Prophylaxe und Therapie NSAR-induzierter Ulzera: ein Update

 

 Buy Article Permissions and Reprints

Nicht-steroidale Antirheumatika (NSAR) können bei bis zur Hälfte der Patienten Symptome wie Dyspepsie und Übelkeit sowie eine Anorexie verursachen ([26]). Nur 2-4 % der Patienten entwickeln symptomatische Ulzera und Ulkuskomplikationen wie Blutung, Perforation und Obstruktion. Schwere gastrointestinale Nebenwirkungen, die zu einer Hospitalisation oder sogar zum Tod des Patienten führen, treten nur in ca. 2 % der Fälle auf. Dies erscheint wenig, ist jedoch angesichts der großen Zahl an Patienten, die NSAR einnehmen, von großer Bedeutung. Im Folgenden werden die heute gesicherten Kenntnisse über die Ulkusprophylaxe mit säurehemmenden Medikamenten und Prostaglandin sowie die Behandlung von Ulzera, die unter einer Therapie mit NSAR auftreten, besprochen.

Literatur

• 1 Agrawal N M, Roth S, Graham D Y, White R H, Germain B, Brown J A, Stromatt S C. Misoprostol compared with sucralfate in the prevention of nonsteroidal anti-inflammatory drug-induced gastric ulcer. A randomized, controlled trial.  Ann Intern Med. 1991;  115 195-200
  Google Scholar
• 2 Agrawal N, Safdi M, Wruble L, Karvois D, Greski-Rose P, Huang B. Effectiveness of Lansoprazole in the healing of NSAID-induced ulcer in patients continuing to take NSAIDs.  Gastroenterology (abstract). 1998;  114 A52-A53
  Google Scholar
• 3 Bianchi Porro G, Parente F, Imbesi V, Montrone F, Caruso I. Role of Helicobacter pylori in ulcer healing and recurrence of gastric and duodenal ulcers in longterm NSAID users.  Gut. 1996;  39 22-26
  Google Scholar
• 4 Bradley J D, Brandt K D, Katz B P, Kalasinski L A, Ryan S I. Comparison of an antiinflammatory dose of ibuprofen, an analgesic dose of ibuprofen, and acetaminophen in the treatment of patients with osteoarthritis of the knee.  New Engl J Med. 1991;  325 87-91
  Google Scholar
• 5 Chan F K, Sung J J, Chung S C. et al . Randomised controlled trial of Helicobacter pylori before non-steroidal anti-inflammatory drug therapy to prevent peptic ulcers.  Lancet. 1997;  350 975-979
  Google Scholar
• 6 Cullen D J, Hawkey G M, Greenwood D C. et al . Peptic ulcer bleeding in the elderly: Relative roles of Helicobacter pylori and nonsteroidal anti-inflammatory drugs.  Gut. 1979;  41 459-462
  Google Scholar
• 7 Donnelly M T, Stack W A, Courtauld E M, Garlick N, Del Soldato P, Hawkey C J. Nitric oxide donating flurbiprofen (HCT 1026) causes less endoscopic damage in healthy volunteers than flurbiprofen.  Gastroenterology (abstract). 1998;  114 A107
  Google Scholar
• 8 Ehsanullah R S, Page M C, Tildesley G, Wood J R. Prevention of gastroduodenal damage induced by nonsteroidal antiinflammatory drugs: Controlled trial of ranitidine.  Br Med J. 1988;  297 1017-1021
  Google Scholar
• 9 Ekstrom P, Carling L, Wetterhus S. et al . Prevention of peptic ulcer and dyspeptic symptoms with omeprazole in patients receiving continous non-steroidal anti-inflammatory drug therapy. A Nordic multicentre study.  Scand J Gastroenterol. 1996;  31 753-758
  Google Scholar
• 10 Gabriel S E, Jaakkimainen L, Bombardier C. Risk for serious gastrointestinal complications related to use of nonsteroidal anti-inflammatory drugs. A meta-analysis.  Ann Intern Med. 1991;  115 787-796
  Google Scholar
• 11 Goldstein J L, Agrawal N M, Silverstein F. et al . Celecoxib is associated with a significantly lower incidence of clinically significant upper gastrointestinal events in osteoarthritis and rheumatoid arthritis patients as compared to NSAIDS.  Gastroenterology (abstract). 1999;  116 A174
  Google Scholar
• 12 Graham D Y, White R H, Moreland W. et al . Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs. Misoprostol Study Group.  Ann Intern Med. 1993;  119 257-262
  Google Scholar
• 13 Hawkey C J, Karrasch J A, Szczepanski L, Walker D K, Barkun A, Swannell A J, Yeomans N D. Omeprazole compared with misoprostol for ulcers associated with nonsteroidal antiinflammatory drugs. Omeprazole versus Misoprostol for NSAID-induced Ulcer Management (OMNIUM) Study Group.  New Engl J Med. 1998;  338 727-734
  Google Scholar
• 14 Hawkey C J, Tulassay Z, Szczepanski L. et al . Randomised controlled trial of Helicobacter pylori eradication in patients on non-steroidal anti-inflammatory drugs: HELP NSAIDs Study.  Lancet. 1998;  352 1016-1021
  Google Scholar
• 15 Huskisson E C, Ghozian R, Kurthen R, Degner F L, Bluhmki E. A long-term study to evaluate the safety and efficacy of meloxicam therapy in patients with rheumatoid arthritis.  Br J Rheumatol. 1996;  35 29-34
  Google Scholar
• 16 Koch M, Dezi A, Ferrario F, Capurso I. Prevention of nonsteroidal anti-inflammatory drug-induced gastrointestinal mucosal injury. A meta-analysis of randomized controlled clinical trials.  Arch Intern Med. 1996;  156 2321-2322
  Google Scholar
• 17 Laine L, Hawkey C, Harper, Mortensen E, Beaulieu A, Quan H, Bolognese J, Simon T. Effect of the COX-2 specific inhibitor (C-2SI) rofecoxib on ulcer formation.  Gastroenterology (abstract). 1999;  116 A229
  Google Scholar
• 18 Lancaster-Smith M J, Jaderberg M E, Jackson D A. Ranitidine in the treatment of nonsteroidal anti-inflammatory drug associated with gastric and duodenal ulcers.  Gut. 1991;  32 69-75
  Google Scholar
• 19 Lanza F L, Rack M F, Callison D A. et al . A pilot endoscopic study of the gastroduodenal effects of SC-58635, a novel COX-2-selective inhibitor.  Gastroenterology (abstract). 1997;  112 A194
  Google Scholar
• 20 Raskin J B, White R H, Jaszewski R, Korsten M A, Schubert T T, Fort J G. Misoprostol and ranitidine in the prevention of NSAID-induced ulcers.  Am J Gastroenterol. 1996;  91 223-227
  Google Scholar
• 21 Robinson M G, Griffin J W, Bowers J, Kogan F J, Kogut D G, Lanza F L, Warner C W. Effect of ranitidine on gastroduodenal damage induced by nonsteroidal antiinflammatory drugs.  Dig Dis Sci. 1989;  34 424-428
  Google Scholar
• 22 Roth S, Agarwal N, Mahowald M. et al . Misoprostol heals gastroduodenal injury in patients with rheumatoid arthritis receiving aspirin.  Arch Intern Med. 1989;  149 775-779
  Google Scholar
• 23 Scheiman J M, Behier E M, Loeffler K M, Elta G H. Omeprazole ameliorates aspirin-induced gastroduodenal injury.  Dig Dis Sci. 1994;  39 97-103
  Google Scholar
• 24 Shorr R J, Ray W A, Daugherty J R, Griffin M R. Concurrent use of nonsteroidal anti-inflammatory drugs and oral anticoagulants places elderly persons at risk for hemorrhagic peptic ulcer disease.  Arch Intern Med. 1993;  153 1665-1670
  Google Scholar
• 25 Silverstein F E, Graham D Y, Senior J R, Davies H W, Struthers B J, Bittman R M, Geis G S. Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammtory drugs.  Ann Intern Med. 1995;  123 241-249
  Google Scholar
• 26 Singh G, Ramey D R, Morfeld D, Shi H, Hatoum H T, Fries J F. Gastrointestinal tract complications of nonsteroidal anti-inflammatory drug treatment in rheumatoid arthritis. A prospective observational cohort study.  Arch Intern Med. 1996;  156 1530-1536
  Google Scholar
• 27 Taha A S, Hudson N, Hawkey C J. et al . Famotidine for the prevention of gastric and duodenal ulcers caused by nonsteroidal antiinflammatory drugs.  New Engl J Med. 1996;  334 1435-1439
  Google Scholar
• 28 Taha A S, Dahill S, Nakshabendi I. et al . Duodenal histology, ulceration, and Helicobacter pylori in the presence or absence of nonsteroidal anti-inflammatory drugs.  Gut. 1993;  34 1162-1166
  Google Scholar
• 29 Ten-Wolde S, Dijkmans B A, Janssen M, Hermans J, Lamers C B. High-dose ranitidine for the prevention of recurrent peptic ulcer disease in rheumatoid arthritis patients taking NSAIDs.  Aliment Pharmacol Ther. 1996;  10 347-351
  Google Scholar
• 30 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.  New Engl J Med. 1989;  320 59-75
  Google Scholar
• 31 Walt R P. Misoprostol for the treatment of peptic ulcer and antiinflammatory-drug-induced gastroduodenal ulceration.  New Engl J Med. 1992;  327 1575-1580
  Google Scholar
• 32 Yeomans N D, Tulassay Z, Juhasz L. et al . A comparison of omeprazole with ranitidine for ulcers associated with nonsteroidal anti-inflammatory drugs.  New Engl J Med. 1998;  338 719-726
  Google Scholar

Korrespondenz

Dr. Miriam Thumshirn
Prof. Dr. Michael Fried

Abteilung für Gastroenterologie Departement Innere Medizin Universitätsspital Zürich

Rämistrasse 100

CH-8091 Zürich

Fax: 0041/1/2554503