Advertisement

Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: Prophylactic and therapeutic strategies

  • Daniel Hollander
    Correspondence
    Requests for reprints should be addressed to Daniel Hollander, M.D., Dean's Office, University of Kansas Medical Center, Kansas City, Kansas 66160.
    Affiliations
    Division of Gastroenterology, University of California, Irvine, California USA
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Nonsteroidal anti-inflammatory drugs (NSAIDs) are some of the most commonly used drugs in the Western world. Patients undergoing NSAID therapy often experience abdominal discomfort, and some of them develop serious complications, such as ulceration, perforation, or bleeding. Since serious complications of NSAID therapy can occur in relatively asymptomatic patients and abdominal symptoms do not serve as a signal of impending difficulties, there is a need for methods to identify those patients who may benefit from prophylactic therapy to prevent NSAID-induced injury.
      Therapy to prevent NSAID-associated gastrointestinal ulcerations is most effective when prostaglandins are used. H2-receptor antagonists prevent duodenal ulcerations but not gastric ulcerations. The role of omeprazole (hydrogen-potassium pump inhibitor) and sucralfate in the prevention of gastroduodenal ulcerations has not been firmly established.
      Healing of existing ulcerations in the face of continuing therapy with NSAIDs is marginally accelerated by H2-receptor antagonists, but the rate of healing in the presence of continued NSAID therapy is much slower than when NSAIDs are discontinued. Omeprazole may prove to accelerate the healing of NSAID-associated ulcerations even when NSAID therapy is continued, but more information is needed to substantiate this possibility.
      New methods are needed for early noninvasive detection of mucosal damage by NSAIDs and for the identification of individuals who should receive prophylactic therapy. New agents are also needed to provide cost-effective prophylaxis against the development of ulcerations and serious complications from NSAIDs.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The American Journal of Medicine
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Baum C
        • Kennedy DL
        • Forbes MB
        Utilization of nonsteroidal anti-inflammatory drugs.
        Arthritis Rheum. 1985; 28: 686-692
        • Geis GS
        • Stead H
        • Wallemark C-B
        • Nicholson PA
        Prevalence of mucosal lesions in the stomach and duodeum due to chronic use of NSAIDs in patients with RA or OA, and interim report on prevention by misoprostol of diclofenac-associated lesions.
        J Rheumatol. 1991; 18: 11-14
        • Roth S
        • Agrawal N
        • Mahowald M
        • et al.
        Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin.
        Arch Intern Med. 1989; 149: 775-779
        • Farah D
        • Sturrock RD
        • Russell RI
        Peptic ulcer in rheumatoid arthritis.
        Ann Rheum Dis. 1988; 47: 472-480
        • Collins AJ
        • Davies J
        • Dixon ASJ
        Contrasting presentation and findings between patients with rheumatic complaints taking nonsteroidal anti-inflammatory drugs with a general population referred for endoscopy.
        Br J Rheumatol. 1986; 25: 50-53
        • Sontag S
        • Schnell T
        • Mak E
        • et al.
        NSAIDs with or without prednisone: bad news for the gut mucosa.
        Gastroenterology. 1989; 96 (abstract): A483
        • Collins AJ
        • Du Toit JA
        Upper gastrointestinal findings and faecal occult blood in patients with rheumatic diseases taking nonsteroidal anti-inflammatory drugs.
        Br J Rheumatol. 1987; 26: 295-298
        • Morris AD
        • Holt SD
        • Silvaso GR
        • et al.
        Effect of anti-inflammatory drug administration in patients with rheumatoid arthritis: an endoscopic assessment.
        Scand J Gastroenterol. 1981; 67 (Suppl): 131-135
        • Beard K
        • Walker AM
        • Perera DR
        • Jick H
        Non-steroidal anti-inflammatory drugs and hospitalization for gastroesophageal bleeding in the elderly.
        Arch Intern Med. 1987; 5: 84-91
        • Griffin MR
        • Piper JM
        • Daugherty JR
        • Snowden M
        • Ray WA
        Nonsteroidal anti-inflammatory drug use increased risk for peptic ulcer disease in elderly persons.
        Ann Intern Med. 1991; 114: 257-263
        • Caruso I
        • Bianchi Porro G
        Gastroscopic evaluation of anti-inflammatory agents.
        BMJ. 1980; 280: 75-78
        • Silvoso G
        • Ivey KJ
        • But J
        • et al.
        Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy.
        Ann Intern Med. 1979; 91: 517-520
        • Armstrong CP
        • Blower AL
        Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration.
        Gut. 1987; 28: 527-532
        • Bloom BS
        Direct medical costs of disease and gastrointestinal side effects during treatment for arthritis.
        Am J Med. 1988; 84: 20-24
        • Fries JF
        • Miller SR
        • Spilz PW
        • Williams CA
        • Hubert HB
        • Block DA
        Toward an epidemiology of gastropathy associated with nonsteroidal anti-inflammatory drug use.
        Gastroenterology. 1989; 96: 647-655
        • Rainsford KD
        Mechanisms of gastrointestinal toxicity of non-steroidal anti-inflammatory drugs.
        Scand J Gastroenterol Suppl. 1989; 163: 9-16
        • Bugat R
        • Thompson MR
        • Aures D
        • Grossman MI
        Gastric mucosal lesions produced by intravenous infusion of aspirin in cats.
        Gastroenterology. 1976; 71: 754-759
        • Lanza FL
        • Karlin DA
        • Yee JP
        A double-blind placebo controlled endoscopic study comparing the mucosal injury seen with orally and parenterally administered nonsteroidal analgesic ketorolac tromethamine at therapeutic and supratherapeutic doses.
        Am J Gastroenterol. 1987; 82 (abstract): 939
        • Tarnawski A
        • Stachura J
        • Gergely H
        • Hollander D
        Gastric microvascular endothelium: a major target for aspirin-induced injury and arachidonic acid protection.
        in: An ultrastructural analysis in the rat. Eur J Clin Invest. 20. 1990: 432-440
        • Hollander D
        • Tarnawski A
        The protection and therapeutic mechanisms of sucralfate.
        Scand J Gastroenterol. 1990; 173 (Suppl): 1-5
        • Konturek SJ
        • Kwiecien N
        • Obtulowicz W
        • Kopp B
        • Oleksy J
        Double blind controlled study on the effect of sucralfate on gastric prostaglandin formation and microbleeding in normal and aspirin treated man.
        Gut. 1986; 27: 1450-1456
        • Brzozowski T
        • Tarnawski A
        • Hollander D
        • Stachura J
        • Krause WJ
        • Gergely H
        Prostaglandin but not cimetidine reduces spontaneous degeneration of isolated gastric gland cells.
        in: Direct protective effect, independent of vascular, neural and hormonal factors. J Clin Gastroenterol. 14. 1992: S34-S38 (Suppl 1)
        • Hollander D
        • Dadufalza D
        • Fairchild PA
        Intestinal absorption of aspirin influence of pH, taurocholate, ascorbate and ethanol.
        J Lab Clin Med. 1981; 98: 591-598
        • Abramson SB
        • Weissmann G
        The mechanisms of action of nonsteroidal anti-inflammatory drugs.
        Arthritis Rheum. 1989; 32: 1-9
        • Hollander D
        • Tarnawski A
        The role of essential fatty acids in gastric and duodenal protection and ulcer therapy.
        in: Benjamin SM Collen MJ Handbook of experimental pharmacology of peptic ulcer disease. Springer Verlag Publishers, Berlin1991: 89-105
        • Hollander D
        • Tarnawski A
        Gastric cytoprotection—a clinician's guide.
        Plenum Publishing, New York1989
        • Graham DY
        • Agrawal NM
        • Roth SH
        Prevention of NSAID-induced gastric ulcer with misoprostol: multicenter, double-blind, placebo controlled trial.
        Lancet. 1988; 2: 1277-1280
        • Simchowitz L
        • Mehta J
        • Spilberg I
        Chemotactic factor-induced generation of superoxide radicals by human neutrophils: effect of metabolic inhibitors and anti-inflammatory drugs.
        Arthritis Rheum. 1979; 22: 755-763
        • Minta JO
        • Williams MD
        Some nonsteroidal anti-inflammatory drugs inhibit the generation of superoxide anions by activated polymorphs by blocking ligand-receptor interactions.
        J Rheumatol. 1985; 2: 751-757
        • Weissmann G
        The action of NSAIDS.
        Hosp Prac. 1991 August; 15: 60-76
      1. Nonsteroidal anti-inflammatory drugs and serious gastrointestinal adverse reaction.
        BMJ. 1986; 292: 614
        • Langman MJS
        Epidemiologic evidence on the association between peptic ulceration and anti-inflammatory drug use.
        Gastroenterology. 1989; 96: 640-646
        • Piper JM
        • Daugherty WA
        • Griffin MR
        Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs.
        Ann Intern Med. 1991; 114: 735-740
        • Holvoet J
        • Terriere L
        • Van Hee W
        • Verbist L
        • Fierens E
        • Hautekeete ML
        Relation of upper gastrointestinal bleeding to nonsteroidal anti-inflammatory drugs and aspirin: a case-control study.
        Gut. 1991; 32: 730-734
        • Klein L
        • Sessoms SL
        • Michaletz PA
        • Saeed ZA
        Long-term nonsteroidal anti-inflammatory drug use and Helicobacter pylori infection.
        Gastroenterology. 1991; 100: 1653-1657
        • Laine L
        • Marin-Sorensen M
        • Weinstein WM
        Is Compylobacter pylori (CP) prevalence lower in gastric ulcers (GU's) because of nonsteroidal anti-inflammatory drug (NSAID) use.
        in: A prospective evaluation (abstract). Gastroenterology. 96. 1989: A282 (Suppl)
        • Loeb DS
        • Talley NJ
        • Ahlquist DA
        • Carpenter HA
        • Zinsmeister AR
        Chronic nonsteroidal anti-inflammatory drug use and gastroduodenal injury: the role of Helicobacter pylori.
        Gastroenterology. 1992; 102: 1899-1905
        • Capell HA
        • MacKenzie JF
        Enteroscopic diagnosis of small bowel ulceration in patients receiving nonsteroidal anti-inflammatory drugs.
        Lancet. 1991; : 337-520
        • Day TK
        Intestinal perforation associated with osmotic slow release indomethacin capsules.
        BMJ. 1983; 287: 1671-1672
        • Duggan DE
        • Hooke KF
        • Noll RM
        • Kwan KC
        Enterohepatic circulation of indomethacin and its role in intestinal irritation.
        Biochem Pharmacol. 1975; 25: 1749-1754
        • Erickson RA
        Effect of 16, 16-dimethyl PGE2 and indomethacin on bile acid-induced intestinal injury and restitution in rats.
        J Lab Clin Med. 1988; 112: 735-744
        • Kruglaik P
        • Hollander D
        • Le K
        • Ma T
        • Dadufalza VD
        • Katz KD
        Regulation of polyethylene glycol 400 intestinal permeability by endogenous and exogenous prostanoids.
        in: Influence of nonsteroidal, anti-inflammatory drugs. Gut. 31. 1990: 417-421
        • Bjarnason I
        • Fehilly B
        • Smethurst P
        • Menzies IS
        • Levi AJ
        Importance of local versus systemic effects of nonsteroidal anti-inflammatory drugs in increasing small intestinal permeability in man.
        Gut. 1991; 21: 275-277
        • Katz KD
        • Hollander D
        Intestinal mucosal permeability and rheumatologic diseases.
        in: Bailliere. Clinical rheumatology. Raven Press, New York1988
        • Agrawal NM
        • Roth S
        • Graham DY
        • et al.
        Comparison of misoprostol and sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer: a randomized, controlled trial.
        Ann Intern Med. 1991; 115: 195-200
        • Graham DY
        • White RH
        • Moreland LW
        • et al.
        Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs.
        in: Misoprostol study groups. Ann Intern Med. 119. 1993: 257-262
        • Ehsanullah RSB
        • Page MD
        • Tildesley G
        • Wood JR
        Prevention of gastroduodenal damage induced by nonsteroidal anti-inflammatory drugs: controlled trial with ranitidine.
        BMJ. 1988; 297: 1017-1021
        • Robinson MG
        • Griffin JW
        • Bowers J
        • et al.
        Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal anti-inflammatory drugs.
        Dig Dis Sci. 1989; 34: 424-428
        • Raskin J
        • White R
        • Jasjewski R
        Double-blind comparative study of the efficacy and safety of misoprostol and ranitidine in the prevention of NSAID-induced gastric ulcers and upper GI symptoms: preliminary findings.
        in: Abstract presented at 7th International Conference on Experimental Ulcer, Berlin, GermanyOctober 1991
      2. Holt K, Hollander D. Gastric mucosal injury. In: Creger WP, editor. Annual review of medicine, Vol. 37. Palo Alto, California: Annual Reviews, 107–125.

        • Walan A
        • Bader J-P
        • Classen M
        • et al.
        Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.
        N Engl J Med. 1989; 320: 69-75
        • O'Laughlin JC
        • Silvoso GK
        • Ivey KJ
        Resistance to medical therapy of gastric ulcers in rheumatic disease patients taking aspirin: a double-blind study with cimetidine and follow-up.
        Dig Dis Sci. 1982; 27: 976-980
        • Lancaster-Smith MJ
        • Jaderberg ME
        • Jackson DA
        Ranitidine in the treatment of nonsteroidal anti-inflammatory drug associated gastric and duodenal ulcers.
        Gut. 1991; 32: 252-255
        • Meddings JB
        • Byles NI
        • Sutherland LR
        • Wallace JL
        Sucrose, a novel, site specific permeability marker for gastric damage.
        Gastroenterology. 1992; 102 ([abstract]): A123
        • Meddings JB
        • Sutherland LR
        • Byles NI
        • Wallace JL
        Sucrose: a novel permeability marker for gastroduodenal disease.
        Gastroenterology. 1993; 104: 1619-1626
        • Hollander D
        Permeability in Crohn's disease—altered barrier functions in healthy relatives.
        Gastroenterology. 1993; 104: 1848-1851