集关于NSAIDs治疗中国中老年OA患者的随机对照试验,检索时限均从建库至2020年11月17日.由两位研究人员独...     

2006～2008年我院非甾体抗炎药的应用分析

目的研究中山大学附属第二医院非甾体抗炎药的应用状况和发展趋势,并进行临床利用评价,为临床合理、有效、经济地选用药物提供科学依据。方法采用金额排序和用药频度（DDDs）、日治疗费用方法对中山大学附属第二医院2006～2008年非甾体抗炎药的使用情况进行统计分析。结果2006—2008年间非甾体抗炎药用药金额呈逐年上升趋势,临床的用药量相对稳定。结论非甾体抗炎药的使用数量和频率呈现上升状态。安全、有效、价格低廉且与其他药物相互作用小的非甾体抗炎将成为临床治疗的主要药物。     

我院门诊解热镇痛抗炎药物应用分析

目的分析门诊解热镇痛抗炎药物的使用情况,以期为临床合理选择解热镇痛抗炎药物提供参考。方法采用金额统计法,回顾性统计2016年6月门诊各类解热镇痛抗炎药物应用情况,对解热镇痛抗炎药物销售金额、构成比、各用药科室使用频率及其排序进行分析。结果 2016年6月门诊使用解热镇痛抗炎药物处方总金额为30 682.40元,占门诊药品销售总金额的1.17%;塞来昔布胶囊总销售金额排在解热镇痛抗炎药物第一位占47.33%;门诊解热镇痛抗炎药物使用频率最高的是外科门诊。结论解热镇痛抗炎药物合理使用疗效显著,不合理使用可导致严重不良反应。临床医师应正确合理地选择解热镇痛抗炎药物,更好地为患者的健康服务。     

非甾体类抗炎镇痛药的研究进展与应用评价

非甾体类抗炎镇痛药物是一类临床常用药物,本文介绍了它们的研究进展,并对应用前景进行了展望。     

白内障超声乳化术后应用激素和非甾体抗炎药的临床观察

目的探讨糖皮质激素药物联合非甾体抗炎药对超声乳化白内障吸除术后炎症的临床疗效。方法选择临床确诊为单纯性白内障的128例患者,测量眼压,均进行超声乳化白内障吸除并联合人工晶体植入手术,分为3组,术后均使用滴眼液控制炎症反应。其中,典必殊组单用典必殊滴眼液4周;普南扑灵组单用普南扑灵滴眼液4周;联合组先将典必殊和普南扑灵分别轮换、联用1周,后3周只单用普南扑灵滴眼液。术后第3天、第7天,第14天及第30天,分别观察三组患者的症状、体征,测量房水闪辉及细胞反应及眼压。结果术后第3天、第7天及第14天时,联合组症状和体征的综合评分显著低于典必殊组及普南扑灵组,差异有统计学意义(P<0.05)。手术后,除第30天外,其余几个时间点联合组房水闪辉值均显著低于两单用药组(P<0.05)。在各时间点,三组房水细胞比较差异无统计学意义(P>0.05)。眼压与术前比,除典必殊组术后第30天眼压较术前增加(P<0.05),其余时间点内三组患者术后眼压与术前比较,差异均无统计学意义(P>0.05)。结论超声乳化白内障吸除并联合人工晶体植入术后,典必殊和普南扑灵联用1周,再单用普南扑灵的抗炎效果优于单用典必殊或普南扑灵,并能避免长期使用典必殊等激素而引起的眼压升高。