Non-Steroidal Drug-induced Gastrointestinal Toxicity: Mechanisms And Management (original) (raw)
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Management of Gastroduodenopathy Associated With Use of Nonsteroidal Anti-Inflammatory Drugs
Mayo Clinic Proceedings, 1992
Adverse events associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) are reported more frequently to the Food and Drug Administration than are those associated with any other group of drugs. The absolute risk for serious gastrointestinal events-in particular, ulcer bleeding, perforation, and death-is controversial; some investigators believe that an epidemic of NSAIDrelated complications is being experienced, whereas others suggest that the risks are being overemphasized. The management of patients who take NSAIDs regularly also remains controversial. Key unresolved issues include how best to identify those patients at particularly high risk for the development of ulcer complications and whether such patients should receive prophylactic therapy in an attempt to prevent such problems. In this review, we critically evaluate the currently available literature and present a management algorithm for the treatment and prevention of NSAID-associated gastroduodenopathy. Although the frequent side effects associated with nonsteroidal anti-inflammatory drugs (NSAIDs) have been increasingly recognized, more than 30 billion NSAIDs are consumed annually in the United States alone; an estimated 1.2% of the population take NSAIDs regularly, and many more persons take them intermittently.P The physician who prescribes an NSAID must balance the analgesic and antiinflammatory benefit against the potential toxic effects, particularly those that involve the gastrointestinal tract. The management of NSAID-induced gastroduodenopathy, however, remains controversial, especially in regard to long-term prophylaxis. Herein we review gastrointestinal NSAID toxicity, risk factors for development, and options for treatment and prevention. MAGNITUDE OF THE PROBLEM Adverse effects from NSAIDs, predominantly gastrointestinal, are reported more frequently to the Food and Drug
Intestinal toxicity of non-steroidal anti-inflammatory drugs
Pharmacology & Therapeutics, 1994
We review the adverse effect of non-steroidal anti-inflammatory drugs (NSAIDs) on the small and large intestine. NSAIDs cause small intestinal inflammation in 65% of patients receiving the drugs long-term. The clinical implications of NSAID-induced enteropathy are that patients bleed and lose protein from the inflammatory site, contributing to iron deficiency and hypoalbuminemia, respectively. Some patients develop intestinal strictures, which may require surgery, and the occasional one may develop discrete ulcers with perforations. There are a number of therapeutic options available to treat the enteropathy and the attendant complications, including antibiotics, sulphasalazine and misoprostol. The colon, by comparison, is only rarely affected by NSAIDs, but colitis is well recognized and NSAIDs may be an important factor in diverticular complications and the relapse of inflammatory bowel disease. There is an association between NSAID intake and appendicitis in the elderly.
BMJ, 2004
Objectives To assess the effectiveness of five gastroprotective strategies for people taking non-steroidal anti-inflammatory drugs (NSAIDs)-H 2 receptor antagonists plus non-selective (or cyclo-oxygenase-1) NSAIDs; proton pump inhibitors plus non-selective NSAIDs; misoprostol plus non-selective NSAIDs; COX-2 selective NSAIDs; or COX-2 specific NSAIDs-in reducing serious gastrointestinal complications, symptomatic ulcers, serious cardiovascular or renal disease, and deaths, and improving quality of life. Data sources The Cochrane Library, Medline, Embase, Current Controlled Trials, and System for Information on Grey Literature in Europe (SIGLE) were searched to May 2002. Bibliographies and author contacts were used to identify further studies; non-English articles were included. Review methods Trial selection, data extraction, and quality assessment were performed independently, in duplicate. Articles were rejected only if the study was not a randomised controlled trial; did not assess a gastroprotective strategy versus placebo; included exclusively children or healthy volunteers; lasted less than 21 days; or no review outcomes were measured. Quality assessment included allocation concealment and baseline similarity. Random effects meta-analysis, meta-regression and subgrouping were used to pool effects and analyse associations with length of follow up, mean age, and baseline gastrointestinal status. Heterogeneity was examined and sensitivity analyses performed. Results Of 112 included randomised controlled trials (74 666 participants), five were judged to be at low risk of bias, and 138 deaths and 248 serious gastrointestinal events were reported overall. On comparing gastroprotective strategies versus placebo we found no evidence of effectiveness of H 2 receptor antagonists for any primary outcomes (few events reported); proton pump inhibitors may reduce the risk of symptomatic ulcers (relative risk 0.09, 95% confidence interval 0.02 to 0.47); misoprostol reduces the risk of serious gastrointestinal complications (0.57, 0.36 to 0.91) and symptomatic ulcers (0.36, 0.20 to 0.67); COX-2 selectives reduce the risk of symptomatic ulcers (0.41, 0.26 to 0.65) and COX-2 specifics reduce the risk of symptomatic ulcers (0.49, 0.38 to 0.62) and possibly serious gastrointestinal complications (0.55, 0.38 to 0.80). All strategies except COX-2 selectives reduce the risk of endoscopic ulcers (at least 3 mm in diameter). Conclusions Misoprostol, COX-2 specific and selective NSAIDs, and probably proton pump inhibitors significantly reduce the risk of symptomatic ulcers, and misoprostol and probably COX-2 specifics significantly reduce the risk of serious gastrointestinal complications, but data quality is low. More data on H 2 receptor antagonists and proton pump inhibitors are needed, as is better reporting of rare but important outcomes.
Current Perspectives in NSAID-Induced Gastropathy
Mediators of Inflammation, 2013
Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most highly prescribed drugs in the world. Their analgesic, antiinflammatory, and antipyretic actions may be beneficial; however, they are associated with severe side effects including gastrointestinal injury and peptic ulceration. Though several approaches for limiting these side effects have been adopted, like the use of COX-2 specific drugs, comedication of acid suppressants like proton pump inhibitors and prostaglandin analogs, these alternatives have limitations in terms of efficacy and side effects. In this paper, the mechanism of action of NSAIDs and their critical gastrointestinal complications have been reviewed. This paper also provides the information on different preventive measures prescribed to minimize such adverse effects and analyses the new suggested strategies for development of novel drugs to maintain the anti-inflammatory functions of NSAIDs along with effective gastrointestinal protection.
Gastroenterology Clinics of North America, 2010
Increasing life expectancy in developed countries has led to a growing prevalence of arthritic disorders, which has been accompanied by increasing prescriptions for nonsteroidal antiinflammatory drugs (NSAIDs). 1 These are the most widely used agents for musculoskeletal and arthritic conditions, representing more than 7.7% of all prescriptions in Europe. 1 However, these figures are probably underestimated, because over-the-counter (OTC) use is not included. In absolute terms, in 2004, there were 111 million NSAID prescriptions in the United States. 2 The reason for such widespread use is the clinical effectiveness of NSAIDs, which have been consistently shown to be more effective than acetaminophen (paracetamol) for the management of osteoarthritis (OA), 3,4 and the fact that NSAIDs are endorsed in current OA management guidelines. 5,6 Conflict of interest statement. The authors have received consulting and/or lecture fees from several pharmaceutical companies and other organizations. The authors have also received research support from charities and government sources at various times. No author has any direct stock holding in any pharmaceutical company.
Non-Steroidal Anti-Inflammatory Drugs: Identifying the Risk Factors in the Patients
Journal of the Liaquat University of Medical and Health Sciences, 2009
MATERIALS AND METHODS: This study was performed on endoscopically diagnosed patients of NSAID induced peptic ulcers, in whom a clinical trial was performed between Ranitidine (H2 Receptor blocker) and new proton pump inhibitor Esomeprazole. Eighty Patients were selected and evaluated for presence of risk factors and dyspepsia after consumption of NSAIDs or low dose aspirin for last 6 months to 1 year. They were asked to fill in a specially designed proforma regarding the use of NSAIDs, which also included the questions for their social setup, habits and diseases for which they were taking them. All the patients were tested for presence of H. pylori infection and anti-H. pylori IgG antibody titers were determined by enzyme-linked immunosorbent assay. Patients taking anticoagulants and steroids were excluded from the study. RESULTS: Important factors that have been shown to increase the risk of NSAID-associated GI complications in our study included female gender (76%) presence of H.pylori infection (71%), combination of two NSAIDs (23.75%) and high-dose NSAID use (20%). Other factors that may increase risk include social habits like heavy consumption of tea (30%), pan or Gutka consumption (8.75%). Current evidence supports that H. pylorus potentates the risk of NSAID-induced gastrointestinal ulcers or clinical events, and a strategy of H. pylori testing and treatment in NSAID users may be adopted. CONCLUSIONS: The incidence of NSAID related gastrointestinal problems was present in 10-15% of patients who belonged to high risk group. Identifying them is strongly recommended to avoid serious complications. H. pylori infection may also be eradicated before initiating NSAID therapy.
Address of the authors GASTROINTESTINAL COMPLICATIONS DURING USE OF ANTI-INFLAMMATORY DRUGS
INTRODUCTION Inflammation can be triggered by infectious, chemical and physical causes. Several fac-tors contribute to its development, such as E-, P-, L-selectin, intercellular adhesion mole-cules (ICAM-1), vascular adhesion molecules (VCAM-1), soluble mediators such as inter-leukins (IL)-1, (IL)-2, (IL)-6 and (IL)-8, as well as tumor necrosis factor, whose concentra-tion increases significantly in the synovium of patients with joint diseases. The soluble inflammation mediators are responsible for the production of PGE 1 and PGE 2 that insti-gate the development of clinical signs of inflammation. The use of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) is essential for reaching therapeutic goals. The main ef-fects of NSAIDs derive from their ability to inhibit the synthesis of prostaglandins by blocking the function of cyclooxygenase. There are two isoforms of cyclooxygenase (COX); the first, COX-1[1], is the constitutive isoform found in most tissues, while the second, COX-2, is ...