NSAR-Wirkungen auf den Gastrointestinaltrakt

Zusammenfassung

Der häufige Einsatz von nichtsteroidalen Antirheumatika (NSAR) vor allem zur Schmerzbekämpfung ist weltweit verbreitet. Die Einnahme von NSAR ist jedoch mit einer erheblichen Anzahl von Nebenwirkungen verbunden. Die Risiken von NSAR bestehen vor allem in Schleimhautläsio­nen, Dyspepsie, gastrointestinalen Blutungen, Ulze­rationen, Perforationen und Stenosen. NSAR können in sogenannte traditionelle und selektive NSAR (Zyklooxygenase-Hemmer, COX-1- und COX-2-Inhibitoren) sowie Aspirin unterteilt werden. Die Einführung von COX-2-Inhibitoren wurde kurzzeitig als ersehnte Besserung des Nebenwirkungsprofils gesehen, jedoch zeigten große Studien eine zu hohe Anzahl von kardiovaskulären Ereignissen, was den viel versprechenden Einsatz mit der Rücknahme einiger Präparaten vom Markt überschattete. Zunächst lag der Fokus der Nebenwirkungen von NSAR auf Läsionen im oberen Gastrointestinaltrakt. Mit der ­Einführung der Kapselendoskopie, der Ballon­ente­roskopie und der stärkeren Beachtung von Kolonläsionen zeigte sich ein ähnlich häufiges Auftreten von Neben­wirkungen von NSAR im unte­ren Gastro­intestinaltrakt. In diesem Artikel werden die ­gastrointestinalen Risiken vom Ösophagus bis zum Kolon erörtert und die Praxis der Gegenwart und der möglichen Zukunftsperspektiven dargestellt.

Abstract

The application of nonsteroidal antiinflammatory drugs (NSAID) against pain is worldwide ac­cept­ed, although NSAIDs are well known to cause ­potentially serious adverse effects. The risk of NSAIDs consists of mucosal lesions in the gastrointestinal (GI) tract, dyspepsia, gastrointestinal bleeding, ulcera, perforation and stenosis. NSAIDs can be classified in traditional and selective in­hib­itors of cyclooxygenase (COX-1 and COX-2 inhibitor, respectively) and aspirin. The discovery of COX-2 inhibitors was celebrated as a new desired improvement for adverse events for a short time period. But large studies revealed a significant inci­dence of cardiovascular events in combination with COX-2 inhibitors, which ended in a partial withdrawal from COX-2 inhibitors from the market. Adverse events were first only registered in the upper GI-tract, but with the introduction of ballon enteroscopy and capsule endoscopy and the intensified view on detected lesions in the ­colon, a similar number of adverse events from NSAIDs could be registered in the lower GI-tract. In this article gastrointestinal adverse events from the oesophagus up to the colon will be discussed. Finally an overview about the present ­recommendations and possible features in the ­future is given.

Schlüsselwörter

NSAR - Ulzera - Ösophagitis - Perforationsblutung - Diaphragma - Magenausgangsstenose - singuläres Ulkus - Kolopathie - Enteropathie

Key words

NSAIDs - ulcer - oesophagitis - GI tract bleeding - perforation - diaphragm - gastric outlet syndrome - singular ulcer - colonopathie - enteropathie

Literatur

• 1 Zimmermann F. Schmerz. In: Schwabe U, Paffrath D, Hrsg. Arzneimittelverordnungs-Report 2004
• 2 Patrono C, Rocca B. Aspirin, 110 years later.  J Thromb Haemost. 2009;  7 Suppl 1 258-261
• 3 Patrono C, Rocca B. Nonsteroidal antiinflammatory drugs: past, present and future.  Pharmacol Res. 2009;  59 285-289
• 4 Garcia Rodriguez L A, Barreales Tolosa L. Risk of upper gastrointestinal complications among users of traditional NSAIDs and COXIBs in the general population.  Gastroenterology. 2007;  132 498-506
• 5 Lanas A. Nonsteroidal antiinflammatory drugs and cyclooxygenase ­inhibition in the gastrointestinal tract: a trip from peptic ulcer to colon cancer.  Am J Med Sci. 2009;  338 96-106
• 6 Vieth M. NSAR-Kolopathie.  Pathologe. 2006;  27 65-72
• 7 Stolte M, Karimi D, Vieth M et al. Strictures, diaphragms, erosions or ­ulcerations of ischemic type in the colon should always prompt consideration of nonsteroidal anti-inflammatory drug-induced lesions.  World J Gastroenterol. 2005;  11 5828-5833
• 8 Maiden L. Capsule endoscopic diagnosis of nonsteroidal antiinflammatory drug-induced enteropathy.  J Gastroenterol. 2009;  44 Suppl 19 64-71
• 9 Evans S M, Whittle B J. Interactive roles of superoxide and inducible ­nitric oxide synthase in rat intestinal injury provoked by non-steroidal anti-inflammatory drugs.  Eur J Pharmacol. 2001;  429 287-296
• 10 Lanza F L, Chan F K, Quigley E M. Guidelines for prevention of NSAID-related ulcer complications.  Am J Gastroenterol. 2009;  104 728-738
• 11 Thun M J, Henley S J, Patrono C. Nonsteroidal anti-inflammatory drugs as anticancer agents: mechanistic, pharmacologic, and clinical issues.  J Natl Cancer Inst. 2002;  94 252-266
• 12 Chan F K, Cryer B, Goldstein J L et al. A novel composite endpoint to evaluate the gastrointestinal (GI) effects of nonsteroidal antiinflammatory drugs through the entire GI tract.  J Rheumatol. 2010;  37 167-174
• 13 Lanas A, Hirschowitz B I. Significant role of aspirin use in patients with esophagitis.  J Clin Gastroenterol. 1991;  13 622-627
• 14 Taha A S, McCloskey C, Prasad R et al. Famotidine for the prevention of peptic ulcers and oesophagitis in patients taking low-dose aspirin ­(FAMOUS): a phase III, randomised, double-blind, placebo-controlled trial.  Lancet. 2009;  374 119-125
• 15 Singh N P, Rizk J G. Oesophageal perforation following ingestion of over-the-counter ibuprofen capsules.  J Laryngol Otol. 2008;  122 864-866
• 16 Wallander M A, Johansson S, Ruigomez A et al. Dyspepsia in general practice: incidence, risk factors, comorbidity and mortality.  Fam Prac. 2007;  24 403-411
• 17 Lanas A, Sopena F. Nonsteroidal anti-inflammatory drugs and lower gastrointestinal complications.  Gastroenterol Clin N Am. 2009;  38 333-352
• 18 Hawkey C J, Svedberg L E, Naesdal J et al. Esomeprazole for the management of upper gastrointestinal symptoms in patients who require NSAIDs: a review of the NASA and SPACE double-blind, placebo-controlled studies.  Clin Drug Investig. 2009;  29 677-687
• 19 Huang J Q, Sridhar S, Hunt R H. Role of Helicobacter pylori infection and non-steroidal anti-inflammatory drugs in peptic-ulcer disease: a meta-analysis.  Lancet. 2002;  359 14-22
• 20 Adebayo D, Bjarnason I. Is non-steroidal anti-inflammaory drug (NSAID) enteropathy clinically more important than NSAID gastro­pathy?.  Postgrad Med J. 2006;  82 186-191
• 21 Bjarnason I, Takeuchi K. Intestinal permeability in the pathogenesis of NSAID-induced enteropathy.  J Gastroenterol. 2009;  44 Suppl 19 23-29
• 22 Laine L, Smith R, Min K et al. Systematic review: the lower gastrointestinal adverse effects of non-steroidal anti-inflammatory drugs.  Aliment Pharmacol Ther. 2006;  24 751-767
• 23 Wilcox C M, Alexander L N, Cotsonis G A et al. Nonsteroidal antiinflammatory drugs are associated with both upper and lower gastrointestinal bleeding.  Dig Dis Sci. 1997;  42 990-997
• 24 Lanas A, Ferrandez A. NSAIDs and the colon.  Curr Opin Gastroenterol. 2009;  25 44-49
• 25 Maiden L, Thjodleifsson B, Theodors A et al. A quantitative analysis of NSAID-induced small bowel pathology by capsule enteroscopy.  Gastroenterol. 2005;  128 1172-1178
• 26 De Petris G, Lopez J I. Histopathology of diaphragm disease of the small intestine: a study of 10 cases from a single institution.  Am J Clin Pathol. 2008;  130 518-525
• 27 Allison M C, Howatson A G, Torrance C J et al. Gastrointestinal damage associated with the use of nonsteroidal antiinflammatory drugs.  N Engl J Med. 1992;  327 749-754
• 28 Lanas A, Garcia-Rodriguez L A, Polo-Tomas M et al. Time trends and ­impact of upper and lower gastrointestinal bleeding and perforation in clinical practice.  Am J Gastroenterol. 2009;  104 1633-1641
• 29 Zhao Y E, Encinosa W. Hospitalizations for gastrointestinal bleeding in 1998 and 2006. Rockville, MD: Agency fro Healthcare Research and Quality; 2009 http://hcup-us.ahrq.gov/reports/statbriefs/sb65.pdf
• 30 Nagar A B. Isolated colonic ulcers: diagnosis and management.  Curr Gastroenterol Rep. 2007;  9 422-428
• 31 Pan Y S, Chen L T, Tseng C A et al. Clinical and endoscopic features of non-steroidal anti-inflammatory drug-induced colorectal ulcerations.  J Formos Med Assoc = Taiwan yi zhi. 2005;  104 804-810
• 32 Newton J L, Johns C E, May F E. Review article: the ageing bowel and ­intolerance to aspirin.  Aliment Pharmacol Ther. 2004;  19 39-45
• 33 Byrne M F, McGuinness J, Smyth C M et al. Nonsteroidal anti-inflammatory drug-induced diaphragms and ulceration in the colon.  Eur J Gastroenterol Hepatol. 2002;  14 1265-1269
• 34 Pihan G, Rogers C, Szabo S. Vascular injury in acute gastric mucosal damage. Mediatory role of leukotrienes.  Dig Dis Sci. 1988;  33 625-632
• 35 Hogenauer C, Eherer A, Pfeifer J et al. Chronic longitudinal NSAID-related ulcer of the colon (“colon single-stripe sign”) in Munchhausen syndrome.  Endoscopy. 2008;  40 Suppl 2 E 233
• 36 Schick V, Schröder G, Nauck C et al. Die NSAR-Kolopathie.  Endoskopie heute. 2009;  22 252-255
• 37 Geramizadeh B, Taghavi A, Banan B. Clinical, endoscopic and pathologic spectrum of non-steroidal anti-inflammatory drug-induced colitis.  ­Indian J Gastroenterol. 2009;  28 150-153
• 38 Kakar S, Pardi D S, Burgart L J. Colonic ulcers accompanying collagenous colitis: implication of nonsteroidal anti-inflammatory drugs.  Am J Gastroenterol. 2003;  98 1834-1837
• 39 Kefalakes H, Stylianides T J, Amanakis G et al. Exacerbation of inflammatory bowel diseases associated with the use of nonsteroidal anti-inflammatory drugs: myth or reality?.  Eur J Clin Pharmacol. 2009;  65 963-970
• 40 Chan F K, Abraham N S, Scheiman J M et al. Management of patients on nonsteroidal anti-inflammatory drugs: a clinical practice recommendation from the First International Working Party on Gastrointestinal and Cardiovascular Effects of Nonsteroidal Anti-inflammatory Drugs and Anti-platelet Agents.  Am J Gastroenterol. 2008;  103 2908-2918
• 41 Latimer N, Lord J, Grant R L et al. Cost effectiveness of COX 2 selective ­inhibitors and traditional NSAIDs alone or in combination with a proton pump inhibitor for people with osteoarthritis.  BMJ (Clin Res Ed). 2009;  339 b2538
• 42 Kearney P M, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials.  BMJ (Clin Res Ed). 2006;  332 1302-1308
• 43 Lai K C, Chu K M, Hui W M et al. Celecoxib compared with lansoprazole and naproxen to prevent gastrointestinal ulcer complications.  Am J Med. 2005;  118 1271-1278
• 44 Watanabe T, Sugimori S, Kameda N et al. Small bowel injury by low-dose enteric-coated aspirin and treatment with misoprostol: a pilot study.  Clin Gastroenterol Hepatol. 2008;  6 1279-1282
• 45 Strand V. Are COX-2 inhibitors preferable to non-selective non-steroidal anti-inflammatory drugs in patients with risk of cardiovascular events taking low-dose aspirin?.  Lancet. 2007;  370 2138-2151
• 46 Antman E M, Bennett J S, Daugherty A et al. Use of nonsteroidal anti­inflammatory drugs: an update for clinicians: a scientific statement from the American Heart Association.  Circulation. 2007;  115 1634-1642
• 47 Desai S P, Solomon D H, Abramson S H et al. Recommendations for use of selective and nonselective nonsteroidal antiinflammatory drugs: an American College of Rheumatology white paper.  Arthritis Rheum. 2008;  59 1058-1073
• 48 Niwa Y, Nakamura M, Miyahara R et al. Geranylgeranylacetone protects against diclofenac-induced gastric and small intestinal mucosal injuries in healthy subjects: a prospective randomized placebo-controlled double-blind cross-over study.  Digestion. 2009;  80 260-266
• 49 Higuchi K, Yoda Y, Amagase K et al. Prevention of NSAID-Induced small intestinal mucosal injury: prophylactic potential of lansoprazole.  J Clin Biochem Nutr. 2009;  45 125-130