Role of nonsteroidal anti-inflammatory drugs in the prevention of post-ERCP pancreatitis:a meta-analysis

BACKGROUND: The role of prophylactic nonsteroidal anti-inflammatory drugs (NSAIDs) for reduction of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP) is debated. We performed a meta-analysis of all published randomized controlled trials to evaluate the efficacy of NSAIDs in the prevention of post-ERCP pancreatitis. DATA SOURCES: Searches were conducted in the databases PubMed, EMBASE and the Cochrane Library. Six randomized clinical trials that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. Data were extracted by two independent observers according to predetermined criteria. RESULTS: The risk of pancreatitis was lower in the NSAID group than in the placebo, group (OR: 0.46, 95% CI: 0.32 to 0.65, P < 0.0001). Two hours after ERCP, prophylactic administration of NSAIDs was associated with a lower serum amylase level (WMD: -91.09,95% CI: -149.78 to -32.40, P=0.002), but there was no difference in mean 24-hour serum amylase values (WMD: -379.00, 95% CI: -805.75 to 47.76, P=0.08). No deaths or NSAID-related complications were noted. CONCLUSIONS: Prophylactic administration of NSAIDs can reduce the incidence of post-ERCP pancreatitis; this administration in patients undergoing ERCP is recommended. Further randomized controlled trials are required before its introduction into routine care.

Effectiveness of nonsteroidal anti-inflammatory drugs in prevention of post-ERCP pancreatitis:A meta-analysis

AIM: To investigate the effect of nonsteroidal anti-inflammatory drugs (NSAIDs) on the incidence of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP). METHODS: Two independent reviewers searched Pub Med (1966 to October 2013), Embase (1984 to October 2013) and the Cochrane Central Register of Controlled Trials (CENTRAL; Issue 4, 2013) for relevant randomized controlled trials (RCTs) studying the effectiveness of prophylactic NSAID administration in the prevention of PEP. Using the Cochrane Collaboration Handbook, meta-analyses were conducted to evaluate the overall effect of NSAIDs in preventing the incidences of PEP and moderate to severe pancreatitis. RESULTS: Eight RCTs were identified from the literature search and included 1883 patients that underwent ERCP, with 971 patients in the NSAID group and 912 patients in the placebo group. Sixty-nine out of 971 (7.11%) patients developed PEP in the NSAID group in comparison to 143 out of 912 (15.68%) patients in the placebo group. The pooled RR of PEP incidence with prophylactic NSAID administration was 0.43 (95%CI: 0.33-0.56), which demonstrates that NSAID administration after ERCP significantly reduced the incidence of PEP when compared to the placebo group (P < 0.0001). Subgroup analysis was performed and revealed that the presence (NSAID group) or absence (placebo group) of NSAIDs had no significant effect on the development of moderate to severe pancreatitis (RR = 0.79, 95%CI: 0.52-1.18). Moreover, the administration of NSAIDs as a rectal suppository (RR = 0.35, 95%CI: 0.26-0.48; P < 0.0001) was more effective than oral administration (RR = 0.97, 95%CI: 0.53-1.80) or through infusion (RR = 0.43, 95%CI: 0.12-1.54). CONCLUSION: NSAIDs effectively reduce the incidence of PEP but not of moderate to severe pancreatitis. (C) 2014 Baishideng Publishing Group Inc. All rights reserved.

Interaction between Helicobacter pylori infection, nonsteroidal anti-inflammatory drugs and/or low-dose aspirin use: Old question new insights

Previous reports clearly demonstrated that Helicobacter pylori(H.pylori)infection,nonsteroidal anti-inflammatory drugs(NSAID)or low dose aspirin(ASA)use significantly and independently increased the risk for the development of peptic ulcer disease.Today,the presence of H.pylori infection associated with low dose ASA and/or NSAID use in the same patient is becoming more frequent and therefore the potential interaction between these factors and the consequences of it has important implications.Whether NSAID intake in the presence of H.pylori infection may further increase the risk of peptic ulcer carried by the presence of only one risk factor is still a matter of debate.Studies on the interaction between the two risk factors yielded conflicting data and no consensus has been reached in the last years.In addition,the interaction between H.pylori infection and low-dose ASA remains even more controversial.In real clinical practice,we can find different clinical scenarios involving these three factors associated with the presence of different gastrointestinal and cardiovascular risk factors.These huge variety of possible combinations greatly hinder the decision making process of physicians.

Gastric body diaphragm-like stricture as a rare complication of nonsteroidal anti-inflammatory drugs

Increased risk due to nonsteroidal anti-inflammatory drugs (NSAIDs) therapy has been observed in patients. Although diaphragm-like stricture in the small bowel and colon induced by NSAIDs therapy has been rarely reported, gastric body diaphragm-like stricture has not been reported. We describe the first case of gastric body diaphragm-like stricture due to NSAIDs in a 44-year-old male patient who was successfully treated by an endoscopic approach to avoid complicated surgery. This case highlights new insight into the disadvantages of NSAIDs and provides new data for future clinical studies.

Non-steroidal anti-inflammatory drugs(NSAIDs) and neuroprotection in the elderly a view from the mitochondria

The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. In fact, recovery after brain artery occlusion is dramatically worsened by aging, even normal aging is associated with neuron damage and cognitive decline. Mechanisms involved in aging-related, cognitive decline and susceptibility to neuron damage in stroke and neurode- generation are largely unknown. One of the most important mech- anisms contributing to neural dysfunction and death is excitotox- icity. This process is based on the fact that the excessive glutamate receptor stimulation may lead to neuronal damage. This overstim- ulation may be due to increased concentration of glutamate, or the prolonged activation of receptors.

NSAIDs抗RSV作用机制的网络药理学分析

目的:通过网络药理学方法探寻非甾体抗炎药(nonsteroidal anti-inflammatory drugs,NSAIDs)作为抗炎止痛药对呼吸道合胞病毒(RSV)的潜在作用机制,通过网络药理学研究筛选抗RSV的最有影响力的NSAIDs药物。方法:将美国食品和药物管理局(FDA)批准的NSAIDs(19种活性药物和一种前药)用于本研究。通过Swiss Target Prediction和PubChem数据库收集NSAIDs的靶点,在GeneCards数据库中检索疾病RSV靶标。利用韦恩网绘制NSAIDs靶点蛋白与RSV靶点蛋白的交集,在STRING数据库对药物-疾病交集靶蛋白进行蛋白互作分析,在Cytoscape 3.9.0中对该网络进行美化。在DAVID数据库中对交集靶蛋白进行京都基因和基因组百科全书(KEGG)通路富集分析,利用微生信在线绘图工具绘制KEGG通路富集分析的气泡图,通过Cytoscape 3.9.0进行通路-靶点-成分网络分析,最后通过分子对接(AutoDock Vina)确定NSAIDs对靶蛋白的结合亲和力。结果:共搜集到421个NSAIDs靶点,391个与RSV相关的靶点,39个重叠的靶蛋白,基因组富集分析显示了37条抗RSV的信号通路,探索出MAPK1、AKT1和MAP2K1是与B细胞受体信号通路相关性最大的靶蛋白。结论:三种NSAIDs(舒林酸、罗非昔布、双氯芬酸)可能通过使MAPK1、AKT1和MAP2K1等相关靶蛋白失活来阻断B细胞受体信号通路,从而缓解RSV引起的支气管炎和肺炎。

Characteristics and clinical outcome of nonsteroidal anti-inflammatory drug-induced acute hepato-nephrotoxicity among Chinese patients

AIM: To determine the clinicopathological characteristics of nonsteroidal anti-inflammatory drug (NSAID)-induced acute hepato-nephrotoxicity among Chinese patients.

Endoscopic and histopathological evaluation of acute gastric injury in high-dose acetaminophen and nonsteroidal anti-inflammatory drug ingestion with suicidal intent

AIM： To evaluate endoscopic and histopathologic aspects of acute gastric injury due to ingestion of high-dose acetaminophen and nonsteroidal antiinflammatory drugs （NSAIDs） with respect to some risk factors and patient characteristics. METHODS： The study group consists of 50 patients admitted to emergency department with high dose analgesic ingestion （group Ⅰ ） with suicidal intent. Thirty patients with or without mild complaints of dyspepsia （group Ⅱ） were selected as the control group. The study group was stratified according to the use of type and number of analgesics. Endoscopic findings were evaluated according to the Lanza score （LS）, expressing the severity of the gastroduodenal damage and biopsies according to a scoring system based on histopathologic findings of acute erosive gastritis. RESULTS： Gastroduodenal damage was significantly more severe in group Ⅰ compared to group Ⅱ （P 〈 0.01）. The LS was similar in both groups Ⅰ a and Ⅰb. However LS was significantly higher in patients who had ingested multiple NSAIDs （group Ⅰ c） compared to other patients （P 〈 0.01）. The LS was correlated to age （P 〈 0.01） and total amount of drug ingested （P 〈 0.05） in group Ⅰ ; but it was not correlated with Helicobacter pylori （H pylori） infection or duration of exposure （P 〉 0.05）. The biopsy score （BS） was higher in group Ⅰ than group Ⅱ （P 〈 0.01）, and higher in group Ⅰb than group Ⅰa （P 〈 0.05）. CONCLUSION： The histopathologic damage was more severe among NSAID ingesting patients compared to those ingesting only acetaminophen and there is no significant difference in the endoscopic findings between the groups. There is no significant difference in the LS between the groups. This lack of significance is remarkable in terms of the gastric effects of highdose acetaminophen.

Non-steroidal anti-inflammatory drugs in prevention of gastric cancer

Non-steroidal anti-inflammatory drugs （NSAIDs） including cydooxygenase 2 （COX-2） selective inhibitors, are potential agents for the chemoprevention of gastric cancer. Epidemiological and experimental studies have shown that NSAID use is associated with a reduced risk of gastric cancer although many questions remain unanswered such as the optimal dose and duration of treatment. The possible mechanisms for the suppressor effect of NSAIDs on carcinogenesis are the ability to induce apoptosis in epithelial cells and regulation of angiogenesis. Both COX-dependent and COX- independent pathways have a role in the biological activity of NSAIDs. Knowledge of how NSAIDs prevent neoplastic growth will greatly aid the design of better chemopreventive drugs and novel treatments for gastric cancer.

Health Related Quality of Life among Osteoarthritis Patients: A Comparison of Traditional Non-Steroidal Anti-Inflammatory Drugs and Selective COX-2 Inhibitors in the United Arab Emirates Using the SF-36

Objectives: Osteoarthritis (OA) has a dramatic impact on patients’ health related quality of life (HRQoL). Chronic use of analgesics and anti-inflammatory medications for pain management may improve symptoms but on long term may affect HRQoL negatively. The objective of the present study was to compare the impact of two different classes of analgesics, traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 (COX-2) inhibitors on HRQoL among osteoarthritis patients using the SF-36 questionnaire. Methods: Clinic based cross-sectional study conducted at Al-Qassimi Hospital, Sharjah, United Arab Emirates (UAE), over a period of six months. Ethical Approval was obtained from the ethics committee at Al-Qassimi Clinical Research Center. Total of 200 osteoarthritis patients fulfilling the inclusion and exclusion criteria were involved in the study. Patients’ demographics were collected from their medical records. The Medical Outcome Study Short-Form 36 (SF-36) questionnaire was used to measure patients’ HRQoL. SF-36 data were scored using health outcomes scoring software 4.5. Results: Mean age of the subjects was 62.19 ± 9.81 years with females constituting 151 (75.5%) of the patients. In general, females scored lower in most of the HRQoL domains compared to males and there was significant difference between the two groups in the mental health (p = 0.005) & mental component (p = 0.042) domains. Compared to selective COX-2 inhibitors, patients on NSAIDs scored higher on all domains of SF-36 except physical functioning. There was significant difference in mental health domain for patients treated with NSAIDs (p = 0.02). Celecoxib was only better than NSAIDs in osteoarthritis patients with more than one musculoskeletal disorders in the domain of bodily pain (p = 0.009). Conclusion: NSAIDs-treated patients did not differ significantly from celecoxib-treated patients in all domains of the SF-36 except for the mental health domain.

NSAIDs在幽门螺杆菌相关性胃黏膜病变中的作用

目的了解NSAIDs与Hellicobecterpylori感染在胃黏膜病变中的作用。方法患者190例,①病例选择:连续服用NSAIDs治疗2周～12周190例。男性121例,女性69例。平均年龄55岁。②均经胃镜检查和病理组织学检查。对糜烂性胃炎的胃镜诊断和病理诊断胃黏膜炎症分级。③进行H.pylori感染的检测。分为H.pylori感染组与H.pylori阴性组。分析两组的病理组织学改变的特点,了解是否有显著性差异。结果①胃镜检查,轻度糜烂106例(55.8%,106/190)。中重度糜烂84例(44.2%,84/190)。糜烂性胃炎的轻重程度与服药的剂量时间无明显的相关性。②H.pylori感染组46例(24.2%)。H.pylori阴性组144例(75.8%)。③两组病人胃镜诊断的糜烂性胃炎程度无显著性差异(P>0.05)。④病理情况:H.pylori感染组黏膜中重度胃炎明显多于H.pylori阴性组(P<0.01)。⑤病理改变中有淋巴组织增生56例。其中H.pylori感染组有淋巴组织增生22例(47.8%),H.pylori阴性组34例(23.6%)。134例未见淋巴组织增生,其中H.pylori感染组24例(52.2%),H.pylori阴性组110例(76.4%)。两组相比,有显著性差异(P<0.01)。结论服用NSAIDs2周以上对胃黏膜有不同程度的损伤。服用NSAIDs同时合并H.pylori感染的患者的胃黏膜损伤的严重程度远远高于非感染组。NSAIDs与H.pylori感染是导致胃黏膜损伤的独立危险因子,它们对胃黏膜的损伤作用是叠加的。NSAIDs相关性胃病合并H.pylori感染,根除H.pylori治疗是必要的。

Identification of specific genes and pathways involved in NSAIDs-induced apoptosis of human colon cancer cells

AIM: To study whether indomethacin (IND), a nonselective cyclooxygenase (COX) inhibitor or NS-398 (NS), a COX-2-selective inhibitor, induces apoptosis in human colon cancer cells and which apoptosis-related genes and pathways are involved. METHODS: Human colon cancer Caco-2 cells were treated with either: placebo, IND (0.05-0.5 mmol/L) or NS (0.01-0.2 mmol/L) for 1, 5 and 18 h. We then studied: (1) Cell death by the TUNEL method, (2) mRNA expression of 96 apoptosis-related genes using DNA microarray, (3) expression of selected apoptosis related proteins by Western blotting. RESULTS: Both IND and NS induced apoptosis in 30%-50% of Caco-2 cells in a dose dependent manner. IND (0.1 mmol/L for 1 h) significantly up-regulated pro-apoptotic genes in four families: (1) TNF receptor and ligand, (2) Caspase, (3) Bcl-2 and (4) Caspase recruiting domain. NS treatment up-regulated similar pro-apoptotic genes as IND. In addition, IND also down-regulated anti-apoptotic genes of the IAP family. CONCLUSION: (1) Both non-selective and COX-2-selective NSAIDs induce apoptosis in colon cancer cells in a dose dependent manner. (2) Both NSAIDs induce apoptosis by activating two main apoptotic pathways: the death receptor pathway (involving TNF-R) and the mitochondrial pathway. (3) IND induces apoptosis by up-regulating pro-apoptotic genes and down-regulating anti-apoptotic genes, while NS only up-regulates pro-apoptotic genes. (4) Induction of apoptosis in coloncancer cells by NSAIDs may explain in part, their inhibitory action on colon cancer growth.

Muscovite is protective against non-steroidal anti-inflammatory drug-induced small bowel injury

AIM: To evaluate the effect of muscovite in preventing small bowel injury induced by nonsteroidal anti-inflammatory drugs (NSAIDs).

Optimised NSAIDs-loaded Biocompatible Nanoparticles

In this formulation study,biocompatible non steroidal anti-inflammatory(NSAIDs)-loaded nanoparticles were designed as models to be further integrated in a prosthesis surface functionalization.A modified spontaneous emulsion-solvent diffusion methodology was used to produce drug-loaded PLGA nanoparticles without any purification or solvent evaporation requirements.Formulation parameters,such as lactide/glycolide ratio,polymer concentration,solvent/non solvent ratio and non solvent phase,as well as the non ionic tensioactive P188 co-precipitation composition were systematically explored.The optimized formulation(mean size:145 nm,surface charge:-13 m V) was employed to encapsulate various amounts of NSAIDs in a simple and scalable manner.The drug release was characterized in vitro by a complete release for 48 h.These results encourage upcoming preliminary steps for in vivo experiments of prosthesis surface functionalization.

433例非甾体抗炎药物不良反应报告分析

目的通过对非甾体抗炎药物(NSAIDs)致药品不良反应(ADRs)进行分析,了解NSAIDs致ADRs发生特点,为临床合理安全用药作参考。方法收集2022年10月1日至2023年9月30日,国家药品不良反应监测系统接收的济南市范围内的所有NSAIDs相关ADRs报告,共计535例;剔除药品等相关信息不详报告,最终433例纳入统计分析,对报告一般情况、性别和年龄、NSAIDs类别、ADR发生时间、给药途径以及ADRs累及系统/器官和临床表现等进行统计分析。结果NSAIDs所致ADRs患者中,一般报告379例;严重ADR报告54例,转归情况大部分为痊愈或好转;男女性别比为1∶1.23,多发生于≥60岁人群(66.7%);NSAIDs涉及乙酸类(24.2%)、丙酸类(22.2%)、甲酸类(21.5%)等十大类别:ADRs发生时间≤1天(264例,61.0%);给药途径以口服(256例,59.1%)和静脉(133例,30.7%)为主。433例ADRs报告中累及多个系统/器官,共计551例次,其中排名前3位分别为胃肠系统(310,56.3%)、皮肤及其附件(122,22.1%)和视觉障碍(25,8.7%);54例严重报告累及多个系统/器官共计76例次,主要累及皮肤及其附件系统(40,52.6%)、胃肠系统(14,18.4%)和泌尿系统(4,5.3%),临床表现主要以皮疹、瘙痒、呕吐等为主。结论NSAIDs在临床上使用广泛,会导致不同程度ADRs,临床中应合理用药,确保用药安全。

Efficacy of Nonsteroidal Anti-inflammatory Drugs for Treatment of Uncomplicated Lower Urinary Tract Infections in Women:A Meta-analysis

Urinary tract infections(UTIs)are among the most frequent causes for antibiotic prescription and;therefore,alternative treatment options for UTIs can potentially reduce antibiotic usage and development of resistance.To evaluate the efficacy of nonsteroidal antiinflammatory drugs(NSAIDS)for the treatment of uncomplicated lower UTIs in women,this study implemented a meta-analytic approach to evaluate the results of available randomized clinical studies from online databases.A total of four trials involving 1144 patients with uncomplicated lower UTIs were included in the final evaluation.Results showed that symptom resolution at Day 3-4 in the NSAIDs group was significantly lower than that in the antibiotics group[pooled odds ratio(OR)=0.41,95%confidence interval(CI):0.23-0.74,P<0.05].However,there was no significant difference between the NSAIDs and antibiotics groups in symptom resolution at Day 7(pooled OR=0.43,95%CI:0.17-1.06,P=0.07),secondary antibiotic treatment rate at Day 28-30(pooled OR=1.15,95%CI:0.16-7.98,P=0.89)and adverse events rate(pooled OR=1.09,95%CI:0.61-1.96,P=0.77).Therefore,this metaanalysis suggests that,although inferior to antibiotics in fast symptom resolution,symptomatic treatment with NSAIDs can be considered as an alternative treatment option for uncomplicated lower UTIs in women.However,given the low number of randomized controlled trials that met inclusion criteria in this meta-analysis,efficacy of NSAIDs for treatment of uncomplicated lower UTIs should be further evaluated in more comprehensive clinical studies.

Synthesis and Characterization of Naproxen-Salicylate Derivatives as Potential Dual-Targeted Inhibitors of Dihydrofolate Reductase

Dihydrofolate reductase (DHFR) is an enzyme that catalyzes the reduction of dihydrofolate (DHF) to tetrahydrofolate (THF). Chemotherapy drugs such as methotrexate help to slow the progression of cancer by limiting the ability of dividing cells to make nucleotides by competitively inhibiting DHFR. Nonsteroidal anti-inflammatory drugs (NSAIDs) have been previously reported to exhibit competitive inhibition of DHFR, in addition to their primary action on cyclooxygenase enzymes. This interaction interferes with the enzymatic reduction of dihydrofolate to tetrahydrofolate, thereby impeding the folate metabolism pathway essential for nucleotide synthesis and cell proliferation. This activity stems from their structural resemblance to the p-aminobenzoyl-l-glutamate (pABG) moiety of folate, a substrate of DHFR. It has been established that NSAIDs containing a salicylate group (which has structural similarities to pABG), such as diflunisal, exhibit stronger DHFR-binding activity. In this study, we synthesized salicylate derivatives of naproxen with the aim of exploring their potential as inhibitors of DHFR. The interactions between these derivatives and human DHFR were characterized using a combination of biochemical, biophysical, and structural methods. Through polyacrylamide gel electrophoresis (PAGE) analysis, enzymatic assays, and quantitative ELISA, we investigated the binding affinity and inhibitory potency of the synthesized salicylate derivatives towards DHFR. The findings of this study suggest the potential of salicylate derivatives of naproxen as promising candidates for the inhibition of DHFR, thereby offering novel therapeutic opportunities for modulating the inflammatory process through multiple pathways. Further optimization of these derivatives could lead to the development of more efficacious dual-targeted analogs with enhanced therapeutic benefits.

Unbalance of the Physiological System May Cause Trouble —The Other Side of the Story from the Very Successful Drug, VIOXX

Selective cyclo-oxygenase-2 (CQX-2) inhibitor, VIOXX (rofecoxib), wasvoluntarily withdrawn worldwide from drugstores by its maker Merck & Co., Inc. on September 30,2004, for its potential lethal side effects of heart attack or stroke, The Merck' s decision wasbased on new, three-year data from a prospective, multi-center, randomized, placebo-controlled,double-blind clinical trial of VIOXX with an unrelated study, the APPROVe (Adenomatous PolypPrevention on VIOXX) trial. The trial has been enrolling 2 600 patients and comparing 156 weeks(three years) of treatment with VIOXX 25 mg to placebo since 2000.

Clinical profile of medication-related emergencies among patients presenting to the emergency department:An observational study

Objective:To determine the clinical profile of patients presenting with medication-related emergencies to the Emergency Department of our institute.Methods:This was an observational study conducted between November 2018 and September 2020 at Bangalore Baptist Hospital,Karnataka.A total of 138 subjects who satisfied the inclusion criteria were included in the study.The severity of adverse drug reactions(ADR)is assessed based on the Hurwitz severity assessment scale of ADR.Glasgow coma scale at the time of presentation and source of medication were noted.The type of drug overdose,requirement of advanced airway and vasopressors,and the outcome were also assessed.Results:Among medication-related emergencies(n=138)in our study,ADR contributed to 70.3%(n=97)of the study population,and drug overdose accounted for 29.7%(n=41).One-third of the ADR occurred in patients aged above 60 years.Most patients were hemodynamically stable and did not require vasopressors,or advanced airway in both groups.Most patients had Glasgow coma scale ranging from 13-15 in both groups.Nonsteroidal anti-inflammatory drugs were the most used medicine(17/41,41.5%)and most medications were over the counter drugs(25/41,61.0%)in the drug overdose group;meanwhile in the ADR group,anti-diabetic medication was the most used medicine(34/97,35.1%)and most medications were prescribed in the ADR group(93/97,95.9%).Conclusions:Our study shows that ADR is the most common type of medication-related emergency.

芳基烷酸类非甾体抗炎药的手性药动学和药效学研究

非甾体抗炎药(nonsteroidal antiinflammatory drugs,NSAIDs)是一类常见的具有抗炎、解热、镇痛及抗风湿作用的药物,临床应用广泛。大多数芳基烷酸类非甾体抗炎药都具有手性,它们的2个对映体在体内的药理活性、代谢过程及不良反应存在显著的差异。文中对常见芳基烷酸类NSAID对映体的药效学和药动学特点,年龄、性别、疾病状态等因素对其药动学过程的影响,以及临床应用进行了综述。