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。     

Upper gastrointestinal disorders induced by non-steroidal anti-inflammatory drugs

Aims: We examined the characteristics of upper gastrointestinal disorders induced by non-steroidal anti-inflammatory drugs (NSAIDs). Methodology: The questionnaire investigation was performed over a five year period. Results: A study was performed on 354 patients (161 men and 193 women with mean ages of 66.0 and 70.7 years, respectively) who developed NSAIDs associated upper GI disorders: 21 patients had AGML, 212 had gastric ulcer, 63 had duodenal ulcer, 17 had gastroduodenal ulcers and 41 other cases. About 75 % of patients received NSAIDs for orthopedic conditions. Sixty percent of gastric disorders induced by NSAIDs affected the antrum or angulus of the stomach. The incidence of disorders of the gastric antrum was significantly higher in women than in men whilst the incidence of disorders on the gastric angulus was significantly higher in men than in women (p < 0.05). The proportion of patients with abdominal pain was significantly lower in patients over 65 years old than in those under 65 years old, and the proportion of patients with hematemesis or melena was significantly higher in patients over 80 years old than in those under 80 years old (p < 0.05). The time taken to achieve the healing stage was significantly longer in patients with greater than 3 months NSAIDs ingestion compared to patients that had received NSAIDs for less than 3 months (p < 0.05). Conclusions: Patients 65 years old and over with continuous NSAIDs use had asymptomatic ulcers, and patients 80 years old and over had hemorrhagic ulcers. Received and accepted 20 September 2006     

The potential role of non-steroidal anti-inflammatory drugs in treating Alzheimer’s disease

Epidemiological studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) may protect against Alzheimer's disease (AD). Despite encouraging evidence, all large, long-term, placebo-controlled clinical trials aimed at reducing inflammation in the brain of AD patients produced negative results. More recently it has been shown that some NSAIDs decrease the production of amyloid-β_1-42 (Aβ42), the major component of senile plaques of the AD brain, and counteract the progression of Aβ42 pathology in transgenic mouse models of AD. The proposed mechanism for this activity is an allosteric modulation of γ-secretase activity, the enzyme responsible for the formation of amyloid-β. The inhibition of Aβ42 production is independent from the anti-cyclooxygenase (COX) activity and is related to the chemical structure of the compounds, with some NSAIDs being active (ibuprofen, sulindac, flurbiprofen, indomethacin, diclofenac) and others not (naproxen, aspirin, celecoxib). This could explain the negative results of the large AD trials carried out so far, as they were conducted with compounds (naproxen, hydroxychloroquine, dapsone, prednisone, rofecoxib and celecoxib) that are not able to decrease Aβ42 production. Unfortunately, the use of these NSAIDs in AD is hampered by a significant gastrointestinal toxicity associated with COX inhibition. Thus, new NSAID analogues are being developed with potent and selective inhibitory activity on Aβ42 but with either lack of COX inhibitory activity or reduced gastrointestinal toxicity potential.     

非甾体类抗炎药抗阿尔采末病作用的研究进展

神经炎症过程可能是阿尔采末病(AD)的重要发病原因之一。AD的流行病学研究显示,长期服用非甾体类抗炎药(NSAIDs)可减低AD的发病率;实验研究还发现,NSAIDs的作用除了调节COX机制外,还可能涉及一些非COX机制。     

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...     

An update on the novel and approved drugs for Alzheimer disease

IntroductionGiven the severity of the condition and the increasing number of patients, developing effective therapies for Alzheimer's disease has become a significant necessity. Aggregation of Amyloid-Beta (Aβ) plaques and Tau Protein Tangles in the brain's nerve tissue are two of the most histopathological/pathophysiological symptoms. Another important element involved in the etiology of Alzheimer's disease is the reduction in acetylcholine (ACh) levels in the brain. Currently available medications for Alzheimer's disease treatment, such as cholinesterase inhibitors and an antagonist of the N-methyl-d-aspartate receptor, can temporarily reduce dementia symptoms but not stop or reverse disease development. In addition, several medicinal plants have been shown to diminish the degenerative characteristics associated with Alzheimer's disease, either in its crude form or as isolated chemicals.AimThis review summarises the results from previous studies that reflect an array of novel therapies underway in various phases of clinical trials. Many are discontinued due to non-adherence to the designed endpoints or the surfacing of unavoidable side effects. The present piece of article focuses on the approved drugs for the treatment of Alzheimer's disease and their related mode of action as well as the promising therapies for the treatment of the said disease. Special attention has been placed on the researched herbal drugs, with the pipeline of novel therapies underway in various phases of clinical trials.ResultThe current article includes a list of approved pharmaceuticals for treating Alzheimer's disease, prospective therapies for the illness's treatment, and a pipeline of novel therapies in various stages of clinical trials.ConclusionThe results suggest that the drugs under clinical trials may open new pathways for the effective treatment of patients with Alzheimer's disease while improving their quality of life.     

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。     

Rivastigmine: an update on therapeutic efficacy in Alzheimer's disease and other conditions

SUMMARY

The results of recent clinical trials with rivastigmine show that in the approved indication of mild to moderate Alzheimer's disease (AD), the drug is effective in the long term. Rivastigmine produces a significant delay in the decline of the three components of AD that have been identified by European guidelines as essential parameters for the assessment of therapeutic efficacy of medicinal products with this indication. These are cognitive function, the ability to perform the usual activities of daily living, and global judgement of the patient's condition by the patient himself, his caregiver and his doctor. Moreover, rivastigmine produces significant control of AD behavioural disorders. This further reduces caregiver burden, reduces the probability of institutionalisation, and enables the reduction or discontinuation of expensive and poorly tolerated antipsychotics. Recent trials also suggest that rivastigmine is effective in moderate to severe Alzheimer's disease, 'mixed' dementia (AD associated with vascular disorders) and Lewy body dementia. Preliminary investigations have also indicated that the drug may provide important benefits in patients with vascular dementia or dementia associated with Parkinson's disease. Pharmacoeconomic studies show that the therapeutic properties of rivastigmine result in economic savings for the care of demented patients living in the community.     

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。     

The value and limitations of transgenic mouse models used in drug discovery for Alzheimer's disease: an update

Introduction: The exponential growth in the world's aged population has increased pressure on drug discovery efforts to identify innovative therapies for Alzheimer's disease (AD). The long and uncertain clinical trial path utilized to test the potential efficacy of these novel agents is challenging. For these and other reasons, there has been an explosion in the generation and availability of transgenic mouse models that mimic some, but not all aspects of AD. The largely overwhelmingly positive results obtained when testing potential clinical agents in these same animal models have failed to translate into similar positive clinical outcomes.

Areas covered: This review discusses the value and limitations associated with currently available transgenic mouse models of AD. Furthermore, the article proposes ways in which researchers can better characterize pharmacodynamic and pharmacokinetic endpoints to increase the success rate for novel therapies advancing into clinical development. Lastly, the author discusses ways in which researchers can supplement, expand and improve transgenic mouse models used in AD drug discovery.

Expert opinion: The use of transgenic mouse models that recapitulate various aspects of AD has expanded our knowledge and understanding of disease pathogenesis immensely. Further success in testing and translating novel therapies from animal models into bona fide medicines would be enhanced by i) the availability of better models that more fully recapitulate the disease spectrum, ii) defining and measuring standardized endpoints that display a pharmacodynamic range, iii) building and including translatable biomarkers and iv) including novel endpoints that would be expected to translate into clinically beneficial outcomes.     

Non-cholinergic drug development for Alzheimer's disease

Background: Recent advances in the understanding of the pathobiology of Alzheimer's disease have led to a large number of non-cholinergic targets for the development of therapeutic agents. These include, for example, neurotransmitter-based, anti-amyloid, antitangle, antioxidant, anti-excitotoxic, and growth factor strategies. There are several hundred agents in, or approaching, clinical trials. Some hold promise for treatment of those affected, some may have potential for prevention, some for both. Objectives: Key examples of each of these development approaches will be summarized. Conclusions: It is too soon to predict which, if any, of these approaches will bear fruit. At the moment, it appears that the amyloid-based therapies are the farthest along in development, and have shown in some cases that the amyloid dysregulation cascade can be interrupted. It is unknown, however, whether altering this aspect of the pathobiology of Alzheimer's will actually yield clinical benefit. Efforts to affect tangle development would appear to be a fruitful approach, although these efforts lag behind the anti-amyloid efforts. The same is essentially true for the other approaches reviewed as well. Given the fact that many new interventions target specific pathways that can be measured biologically in go–no go proof of concept studies, the opportunity exists to capitalize on biomarkers in earlier stages of development. The same can be said for evolving imaging techniques. Given the number of agents in development, we offer the provocative suggestion that the biggest threat to identifying effective therapies may prove to be the implementation of enough treatment trials, and applying out-of-the-box prevention methodologies, rather than the discovery of promising candidates. This prediction may or may not hold true.     

Measuring the effects of anti-dementia drugs in patients with Alzheimer's disease

A large number of experimental compounds are being developed for the treatment of patients with Alzheimer's disease (AD). As different compounds may have different effects on CNS function, depending on which neurotransmitters they affect, adequate profiling will require the use of several tests. The difficulties facing the psychopharmacologist in a clinical trial setting of dementia are numerous. Many of the current measures, particularly ratings scales, measure a complex range of variables in the same instrument and this makes interpretation of results difficult. More objective measures are needed but these are often chosen without regard to what the instrument measures in terms of psychological function. Despite these difficulties the need to evaluate anti-dementia drugs will become increasingly important now that specific drugs for the treatment of AD have become available. It is likely that the best strategy for evaluating such compounds will be via a test battery, comprising a range of instruments (psychometric, clinical and neuropsychological) each measuring a clearly defined aspect of cognitive function. It may be time to rethink the evaluation of anti-dementia drugs from a psychopharmacological perspective and, in particular, to develop more objective and quantitative measures to be used alongside more ‘traditional’ instruments. © 1997 John Wiley & Sons, Ltd.     

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。     

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.     

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。     

New pharmacological strategies for treatment of Alzheimer's disease: focus on disease modifying drugs

Current approved drug treatments for Alzheimer disease (AD) include cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and the NMDA receptor antagonist memantine. These drugs provide symptomatic relief but poorly affect the progression of the disease. Drug discovery has been directed, in the last 10 years, to develop 'disease modifying drugs' hopefully able to counteract the progression of AD. Because in a chronic, slow progressing pathological process, such as AD, an early start of treatment enhances the chance of success, it is crucial to have biomarkers for early detection of AD-related brain dysfunction, usable before clinical onset. Reliable early biomarkers need therefore to be prospectively tested for predictive accuracy, with specific cut off values validated in clinical practice. Disease modifying drugs developed so far include drugs to reduce β amyloid (Aβ) production, drugs to prevent Aβ aggregation, drugs to promote Aβ clearance, drugs targeting tau phosphorylation and assembly and other approaches. Unfortunately none of these drugs has demonstrated efficacy in phase 3 studies. The failure of clinical trials with disease modifying drugs raises a number of questions, spanning from methodological flaws to fundamental understanding of AD pathophysiology and biology. Recently, new diagnostic criteria applicable to presymptomatic stages of AD have been published. These new criteria may impact on drug development, such that future trials on disease modifying drugs will include populations susceptible to AD, before clinical onset. Specific problems with completed trials and hopes with ongoing trials are discussed in this review.     

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.