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Epidemiology and differential diagnosis of NSAID-induced injury to the mucosa of the small intestine

https://doi.org/10.1053/bega.2001.0231Get rights and content

Abstract

Non-steroidal anti-inflammatory drugs cause small-bowel inflammation in about 60% of patients receiving these drugs long-term. The inflammation is associated with small intestinal bleeding, protein loss, ulcers and occasionally strictures. Treatment options for NSAID enteropathy include metronidazole, sulphasalazine and misoprostol, and some patients may require surgery. The diagnosis of NSAID enteropathy is not always straightforward. It is especially difficult to differentiate it from the ileitis associated with spondylarthropathy and, at times, that of Crohn's disease. An investigational algorithm is suggested for this purpose.

In the last decade a number of small-bowel diseases have been identified, where none were thought to exist, because of the increasing use of enteroscopy and new sensitive tests for intestinal inflammation. Optimal treatments of these conditions are still to be studied.

References (87)

  • l Bjarnason et al.

    Intestinal permeability and inflammation in rheumatoid arthritis: effects of non-steroidal anti-inflammatory drugs

    Lancet

    (1984)
  • G Sigthorsson et al.

    Intestinal permeability and inflammation in patients on NSAIDs

    Gut

    (1998)
  • J Tibble et al.

    Faecal calprotectin: a simple method for the diagnosis of NSAID-induced enteropathy

    Gut

    (1999)
  • AJ Morris et al.

    Small bowel enteroscopy in undiagnosed gastrointestinal blood loss

    Gut

    (1992)
  • M JS Langman et al.

    Use of anti-inflammatory drugs by patients with small or large bowel perforation and haemorrhage

    British Medical Journal

    (1985)
  • MC Allison et al.

    Gastrointestinal damage associated with the use of nonsteroidal anti-inflammatory drugs

    New England Journal of Medicine

    (1992)
  • DA Brodie et al.

    Aspirin: intestinal damage in rats

    Science

    (1970)
  • R Melrange et al.

    Antiinflammatory and gastrointestinal effects of nabumetone or its active metabolite, 6-methoxy-6-naphthylacetic acid (6MNA)

    Digestive Diseases and Sciences

    (1992)
  • R Melrange et al.

    A comparison of indomethacin with ibuprofen on gastrointestinal mucosal integrity in conventional and germ free rats

    Alimentary Pharmacology and Therapeutics

    (1992)
  • JR Vane

    Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs

    Nature

    (1971)
  • JR Vane

    Towards a better aspirin

    Nature

    (1994)
  • JR Vane

    NSAIDs, Cox-2 inhibitors, and the gut

    Lancet

    (1995)
  • JR Vane et al.

    Overview– mechanisms of action of anti-inflammatory drugs

  • S Somasundaram et al.

    The biochemical basis of NSAID-induced damage to the gastrointestinal tract: a review and a hypothesis

    Scandinavian Journal of Gastroenterology

    (1995)
  • KD Rainsford

    Profile and mechanisms of gastrointestinal and other side effects of nonsteroidal anti-inflammatory drugs (NSAIDs)

    American Journal of Medicine

    (1999)
  • C Scarpignatio et al.

    Towards a GI safer antiinflammatory therapy

    Gastroenterology International

    (1999)
  • GW Gullikson et al.

    Laxative-like effects of nonsteroidal anti-inflammatory drugs on intestinal fluid movement and membrane integrity

    Journal of Pharmacology and Experimental Therapeutics

    (1981)
  • LM Lichtenberger et al.

    ASA forms an ionic complex with phosphatidylcholine: possible molecular explanation for its ulcerogenic action

    Gastroenterology

    (1994)
  • LM Lichtenberger et al.

    Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospholipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury

    Nature Medicine

    (1995)
  • S Somasundaram et al.

    The relative importance of inhibition of cyclooxygenase and uncoupling of oxidative phosphorylation in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs

    Alimentary Pharmacology and Therapeutics

    (2000)
  • T Mahmud et al.

    Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation

    Arthritis and Rheumatism

    (1996)
  • T Mahmud et al.

    A unifying hypothesis for the mechanism of NSAID related gastrointestinal toxicity

    Annals of the Rheumatic Diseases

    (1996)
  • K Brune et al.

    Parietal cells of the stomach trap salicylates during absorption

    Biochemical Pharmacology

    (1997)
  • K Brune et al.

    Recent insight into the mechanism of gastrointestinal tract ulceration

    Scandinavian Journal of Rheumatology

    (1987)
  • JG Spenny et al.

    Effect of prostaglandin acid on gastric mucosa II. Mucosal ATP and phosphocreatinine content and salicylic effects on mitochondrial metabolism

    Gastroenterology

    (1977)
  • Jacob, M, Mechanism of nonsteroidal anti-inflammatory drug-induced damage in the small bowel. PhD thesis, University of...
  • S Somasundaram et al.

    Mitochondrial damage: a possible mechanism of the ‘topical’ phase of NSAID-induced injury to the rat intestine

    Gut

    (1997)
  • NM Davies et al.

    Anti-inflammatory drug induced small intestinal permeability: the rat is a suitable model

    Pharmacology Research

    (1994)
  • T Mahmud et al.

    Enantiomers of flurbiprofen can distinguish key pathophysiological steps of NSAID-enteropathy in the rat by steroselective inhibition of cyclooxygenase

    Gut

    (1998)
  • JL Wallace et al.

    Gastric ulceration induced by nonsteroidal antiinflammatory drugs is a neutrophil dependent process

    American Journal of Physiology

    (1990)
  • JL Wallace et al.

    Pathogenesis of NSAID gastropathy: are neutrophils the culprits?

    Trends in Pharmacological Science

    (1992)
  • A Anthony et al.

    Pre-ulcerative villous contraction and microvascular occlusion induced by indomethacin in the rat jejunum

    Alimentary Pharmacology and Therapeutics

    (1995)
  • A Anthony et al.

    Vascular anatomy defines sites of indomethacin induced jejunal ulceration along the mesenteric margin

    Gut

    (1997)

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