NSAID Gastropathy

  • M. Guslandi
Conference paper


Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly prescribed drugs all over the world. In the United States the number of prescriptions is more than 100 million per year (for about 45 million patients), let alone another 40 billion aspirin tablets sold as over-the-counter drugs [2]. In the United Kingdom and in France the number of NSAID prescriptions reaches 23 million [15, 30].


Gastric Mucosa Gastric Ulcer Nsaid User Human Gastric Mucosa Nsaid Intake 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Agrawal N, Roth S, Graham DY, White RH, Germain B, Brown JA, Stromatt SC (1991) Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial. Ann Intern Med 115: 195–200PubMedGoogle Scholar
  2. 2.
    Baum C, Kennedy DL, Forbes MB (1985) Utilization of nonsteroidal antiinflammatory drugs. Arthr Rheum 28: 686–692CrossRefGoogle Scholar
  3. 3.
    Beck WS, Schneider HT, Dietzel K, Nuernberg B, Brune K (1990) Gastrointestinal ulcerations induced by anti-inflammatory drugs in the rats. Physicochemical and biochemical factors involved. Arch Toxicol 64: 210–217PubMedCrossRefGoogle Scholar
  4. 4.
    Bigard MA, Joubert M (1991) Prevention par le lansoprazole des lesiomnes gastriques induites chez le sujet sain par prise unique d’aspirine. Etude de doses. Gastroenterol. Clin Biol 15 (2 bis): A122Google Scholar
  5. 5.
    Bjisma JW (1988) Treatment of NSAID-induced gastrointestinal lesions with Cimetidine : an international multicentre collaborative study. Aliment Pharmacol Therap 2 (suppl 1): 85–96Google Scholar
  6. 6.
    Carson JL, Strome BL, Morse L (1987) The relative gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. Arch Intern Med 147: 1054–1059PubMedCrossRefGoogle Scholar
  7. 7.
    Caruso I, Bianchi Porro G (1980) Gastroscopic evaluation of anti-inflammatory agents. Br Med J 280: 75–78PubMedCrossRefGoogle Scholar
  8. 8.
    Caselli M, Pazzi P, Lacorte R, Aleotti A, Trevisani L, Stabellini G (1989). Campylobacter-like organisms, nonsteroidal anti-inflammatory drugs and gastric lesions in patients with rheumathoid arthritis. Digestion 44: 101–104PubMedCrossRefGoogle Scholar
  9. 9.
    Clinch D, Banerjee AK, Levy DW, Ostick G, Feracher EB (1987) Non-steroidal antiinflammatory drugs and peptic ulceration. JR Coll Physicians Lond 21: 183–187Google Scholar
  10. 10.
    Cole AT, Brundell S, Hudson N, Hawthorne AB, Mahida YR, Hawkey CJ (1991) Aspirin : take without food to limit gastric mucosal injury and with ranitidine to reduce bleeding? Gastroenterology 100: A45Google Scholar
  11. 11.
    Collins AJ, Davis J, Dixon ASJ (1988) A prospective endoscopic study of the effects of Orudis and Oruvail on the super gastrointestinal tract in patients with osteoarthritis. Br J Rheumathol 27: 106–109CrossRefGoogle Scholar
  12. 12.
    De Schepper PJ, Tjandramaga T, De Roo B (1978) Gastrointestinal blood loss after diflunisal and after aspirin: effect of ethanol Clin Pharmacol Ther 23: 669–676Google Scholar
  13. 13.
    Dorta G, Saraga E, Nicolet M, Schnegg JF, Vouillamoz D, Armstrong D, Blum AL (1991) Influence of omeprazole on healing and prevention of gastroduodenal mucosal lesions during administration of NSAIDs. Gastroenterology 100: A55Google Scholar
  14. 14.
    Fellows IW, Bhaskar NK, Hawkey CJ (1989) Nature and time-course of piroxicam-induced injury to human gastric mucosa. Aliment Pharmacol Therap 3: 481–488CrossRefGoogle Scholar
  15. 15.
    Florent C, Deasaint B (1989) Fréquence et gravité des lésions gastriques et duodenales induites par les anti-inflammatoires non stéroidiens et l’aspirine. Gastroenterol Clin Biol 13: 235–238PubMedGoogle Scholar
  16. 16.
    Fries JF (1988) Postmarketing drug surveillance: are our priorities right? J Rheumathol 15: 389–390Google Scholar
  17. 17.
    Fries JF, Miller SR, Spitz PW, Williams CA, Hubert HB, Bloch DA (1989) Toward an epidemiology of gastropathy associated with nonsteroidal antiinflammatory drug use. Gastroenterology 96: 647–655PubMedGoogle Scholar
  18. 18.
    Fries JF, Williams CA, Bloch DA, Michel BA (1991) Nonsteroidal antiinflammatory drug-associated gastropathy: incidence and risk factors models. Am J Med 91: 213–222PubMedCrossRefGoogle Scholar
  19. 19.
    Gabriel SE, Jaajjimainen L, Bombardier C (1991) Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. Ann Intern Med 115: 787–796PubMedGoogle Scholar
  20. 20.
    Graham DY, Agrawal NM, Roth Sh (1988) Prevention of NSAID-induced gastric ulcer with misprostol: multicentre double-blind, placebo-controlled trial. Lancet II: 1277–1280CrossRefGoogle Scholar
  21. 21.
    Graham DY, Lacey Smith J (1988) Gastroduodenal complications of chronic NSAID therapy. Am J Gastroenterol 83: 1081–1084PubMedGoogle Scholar
  22. 22.
    Graham DY, Lacey Smith J, Spjut HJ, Torres E (1988) Gastric adaptation. Studies in humans during continuous aspirin administration. Gastroenterology 95 : 327–333PubMedGoogle Scholar
  23. 23.
    Graham DY, Lindski M, Cox AM, Evans DJ, Evans DG, Alpert L, Klein PD, Sessoms SL, Michaletz PA, Saeed ZA (1991) Long-term nonsteroidal antiinflammatory drug use and Helicobacter pylori infection. Gastroenterology 100: 1653–1657PubMedGoogle Scholar
  24. 24.
    Graham DY, Stromatt SC, Jaszewski R, White RH, Triadafilopoulos G (1991) Prevention of duodenal ulcer in arthritic who are chronic NSAID users: a multi-center trial of the role of misoprostol. Gastroenterology 100: A75Google Scholar
  25. 25.
    Griffin MR, Piper JM, Daugherty JR, Snowden M, Ray WA (1991) Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 114: 257–263PubMedGoogle Scholar
  26. 26.
    Guslandi M (1987) Gastric effects of leukotrienes. Prostagl Leukotr Med 26: 203–206CrossRefGoogle Scholar
  27. 27.
    Guslandi M (1990) Pharmacological prevention and treatment of NSAID-induced gastroduodenal lesions. Drugs Today 26: 413–422Google Scholar
  28. 28.
    Guslandi M, Tittobello A (1991) Basic pathophysiology of gastric mucosal protection. In: Braga PC, Guslandi M, Tittobello A (eds) Drugs in gastroenterology. Raven, New York, pp 199–202Google Scholar
  29. 29.
    Hansen TN, Matzen P, Madsen P (1984) Endoscopic evaluation of the effect of indomethacin capsules and suppositories on the gastric mucosa in rheumathic patients. J Rheumathol 11: 484–487Google Scholar
  30. 30.
    Hazleman BL (1989) Incidence of gastropathy in destructive arthropathies. Scand J Rheumathol 78 (suppl): 1–4CrossRefGoogle Scholar
  31. 31.
    Heller CA, Ingelfinger MD, Goldman P (1985) Nonsteroidal anti-inflammatory drugs and aspirin. Analyzing the scores. Pharmacotherapy 5: 30–38PubMedGoogle Scholar
  32. 32.
    Hill BA, Butler BD, Lichtenberger LM (1983) Gastric mucosal barrier: hydrophobic lining to the lumen of the stomach. Am J Physiol 7: G561–G568Google Scholar
  33. 33.
    Hingson D, Ito S (1971) Effect of aspirin and related compounds on the fine structure of mouse gastric mucosa. Gastroenterology 61: 156–177PubMedGoogle Scholar
  34. 34.
    Hoftiezer JW, Silvoso GR, Burks M, Ivey KJ (1980) Comparison of the effects of regular and enteric-coated aspirin on the gastroduodenal mucosa in man Lancet 2: 609–612PubMedCrossRefGoogle Scholar
  35. 35.
    Hoftiezer JW, O’Laughlin JC, Ivey KJ (1982) Effects of 24 hours of aspirin, bufferin, paracetamol and placebo on normal human gastroduodenal mucosa. Gut 23: 692–697PubMedCrossRefGoogle Scholar
  36. 36.
    Howden CW (1988) Review: interactions between H2-antagonists and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Therap 2: 93–100CrossRefGoogle Scholar
  37. 37.
    Hudson N, Balsitis M, Hawkey CI (1991) Reduction in angiogenesis in NSAID associated gastric ulcers. Gut 32: A1246Google Scholar
  38. 38.
    Ivey KJ, Morrison S, Gray C (1972) Effects of salycilates on the gastric mucosal barrier in man. J Appl Physiol 33: 81–85PubMedGoogle Scholar
  39. 39.
    Ivey KJ, Silvoso G, Krause WJ (1978) Effect of paracetamol on human gastric mucosa. Br Med J 1: 1586–1588PubMedCrossRefGoogle Scholar
  40. 40.
    Ivey KJ, Paone DB, Krause WJ (1980) Acute effect of systemic aspirin on gastric mucosa in man. Dig Dis Sci 25: 97–99PubMedCrossRefGoogle Scholar
  41. 41.
    Jaszewski R (1990) Frequency of gastroduodenal lesions in asymptomatic patients on chronic aspirin or nonsteroidal antiinflammatory drug therapy. J Clin Gastroenterol 12: 10–13PubMedCrossRefGoogle Scholar
  42. 42.
    Kelly SM, Dickinson RJ, Jenner JR, Hunter JO (1991) Gastric mucosal adaptation to continued non-steroidal anti-inflammatory drug administration : role of epidermal growth factor. Gut 32: A58CrossRefGoogle Scholar
  43. 43.
    Konturek SJ, Kwiecien N, Obtulowitz W (1982) Effect of carpofen and indomethacin on gastric function, mucosal integrity and generation of prostaglandins in man. Hepato-Gastroenterol 29: 267–270Google Scholar
  44. 44.
    Konturek SJ, Brzozowski T, Piastucki I, Radecki T (1982) Prevention of ethanol and aspirin-induced gastric mucosal lesions by paracetamol and salicylate in rats: role of endogenous prostaglandins. Gut 23: 536–540PubMedCrossRefGoogle Scholar
  45. 45.
    Konturek SJ, Obtulowitz W, Kwiecien N (1984) Generation of prostaglandins in gastric mucosa in patients with peptic ulcer disease : effect of nonsteroidal antiinflammatory compounds. Scand J Gastroenterol 19 (suppl 101): 75–77Google Scholar
  46. 46.
    Lancaster-Smith MJ, Jaderberg ME, Jackson DA (1991) Ranitidine in the treatment of non-steroidal anti-inflammatory drug associated gastric and duodenal ulcers. Gut 32: 252–255PubMedCrossRefGoogle Scholar
  47. 47.
    Lanza FL, Royer GL, Nelson RS, Chen TT, Seckman CE, Rack MF (1979) The effects of ibuprofen, indomethacin, aspirin, naproxen and placebo on the gastric mucosa of normal volunteers. Dig Dis Sci 24: 823–828PubMedCrossRefGoogle Scholar
  48. 48.
    Lanza FL, Umbenhauer ER, Nelson RS, Rack MF, Daurio MS, White LA (1982) A double-blind randomized placebo controlled gastroscopic study to compare the effects of indomethacin capsules and suppositories on the gastric mucosa of helthy volunteers. J Rheumatho 19: 415–419Google Scholar
  49. 49.
    Lanza FL, Rack MF, Wagner GS, Balm TK (1985) Reduction in gastric mucosal hemorrhage and ulceration with chronic high-level qid and bid dosing of enteric coated aspirin granules. Dig Dis Sci 30: 509–512PubMedCrossRefGoogle Scholar
  50. 50.
    Lanza FL, Panagides J, Salom IL (1986) Etodolac compared with aspirin: an endoscopic study of the gastrointestinal tracts of normal volunteers. J Rheumathol 13: 299–303Google Scholar
  51. 51.
    Lanza FL, Graham DY, Davis RE, Rack MF (1990) Endoscopic comparison of Cimetidine and sucralfate for prevention of naproxen-induced acute gastroduodenal injury. Effect of scoring method. Dig Dis Sci 35: 1494–1499PubMedCrossRefGoogle Scholar
  52. 52.
    Lanza FL, Evans DG, Graham DY (1991) Effect of Helicobacter pylori infection on the severity of gastroduodenal mucosal injury after the acute administration of naproxen or aspirin to normal volunteers. Am J Gastroenterol 86: 735–737PubMedGoogle Scholar
  53. 53.
    Lanza FL, Kochman RL, Geis GS, Rack EMF, Deysach LG (1991) A double-blind placebo controlled 6-day evaluation of two doses of misoprostol in gastroduodenal mucosal protection against damage from aspirin and effect on bowel habits. Am J Gastroenterol 86: 1743–1748PubMedGoogle Scholar
  54. 54.
    Laporte JR, Carné X, Vidal X, Moreno V, Juan J (1991) Upper gastrointestinal bleeding in relation to previous use of analgesics and non-steroidal antiinflammatory drugs. Lancet 337: 85–89PubMedCrossRefGoogle Scholar
  55. 55.
    Larkai EN, Lacey Smith J, Lidsky MD, Sessoms SL, Graham DY (1989) Dyspepsia in NSAID users: the size of the problem J Clin Gastroenterol 11:158–162PubMedCrossRefGoogle Scholar
  56. 56.
    Levi S, Goodlad RA, Lee CY, Stamp G, Walport MJ, Wright NA, Hodgson HJF (1990) Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing. Lancet 336: 840–843PubMedCrossRefGoogle Scholar
  57. 57.
    Levi S, Goodlad RA, Lee CY, Walport MJ, Wright NA, Hodgson HJF (1992) Effects of nonsteroidal anti-inflammatory drugs and misoprostol on gastroduodenal epithelial proliferation in arthritis. Gastroenterology 102: 1605–1611PubMedGoogle Scholar
  58. 58.
    Levine RA, Petokas S, Nandi J, Enthoven D (1988) Effects of nonsteroidal antiinflammatory drugs on gastrointestinal injury and prostanoid generation in healthy volunteers. Dig Dis Sci 33: 660–666PubMedCrossRefGoogle Scholar
  59. 59.
    Ligumski M, Sestieri M, Karmeli F, Zimmerman J, Okon E, Rachmilewitz D (1990) Rectal administration of nonsteroidal antiinflammatory drugs. Effect of rat gastric ulcerogenicity and prostaglandin E2 synthesis. Gastroenterology 98: 1245–1249Google Scholar
  60. 60.
    Lockard O, Ivey KJ, Butt JH, Silvoso G, Sisjk C, Holt S (1980) The prevalence of duodenal lesions in patients with rheumatic disease on chronic aspirin therapy. Gastrointest Endosc 26: 5–72PubMedCrossRefGoogle Scholar
  61. 61.
    Loeb DS, Talley NJ, Ahlquist DA, Carpenter HA, Zinsmeister AR (1992) Longterm nonsteroidal anti-inflammatory drug use and gastroduodenal injury: the role of Helicobacter pylori. Gastroenterology 102: 1899–1905PubMedGoogle Scholar
  62. 62.
    Loizzi P, D’Ingianna E, Ferri S (1990) Effectiveness of sulglycotide in prevention of gastric lesions by non-steroidal anti-inflammatory drugs in patients with rheumathic disease. A controlled double-blind endoscopic study vs placebo. Clin Trials J 27: 164–174Google Scholar
  63. 63.
    McCormack K, Brune K (1987) Classical absorption theory and the development of gastric mucosal damage associated with non-steroidal anti-inflammatory drugs. Arch Toxicol 60: 261–269PubMedCrossRefGoogle Scholar
  64. 64.
    Meyer RA, McGinley D, Posalaky Z (1986) Effects of aspirin on tight junction structure of the canine gastric mucosa. Gastroenterology 91: 351–359PubMedGoogle Scholar
  65. 65.
    Moore JG, Bjorkman DJ (1988) NSAID-induced gastropathy, deaths and medieval practice. Ann Intern Med 109: 353–354Google Scholar
  66. 66.
    Myszor M, Hodgson HJF (1990) Non-steroidal anti-inflammatory drugs and gastric DNA synthesis. Scand J Gastroenterol 25: 197–202PubMedGoogle Scholar
  67. 67.
    Oddson E, Gudjonsson H, Thjodleifsson B (1990) Endoscopic findings in the stomach and duodenum after treatment with enteric-coated and plain naproxen tablets in healthy subjects. Scand J Gastroenterol 25: 231–234Google Scholar
  68. 68.
    Petrillo M, Bianchi Porro G, Ardizzone S (1991) Prevention of NSAID-induced gastrolesivity with sulglycotide. Hepato-Gastroenterol 38 (suppl): 45Google Scholar
  69. 69.
    Petroski D (1986) A comparison of enteric-coated aspirin granules with plain and buffered aspirin: a report of two studies. Am J Gastroenterol 81: 26–28PubMedGoogle Scholar
  70. 70.
    Rainsford KD (1988) Mechanisms of NSAID-induced gastrointestinal mucosal injury: a basis for preventing ulceration and symptoms for these agents. Aliment Pharmacol Therap 2 (suppl 1) : 43–55Google Scholar
  71. 71.
    Rainsford KD, Willis C (1982) Relationship of gastric mucosal damage induced in pigs by anti-inflammatory drugs to their effect on prostaglandin production. Dig Dis Sci 27: 624–635PubMedCrossRefGoogle Scholar
  72. 72.
    Robinson M, Mills RJ, Euler AR (1991) Ranitidine prevents duodenal ulcers associated with non-steroidal anti-inflammatory drug therapy. Aliment Pharmacol Therap 5: 143–150CrossRefGoogle Scholar
  73. 73.
    Rossi AD, Hsu JP, Falch G A (1987) Ulcerogenicity of piroxicam: an analysis of spontaneously reported data. Br Med J 294: 147–150CrossRefGoogle Scholar
  74. 74.
    Schoen RT, Vender RJ (1989) Mechanisms of nonsteroidal anti-inflammatory drug-induced gastric damage. Am J Med 86: 449–458PubMedCrossRefGoogle Scholar
  75. 75.
    Semble EL, Wu WC (1987) Antiinflammatory drugs and gastric mucosal damage. Semin Arthritis Rheum 16: 271–286PubMedCrossRefGoogle Scholar
  76. 76.
    Silverstein FE, Feld AD, Gilbert DA (1981) Upper gastrointestinal tract bleeding. Predisposing factors, diagnosis and therapy. Arch Intern Med 141: 322–327PubMedCrossRefGoogle Scholar
  77. 77.
    Stadler P, Armstrong D, Margalith D, Saraga E, Stolte M, Lualdi P, Mautone G, Blum AL (1991) Diclofenac delays healing of gastroduodenal mucosal lesions. Double-blind, placebo-controlled endoscopic study in healthy volunteers. Dig Dis Sci 36: 594–600PubMedCrossRefGoogle Scholar
  78. 78.
    Szabo S, Spill WF, Rainsford KD (1989) Non-steroidal anti-inflammatory drug-induced gastropathy: mechanisms and management. Med Toxicol Adv Drug Exp 4: 77–94Google Scholar
  79. 79.
    Taha AS, Najhshabendi I, Lee FD, Sturrock RD, Russell RI (1992) Chemical gastritis and Helicobacter pylori related gastritis in patients receiving non-steroidal anti-inflammatory drugs: comparison and correlation with peptic ulceration. J Clin Pathol 45: 135–139PubMedCrossRefGoogle Scholar
  80. 80.
    Tavares IA, Collins PO, Bennett A (1987) Inhibition of prostanoid synthesis by human gastric mucosa. Aliment Pharmacol Therap 1: 617–623CrossRefGoogle Scholar
  81. 81.
    Tronstad RI, Aaland E, Holler T, Olaussen B (1985) Gastroscopic findings after treatment with enteric coated and plain naproxen tablets in healthy subjects. Scand J Gastroenterol 20: 239–242CrossRefGoogle Scholar
  82. 82.
    Walan A, Bader JP, Classen M, Lamers CBHW, Piper DW, Rutgersson K, Eriksson S (1989) Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer. N Engl J Med 320: 69–75PubMedCrossRefGoogle Scholar
  83. 83.
    Wallace JL (1992) Non-steroidal anti-inflammatory drug gastropathy and eytoprotection: pathogenesis and mechanisms re-examined. Scand J Gastroenterol 27 (suppll 92):3–8CrossRefGoogle Scholar
  84. 84.
    Wallin BA, Grier CE, Fox MJ, McCafferty JP, Wetherington JD, Palmer RH (1990) Prevention of NSAID-induced ulcers with Cimetidine: results of a double-blind placebo controlled trial. Gastroenterology 98: A146Google Scholar
  85. 85.
    Welsh RW, Bench HL, Harris SC (1978) Reduction of aspirin-induced gastrointestinal bleeding with Cimetidine. Gastroenterology 74: 459–463Google Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1993

Authors and Affiliations

  • M. Guslandi
    • 1
  1. 1.Gastroenterology Unit, S. Raffaele Hospital and Department of Biomedical SciencesUniversity of MilanItaly

Personalised recommendations