Abstract
The associations between nonsteroidal anti-inflammatory drugs (NSAIDs) and the presence and complications of gastroduodenal erosions and ulcers are well established. Evidence that acid aggravates NSAID-induced injury provides a rationale for minimising such damage by acid suppression. Other strategies discussed include avoidance of NSAIDs or minimising their dosage, selecting NSAIDs known to cause less damage, and co-prescription of various agents.
Cytoprotection with misoprostol, a prostaglandin analogue, has been shown to be effective in reducing NSAID-related peptic ulcers and their complications. Unfortunately, adverse effects may limit compliance in some patients. Histamine H2 antagonists have only limited efficacy in the prevention of NSAID-induced ulcers in humans, particularly in the stomach, except at higher than standard dosages. This may relate to their relatively modest effect in elevating gastric pH, especially in comparison with proton pump inhibitors.
Several studies now confirm the efficacy of proton pump inhibitors in the short and longer term prevention of NSAID-induced upper gastrointestinal injury. Placebo-controlled studies suggest reductions of over 70% in gastric and duodenal ulcerrates over 3 to 6 months. The recent ASTRONAUT (Acid Suppression Trial: Ranitidine versus Omeprazole for NSAID-Associated Ulcer Treatment) study documented the greater prophylactic efficacy of omeprazole over ranitidine at standard dosages for 6 months. The OMNIUM (Omeprazole versus Misoprostol for NSAID-Induced Ulcer Management) study showed omeprazole to be slightly more effective overall than misoprostol in preventing the upper gastrointestinal adverse effects of NSAIDs, with both substantially more effective than placebo, although misoprostol was somewhat less well tolerated.
Although substantial reductions in NSAID ulceration are now achievable when co-therapy with a proton pump inhibitor is given, a few patients will still develop ulcers and their complications. Hence the judicious use of NSAIDs in the first instance cannot be overemphasised.
Similar content being viewed by others
References
Griffin MR. Epidemiology of nonsteroidal anti-inflammatory drug-associated gastrointestinal injury. Am J Med 1998; 104(3A): 23S–9S
Henry D, Robertson J. Non-steroidal anti-inflammatory drugs and peptic ulcer hospitalisation rates in New South Wales. Gastroenterology 1993; 104: 1083–91
Elliott SL, Yeomans ND, Buchanan RRC, et al. Efficacy of 12 months’ misoprostol as prophylaxis against NSAID-induced gastric ulcers: a placebo controlled trial. Scand J Gastroenterol 1994; 23: 171–6
Langman MJS, Brooks P, Hawkey CJ, et al. Management of non-steroidal anti-inflammatory drug associated ulcer: epidemiology, causation and treatment. J Gastroenterol Hepatol 1991; 6: 442–9
Weil J, Colin-Jones D, Langman M, et al. Prophylactic aspirin and risk of peptic ulcer bleeding. BMJ 1995; 310: 827–30
Schanker LS, Shore PA, Brodie BB, et al. Absorption of drugs from the stomach: I: the rat. J Pharmacol Exp Ther 1957; 120: 528–39
Hogben CAM, Schanker LS, Tocco DJ, et al. Absorption of drugs from the stomach: II: the human. J Pharmacol Exp Ther 1957; 120: 540–5
Skeljo MV, Giraud AS, Yeomans ND. Gastric mucosal damage induced by non-salicylate nonsteroidal antiinflammatory drugs in rats is mediated systemically. Dig Dis Sci 1993; 38: 2038–42
Yeomans ND, St John DJB, de Boer WGRM. Regeneration of the gastric mucosa after aspirin-induced injury in the rat. Am J Dig Dis 1973; 18: 773–80
Dagle GE, Brodie DA, Bauer BG. Comparison of gross and microscopic gastric lesions produced in rats after single doses of aspirin and 2-deoxyglucose. Toxicol Appl Pharmacol 1970; 16: 638–45
Brodie DA, Chase BJ. Role of gastric acid in aspirin-induced gastric irritation in the rat. Gastroenterology 1967; 53: 604–10
Elliott SL, Ferris RJ, Giraud AS, et al. Indomethacin damage to rat gastric mucosa is markedly dependent on luminal pH. Clin Exp Pharmacol Physiol 1996; 23: 432–34
Prichard PJ, Yeomans ND, Mihaly GW, et al. Omeprazole: a study of its inhibition of gastric pH and oral pharmacokinetics, after morning or evening dosage. Gastroenterology 1985; 88: 64–9
Walt RP, Gomes MdA, Wood EC, et al. Effect of daily oral omeprazole on 24 hour intragastric acidity. BMJ 1983; 287: 12–4
Henry D, Lim LL, Garcia Rodriguez LA, et al. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative metaanalysis. BMJ 1996; 312: 1563–6
Lanza FL, Aspinall RL, Swabb EA, et al. Double-blind placebo-controlled endoscopic comparison of the mucosal protective effects of misoprostol versus cimetidine on tolmetin-induced mucosal injury to the stomach and duodenum. Gastroenterology 1988; 95: 289–94
Lanza FL, Fakouhi D, Rubin A, et al. A double-blind placebo-controlled comparison of the efficacy and safety of 50, 100, and 200 μg of misoprostol QID in the prevention of ibuprofen-induced gastric and duodenal mucosal lesions and symptoms. Am J Gastroenterol 1989; 84: 633–6
Jiranek GC, Kimmey MB, Saunders DR, et al. Misoprostol reduced gastroduodenal injury from one week of aspirin: an endoscopic study. Gastroenterology 1989; 96: 656–61
Raskin JB, White RH, Jackson JE, et al. Misoprostol dosage in the prevention of nonsteroidal anti-inflammatory drug-induced gastric and duodenal ulcers: a comparison of three regimens. Ann Intern Med 1995; 123: 344–50
Graham DY, White RH, Moreland LW, et al. Duodenal and gastric ulcer prevention with misoprostol in arthritic patients taking NSAIDs: misoprostol study group. Ann Intern Med 1993; 119: 257–62
Silverstein FE, Graham DY, Senior JR, et al. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomised, double-blind, placebo controlled trial. Ann Intern Med 1995; 123: 241–9
Ehsanullah RSB, Page MC, Tildesley G, et al. Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine. BMJ 1988; 297: 1017–21
Robinson MG, Griffin JW, Bowers J, et al. Effect of ranitidine gastroduodenal mucosal damage induced by nonsteroidal antiinflammatory drugs. Dig Dis Sci 1989; 34: 424–8
Roth SH, Bennett RE, Mitchell CS, et al. Cimetidine therapy in nonsteroidal anti-inflammatory drug gastropathy: double-blind long-term evaluation. Arch Intern Med 1987; 147: 1798–801
Taha AS, Hudson N, Hawkey CJ, et al. Famotidine for the prevention of gastric and duodenal ulcers caused by non steroidal antiinflammatory drugs. N Engl J Med 1996; 334: 1435–9
Bianchi Porro G, Lazzaroni M, Petrillo M, et al. Prevention of gastroduodenal damage with omeprazole in patients receiving continuous NSAIDs treatment: a double blind placebo controlled study. Ital J Gastroenterol Hepatol 1998; 30: 43–7
Daneshmend TK, Stein AG, Bhaskar NK, et al. Abolition by omeprazole of aspirin induced gastric mucosal injury in man. Gut 1990; 31: 514–7
Bigard MA. Effet protecteur de 1’oméprazole sur les lésions gastriques induites par une prise unique d’aspirine chez l’homme. Gastroenterol Clin Biol 1988; 12: 770–1
Bergmann JF, Chassany O, Simoneau G, et al. Protection against aspirin-induced gastric lesions by lansoprazole: simultaneous evaluation of functional and morphologic responses. Clin Pharmacol Ther 1992; 52: 413–6
Müller P, Fuchs W, Simon B. Untersuchungen zur schutzwirkung von lansoprazol auf die menschliche magenschleimhaut gegenüber niedrig dosierter acetylsalicylsäure. Arzneimittel Forschung 1997; 47: 758–60
Oddsson E, Gudjónsson H, Thjódleifsson B. Comparison between ranitidine and omeprazole for protection against gastroduodenal damage caused by naproxen. Scand J Gastroenterol 1992; 27: 1045–8
Scheiman JM, Behler EM, Loeffler KM, et al. Omeprazole ameliorates aspirin-induced gastroduodenal injury. Dig Dis Sci 1994; 39: 97–103
Simon B, Eisner H, Müller P. Schutzwirkung von omeprazol gegenüber niedrig dosierter acetylsalicylsäure. Arzneimittel Forschung 1995; 45: 701–3
Cook GA, Elliott SL, Skeljo MV, et al. Correlation between transmucosal potential difference and morphological damage during aspirin injury of gastric mucosa in rats. J Gastroenterol Hepatol 1996; 11: 264–9
Cullen D, Bardhan KD, Eisner M, et al. Primary gastroduodenal prophylaxis with omeprazole for non-steroidal anti-inflammatory drug users. Aliment Pharmacol Ther 1998; 12: 135–40
Ekström P, Carling L, Wetterhus S, et al. Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continuous non-steroidal anti-inflammatory drug therapy — a Nordic multicentre study. Scand J Gastroenterol 1996; 31: 753–8
Bianchi Porro G, Imbesi V, Lazzaroni M, et al. Pantoprazole vs placebo in prevention of NSAID-induced ulcers [abstract]. Gastroenterology 1998; 114: A74
Yeomans ND, Tulassay Z, Juhász L, et al. A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 719–26
Hawkey CJ, Karrasch JA, Szczepañski L, et al. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. N Engl J Med 1998; 338: 727–34
Chan FKL, Sung JY, Suen R, et al. Eradication of H. pylori versus maintenance acid suppression to prevent recurrent ulcer hemorrhage in high-risk NSAID users: a prospective randomized study [abstract]. Gastroenterology 1998; 114: A87
Walan A, Wahlqvist P. Pharmacoeconomic aspects of non-steroidal anti-inflammatory drug gastropathy. Ital J Gastroenterol Hepatol 1999; 31 Suppl. 1: S79–88
Chan FK, Sung JJ, Chung SC, et al. Randomised trial of eradication of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers. Lancet 1997; 350: 975–9
Hawkey CJ, Tulassay Z, Szczepanski L, et al. Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELPNSAIDs study. Lancet 1998; 352: 1016–21
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Brown, G.J.E., Yeomans, N.D. Prevention of the Gastrointestinal Adverse Effects of Nonsteroidal Anti-Inflammatory Drugs. Drug-Safety 21, 503–512 (1999). https://doi.org/10.2165/00002018-199921060-00006
Published:
Issue Date:
DOI: https://doi.org/10.2165/00002018-199921060-00006