Anästhesiol Intensivmed Notfallmed Schmerzther 2000; 35(11): 677-684
DOI: 10.1055/s-2000-8161
ÜBERSICHT
ORIGINALIA
© Georg Thieme Verlag Stuttgart · New York

Nicht-Opioid-Analgetika - unersetzlich in der Tumorschmerztherapie?

E. Ladner1 , R. Plattner1 , B. Friesenecker2 , J. Berger2 , F. Javorsky3
  • 1Abteilung für Anästhesie, Bezirkskrankenhaus Reutte
  • 2Univ.-Klinik für Anästhesie und Allgemeine Intensivmedizin, Leopold-Franzens-Universität Innsbruck
  • 3Abt. für Anästhesie und Intensivmedizin, SMZ Ost Wien
Further Information

Publication History

Publication Date:
31 December 2000 (online)

Zusammenfassung.

Eine ausreichende Therapie der Schmerzen hat für Tumorpatienten höchste Priorität. WHO-Richtlinien schlagen eine - in der deutschsprachigen Literatur obligate - Kombination von Opioiden mit Nichtopioid-Analgetika (NOA) für Patienten mit mittleren bis starken Schmerzen vor. Tumorschmerzen können durch den Tumor selbst verursacht, tumorassoziiert, therapiebedingt sowie therapieunabhängig sein, und nur durch eine Kombinationstherapie von Opioiden mit NOA, wie den Cyclooxygenase-Inhibitoren (nicht-steroidalen Antirheumatika = NSAR) beherrscht werden. Eine Kombination von Opioiden mit Nichtopioidanalgetika bringt, unter Wahrung von Vorsichtsmaßnahmen, eine bessere Effizienz bei akzeptablem Risikoprofil.

Non-opioid-analgesics - irreplaceable in cancer pain therapy?

Sufficient therapy of pain is essential for the treatment of tumor patients. World Health Organisation (WHO)-guidelines recommend a combination of opioids with non-opioid-analgesics (NOA) for patients with medium to strong pain. Cancer pain is often a combination of pain caused by the tumor itself, tumor associated and pain caused by therapy. Various substances act by different mechanisms and therefore combinations may demonstrate superior effects. Opioids („central analgesics”) inhibit neuronal transduction within the spinal cord, enhance inhibiting function of midbrain nuclei on ascending pain transduction and influence pain perception via modulation of the limbic system. NOAs („peripheral analgesics”) inhibit cyclooxygenase hindering activation of the peripheral nociceptorsystem. There are 2 different classes of NOAs: 1) non-acidic, antipyretic analgesics like pyrazolones (metamizol) and anilin-derivates (paracetamol) and 2) non-steroidal antirheumatics (NSAR) like salicylates (acetylsalicylic acid), derivates of propionic acid (ibuprofen, naproxen), acetate acid (indomethacin, diclofenac), enolic acid (piroxicam, meloxicam) and anthranil acid (mefenamin). Adjuvant therapy is necessary to control common NSAR-side-effects like dyspepsia, ulcer and gastrointestinal bleeding. Due to its exceptional analgesic, antipyretic and spasmolytic properties, metamizol is an essential substance in tumor therapy. As agranulocytosis-incidence of 1:1.000.000 is low, good gastrointestinal and renal tolerance makes metamizol an excellent alternative to NSAR. There is scientific evidence that adequate combinations of non-opioids, opioids and adjuvant drugs, considering adverse side effects, were effective and safe in the treatment of cancer pain.

Literaturverzeichnis

  • 1 Agrawal N M, Roth S, Graham D Y. 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
  • 2 Alpermann H G, Scholtholt J. Pharmacology of dipyrone. Internal Report Hoechst AG, Pharma Research, Pharmacology, Document No.: 002 601 Nov./1982: F1-F36
  • 3 Arisz L, Donker A JM, Brentjens J RH, van der Hem G K. The effect of indomethacin on proteinuria and kidney function in the nephrotic syndrome.  Acta Med Scand. 1976;  199 121
  • 4 Armstrong C P, Blower A L. Non-steroidal anti-inflammatory drugs and life threatening complications of peptic ulceration.  Gut. 1987;  28 527
  • 5 Bannwarth B, Demotes-Mainard F, Schaeverbeke T, Labat L, Derhaus J. Central analgesic effect of aspirin-like drugs.  Fundam Clin Pharmacol. 1995;  9 1
  • 6 Bardhan K D, Bjarnason I, Scott D L. The prevention and healing of acute nonsteroidal anti-inflammatory drug-associated gastroduodenal mucosal damage by misoprostol.  Br J Rheum. 1993;  32 990
  • 7 Beckmann M L, Gerber J G, Bynny R L. Propanolol increases prostacyclin synthesis in patients with hypertension.  Hypertension. 1988;  12 582
  • 8 Bigard M A. Complete prevention by omeprazole of aspirin induced gastric lesions in healthy subjects [abstract].  Gastroenterology. 1988;  94 A34
  • 9 Bolton W, Brodenfeldt R. Efficiacy of Misoprostol in the therapy of NSAID-induced symptoms and lesions of the upper GI-tract under continued NSAID medication[abstract].  Clin Exp Rheumatol. 1990;  8 ((S4)) 59P
  • 10 Bolton W. Treatment of NSAID-induced gastrointestinal complaints by co-medication of the prostaglandin analog misoprostol in rheumatoid arthritis patients; a multicenter, double-blind, placebo-controlled study.  Akt Rheumatol. 1989;  14 214
  • 11 Bridoux F, Hazzan M, Pallot J L. Acute renal failure after the use of angiotensin-converting-enzyme inhibitors in patients without renal artery stenosis.  Nephrol Dial Transplant. 1992;  7 100
  • 12 Brune K, Peskar B A. Modulation by drugs of leucotriene and prostaglandin production from mouse peritoneal macrophages.  Int J Tissue React. 1985;  7 ((2)) 97
  • 13 Carlsson K H, Helmreich J, Jurna I. Comparison of central antinociceptive and analgetic effects of the pyrazolone derivates, metamizol (dipyrone) and aminophenazone („Pyramidon”).  Schmerz-Pain-Doleur. 1986;  7 93
  • 14 Carlsson K H, Jurna I. The role of descending inhibition in the antinociceptive effects of the pyrazolone derivates, metamizol (dipyrone) and aminophenazone („Pyramidon”).  Naunyn-Schmiedeberg's Arch Pharmacol. 1987;  335 154
  • 15 Clive D M, Stoff J S. Renal syndromes associated with anti-inflammatory drugs.  New Engl J Med. 1984;  310 563
  • 16 Dajani E Z, Wilson D E, Agrawal N M. Prostaglandins: an overview of the worldwide clinical experience.  J Assoc Acad Minor Phys. 1991;  2 ((1)) 23,27
  • 17 De Witt D, Smith W L. Yes, but they still got headaches?.  Cell. 1995;  83 ((22)) 345
  • 18 Dinchuk J E, Car B D, Focht J, Johnston J J, Jaffee B D, Covington M B, Contel N R, Eng V M, Collins R J, Czerniak P M, Gorry S A, Trzaskos J M. Renal abnormalities and an altered inflammatory response in mice lacking cycloxygenase II.  Nature. 1995;  378 ((23)) 406
  • 19 Dubois R N, Abramson S B, Crofford L, Gupta R A. Cyclooxygenase in biology and disease.  FASEB J. 1198;  12 ((12)) 1063-1073
  • 20 Ehsanullah R SB, Page M C, Tildesley G. Prevention of gastroduodenal damage induced by nonsteroidal anti-inflammatory drugs: controlled trial with ranitidine.  BMJ. 1988;  297 1017
  • 21 Eisenberg E, Berkey C S, Carr D B, Mosteller F, Chalmers T C. Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.  J Clin Oncol. 1994;  12 2756
  • 22 Farah D, Sturrock R D, Russel R I. Peptic ulcers in rheumatoid arthritis.  Ann Intern Med. 1988;  47 472
  • 23 Freston M S, Freston J W. Peptic ulcers in the elderly: unique features and management.  Geriatrics. 1990;  45 39
  • 24 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
  • 25 Gardella S, Maltarese R A. Renal effects of prostaglandins and clinical adverse effects of nonsteroidal anti-inflammatory agents.  Medicine (Baltimore). 1984;  63 165
  • 26 Geis G S, Stead H, Wallemark C B. Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAIDs in patients with RA or OA, and interim report on prevention of diclofenac-associated lesions.  J Rheumatol. 1991;  18 ((Suppl. 28)) 11
  • 27 Goodlad R A, Madgwick A J, Moffatt M R, Levin S, Allen S J, Wright N A. The effects of the prostaglandin analogue, misoprostol, on cell proliferation and cell migration in the canine stomach.  Digestion. 1990;  46 ((Suppl. 2)) 182
  • 28 Graham D J, Agrawal N M, Roth S H. Prevention of NSAID-induced gastric ulcer with misoprostol: multicentre, double-blind, placebo-controlled trial.  Lancet. 1988;  II 1277
  • 29 Graham D J, White R H, Moreland L W. Duodenal and gastric ulcer prevention with misoprostol in arthritis patients taking NSAIDs.  Ann Intern Med. 1993;  119 257
  • 30 Griffin M R, Ray W A, Schaffner W. Nonsteroidal anti-inflammatory drug use and death from peptic ulcer in elderly persons.  Ann Intern Med. 1988;  109 359
  • 31 Grond S, Zech D, Dahlmann H, Schug S A, Stobbe B, Lehmann K A. Überweisungsgrund: „therapieresistente” Tumorschmerzen.  Der Schmerz. 1990;  4 193-200
  • 32 Grond S, Zech D, Horrichs-Haermeyer G, Lehmann K A. Schmerztherapie in der Finalphase maligner Erkrankungen.  Der Schmerz. 1990;  4 22-28
  • 33 Grond S, Zech D, Schug S A, Lynch J, Lehmann K A. The importance of non opioid analgesics for cancer pain relief according to the guidelines of the world health organisation.  Int J Clin Pharm Res. 1991;  11 ((6)) 253
  • 34 Hanks G W, Justins D M. Cancer pain: management.  Lancet. 1992;  339 1031
  • 35 Hawkey C, Kahan A, Steinbruck K. Gastrointestinal tolerability of meloxicam compared to diclofenac in osteoarthritis patients. International MELISSA Study Group.  Br J Rheumatol . 1998;  37 ((9)) 937-945
  • 36 Hayllar J, Bjarnason I. NSAIDs, Cox- 2 inhibitors, and the gut.  Lancet. 1995;  346 521
  • 37 He X, Neugebauer V, Schaible H G, Schmidt R F. New aspects of the mode of action of dipyrone. In: Brune K (Hrsg.) New Pharmacological and Epidemiological Data in Analgesic Research, Adelaide, April 1990:9. Birkhäuser Verlag Basel-Boston-Berlin; 1990
  • 38 Henrich W L. Nephrotoxicity of nosteroidal antiinflammatory agents. In: Schrier RW, Gottschalk CW (eds.) Diseases of the Kidney. Little, Brown and Company Boston; 1993 5th ed.: 1203
  • 39 Henry D, Lim L, Rodriguez L, Perez Gutthann S, Carson J, Griffin M, Savage R, Logan R, Moride Y, Hawkey C, Hill S, Fries J. Variability in risk of gastrointestinal complications with individual non-steroidal anti-inflammatory drugs: results of a collaborative meta-analysis.  Br Med J. 1996;  312 1563
  • 40 Hochberg M C, Altman R D, Brand K D. Guidelines for the medical management of osteoarthritis: Pt I. Osteoarthritis of the hip.  Arthritis Rheum. 1995;  38 1535
  • 41 Hochberg M C, Altman R D, Brand K D. Guidelines for the medical management of osteoarthritis: Pt II. Osteoarthritis of the knee.  Arthritis Rheum. 1995;  38 1541
  • 42 Houston M C. Nonsteroidal anti-inflammatory drugs and antihypertensives.  Am J Med. 1991;  90 ( (suppl. 5 A)) 42
  • 43 Inman WHW ed Drug Safety Research Unit (Southampton). PEM News 1991 7: 32
  • 44 Jurna I. Mechanismen der Schmerzunterdrückung durch Pharmaka.  Münch Med Wschr. 1985;  127 573
  • 45 Lane N E. Pain management in osteoarthritis: The role of cox- 2 inhibitors.  J Rheumatol. 1997;  24 ((suppl 49)) 20-24
  • 46 Laine L, Harper S, Simon T, Bath R. 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 ((4)) 776-783
  • 47 Leung F W, Miller J C, Guth P H. Dissociated effects of misoprostol on gastric acid secretion amd mucosal blood flow.  Dig Dis Sci. 1986;  31 ((suppl.)) 86S
  • 48 Levi S, Goodlad R A, Lee C J. Inhibitory effect of non-steroidal anti-inflammatory drugs on mucosal cell proliferation associated with gastric ulcer healing.  Lancet. 1990;  336 840
  • 49 Levy M H. Pharmacologic treatment of cancer pain.  N Engl J Med. 1996;  10 1124
  • 50 Marnett L J, Chen Y N, Maddipatti K R, Ple¿ P, Labeque R. Functional differentiation of cycloxygenase an peroxidase activities of prostaglandin synthase by trypsin treatment.  J Biol Chem. 1988;  263 16 532
  • 51 Marnett L J, Kalgutkar A S. Cyclooxygenase 2 inhibitors: discovery, selectivity and the future.  Trends Pharmacol Sci . 1999;  20 ((11)) 465-469
  • 52 Mene P, Pugliese F, Patrono G. The effects of nonsteroidal anti-inflammatory drugs on human hypertensive vascular disease.  Semin Nephrol. 1995;  15 244
  • 53 Morham S G, Langenbach R, Loftin C D, Tiano H F, Vouloumanos N, Jennette J C, Mahler J F, Kluckman K D, Ledford A, Lee C A, Smithies O. Prostaglandin synthase- 2 gene disruption causes severe renal pathology in the mouse.  Cell. 1995;  83 ((53)) 473
  • 54 Morris A D, Holt S D, Silvoso G R. Effect of anti-inflammatory drug administration in patients with rheumatoid arthritis: an endoscopic assessment.  Scand J Gastroenterol. 1981;  67 ((Suppl.)) 131
  • 55 Muller V P, Dammann H G, Simon B. Akute Schädigung der Magenschleimhaut durch Acetylsalizylsäure: eine endoskopische Vergleichsstudie mit oral wirksamen Prostaglandinanaloga, Omeprazol und Ranitidin [abstract].  Arzneimittelforschung. 1986;  36 265
  • 56 Nobunaga M. NSAID-induced GI damage: a serious problem?. In: Nasution AR, Darmawan J, Isbagio, (eds.) Proceedings of the 7th APLAR Congress of Rheumatology: 1992 Sep 13 - 18; Bali. 
  • 57 Oberle G P, Stahl R AK. Akute Nebenwirkungen nicht steroidaler Antiphlogistika auf die Nieren.  Dtsch med Wschr. 1990;  115 309
  • 58 Raskin J B, White R H, Jaszewski R. Misoprostol and ranitidine in the prevention of NSAID-induced ulcers: a prospective, double-blind, multicenter study.  Am J Gastroenterol. 1996;  91 ((2)) 223
  • 59 Robinson M G, Griffin J W, Bowers J. Effect of ranitidine on gastroduodenal mucosal damage induced by nonsteroidal anti-inflammatory drugs.  Dig Dis Sci. 1989;  34 424
  • 60 Seelig C B, Maloley P A, Campbell J R. Nephrotoxicity assotiated with concomitant ACE inhibitor and NSAID therapy.  South Med J. 1990;  33 232
  • 61 Semble E L, Turner R A, Wu W C. Clinical and genetic characteristics of upper gastrointestinal disease in rheumatoid arthritis.  J Rheumatol. 1987;  14 692
  • 62 Shiokawa Y, Nobunaga M, Saito N. Epidemiology study of upper GI tract lesions induced by NSAIDs.  Ryumachi. 1991;  31 96
  • 63 Silverstein F E, Graham D Y, Senior J R. Misoprostol reduced serious gastrointestinal complications in patients with rheumatoid arthritis recieving nos-steroidal anti-inflammatory drugs: a randomized, double-blind placebo-controlled study.  Ann Intern Med. 1995;  123 241
  • 64 Silvoso G R, Ivey K J, Butt J H. Incidence of gatric lesions in patients with rheumatic disease on chronic aspirin therapy.  Ann Intern Med. 1979;  91 517
  • 65 Tan S Y, Shapiro R, Franco R. Indomethacin.induced prostaglandin inhibition with hyperkalemia: a reversible cause of hyporeninemic hypoaldosteronism.  Ann Intern Med. 1979;  9 783
  • 66 Thun M J, Namboodiri M M, Heath C W. Aspirin use and reduced risk of fatal colon cancer.  N Engl J Med. 1991;  5325 ((23)) 1593-1596
  • 67 Taylor I N, Kenny G NC. Non-steroidal anti-inflammatory drugs.  Curr Opin Anaest. 1993;  6 696
  • 68 Tsuji M, Kawano S, Tsuji S. Cyclooxygenase regulates angiogenesis induced by colon cancer cells.  Cell. 1998;  93 ((5)) 705-716
  • 69 Van Duin C M, Van Essen J A, Van Miert A SJPAM. Mechanism of the antipyretic action of salicylates and pyrazolone derivates.  Zbl Vet Med. 1975;  A 22 510
  • 70 Van Miert A SJPAM, Van Der Wal-Komproe L E, Van Duin C TM. Effects of antipyretic agents on fever and ruminal stasis induced by endotoxins in conscious goats.  Arch Int Pharmacodyn. 1977;  225 39
  • 71 Vane J R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like-drugs.  Nature. 1971;  231 232
  • 72 Ventafridda V, Tamburini M, Caraceni A, De Conno F. Naldi F. A validation study of the WHO method for cancer pain relief.  Cancer. 1987;  59 850
  • 73 Walan A, Bader J P, Classen M. Effect of omeprazole and ranitidine on ulcer healing and relapse rates in patients with benign gastric ulcer.  N Engl J Med. 1989;  32 69
  • 74 Walt R P. Misoprostol for the treatment of peptic ulcer and antiinflammatory-drug-induced gastroduodenal ulceration.  N Engl J Med. 1992;  327 1575
  • 75 Wallace J L. Selective COX- 2 inhibitors: is the water becoming muddy?.  Trends Pharmacol Sci. 1999;  2 ((1)) 4-6
  • 76 Weithmann K U, Alpermann H G. Biochemical and pharmacological effects of dipyrone and ist metabolites in model systems related to arachidonic acid cascade.  Arzneim.-Forsch./Drug Res.. 1985;  35 ((I)) 947
  • 77 Wen S F. Nephrotoxicities of nonsteroidal anti-inflammatory drugs.  J Formos Med Assoc. 1997;  96 157
  • 78 World Health Organisation .Cancer Pain Relief. Office of Publications, WHO Geneva; 1986: 74
  • 79 Zech D, Schug S A. Medikamentöse Therapie. In: Hankemeier UB, Bowdler I, Zech D (Hrsg.) Tumorschmerztherapie. Springer Berlin, Heidelberg, New York; 1989
  • 80 Zenz M, Zenz T h, Tryba M, Strumpf M. Severe undertreatment of cancer pain: A 3-year survey of the german situation.  J Pain Symptom Manage. 1995;  10 187

Dr. Eugen Ladner

Abteilung für Anästhesie Bezirkskrankenhaus Reutte

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