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non-steroidal anti-inflammatory drugs:What is the actual risk of liver damage?

World Journal of Gastroenterology 2010年第45期16卷 5651-5661页

作者： Fernando Bessone Department of Gastroenterology and Hepatology University of Rosario School of Medicine2000RosarioArgentina

non-steroidal anti-inflammatory drugs (NSAIDs) constitute a family of drugs, which taken as a group, represents one of the most frequently prescribed around the world. Thus, not surprisingly NSAIDs, along with antiinfectious agents, list on the top for causes of DrugInduced Liver Injury (DILI). The incidence of liver disease induced by NSAIDs reported in clinical studies is fairly uniform ranging from 0.29/100 000 [95% confidence interval (CI): 0.17-051] to 9/100 000 (95% CI: 6-15). However, compared with these results, a higher risk of liver-related hospitalizations was reported (3-23 per 100 000 patients). NSAIDs exhibit a broad spectrum of liver damage ranging from asymptomatic, transient, hyper-transaminasemia to fulminant hepatic failure. However, under-reporting of asymptomatic, mild cases, as well as of those with transient liver-tests alteration, in conjunction with reports non-compliant with pharmacovigilance criteria to ascertain DILI and flawed epidemiological studies, jeopardize the chance to ascertain the actual risk of NSAIDs hepatotoxicity. Several NSAIDs, namely bromfenac, ibufenac and benoxaprofen, have been withdrawn from the market due to hepatotoxicity; others like nimesulide were never marketed in some countries and withdrawn in others. Indeed, the contro-versy concerning the actual risk of severe liver disease persists within NSAIDs research. The present work intends (1) to provide a critical analysis of the dissimilar results currently available in the literature concerning the epidemiology of NSAIDS hepatotoxicity; and (2) to review the risk of hepatotoxicity for each one of the most commonly employed compounds of the NSAIDs family, based on past and recently published data.

关键词： non-steroidal anti-inflammatory drugs Side effects Fulminant hepatic failure Cholestasis Liver damage Liver injury Hepatitis Hepatotoxicity

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Beneficial effect of an omega-6 PUFA-rich diet in non-steroidal anti-inflammatory drug-induced mucosal damage in the murine small intestine

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World Journal of Gastroenterology 2015年第1期21卷 177-186页

作者： Toshihide Ueda Ryota Hokari Masaaki Higashiyama Yuichi Yasutake Koji Maruta Chie Kurihara Kengo Tomita Shunsuke Komoto Yoshikiyo Okada Chikako Watanabe Shingo Usui Shigeaki Nagao Soichiro Miura Department of Internal Medicine National Defense Medical CollegeSaitama 359-8513Japan

AIM: To investigate the effect of a fat rich diet onnon-steroidal anti-inflammatory drug(NSAID)-induced mucosal damage in the murine small ***: C57BL6 mice were fed 4 types of diets with or without *** group was fed standard laboratory *** other groups were fed a fat diet consisting of 8% w/w fat,beef tallow(rich in SFA),fish oil,(rich in omega-3 PUFA),or safflower oil(rich in omega-6 PUFA).Indomethacin(3 mg/kg) was injected intraperitoneally from day 8 to day *** day 11,intestines and adhesions to submucosal microvessels were ***: In the indomethacin-treated groups,mucosal damage was exacerbated by diets containing beef tallow and fish oil,and was accompanied by leukocyte infiltration(P < 0.05).The mucosal damage induced by indomethacin was significantly lower in mice fed the safflower oil diet than in mice fed the beef tallow or fish oil diet(P < 0.05).Indomethacin increased monocyte and platelet migration to the intestinal mucosa,whereas safflower oil significantly decreased monocyte and platelet recruitment(P < 0.05).CONCLUSION: A diet rich in SFA and omega-3 PUFA exacerbated NSAID-induced small intestinal damage via increased leukocyte ***,a diet rich in omega-6-PUFA did not aggravate inflammation as monocyte migration was blocked.

关键词： non-steroidal anti-inflammatory drugs Small intest

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Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease?

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World Journal of Gastroenterology 2016年第13期22卷 3679-3686页

作者： Nick E Burr Mark A Hull Venkataraman Subramanian Leeds Institute for Biomedical and Clinical Sciences St James' s University Hospital University of Leeds

AIM: To determine whether aspirin or non-aspirin nonsteroidal anti-inflammatory drugs(NA-NSAIDs) prevent colorectal cancer(CRC) in patients with inflammatory bowel disease(IBD).METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NANSAID use. Pooled odds ratios(OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger's test. Heterogeneity was assessed using Cochran's Q and the I2 ***: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80(95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66(95%CI: 0.06-1.39). There was significant heterogeneity(I2 > 50%) between the studies. There was no change in the effect estimates on subgroup a na ly s e s o f t he po pulat io n s t udie d o r w he t he r adjustment or matching was ***: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD.

关键词： Inflammatory bowel disease Aspirin non-steroidal anti-inflammatory Colorectal cancer Chemoprevention

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Impact of discontinuing non-steroidal antiinflammatory drugs on long-term recurrence in colonic diverticular bleeding

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World Journal of Gastroenterology 2015年第4期21卷 1292-1298页

作者： Naoyoshi Nagata Ryota Niikura Tomonori Aoki Takuro Shimbo Katsunori Sekine Hidetaka Okubo Kazuhiro Watanabe Toshiyuki Sakurai Chizu Yokoi Junichi Akiyama Mikio Yanase Masashi Mizokami Naomi Uemura Department of Gastroenterology and Hepatology National Center for Global Health and MedicineTokyo 162-8655Japan Department of Clinical Research and Informatics National Center for Global Health and MedicineTokyo 162-8655Japan Department of Gastroenterology and Hepatology National Center for Global Health and MedicineKohnodai HospitalChiba 272-8516Japan

AIM: To determine the effect of discontinuing nonsteroidal antiinflammatory drugs(NSAIDs) on recurrence in long-term follow-up patients with colonic diverticular bleeding(CDB).METHODS: A cohort of 132 patients hospitalized for CDB examined by colonoscopy was prospectively enrolled. Comorbidities, lifestyle, and medications(NSAIDs, low-dose aspirin, antiplatelet agents, anticoagulants, acetaminophen, and corticosteroids) were assessed. After discharge, patients were requested to visit the hospital on scheduled days during the followup period. The Kaplan-Meier method was used to estimate ***: Median follow-up was 15 mo. The probability of recurrence at 1, 6, 12, and 24 mo was 3.1%, 19%, 27%, and 38%, respectively. Of the 41 NSAID users on admission, 26(63%) discontinued NSAID use at discharge. Many of the patients who could discontinue NSAIDs were intermittent users, and could be switched to alternative therapies, such as acetaminophen or an antiinflammatory analgesic plaster. The probability of recurrence at 12 mo was 9.4% in discontinuing NSAID users compared with 77% in continuing users(P 70 years, right-sided diverticula, history of hypertension, and hemodialysis. No patients developed cerebrocardiovascular events during ***: There is a substantial recurrence rate after discharge among patients hospitalized for diverticular bleeding. Discontinuation of NSAIDs is an effective preventive measure against recurrence. This study provides new information on risk reduction strategies for diverticular bleeding.

关键词： non-steroidal anti-inflammatories Drug withdrawal

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Effect of non-steroidal anti-inflammatory drugs on post-surgical complications against the backdrop of the opioid crisis

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Burns & Trauma 2018年第3期6卷 190-198页

作者： Hannah Zhao-Fleming Audrey Hand Kelly Zhang Robert Polak Armand Northcut Daron Jacob Sharmila Dissanaike Kendra P.Rumbaugh Department of Surgery Texas Tech University Health Sciences Center3601 4th StreetSTOP 8312LubbockTX 79430USA Burn Center of Excellence Texas Tech University Health Sciences CenterLubbockTXUSA School of Medicine Texas Tech University Health Sciences CenterLubbockTXUSA

The USA is currently going through an opioid crisis, associated with tremendous economic and societal impacts. In response to this crisis, healthcare professionals are looking for alternative pain management methods, and non-steroidal anti-inflammatory drugs (NSAIDs) are a sensible choice because of their effectiveness after surgical procedures. However, before surgeons start prescribing NSAIDs in place of opioids, it is crucial to first understand their potential post-surgical complications. The goal of this review is to summarize the data obtained through both animal and human studies, which suggest how a dramatic increase in NSAID use may affect these post-surgical complications. We first provide a short review outlining the mechanisms of action of NSAIDs, followed by a summary of animal studies, which show a trend towards the negative effects of NSAIDs on wound healing and an association between NSAID use and wound infections. Lastly, we present evidence from human studies on the association of NSAIDs with the following complications:anastomotic leaks, necrotizing soft tissue infections, bleeding complications, orthopedic injuries, wound healing, and cancer care. The human studies are much more variable in their conclusions as to whether NSAIDs are beneficial or not, with the only strong evidence showing that NSAIDs inhibit bone healing. This may partially be explained by male and female differences in response to NSAIDs as many animal studies showing the inhibitory effects of NSAIDs were performed on females, while al the human studies were performed with both sexes. We conclude that strong caution should be used in the prescription of NSAIDs, especially in female patients, but larger scale studies are warranted before solid recommendations can be made.

关键词： NSAIDs Opioids Anastomotic leaks Necrotizing soft tissue infections Bleeding Orthopedic injuries Wound healing Cancer care non-steroidal anti-inflammatory

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Italian survey on non-steroidal anti-inflammatory drugsand gastrointestinal bleeding in children

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World Journal of Gastroenterology 2016年第5期22卷 1877-1883页

作者： Sabrina Cardile Massimo Martinelli Arrigo Barabino Paolo Gandullia Salvatore Oliva Giovanni Di Nardo Luigi Dall'Oglio Francesca Rea Gian Luigi de'Angelis Barbara Bizzarri Graziella Guariso Enzo Masci Annamaria Staiano Erasmo Miele Claudio Romano Gastroenterology and Endoscopic Unit Department of PediatricsUniversity of Messina98100 MessinaItaly Department of Translational Medical Science Section of PediatricsUniversity of Naples“Federico II”80131 NaplesItaly Department of Pediatric Gastroenterology Gaslini Institute16148 GenoaItaly Department of Pediatrics and Infantile Neuropsychiatry Pediatric Gastroenterology and Liver UnitSapienza University of Rome00185 RomeItaly Digestive Surgery and Endoscopy Unit Bambino GesùChildren’s Hospital00165 RomeItaly Gastroenterology and Endoscopy Service University of Parma43126 ParmaItaly Unit of Paediatric Gastroenterology Digestive EndoscopyHepatologyand Care of Children with Liver TransplantationDepartment of Women’s and Children’s HealthUniversity Hospital of Padova35128 PadovaItaly Gastrointestinal Endoscopy Azienda Ospedaliera San Paolo University HospitalUniversity of Milan20142 MilanItaly

AIM: To investigate gastrointestinal complications associated with non-steroidal anti-inflammatory drug(NSAIDs) use in ***: A retrospective, multicenter study was conducted between January 2005 and January 2013, with the participation of 8 Italian pediatric gastroenterology centers. We collected all the cases of patients who refer to emergency room for suspected gastrointestinal bleeding following NSAIDs consumption, and underwent endoscopic evaluation. Previous medical history, associated risk factors, symptoms and signs at presentation, diagnostic procedures, severity of bleeding and management of gastrointestinal bleeding were collected. In addition, data regarding type of drug used, indication, dose, duration of treatment and prescriber(physician or selfmedication) were examined. RESULTS: Fifty-one patients, including 34 males, were enrolled(median age: 7.8 years). Ibuprofen was the most used NSAID [35/51 patients(68.6%)]. Pain was the most frequent indication for NSAIDs use [29/51 patients(56.9%)]. Seven patients had positive family history of Helicobacter pylori(H. pylori) infection or peptic ulcer, and 12 had associated comorbidities. Twenty-four(47%) out of 51 patients used medication inappropriately. Hematemesis was the most frequent symptom(33.3%). Upper gastrointestinal endoscopy revealed gastric lesions in 32/51(62%) patients, duodenal lesions in 17(33%) and esophageal lesions in 8(15%). In 10/51(19.6%) patients, a diagnosis of H. pylori gastritis was made. Forty-eight(94%) patients underwent medical therapy, with spontaneous bleeding resolution, while in 3/51(6%) patients, an endoscopic hemostasis was ***: The data collected in this study confirms that adverse events with the involvement of the gastrointestinal tract secondary to NSAID use are also common in

关键词： Hematemesis Gastrointestinal bleeding non-steroidal anti-inflammatory drug Melena Pediatrics

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Systematic review and meta-analysis on the prophylactic role of non-steroidal anti-inflammatory drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis

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World Journal of Gastrointestinal Endoscopy 2015年第19期7卷 1341-1349页

作者： Muhammad S Sajid Amir H Khawaja Mazin Sayegh Krishna K Singh Zinu Philipose Department of General Endoscopic and Laparoscopic Colorectal Surgery Western Sussex Hospitals NHS Foundation Trust Worthing Hospital Worthing Department of General Upper Gastrointestinal and Hepato-pancreatico-biliary Surgery Western Sussex Hospitals NHS Foundation Trust Worthing Hospital Worthing Department of Gastroenterology and Hepatology Western Sussex Hospitals NHS Foundation Trust Worthing Hospital Worthing

AIM: To critically appraise the published randomized, controlled trials on the prophylactic effectiveness of the non-steroidal anti-inflammatory drugs(NSAIDs), in reducing the risk of post-endoscopic retrograde cholangiopancreatography(ERCP) pancreatitis. METHODS: A systematic literature search(MEDLINE, Embase and the Cochrane Library, from inception of the databases until May 2015) was conducted to identify randomized, clinical trials investigating the role of NSAIDs in reducing the risk of post-ERCP pancreatitis. Random effects model of the meta-analysis was carried out, and results were presented as odds ratios(OR) with corresponding 95%***: Thirteen randomized controlled trials on 3378 patients were included in the final meta-analysis. There were 1718 patients in the NSAIDs group and 1660 patients in non-NSAIDs group undergoing ERCP. The use of NSAIDs(through rectal route or intramuscular route) was associated with the reduced risk of post-ERCP pancreatitis [OR, 0.52(0.38-0.72), P = 0.0001]. The use of pre-procedure NSAIDs was effective in reducing approximately 48% incidence of post-ERCP pancreatitis, number needed to treat were 16 with absolute risk reduction of 0.05. But the risk of post-ERCP pancreattis was reduced by 55% if NSAIDs were administered after procedure. Similarly, diclofenac was more effective(55%) prophylactic agent compared to indomethacin(41%).CONCLUSION: NSAIDs seem to have clinically proven advantage of reducing the risk of post-ERCP pancreatitis.

关键词： non-steroidal drugs Pancreatitis Diclofenac Indomethacin Endoscopic retrograde cholangiopancreatography

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non-steroidal anti-inflammatory drugs in colorectal surgery: A risk factor for anastomotic complications?

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World Journal of Gastrointestinal Surgery 2012年第12期4卷 278-280页

作者： Jrgen Rutegrd Martin Rutegrd Department of Surgical and Perioperative Sciences Ume University S-70187 Ume Sweden Department of Molecular Medicine and Surgery Karolinska Institutet 17177 Stockholm Sweden

In a recent article, Gorissen et al report on 795 patients with primary colorectal anastomosis operated on during the period 2008-2010 for different colorectal conditions at two centres. The leakage rate was significantly higher among patients who were administered non-steroidal anti-inflammatory drugs (NSAIDs) in the perioperative course. A dose-response relationship could also be traced, where longer NSAID use yielded a higher risk of anastomotic breakdown. However, as this study is observational in design, confounding by indication may be present and there is also a risk of residual confounding from unmeasured covariates. Moreover, the question whether different affinity for the cyclooxygenase enzyme is important in different NSAIDs seems to be largely unanswered. The results, conclusions and clinical relevance of the aforementioned study, including the possible effects of different types of NSAIDs, are discussed. While acknowledging that this study represents the best attempt so far in establishing the causal relationship between perioperative NSAID use and anastomotic leakage, the need for further research in this important area is underlined.

关键词： Cancer Colon non-steroidal anti-inflammatory drugs Leakage Rectum Anastomotic leak

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Doping Control Analysis of 16 non-steroidal Anti-Inflammatory Drugs in Equine Plasma Using Liquid Chromatography-Tandem Mass Spectrometry

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American Journal of Analytical Chemistry 2014年第17期5卷 1184-1199页

作者： Youwen You Cornelius E. Uboh Fuyu Guan Lawrence R. Soma Department of Clinical Studies School of Veterinary Medicine University of Pennsylvania Kennett Square PA USA PA Equine Toxicology & Research Center West Chester University West Chester PA USA

non-steroidal anti-inflammatory drugs (NSAIDs) are classified as Class 4 agents by the Association of Racing Commissioners International and are banned in racehorses during competition in Pennsylvania (PA). To control the abuse of these agents in racehorses competing in PA, a forensic method for screening and confirmation of the presence of these agents is needed. Equine plasma (0.5 mL) was acidified with 75 μL 1M H3PO4 to increase recovery of the analytes by liquid-liquid extraction using methyl tert-butyl ether (MTBE). Extracted analytes were separated by reversed-phase liquid chromatography using a C8 column under gradient condition. All 16 analytes were detected, quantified and confirmed using a triple quadrupole tandem mass spectrometry with selected reaction monitoring (SRM) in both negative and positive electrospray ionization modes. The limit of detection, quantification and confirmation of the analytes were 1.0 - 5.0 ng/mL, 1.0 - 5.0 ng/mL and 1.0 - 20 ng/mL, respectively. The linear dynamic range of quantification was 5.0 - 200 ng/mL. The method is routinely used in anti-doping analysis to control the abuse of NSAIDs in racehorses competing in PA.

关键词： Equine Plasma Doping Control non-steroidal Anti-Inflammatory Drugs Liquid

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New innovation of moisturizers containing non-steroidal anti-inflammatory agents for atopic dermatitis

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World Journal of Dermatology 2015年第2期4卷 108-113页

作者： Montree Udompataikul Skin Center Srinakharinwirot University

Atopic dermatitis is a chronic, relapsing and extremely pruritic eczematous disease which commonly affects children. The standard management consists of a combination of anti-inflammatory drugs in adjunctive with skin care management particular moisturizer application. A concern for the side effects associated with long term use of corticosteroids has also been considered. There has been an emerging interest in moisturizer containing non-steroidal anti-inflammatory agents such as herbal extracts, vitamins, mineral and lipids. The in vitro and the in vivo studies of each agent were reviewed. The clinical study on the efficacy of moisturizers containing these agents were also demonstrated including the author's studies and clinicalexperience. These moisturizers might be considered as an alternative treatment in acute flare of mild to moderate atopic dermatitis.

关键词： non-steroidal anti-inflammatory agents Moisturizer Atopic dermatitis

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