NSAID-related Ulcers Research Articles

Helicobacter pyloriand Peptic Ulcer Disease

Helicobacter pylori is associated with diffuse superficial gastritis and is one of the dominant causal factors for duodenal ulcer disease. More recent knowledge has revealed that apart from NSAID-related ulcers, H. pylori is also highly associated with gastric ulcer disease. Follow-up of duodenal ulcer patients has revealed that the prevalence of duodenal ulcer relapse was sharply diminished after successful cure of H. pylori infection. The few data available concerning relapse rates of gastric ulcer disease indicate a striking reduction of recurrence of gastric ulceration after successful eradication of H. pylori. One of the most intriguing questions is why only a small percentage of H. pylori-infected patients develop peptic ulcer disease. The most recent literature is discussed concerning subtypes of H. pylori and virulence factors, making one H. pylori strain more pathogenic compared to the other. In addition, literature is discussed concerning the question whether gastric and duodenal ulcer disease are two different entities, or whether they are at opposite sites of one disease spectrum. Finally, the most current anti-H. pylori-treatment modalities are summarized.

Non-steroidal anti-inflammatory drugs and ulcer complications: a risk factor analysis for clinical decision-making.

Use of non-steroidal anti-inflammatory drugs (NSAIDs) is recognized as an important cause of peptic ulcer complications. The aim of this nested case-control study was to identify risk factors for NSAID-related ulcer complications. Cases were consecutive NSAID users admitted with an ulcer complication (n = 118), and controls were a random sample of all NSAID users without ulcer complication identified by a pharmacoepidemiologic database (n = 540). Ninety-four of 118 cases were interviewed, and 324 of 540 controls answered the questionnaire. Analysis showed no difference between included and non-included subjects. Risk factors for patients at start of NSAID therapy were high age: 60-75 years (odds ratio (OR), 3.5 (95% confidence interval (Cl), 1.8-7.1); > 75 years (OR, 8.9 (4.3-18.3)); male sex (OR 1.7 (1.0-3.0)); ulcer history (OR 2.5 (1.2-5.1)); steroid treatment (OR 2.0 (0.8-4.6)); smoking (OR 1.6 (0.9-2.7)); and alcohol use (OR 1.8 (0.9-3.6)). Risk factors for patients receiving NSAID therapy were high age, male sex, ulcer history, smoking and, furthermore, dyspepsia (OR 2.0 (1.0-4.2)), especially NSAID-related dyspepsia (OR 8.7 (4.0-18.9)). Risk was lower for patients treated more than 3 months. Risk measured from this design can be shown to correlate strongly with the rate difference, a measure that is more clinically relevant than conventional relative risk estimates. Strong risk factors for NSAID-related ulcer complication are high age, male sex, ulcer history, and dyspepsia related to the NSAID therapy. Avoiding NSAID therapy in these high-risk patients, whenever possible, might prevent many adverse events.

Prospective analysis of the role of mucosal neutrophils in chronic NSAID-related ulcer formation, healing, and recurrence, and their response to H2-receptor antagonism with famotidine: [formula omitted], S. Dahill, C. Morran, F.D. Lee, R.D. Sturrock, R.I. Russell, Royal Infirmary, Glasgow, U.K.

Prospective analysis of the role of mucosal neutrophils in chronic NSAID-related ulcer formation, healing, and recurrence, and their response to H2-receptor antagonism with famotidine: [formula omitted], S. Dahill, C. Morran, F.D. Lee, R.D. Sturrock, R.I. Russell, Royal Infirmary, Glasgow, U.K.

Effects of Nonsteroidal Anti-inflammatory Drugs on Endogenous Gastrointestinal Prostaglandins and Therapeutic Strategies for Prevention and Treatment of Nonsteroidal Anti-inflammatory Drug—Induced Damage

Although nonsteroidal anti-inflammatory drugs (NSAIDs) are effective for pain relief and treatment of arthritis, they can induce gastric and duodenal ulcers and life-threatening complications. The mechanisms of their anti-inflammatory action and their gastroduodenal toxic effects are related, in part, to inhibition of prostaglandin synthesis. This review article discusses prostaglandins, their functions in the gastrointestinal tract, anti-inflammatory actions of NSAIDs, and mechanisms by which NSAIDs produce gastroduodenal ulcers. Also reviewed are risk factors associated with the development of NSAID-related ulcers and pharmacologic strategies for the prevention and treatment of NSAID-induced ulcers.

Gastroprotection and nonsteroidal anti-inflammatory drugs (NSAIDS). Rationale and clinical implications.

There is no doubt that nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal injury. The most serious consequences are gastric and duodenal ulcers which can cause bleeding and perforation, and which may lead to the premature death of 3000 to 4000 patients in the UK annually. The immediate actions of NSAIDs operate at a subcellular level; in particular altering of mitochondrial function which causes depletion of ATP and renders the cell vulnerable to oxidant stress. Secondary consequences follow, such as the inhibition of prostaglandin synthesis which delays cellular repair. While adaptation can be shown in volunteers despite continued NSAID ingestion, studies in patients suggest mucosal damage develops continuously and cumulatively even with low doses of aspirin. Histamine H2-receptor antagonists and proton pump inhibitors heal NSAID-related ulcers, though healing rates with H2-antagonists are slower in patients who continue NSAID treatment. They have little role in preventing damage. In addition to acid suppression, prostaglandin analogues cause bicarbonate secretion and enhance mucosal blood flow. They have a specific role in both prevention and treatment of NSAID-related damage. The use of misoprostol offers a rational approach to reduce the high prevalence of unwanted gastroduodenal damage from NSAIDs. On a purely financial basis more information is needed before routine coprescribing can be recommended. However, for any patient on NSAIDs with a previous ulcer or for patients aged over 60 years (where the risks and seriousness of complications are markedly increased), the use of misoprostol should be considered. Further developments in prostaglandin analogues may reduce their adverse effects and perhaps thereby improve their efficacy at symptom control.

Non‐steroidal anti‐inflammatory drug‐induced gastroduodenal injury: therapeutic recommendations

Non-steroidal anti-inflammatory drug (NSAID) use is associated with gastro-duodenal erosions and ulcers. Bleeding and perforation are reported complications in NSAID users. Therapeutic recommendations for NSAID-induced gastroduodenal injury are necessary because of our rapidly growing geriatric population, a steady increase in prescriptions for NSAIDs, and the widespread use of over-the-counter NSAIDs. Studies seem to indicate that there is no relationship between acute NSAID-induced mucosal injury and potential damage from chronic NSAID ingestion. Ranitidine (150 mg) b.d. effectively reduces the incidence of duodenal ulcer in NSAID users, but the same dose does not reduce the incidence of gastric ulcer. Misoprostol is effective in reducing the incidence of gastric ulcer in NSAID users, although confirmatory data on its effectiveness in preventing NSAID-induced duodenal ulcer are lacking. In addition to anti-ulcer therapy, treatment of NSAID-induced ulcers includes discontinuing the drug, reducing the dose, or switching to a less potent NSAID. Longer courses of anti-ulcer treatment may be required to achieve expected healing rates when NSAIDs are not discontinued. Results of treatment of NSAID-related ulcers with currently available anti-ulcer medications vary. Several studies have shown that 150 mg ranitidine b.d heals both gastric and duodenal NSAID-induced ulcers. Sucralfate has also been shown to heal NSAID-induced duodenal ulcers. Misoprostol treatment of NSAID-induced ulcers is not well documented, although there are placebo-controlled data that substantiate its benefit in gastric ulcer patients not taking NSAIDs.

Upper Gastrointestinal Manifestations in Rheumatoid Arthritis Patients: Intrinsic or Extrinsic Pathogenesis?

Apart from the complication of gastrointestinal vasculitis it is not known whether the upper gastrointestinal (UGI) tract has any special disease characteristics in rheumatoid arthritis (RA). However, oesophageal motility disorders have been reported in 30% of RA patients. Hypergastrinaemia has been found in 23-43% of RA patients, usually in combination with a decreased gastric acid output. Another finding suggestive of a decreased secretory state, namely a decreased level of pepsinogen A, was found in RA patients with the sicca syndrome and in patients with active disease. The risk for peptic ulcer disease with regard to nonsteroidal anti-inflammatory drugs (NSAID) is possibly higher in RA patients than in patients with other rheumatic diseases. These findings suggest that in RA patients intrinsic factors play a role in the pathogenesis of the oesophageal motility disorders, in hypergastrinaemia and hypopepsinogenaemia and the related decreased gastric secretory state, and possibly in the increased susceptibility to NSAID-related ulcers. However, there are also indications that oesophageal motility disorders, hypergastrinaemia, and NSAID-related ulcers in RA are the result of extrinsic factors, mainly the use of NSAIDs. The effects of NSAIDs and gold compounds on infection with Helicobacter pylori, a possible pathogenetic factor in ulcer disease, is discussed. It is clear that the discussion about intrinsic and extrinsic factors as a cause of the UGI manifestations in RA remains an intriguing but difficult subject for further studies.