Nonsteroidal Antiinflammatory Drug-Related Injury to the Gastrointestinal Tract: Clinical Picture, Pathogenesis, and Prevention (original) (raw)
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Background: The present study aims at investigation of the gastrointestinal adverse drug reactions (ADRs) with use of NSAIDs in patients of Non-Traumatic musculoskeletal painful disorders. Our study is unique in terms that it aims at investigations and evaluations of the gastrointestinal adverse drug reactions (ADRs) with use of NSAIDs in patients of non-traumatic musculoskeletal painful disorders, where most of the concurrent and concomitant risk factors like hepatobiliary system, renal system are mostly excluded, along with a dedicated follow up of large population included in our study.
GASTROINTESTINAL COMPLICATIONS DURING USE OF ANTI-INFLAMMATORY DRUGS FOR ORTHOPEDIC DISEASES
INTRODUCTION Inflammation can be triggered by infectious, chemical and physical causes. Several factors contribute to its development, such as E-, P-, L-selectin, intercellular adhesion molecules (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 concentration 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 instigate the development of clinical signs of inflammation. The use of Non-Steroidal Anti-inflammatory Drugs (NSAIDs) is essential for reaching therapeutic goals. The main effects 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 induced under conditions of phlogosis by cytokines and inflammatory mediators. For the purposes of this study, it is important to note that only COX-1 is con-stitutively expressed in the stomach. Patients with inflammatory bone and joint problems (tendinitis, bursitis, synovitis, spondylitis, osteoarthritis) are turning to their primary physicians or specialists for pain management in order to improve function and quality of life. Chronic pain occurs frequently, having a negative impact on the patient and society; therefore, it should be seen as an important public health problem [2] deserving more attention. The treatment of choice in such cases is usually nimesulide or diclofenac in a bi-daily dose, with continued monitoring of the patient over time to ensure better care and avoid self-medication abuse. Complications [3] such as hemorrhagic gastritis, peptic ulcer or " non-erosive gastro-esophageal reflux disease " , cause symptoms
Epidemiology of NSAID-related gastroduodenal mucosal injury
Best Practice & Research Clinical Gastroenterology, 2001
Non-steroidal anti-in¯ammatory drugs (NSAIDs) are among the agents most frequently used against musculoskeletal and rheumatic disorders throughout the world. The gastroduodenal adverse eects include dyspepsia without endoscopically proven damage, asymptomatic endoscopic lesions of submucosal haemorrhage, erosions and ulcers, and±most important± ulcer complications. Established risk factors for NSAID-associated ulcer complications include patient-speci®c factors such as advanced age, female gender, a history of peptic ulcer, and drug-speci®c factors such as the use of non-selective NSAIDs (type, dose, duration, multiple use) and concomitant anticoagulant drugs or corticosteroids. Probable risk factors comprise Helicobacter pylori infection and heavy consumption of alcohol, whereas use of selective serotonin re-uptake inhibitors, smoking and a number of other factors have also been proposed to contribute. Knowledge of absolute risk estimates is important for clinical decision making. The aim of this chapter is to summarize the epidemiological data related to the broad spectrum of iatrogenic gastroduodenal mucosal injury.
Towards the safer use of non-steroidal anti-inflammatory drugs
Journal of Quality In Clinical Practice, 1999
Among musculoskeletal conditions, the prevalence of osteoarthritis alone is estimated at 50-60 per 1000 of the population of Australia. As a consequence, the use of non-steroidal anti-inflammatory drugs (NSAID) is high, with use in the over-65-year age group in the order of 20%. The major problem with NSAID is possible adverse effects, the best defined of which being serious upper gastrointestinal bleeding and perforation, secondary to drug-induced peptic ulceration (affecting the stomach in particular). Inhibition of intestinal mucosal prostaglandins secondary to inhibition of the cyclooxygenase-1 enzyme (COX-1) is the accepted key mechanism of this adverse effect. We now know that the risk of gastrointestinal bleeding increases with: (i) the age of the patient; (ii) the dose of the NSAID; (iii) a previous history of peptic ulcer; and (iv) the type of NSAID being used. The last is somewhat controversial but well established, 1,2 for example ibuprofen and diclofenac taken in usual doses are less likely to cause serious upper gastrointestinal bleeding or perforation than piroxicam. There seems to be a loose correlation with the apparent half-life of elimination, the 'safer' NSAID having shorter half-lives. The contention relates to the reason for the 'league' order for risk amongst NSAID. Most believe it relates to relative NSAID potency for the commonly used doses of NSAID.
BMC medicine, 2015
There are several guidelines addressing the issues around the use of NSAIDs. However, none has specifically addressed the upper versus lower gastrointestinal (GI) risk of COX-2 selective and non-selective compounds nor the interaction at both the GI and cardiovascular (CV) level of either class of drugs with low-dose aspirin. This Consensus paper aims to develop statements and guidance devoted to these specific issues through a review of current evidence by a multidisciplinary group of experts. A modified Delphi consensus process was adopted to determine the level of agreement with each statement and to determine the level of agreement with the strength of evidence to be assigned to the statement. For patients with both low GI and CV risks, any non-selective NSAID (ns-NSAID) alone may be acceptable. For those with low GI and high CV risk, naproxen may be preferred because of its potential lower CV risk compared with other ns-NSAIDs or COX-2 selective inhibitors, but celecoxib at the...
Thérapie
Non-steroidal anti-inflammatory drugs (NSAIDs) are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients. Both therapeutic and adverse effects of NSAIDs are due to inhibition of cyclooxygenase (COX) enzyme. NSAIDs are classified as non-selective and COX-2-selective inhibitors (COXIBS) based on their extent of selectivity for COX inhibition. However, regardless of their COX selectivity, reports are still appearing on the GI side effect of NSAIDs particularly on the lower gastrointestinal (GI) tract and the harmful role of their controlled release formulations. In addition, previously unpublished data stored in the sponsor's files, question the GI sparing properties of rofecoxib, a COXIB that has been withdrawn due to cardiovascular (CV) side effects. Presently, the major side effects of NSAIDs are the GI complications, renal disturbances and CV events. There is a tendency to believe that all NSAIDs are associated with renal and CV side effects, a belief that is not supported by solid evidence. Indeed, lower but still therapeutics doses of some NSAIDs may be cardioprotective. In this review, we briefly discuss the GI toxicity of the NSAIDs and assess their renal and CV adverse effects in more detail.
BMC Medicine, 2015
In a recently published article in BMC Medicine, Scarpignato and colleagues present the results of a consensus conference that addressed several aspects of the management of pain in patients with osteoarthritis. The main areas covered include the relative safety in regard to gastrointestinal and cardiovascular adverse events of non-selective 'traditional' non-steroidal anti-inflammatory drugs (NSAIDs) versus cyclooxygenase-2 selective NSAIDs. The role of co-therapy with proton pump inhibitors in enhancing gastrointestinal safety is also reviewed. This commentary focuses on two areas that the consensus conference addressed, i) the whole length of gastrointestinal tract risk profile of the various NSAIDs (not just the ulcer risks in stomach and duodenum); ii) more recent information, but still some uncertainties, about the cardiovascular risks associated with the two classes of NSAID in general, and naproxen in particular.