Schmerztherapie mit selektiven und nichtselektiven Cyclooxygenaseinhibitoren in der Rheumatologie

Zusammenfassung

Nichtselektive und selektive Cyclooxygenaseinhibitoren (Coxibe) sind potente Analgetika und Antiphlogistika und werden erfolgreich bei der Therapie degenerativer und entzündlich-rheumatischer Gelenkerkrankungen eingesetzt. Traditionelle NSAR und Coxibe unterscheiden sich dabei nicht wesentlich in der analgetischen Potenz. Bei der Wahl dieser Prostaglandinsynthesehemmer sollte jedoch eine individuelle patientenorientierte Nutzen-Risiko-Abwägung erfolgen. Kardiovaskuläre und gastrointestinale Risikofaktoren sind dabei für eine differenzialtherapeutische Entscheidung von großer Bedeutung. Bei Patienten mit beiden Risikokonstellationen, Herzinsuffizienz, Leberzirrhose oder renalen Erkrankungen sollte auf eine Behandlung mit COX-Inhibitoren verzichtet und Analgetika anderer Substanzklassen eingesetzt werden. Mithilfe von Studien muss in Zukunft eine individuelle, auf den Patienten zugeschnittene, Evidenz-basierte Therapie und damit ein Konzept zum differenzialtherapeutischen Einsatz der nichtselektiven und selektiven COX-Hemmer in der Rheumatologie entwickelt werden.

Abstract

Non-selective and selective Cyclooxygenase inhibitors (coxibs) are potent analgesics and antiphlogistics and are successfully used in treatment of degenerative and inflammatory joint diseases. Traditional non-steroid anti-inflammatory drugs (NSAID) do not differ from coxibs in their analgesic effects. Physicians should analyse the risks and benefits of prescribing inhibitors of prostaglandin synthesis for each individual patient, especially focusing on both the gastrointestinal and cardiovascular risks. Patients with both risks, heart failure and liver cirrhosis or renal diseases should not be treated with COX-inhibitors. Other analgesic agents should be chosen. Studies must clarify which therapy is appropriate for individual patients to develop an evidence-based concept for the differential use of traditional NSAID and coxibs in rheumatology.

Schlüsselwörter

Cyclooxygenaseinhibitoren - Coxibe - NSAR - Schmerz

Key words

cyclooxygenase inhibitors - coxibs - NSAID - pain

Literatur

• 1 Kneitz C, Tony HP, Krüger K. NSAIDs and COX-2-inhibitors: current status.  Internist (Berl). 2006;  47 533-534 536–538, 540
• 2 Vane JR. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs.  Nat New Biol. 1971;  231 232-235
• 3 Meade EA, Smith WL, DeWitt DL. Differential inhibition of prostaglandin endoperoxide synthase (cyclooxygenase) isozymes by aspirin and other non-steroidal anti-inflammatory drugs.  J Biol Chem. 1993;  268 6610-6614
• 4 Laine L, White WB, Rostom A. et al . COX-2 selective inhibitors in the treatment of osteoarthritis.  Semin Arthritis Rheum. 2008;  38 165-187
• 5 Simon LS, Weaver AL, Graham DY. et al . Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial.  JAMA. 1999;  282 1921-1928
• 6 Shi W, Wang YM, Li LS. et al . Safety and efficacy of oral nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis: a six-month randomised study.  Clin Drug Investig. 2004;  24 89-101
• 7 Matsumoto AK, Melian A, Mandel DR. et al . A randomized, controlled, clinical trial of etoricoxib in the treatment of rheumatoid arthritis.  J Rheumatol. 2002;  29 1623-1630
• 8 Aringer M. Cyclooxygenase 2 selective antirheumatic analgesics.  Wien Med Wochenschr. 2003;  153 100-103
• 9 Schumacher Jr HR, Boice JA, Daikh DI. et al . Randomised double blind trial of etoricoxib and indometacin in treatment of acute gouty arthritis.  BMJ. 2002;  324 1488-1492
• 10 Navarra S, Rubin BR, Yu Q. et al . Association of baseline disease and patient characteristics with response to etoricoxib and indomethacin for acute gout.  Curr Med Res Opin. 2007;  23 1685-1691
• 11 van der Linden S. Issues in the treatment of ankylosing spondylitis with non-steroidal anti-inflammatory drugs.  Wien Med Wochenschr. 2008;  158 195-199
• 12 Feldtkeller E, Hammel L, Kellner H. Distribution of Disease Activity and Drug Use in Ankylosing Spondylitis.  Akt Rheumatol. 2005;  30 223-231
• 13 Wanders A, Heijde D, Landewe R. et al . Nonsteroidal anti-inflammatory drugs reduce radiographic progression in patients with ankylosing spondylitis: a randomized clinical trial.  Arthritis Rheum. 2005;  52 1756-1765
• 14 Shi S, Klotz U. Clinical use and pharmacological properties of selective COX-2 inhibitors.  Eur J Clin Pharmacol. 2008;  64 233-252
• 15 Rintelen B, Sautner J, Herold M. et al . Recommendations for NSAID Therapy-First Experience with a Delphi Process among Austrian Rheumatologists.  Akt Rheumatol. 2007;  32 255-261
• 16 West PM, Fernandez C. Safety of COX-2 inhibitors in asthma patients with aspirin hypersensitivity.  Ann Pharmacother. 2003;  37 1497-1501
• 17 Vonkeman HE, van de Laar MA. Nonsteroidal Anti-Inflammatory Drugs: Adverse Effects and Their Prevention.  Semin Arthritis Rheum. 2010;  39 294-312
• 18 Krum H, Curtis SP, Kaur A. et al . Baseline factors associated with congestive heart failure in patients receiving etoricoxib or diclofenac: multivariate analysis of the MEDAL program.  Eur J Heart Fail. 2009;  11 542-550
• 19 Simon LS, Grierson LM, Naseer Z. et al . Efficacy and safety of topical diclofenac containing dimethyl sulfoxide (DMSO) compared with those of topical placebo, DMSO vehicle and oral diclofenac for knee osteoarthritis.  Pain. 2009;  143 238-245
• 20 Barthel HR, Haselwood D, Longley 3rd S. et al . Randomized controlled trial of diclofenac sodium gel in knee osteoarthritis.  Semin Arthritis Rheum. 2009;  39 203-212
• 21 Miyatake S, Ichiyama H, Kondo E. et al . Randomized clinical comparisons of diclofenac concentration in the soft tissues and blood plasma between topical and oral applications.  Br J Clin Pharmacol. 2009;  67 125-129
• 22 Laine L. Approaches to nonsteroidal anti-inflammatory drug use in the high-risk patient.  Gastroenterology. 2001;  120 594-606
• 23 Rahme E, Nedjar H. Risks and benefits of COX-2 inhibitors vs. non-selective NSAIDs: does their cardiovascular risk exceed their gastrointestinal benefit? A retrospective cohort study.  Rheumatology (Oxford). 2007;  46 435-438
• 24 Farkouh ME, Greenberg BP. An evidence-based review of the cardiovascular risks of nonsteroidal anti-inflammatory drugs.  Am J Cardiol. 2009;  103 1227-1237
• 25 Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs.  Lancet. 1994;  343 769-772
• 26 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 1520-1528 1522 p following 1528
• 27 Schnitzer TJ, Beier J, Geusens P. et al . Efficacy and safety of 4 doses of lumiracoxib versus diclofenac in patients with knee or hip primary osteoarthritis: a phase II, 4-week, multicenter, randomized, double-blind, placebo-controlled trial.  Arthritis Rheum. 2004;  51 549-557
• 28 Schnitzer TJ, Burmester GR, Mysler E. et al . Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), reduction in ulcer complications: randomised controlled trial.  Lancet. 2004;  364 665-674
• 29 Silverstein FE, Faich G, Goldstein JL. et al . Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial Celecoxib Long-term Arthritis Safety Study.  JAMA. 2000;  284 1247-1255
• 30 Chan FK, Hung LC, Suen BY. et al . Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis.  N Engl J Med. 2002;  347 2104-2110
• 31 Vonkeman HE, Brouwers JR, van de Laar MA. Understanding the NSAID related risk of vascular events.  BMJ. 2006;  332 895-898
• 32 Kearney PM, 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. 2006;  332 1302-1308
• 33 Cannon CP, Curtis SP, FitzGerald GA. et al . Cardiovascular outcomes with etoricoxib and diclofenac in patients with osteoarthritis and rheumatoid arthritis in the Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) programme: a randomised comparison.  Lancet. 2006;  368 1771-1781
• 34 Scott PA, Kingsley GH, Smith CM. et al . Non-steroidal anti-inflammatory drugs and myocardial infarctions: comparative systematic review of evidence from observational studies and randomised controlled trials.  Ann Rheum Dis. 2007;  66 1296-1304
• 35 Farkouh ME, Kirshner H, Harrington RA. et al . Comparison of lumiracoxib with naproxen and ibuprofen in the Therapeutic Arthritis Research and Gastrointestinal Event Trial (TARGET), cardiovascular outcomes: randomised controlled trial.  Lancet. 2004;  364 675-684
• 36 Roumie CL, Choma NN, Kaltenbach L. et al . Non-aspirin NSAIDs, cyclooxygenase-2 inhibitors and risk for cardiovascular events – stroke, acute myocardial infarction, and death from coronary heart disease.  Pharmacoepidemiol Drug Saf. 2009;  18 1053-1063
• 37 Fosbol EL, Gislason GH, Jacobsen S. et al . Risk of myocardial infarction and death associated with the use of nonsteroidal anti-inflammatory drugs (NSAIDs) among healthy individuals: a nationwide cohort study.  Clin Pharmacol Ther. 2009;  85 190-197
• 38 MacDonald TM, Wei L. Effect of ibuprofen on cardioprotective effect of aspirin.  Lancet. 2003;  361 573-574
• 39 Krum H, Swergold G, Curtis SP. et al . Factors associated with blood pressure changes in patients receiving diclofenac or etoricoxib: results from the MEDAL study.  J Hypertens. 2009;  27 886-893
• 40 Solomon DH, Schneeweiss S, Levin R. et al . Relationship between COX-2 specific inhibitors and hypertension.  Hypertension. 2004;  44 140-145
• 41 Rubenstein JH, Laine L. Systematic review: the hepatotoxicity of non-steroidal anti-inflammatory drugs.  Aliment Pharmacol Ther. 2004;  20 373-380
• 42 Wallace JL, Viappiani S, Bolla M. Cyclooxygenase-inhibiting nitric oxide donators for osteoarthritis.  Trends Pharmacol Sci. 2009;  30 112-117
• 43 Karlsson J, Pivodic A, Aguirre D. et al . Efficacy, safety, and tolerability of the cyclooxygenase-inhibiting nitric oxide donator naproxcinod in treating osteoarthritis of the hip or knee.  J Rheumatol. 2009;  36 1290-1297
• 44 White WB, Schnitzer TJ, Fleming R. et al . Effects of the cyclooxygenase inhibiting nitric oxide donator naproxcinod versus naproxen on systemic blood pressure in patients with osteoarthritis.  Am J Cardiol. 2009;  104 840-845

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