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Arthritis und Rheuma 2004; 24(04): 122-126
DOI: 10.1055/s-0037-1618469
Rheuma und Darm
Schattauer GmbH

Enteroirritation und Enteroprotektion bei der Rheumatherapie

Enteroirritation and enteroprotection in the treatment of rheumatic diseases
Wolfgang W. Bolten
1   Rheumaklinik Wiesbaden, Klaus Miehlke-Klinik
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Publication History

Publication Date:
23 December 2017 (online)

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Zusammenfassung

Traditionelle nichtsteroidale Antirheumatika (tNSAR) und Acetylsalicylsäure (ASS) schädigen die Schleimhaut des gesamten Intestinaltrakts. Schwere Läsionen, Ulzera und Perforationen, Blutungen und Strikturen führen zur Hospitalisation und gegebenenfalls zum Tod. Besonders bei älteren Patienten über 65 Jahre und bei Patienten mit schweren Allgemeinerkrankungen ist das Blutungsund Perforationsrisiko erhöht. Magen-Darm-Ulzera oder gastrointestinale (GI-) Blutungen in der Anamnese oder die Komedikation mit Antikoagulanzien, Kortikosteroiden und nicht zuletzt hohe tNSAR-Dosierungen oder Multi-tNSAR-Therapien lassen das GI-Komplikationsrisiko mit jedem Faktor weiter ansteigen. Ein erst in letzter Zeit besser analysierter Risikofaktor ist ASS, auch in der niedrigen Dosierung zur kardiovaskulären Prophylaxe. Ein bereits bestehendes tNSAR-Ulkus kann mit Protonenpumpenhemmern (PPI) erfolgreich zur Abheilung gebracht werden, ohne dass die tNSAR-Therapie abgesetzt werden muss. In jedem Fall muss die niedrigste mögliche noch wirksame tNSAR-Dosis gewählt werden. Bei Risikopatienten sollten Präventivmaßnahmen ergriffen werden, z. B. eine Komedikation mit dem allerdings mit Nebenwirkungen belasteten Prostaglandinanalogon Misoprostol oder die Behandlung mit hochdosierten H2-Rezeptorantagonisten. Am besten wirken als Kotherapeutika aber PPI. In gleichem Maß wie durch PPI kann die Ulkusrate auch mit COX-2-selektiven Inhibitoren (Coxibe) anstelle der tNSAR erniedrigt werden. Outcomestudien mit über 8000 Patienten belegen das verminderte GI-Komplikationsrisiko unter Coxiben.

Trotz des großen wissenschaftlichen Fortschritts werden die Möglichkeiten der sicheren Schmerztherapie unzureichend ausgeschöpft. Die Ergebnisse der Forschung müssen effizienter an die behandelnden Ärzte weitergegeben werden.

Summary

Traditional nonsteroidal anti-inflammatory drugs (tNSAIDs) and acetylsalicylic acids (ASA) damage the mucous membrane of the entire intestinal tract. Severe lesions, ulcera and perforations, bleeding and strictures lead to hospitalisation and in some cases death. There is an increased risk of bleeding and perforation particularly in elderly patients over 65 and patients with acute general illnesses. Gastroduodenal ulcera or gastrointestinal (GI) bleeding in the anamnesis or the taking of anticoagulants, corticosteroids and not least of all high tNSAID dosages or multi tNSAID treatments at the same time make the risk of GI complications further increase in every factor. A risk factor which was not more deeply analysed until recently is ASA, also in low dosage for cardiovascular prophylaxis.

An already existing tNSAID ulcer can be successfully healed with proton pump inhibitors (PPI) without having to abandon tNSAID therapy. The lowest possible effective tNSAID dose should always be selected. Preventative measures should be taken for patients who are at risk, e.g. the taking of the prostaglandin analogue Misoprostol which have side effects or the treatment with high dose H2 receptor antagonists.

PPI are most effective as a co-therapeutics. The ulcer rate can also be lowered with cyclooxygenase-2-inhibitors instead of with tNSAIDs to the same extent as with PPI. Outcome studies with over 8,000 patients prove the reduced risk of GI complications using cyclooxygenase-2-inhibitors.

Despite significant scientific progress, the possibilities for safe analgesic therapy are becoming insufficiently exhausted. Research results will have to be more efficiently passed on to physicians.

Schlüsselwörter

Nichtsteroidale Antirheumatika - gastrointestinale Blutung - Magen-Darm-Ulzera - Coxibe

Keywords

Nonsteroidal anti-inflammatory drugs - gastrointestinal bleeding - gastroduodenal ulcera - cyclooxygenase-2-inhibitors
 

  • Literatur

  • 1 Aabakken L., Bjornbeth BA., Hofstad B.. et al Comparison of the gastrointestinal side effects of naproxen formulated as plain tablets, enteric-coated tablets, or enteric-coated granules in capsules. Scand J Gastroenterol Suppl 1989; 163: 65-73.
    Google Scholar
  • 2 Ammori BJ.. Laparoscopic pancreas-preserving distal duodenectomy for duodenal stricture related to nonsteroidal antiinflammatory drugs (NSAIDs). Surg Endosc 2002; 16 (09) 1362-3.
    CrossrefPubMedGoogle Scholar
  • 3 Anand BS., Romero JJ., Sanduja SK., Lichten-berger LM.. Phospholipid association reduces the gastric mucosal toxicity of aspirin in human subjects. Am J Gastroenterol 1999; 94 (07) 1818-22.
    CrossrefPubMedGoogle Scholar
  • 4 Anthony A., Dhillon AP., Thrasivoulou C.. et al Pre-ulcerative villous contraction and micro-vascular occlusion induced by indomethacin in the rat jejunum: a detailed morphological study. Aliment Pharmacol Ther 1995; 9 (06) 605-13.
    Google Scholar
  • 5 Armstrong CP., Blower AL.. Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration. Gut 1987; 28 (05) 527-32.
    CrossrefPubMedGoogle Scholar
  • 6 Bjarnason I., Hayllar J., Macpherson AJ., Russell AS.. Side effects of nonsteroidal anti-inflammatory drugs on the small and large intestine in humans. Gastroenterology 1993; 104 (06) 1832-47.
    CrossrefPubMedGoogle Scholar
  • 7 Bolten WW., Lang B., Wagner AV., Krobot KJ.. Consequences and Costs of NSAID-Induced Gastropathy in Germany. Aktuelle Rheumatologie 1999; 24: 127-34.
    Article in Thieme ConnectGoogle Scholar
  • 8 Bombardier C., Laine L., Reicin A.. et al Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group. N Engl J Med 2000; 343 (21) 1520-8.
    CrossrefPubMedGoogle Scholar
  • 9 Brune K., Dietzel K., Nurnberg B., Schneider HT.. Recent insight into the mechanism of gastrointestinal tract ulceration. Scand J Rheumatol Suppl 1987; 65: 135-40.
    Google Scholar
  • 10 Brune K., Schweitzer A., Eckert H.. Parietal cells of the stomach trap salicylates during absorption. Biochem Pharmacol 1977; 26 (18) 1735-40.
    CrossrefPubMedGoogle Scholar
  • 11 Choi VM., Coates JE., Chooi J.. et al Small bowel permeability – a variable effect of NSAIDS. Clin Invest Med 1995; 18 (05) 357-61.
    PubMedGoogle Scholar
  • 12 Davies NM.. Sustained release and enteric coated NSAIDs: are they really GI safe. J Pharm Pharm Sci 1999; 2 (01) 5-14.
    Google Scholar
  • 13 Davies NM., Saleh JY., Skjodt NM.. Detection and prevention of NSAID-induced enteropathy. J Pharm Pharm Sci 2000; 3 (01) 137-155.
    Google Scholar
  • 14 Dawson J., Linsell L., Zondervan K.. et al Epidemiology of hip and knee pain and its impact on overall health status in older adults. Rheumatology (Oxford) 2004; 43 (04) 497-504.
    CrossrefPubMedGoogle Scholar
  • 15 Day TK.. Intestinal perforation associated with osmotic slow release indomethacin capsules. Br Med J (Clin Res Ed) 1983; 287 6406 1671-2.
    PubMedGoogle Scholar
  • 16 Gesundheitsberichterstattung des Bunde. Stuttgart: Metzler-Poeschel, Statistisches Bun-desamt W; 1998: 144.
    Google Scholar
  • 17 Graham DY., Agrawal NM., Roth SH.. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial. Lancet 1988; 2 8623 1277-80.
    PubMedGoogle Scholar
  • 18 Griffin MR., Piper JM., Daugherty JR.. et al Nonsteroidal anti-inflammatory drug use and increased risk for peptic ulcer disease in elderly persons. Ann Intern Med 1991; 114 (04) 257-63.
    CrossrefPubMedGoogle Scholar
  • 19 Griffin MR., Smalley WE.. Drugs and ulcers: clues about mucosal protection from epidemiologic studies. J Clin Gastroenterol 1995; 21 (Suppl. 01) Suppl S113-9.
    PubMedGoogle Scholar
  • 20 Hawkey C., Laine L., Simon T.. et al Comparison of the effect of rofecoxib (a cyclooxygenase 2 inhibitor), ibuprofen, and placebo on the gastroduodenal mucosa of patients with osteoarthritis: a randomized, double-blind, placebo-controlled trial. The Rofecoxib Osteoarthritis Endoscopy Multinational Study Group. Arthritis Rheum 2000; 43 (02) 370-7.
    CrossrefPubMedGoogle Scholar
  • 21 Hoftiezer JW., O’Laughlin JC., Ivey KJ.. Effects of 24 hours of aspirin, Bufferin, paracetamol and placebo on normal human gastroduodenal mucosa. Gut 1982; 23 (08) 692-7.
    CrossrefPubMedGoogle Scholar
  • 22 Hoftiezer JW., Silvoso GR., Burks M., Ivey KJ.. Comparison of the effects of regular and enteric-coated aspirin on gastroduodenal mucosa of man. Lancet 1980; 2 8195 pt 1 609-12.
    PubMedGoogle Scholar
  • 23 Jordan KM., Arden NK., Doherty M.. et al EULAR Recommendations 2003; an evidence based approach to the management of knee osteoarthritis: Report of a Task Force of the Standing Committee for International Clinical Studies Including Therapeutic Trials (ESCI-SIT). Ann Rheum Dis 2003; 62 (12) 1145-55.
    CrossrefPubMedGoogle Scholar
  • 24 Lanas A., Sekar MC., Hirschowitz I B.. Objective evidence of aspirin use in both ulcer and nonulcer upper and lower gastrointestinal bleeding. Gastroenterology 1992; 103 (03) 862-9.
    CrossrefPubMedGoogle Scholar
  • 25 Lanza FL., Rack MF., Simon TJ.. et al Specific inhibition of cyclooxygenase-2 with MK-0966 is associated with less gastroduodenal damage than either aspirin or ibuprofen. Aliment Pharmacol Ther 1999; 13 (06) 761-767.
    CrossrefPubMedGoogle Scholar
  • 26 Lanza FL., Royer Jr. GL., Nelson RS.. Endoscopic evaluation of the effects of aspirin, buffered aspirin, and enteric-coated aspirin on gastric and duodenal mucosa. N Engl J Med 1980; 303 (03) 136-8.
    CrossrefPubMedGoogle Scholar
  • 27 Lichtenberger LM., Wang ZM., Romero JJ.. et al Non-steroidal anti-inflammatory drugs (NSAIDs) associate with zwitterionic phospho-lipids: insight into the mechanism and reversal of NSAID-induced gastrointestinal injury. Nat Med 1995; 1 (02) 154-8.
    CrossrefPubMedGoogle Scholar
  • 28 Ligumsky M., Golanska EM., Hansen DG., Kauffman Jr GL.. Aspirin can inhibit gastric mucosal cyclooxygenase without causing lesions in rat. Gastroenterology 1983; 84 (04) 756-61.
    PubMedGoogle Scholar
  • 29 Mahmud T., Rafi SS., Scott DL.. et al Nonsteroidal antiinflammatory drugs and uncoupling of mitochondrial oxidative phosphorylation. Arthritis Rheum 1996; 39 (12) 1998-2003.
    CrossrefPubMedGoogle Scholar
  • 30 Masferrer JL., Seibert K., Zweifel B., Needleman P.. Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme. Proc Natl Acad Sci U S A 1992; 89 (09) 3917-21.
    CrossrefPubMedGoogle Scholar
  • 31 Masferrer JL., Zweifel BS., Seibert K., Needle-man P.. Selective regulation of cellular cyclooxygenase by dexamethasone and endotoxin in mice. J Clin Invest 1990; 86 (04) 1375-9.
    CrossrefPubMedGoogle Scholar
  • 32 Piper JM., Ray WA., Daugherty JR., Griffin MR.. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med 1991; 114 (09) 735-40.
    CrossrefPubMedGoogle Scholar
  • 33 Redfern JS., Feldman M.. Role of endogenous prostaglandins in preventing gastrointestinal ulceration: induction of ulcers by antibodies to prostaglandins. Gastroenterology 1989; 96 2 Pt 2 Suppl 596-605.
    CrossrefPubMedGoogle Scholar
  • 34 Savon JJ., Allen ML., DiMarino Jr. AJ.. et al Gastrointestinal blood loss with low dose (325 mg) plain and enteric-coated aspirin administration. Am J Gastroenterol 1995; 90 (04) 581-5.
    Google Scholar
  • 35 Schwartz K.. Über penetrierende Magenund Jejunalgeschwüre. Beitr Klin Chir 1910; 76: 96-128.
    Google Scholar
  • 36 Sigthorsson G., Simpson RJ., Walley M.. et al COX-1 and 2, intestinal integrity, and pathogenesis of nonsteroidal anti-inflammatory drug enteropathy in mice. Gastroenterology 2002; 122 (07) 1913-23.
    CrossrefPubMedGoogle Scholar
  • 37 Silverstein FE., Faich G., Goldstein JL.. et al Gastrointestinal toxicity with celecoxib vs non-steroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study. JAMA 2000; 284 (10) 1247-55.
    CrossrefPubMedGoogle Scholar
  • 38 Silverstein FE., Graham DY., Senior JR.. et al Mi-soprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs. A randomized, double-blind, placebo-controlled trial. Ann Intern Med 1995; 123 (04) 241-9.
    CrossrefPubMedGoogle Scholar
  • 39 Silvoso GR., Ivey KJ., Butt JH.. et al Incidence of gastric lesions in patients with rheumatic disease on chronic aspirin therapy. Ann Intern Med 1979; 91 (04) 517-20.
    CrossrefPubMedGoogle Scholar
  • 40 Simon LS., Weaver AL., Graham DY.. et al. Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a ran-domized controlled trial. JAMA 1999; 282 (20) 1921-8.
    CrossrefPubMedGoogle Scholar
  • 41 Soll AH., Weinstein WM., Kurata J., McCarthy D.. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med 1991; 114 (04) 307-19.
    CrossrefPubMedGoogle Scholar
  • 42 Trondstad I R., Aadland E., Holler T., Olaussen B.. Gastroscopic findings after treatment with enteric-coated and plain naproxen tablets in healthy subjects. Scand J Gastroenterol 1985; 20 (02) 239-42.
    CrossrefPubMedGoogle Scholar
  • 43 Vane JR.. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol 1971; 231 (25) 232-5.
    CrossrefPubMedGoogle Scholar
  • 44 Vane J.. Towards a better aspirin. Nature 1994; 367 6460 215-6.
    CrossrefPubMedGoogle Scholar
  • 45 Wallace JL.. Nonsteroidal anti-inflammatory drugs and gastroenteropathy: the second hundred years. Gastroenterology 1997; 112 (03) 1000-16.
    CrossrefPubMedGoogle Scholar
  • 46 Warner TD., Giuliano F., Vojnovic I.. et al Non-steroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: a full in vitro analysis. Proc Natl Acad Sci U S A 1999; 96 (13) 7563-8.
    CrossrefPubMedGoogle Scholar
  • 47 Whittle BJ.. Unwanted effects of aspirin and related agents on the gastrointestinal trac. In Vane JR., Botting RM.. Editors Aspirin and Other Salicylates.. London: Chapman and Hall Medical; 1992: 465-509.
    Google Scholar
  • 48 Wright MR., Davies NM., Jamali F.. Toxicokinetics of indomethacin-induced intestinal permeability in the rat. Pharmacol Res 1997; 35 (06) 499-504.
    CrossrefPubMedGoogle Scholar