Notfälle durch unerwünschte Arzneimittelwirkungen

Zusammenfassung

Durch die Fortschritte der Pharmakotherapie können Prognose der rheumatischen Erkrankungen und Lebensqualität der Betroffenen entscheidend verbessert werden. Dieser Erfolg wird gelegentlich durch unerwünschte Arzneimittelwirkungen erkauft, so dass eine Nutzen-Risiko-Abwägung zwingend ist. Aus der Vielzahl der unerwünschten Arzneimittelwirkungen im Praxisalltag werden bedeutsame Notfallsituationen ausgewählt. Im Vordergrund steht die NSA-induzierte Gastropathie. Die jährliche Inzidenz klinisch bedeutsamer gastrointestinaler Komplikationen unter NSA liegt bei ca. 2 %. Risikoprofil und Möglichkeiten zur Ausschaltung der NSA-Gastropathie werden dargestellt. Die Niere ist das zweithäufigste Zielorgan der NSA-Schädigung. Ca. 3 % aller Fälle akuten Nierenversagens werden auf NSA zurückgeführt. Infektionen gehören zu den Hauptursachen der Mortalität der Patienten mit entzündlich-rheumatischen Erkrankungen. Sie sind überwiegend der immunsuppressiven Therapie anzulasten. Kortikosteroide, Disease Modifying Antirheumatic Drugs und Biologikals erhöhen das Infektionsrisiko sowohl für bakterielle Infektionen als auch für opportunistische Infektionen deutlich. Hämatologische Komplikationen können durch direkte antiproliferative Wirkung auf das Knochenmark, aber auch Antikörper vermittelt auftreten.

Emergencies due to Drug-Related Adverse Effects

New developments of pharmacological therapies promote fundamental improvements in respect of prognosis and quality of life in rheumatic diseases. This progress is sometimes associated with pharmacological side effects, necessitating a risk-benefit analysis. In the following, we deal with a few important emergency situations selected from the multitude of possible adverse events in daily practice. Emphasis is, first of all, on NSAID-induced gastropathy. The annual incidence of clinically relevant gastrointestinal complications during NSAID therapy is approximately 2 %. The risk factors and the possibilities of avoiding NSAID-induced gastropathy are described. The kidney is the second most important organ impaired by NSAIDs. About 3 % of all cases with acute renal failure are due to NSAIDs. Infections are part of the main reasons for the mortality of patients with inflammatory rheumatic diseases. They are predominantly due to immunosuppressive therapy. Corticosteroids, disease-modifying antirheumatic drugs and biologicals markedly enhance the risk both for bacterial and opportunistic infections. Haematological complications can occur due to direct antiproliferative effects on bone marrow, but may also be due to antibodies.

Literatur

• 1 Anderson G, Coles E, Crane M, Douglas A C, Gibbs A R, Geddes D M. et al . Wegener’s granulomatosis: a series of 265 British cases seen between 1975 and 1985. A report by a sub-committee of the British Thoracic Society Research Committee.  QMJ. 1992;  83 427-438
• 2 Avorn J, Solomon D, Levin R, Lo J. Epidemiologic analysis of prophylactic drug use and NSAID gastropathy.  Arthritis Rheum. 1996;  39 165
• 3 Berthelot J M, Maugars Y, Hamidou M, Chiffoleau A, Barrier J, Grolleau J Y, Prost A. Pancytopenia and severe cytopenia induced by low-dose methotrexate: eight reports and a review of one hundred cases from the literature (with twenty-four deaths).  Rev Rheum Engl Ed. 1995;  62 477-486
• 4 Boerbooms A MT, Kerstens P J, van Loenhout J W, Mulder J, van de Putte L B. Infections during low-dose methotrexate treatment in rheumatoid arthritis.  Semin Arthritis Rheum. 1995;  24 411-421
• 5 Bolten W W, Lang B, Wagner A V, Krobot K J. Konsequenzen und Kosten der NSA-Gastropathie in Deutschland.  Akt Rheumatol. 1999;  24 127-134
• 6 Bombardier C, Laine L, Reicin A, Shapiro D, Burgos-Vargas R . et al . Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis.  New Engl J Med. 2000;  343 1520-1528
• 7 Dale D C, Fauci A S, Wolff S M. Alternate-day prednisone. Leukocyte kinetics and susceptibility to infections.  N Engl J Med. 1974;  291 1154-1158
• 8 Deutsche Gesellschaft für Rheumatologie: .Empfehlungen der Deutschen Gesellschaft für Rheumatologie zur Therapie mit Tumornekrosefaktor-hemmenden Substanzen. 
• 9 Emery P, Zeidler H, Kvien K T. et al . Celecoxib vesus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison.  Lancet. 1999;  354 2106-2111
• 10 Fauci A S, Dale D C, Balow J E. Glucocorticoidtherapie: mechanisms of action and clinical considerations.  Ann Intern Med. 1976;  84 304-315
• 11 Fu J Y, Masferrer J L, Seibert K, Raz A, Needlemann P. The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes.  J Biol Chem. 1990;  265 16 737-16 740
• 12 Genth E, Gromnica-Ihle E, Häntzschel H . et al .Qualitätssicherung in der Rheumatologie. Darmstadt; Steinkopff 1999
• 13 Gierse J, McDonald J, Hauser S, Rangwala S, Seibert K. A single amino acid difference between cyclooxygenase-1 (COX-1) and -2 (COX-2) reverses the selectivity of COX-2 specific inhibitors.  J Biol Chem. 1996;  271 15 810-15 814
• 14 Guillevin L, Cordier J F, Lhote F, Cohen P, Jarrousse B, Royer I . et al . A prospective, multicenter, randomized trial comparing steroids and pulse cyclophosphamide versus steroids and oral cyclophosphamide in the treatment of generalized Wegener’s granulomatosis.  Arthritis Rheum. 1997;  40 2187-2198
• 15 Gutierrez-Urena S, Molina J F, Garcia C O, Cuellar M L, Espinoza L R. Pancytopenia secondary to methotrexate therapy in rheumatoid arthritis.  Arthritis Rheum. 1996;  39 272-276
• 16 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, placeto-controlled trial.  Arthritis Rheum. 2000;  43 370-377
• 17 Hawkey C J, Jeffrey A K, Szczepanski L . et al . A comparison of omeprazole and misoprostol for treating and preventing ulcers associated with non-steroidal anti-inflammatory drugs.  N Engl J Med. 1998;  338 727-734
• 18 Hellmann D B, Petri M, Whiting-O’Keefe Q. Fatal infections in systemic lupus erythematosus: The role of opportunistic infections.  Medicine. 1987;  66 341
• 19 Hoffman G S, Kerr G S, Leavitt R Y . et al . Wegener’s granulomatosis: an analysis of 158 patients.  Ann Intern Med. 1992;  116 488-498
• 20 Jick H, Myers M W, Dean A D. The risk of sulfasalazine- and mesalamine-associated blood disorders.  Pharmacotherapie. 1995;  15 176-181
• 21 Keisu M, Ekman E. Sulfasalazine associated agranulocytosis in Sweden 1972-1989: Clinical features and estimation of its incidence.  Eur J Clin Pharmacol. 1992;  43 215-218
• 22 Kim H A, Yoo C D, Baek H J . et al . Mycobacterium tuberculosis infection in a corticosteroid-treated rheumatic disease patient population.  Clin Exp Rheum. 1998;  16 9-13
• 23 van der Klauw M M, Goudsmit R, Halie M R . et al . A population-based case-cohort study of drug-associated agranulocytosis.  Arch Intern Med. 1999;  159 369-374
• 24 Kremer J M. Major side effects of methotrexate.  UpToDate®. 2000;  8 2
• 25 Krynetski E Y, Tai H L, Yates C R, Fessing M Y, Loennechen T, Schuetz J D, Relling M V, Evans W E. Genetic polymorphism of thiopurine S-methyltransferase: clinical importance and molecular mechanism.  Pharmacogenetics. 1996;  6 279-290
• 26 Laine L, Harper S, Simon T . et al . A randomized trial comparing the effect of rofecoxib, a cyclooxygenase 2-specific inhibitor, with that of ibuprofen on the gastroduodenal mucosa of patients with osteoarthritis.  Gastroenterology. 1999;  117 776-783
• 27 Laine L. Nonsteroidal anti-inflammatory drug gastropathy.  Gastro-intest Endosc Clin North Am. 1996;  6 489-504
• 28 Langman M J, Jensen D M, Watson D J . et al . Adverse upper gastrointestinal effects of rofecoxib compared with NSAIDs.  JAMA. 1999;  282 1929-1933
• 29 Maini R N, Breedveld F C, Kalden J R . et al . Therapeutic efficacy of multiple intravenous infusion of anti-tumor necrosis factor monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.  Arthritis Rheum. 1998;  41 1552-1563
• 30 Matteson E L, Gold K N, Bloch D A, Hunder G G. Long-term survival of patients with Wegener’s granulomatosis from the American College of Rheumatology Wegener’s granulomatosis criteria cohort.  Am J Med. 1996;  101 129-134
• 31 Millar J W, Horne N W. Tuberculosis in immunosuppressed patients.  Lancet. 1979;  1 1176-1178
• 32 Mizuno H, Sakamoto C, Matsuda K, Wada K, Uchida T, Noguchi H, Akamatsu T, Kasuga M. Induction of cyclooxygenase 2 in gastric mucosal lesions and its inhibition by the specific antagonist delays healing in mice.  Gastroenterology. 1997;  112 387-397
• 33 Myllykangas-Luosujarvi R, Aho K, Isomäki H. Death attributed to antirheumatic medication in a nationwide series of 1666 patients with rheumatoid arthritis who have died.  J Rheumatol. 1995;  22 2214-2217
• 34 Rau R. Methotrexat. In: Rau R (Hrsg) Basistherapie der rheumatoiden Arthritis. Bremen; Uni-Med 2000: 184-207
• 35 Reinhold-Keller E, Beuge N, Latza U, de Groot K, Rudert H, Nölle B, Heller M, Gross W L. An interdisciplinary approach to the care of patients with Wegener’s granulomatosis: Long-term outcome in 155 patients.  Arthritis Rheum. 2000;  43 1021-1032
• 36 Segal B H, Sneller M C. Infectious complications of immunsuppressive therapy in patients with rheumatic diseases.  Rheum Dis Clin North Am. 1997;  23 219-237
• 37 Shoenfeld Y, Gurewich Y, Gallant L A . et al . Prednisone-induced leukocytosis. Influence of dosage, method, and duration of administration on the degree of leukocytosis.  Am J Med. 1981;  71 773-778
• 38 Silverstein F E, Faich G, Goldstein J L, Simon L S, Pincus T . et al . Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis. The class study: A randomised controlled trial.  JAMA. 2000;  284 1247-1255
• 39 Silverstein F E, Graham D Y, Senior J R. et al . Misoprostol reduces serious gastrointestinal complications in patients with rheumatoid arthritis receiving nonsteroidal anti-inflammatory drugs: a randomised, double-blind, placebo-controlled trial.  Ann Intern Med. 1995;  123 241-249
• 40 Simon L S, Weaver A L, Graham D Y . et al . Anti-inflammatory and upper gastrointestinal effects of celecoxib in rheumatoid arthritis: a randomized controlled trial.  JAMA. 1999;  282 1921-1928
• 41 Singh G, Fries J F, Williams C A, Zatarain E, Spitz P, Bloch D A. Toxicity profiles of disease-modifying antirheumatic drugs in rheumatoid arthritis.  J Rheumatol. 1991;  18 188-194
• 42 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 oberservational cohort study.  Arch Intern Med. 1996;  156 1530-1536
• 43 Singh G, Triadafilopoulos G. Epidemiology of NSAID-induced GI complications.  J Rheumatol. 1999;  26 18-24
• 44 Singh G. Recent considerations in non-steroidal anti-inflammatory drug gastropathy.  Am J Med. 1998;  105 31-38
• 45 Skogberg K, Ruutu P, Tukiainen P, Valtonen V. Effect of immunosuppressive therapy on the clinical presentation and outcome of tuberculosis.  Clin Infect Dis. 1993;  17 1012-1017
• 46 Stuck A E, Minder C e, Frey J F. Risk of infectious complications in patients taking glucocorticosteroids.  Rev Infect Dis. 1989;  11 954-963
• 47 Swan S K, Rudy D W, Lasseter K D . et al . Effect of cyclooxygenase-2 inhibition on renal function in elderly persons receiving a low-salt diet.  Ann Intern Med. 2000;  133 1-9
• 48 Thomas M H, Gutterman L A. Methotrexate toxicity in a patient receiving trimethoprim-sulfamethoxazole.  J Rheumatol. 1986;  13 440-441
• 49 Vreugdenhil G, Schattenberg A, Dompeling E C . et al . Hematopoietic growth factors in rheumatoid arthritis: A critical approach to their use in view of possible adverse effects.  Am J Med. 1993;  94 229-230
• 50 Wallace J L, Bak A, McKnight W, Asfaha S, Sharkey K A, MacNaughton W K. Cyclooxygenase 1 contributes to inflammatory responses in rats and mice: implications for gastrointestinal toxicity.  Gastroenterology. 1998;  115 101-109
• 51 Ward M M, Donald F. Pneumocystis carinii pneumonia in patients with connective tissue disease: The role of hospital experience in diagnosis and mortality.  Arthritis Rheum. 1999;  42 780-789
• 52 Warner T D, Giuliano F, Vojnovic I, Bukasa J A, Mitchell J A, Vane J R. Nonsteroid 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 USA. 1999;  96 7563-7568
• 53 Wolfe M M, Lichtenstein D R. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs.  New Engl J Med. 1999;  340 1888-1899
• 54 Yeomans N D, Tulassay Z, Juhasz L, Raacz I, Howard J M, van Rensburg C J, Swannell A J, Hawkey C J. A comparison of omeprazole and ranitidine for treating and preventing ulcers associated with non-steroid anti-inflammatory drugs.  N Engl J Med. 1998;  338 719-726