Summary
Pain is a frequent symptom in clinical practice. Elderly and chronically ill patients are particularly affected. On account of the high prevalence of polypharmacy among these patients, pharmacological pain therapy becomes a challenge for physicians. Drug side effects and drug–drug interactions have to be taken into account so as to minimize the health risk for these patients. Especially the group of NSAID has a high risk of adverse drug reactions and drug interactions. The gastrointestinal, the cardiovascular, the renal and the coagulation system are particularly affected. Except for the toxic effect on the liver (in a high dose) Paracetamol (acetaminophen) has similar risks, to a minor degree, though. According to current data Metamizol is actually better than its reputation. The risk of potential drug interactions seems to be low. Beside the risk of sedation in combination with other drugs, Tramadol and other opioids such as Pethidin may induce the Serotonin syndrome. In order to avoid dangerous drug interactions and adverse side effects in the case of polypharmacy, it is recommended to prefer individual choices instead of sticking to the pain management as proposed by the WHO.
Zusammenfassung
Schmerzen betreffen besonders ältere und chronisch kranke Bevölkerungsgruppen. Häufig findet sich die Schmerztherapie als Ergänzung zu einer bereits bestehenden Polypharmazie. Neben unerwünschten Arzneimittelwirkungen sind es vor allem Interaktionen, welche es zu beachten gibt. Die Gruppe der nichtsteriodalen Antirheumatika (NSAR) hat das größte Gefahrenpotential. Im Vordergrund stehen gastrointestinale, kardiovaskuläre und renale Effekte sowie Wirkungen auf das Gerinnungssystem. Paracetamol hat neben der bekannten (in hohen Dosen) toxischen Wirkung auf die Leber, ähnliche Interaktionen wie die NSAR, allerdings in einem geringeren Ausmaß. Metamizol ist nach der aktuellen Studienlage besser als sein Ruf, das Interaktionspotential ist als gering anzusehen. Im Bezug auf Tramadol sowie auch einige stark wirksame Opioide (insbesondere Pethidin) sind vor allen das Serotonin-Syndrom und die ZNS dämpfende Wirkung zu nennen. Auf Grund des erheblichen Gefahrenpotentials bei einer bestehenden Polypharmazie ist es in vielen Fällen ratsam, bei der Auswahl der Analgetika vom WHO-Stufenschema in der Schmerzbehandlung abzusehen.
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Literatur
Basler HD, Hesselbarth S, Schuler M. Schmerzdiagnostik und -therapie in der Geriatrie. Teil 1. Schmerzdiagnostik. Schmerz, 18: 317–326, 2004
Davies MP, Srivastava M. Demographics, assessment and management of pain in the elderly. Drugs Aging, 20: 23–57, 2003
Hadjistavropoulos T, Herr K, Turk DC, et al. An interdisciplinary expert consensus statement on assessment of pain in older persons. Clin J Pain, 23(Suppl): S1–S43, 2007
Stoehr GP, Ganguli M, Seaberg EC, et al. Over-the-counter medication use in an older rural community: the MoVIES Project. J Am Geriatr Soc, 45: 158–165, 1997
Rottlaender D, Scherner M, Schneider T, et al. Multimedikation, Compliance und Zusatzmedikation bei Patienten mit kardiovaskulären Erkrankungen. Dtsch Med Wochenschr, 132: 139–144, 2007
Junius Walker U, Theile G, Hummers-Pradier E. Prevalence and predictors of polypharmacy among older primary care patients in Germany. Fam Pract, 24: 14–19, 2007
Sawyer P, Bodner EV, Ritchie CS, et al. Pain and pain medication use in community-dwelling older adults. Am J Geriatr Pharmacother, 4: 316–324, 2006
Pirmohamed M, James S, Meakin S, et al. Adverse drug reactions as cause of admission to hospital: prospective analysis of 18820 patients. BMJ, 329: 15, 2004
Laroche M, Charmes J, Nouaille Y, et al. Is inappropriate medication use a major cause of adverse drug reactions in the elderly. Br J Clin Pharmacol, 63: 177–186, 1997
Solomon DH, Avorn J, Katz JN, et al. Compliance with osteoporosis medications. Arch Intern Med, 165: 2414–2419, 2005
Schuler J, Dückelmann C, Beindl W, et al. Polypharmacy and inappropriate prescribing in elderly internal-medicine patients in Austria. Wien Klin Wochenschr, 120: 733–741, 2008
Wirth HP, Hürlimann R, Flückiger T. NSAR und Cox-2-Hemmer: die häufigsten unerwünschten Wirkungen. Schweiz Med Forum, 6: 284–289, 2006
Onder G, Pedone C, Landi F, et al. Adverse drug reactions as cause of hospital admissions: Results from the Italian Group of Pharmacoepidemiology in the Elderly (GIFA). JAGS, 50: 1962–1968, 2002
ATC-DDD system (online), available from URL: http://www.whocc.no/atcddd/atsystem.html#6 (assessed 18 February 2008)
Baraldi A, Ballestri M, Rapana R, et al. Acute renal failure of medical type in an elderly population. Nephrol Dial Transplant, 13(Suppl 7): 25–29, 1998
Smets HL, De Haes JF, De Swaef A, et al. Exposure of the elderly to potential nephrotoxic drug combinations in Belgium. Pharmacoepidemiol Drug Saf, 17: 1014–1019, 2008
Page J, Henry D. Consumption of NSAIDs and the development of congestive heart failure in elderly patients: an underecognized public health problem. Arch Intern Med, 160: 777–784, 2000
Johnson AG. NSAIDs and increased blood pressure. What is clinical significance? Drug Saf, 17: 277–289, 1997
Johnson AG, Nguyan TV, Day RO. Do nonsteroidal anti-inflammatory drugs affect blood pressure? A meta-analysis. Ann Intern Med, 121: 289–300, 1994
de Leeuw PW. Nonsteriodal anti-inflammatory drugs and hypertension. The risk in perspective. Drugs, 51: 179–187, 1996
MacDonald TM, Wie L. Effect of ibuprufen on cardioprotective effect of aspirin. Lancet, 361: 573–574, 2003
Garcia-Rodriguez L, Varas-Lorenzo C, Maguire A, et al. Nonsteroidal antiinflammatory drugs and the risk of myocardial infarction in the general population. Circulation, 109: 3000–3006, 2004
Delaney JA, Opatrny L, Brophy JM, et al. Drug–drug interactions between antithrombotic medications and the risk of gastrointestinal bleeding. CMAJ, 177: 347–351, 2007
Skop BP, Brown TM. Potential bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics, 37: 12–16, 1996
Verbeuren TJ. Synthesis, storage, release and metabolism of 5-hydroxyltryptamine in peripheral tissues. In: Fozard JR (ed) The Peripheral Actions of 5-hydroxyltryptamine. New York, NY: Oxford University Press, pp 1–25, 1989
De Clerck F. The role of serotonin in thrombogenesis. Clin Physiol Biochem, 8(Suppl 3): 40–49, 1990
Loke YK, Trivel AN, Ingh S. Meta-analysis: gastrointestinal bleeding due to interaction between selektive serotonin reuptake inhibitors and non steroidal inflammatory drugs. Aliment Pharmacol Ther, 27: 31–40, 2008
Janknegt R. Drug interactions with quinolones. J Antimicrob Chemoter, 26(Suppl D): 7–29, 1990
Iqbal Z, Khan A, Naz A, et al. Pharmacokinetic interaction of ciprofloxacin with diclofenac: a single dose, two-period crossover study in healthy adult volunteers. Clin Drug Investig, 29: 4, 275–281, 2009
Ball P, Tillotson G. Tolerability of flouroquinolone antibiotics: past, present and future, Drug Saf, 13: 343, 1996
Sone H, Takahashi A, Yamada N. Ibuprofen-related hypoglycaemia in a patient receiving sulfonylurea. Ann Intern Med, 134: 344, 2001
Collin M, Mucklow JC. Drug interactions, renal impairment and hypoglycaemia in a patient with Type II diabetes. Br J Clin Pharmacol, 48: 134–137, 1999
Sinatra RS, Jahr JS, Reynolds LW, et al. Efficacy and safety of single and repeated administration of 1 gram intravenous acetominophen injection (paracetamol) for pain management after major orthopedic surgery. Anesthesiology, 102: 822–832, 2005
Gleiter CH. Paracetamol – das sichere Analgetikum. Internist, 38: 707–712, 1997
Hinz B, Cheremina O, Brune K. Acetaminophen (paracetamol) is a selektive cyclooxygenase-2 inhibitor in man. FASEB J, 22: 383–390, 2008
Gonzalez-Perez A, Garcia Rodriguez L. Upper gastrointestinal complications among users of paracetamol. Basic Clin Pharmacol Toxicol, 98: 297–303, 2006
Mahe I, Bertrand N, Drouet L, et al. Interaction between paracetamol and warfarin in patients: a double-blind, pacebo-controlled, randomized study. Haematologica, 91: 1621–1627, 2006
Forman JP, Stampfer MJ, Curhan GC. Non-narcotic analgesic dose and risk of incident hypertension in US women. Hypertension, 46: 500–507, 2005
Chan AT, Manson JE, Albert CM, et al. Nonsteroidal antiinflammatory drugs, acetaminophen, and the risk of cardiovascular events. Circulation, 113: 1578–1587, 2006
Larsen A, Poison J, Fontana R, et al. Acetaminophen-induced acute liver failure: results of a US Multicenter, prospective study. Hepatology, 42: 1364–1372, 2005
Perucca E, Richens A. Paracetamol disposition in normal subjects and in patients treated with antiepileptic drugs. Br J Clin Pharmacol, 7: 201–206, 1979
Toes MJ, Jones AL, Prescott L. Drug interactions with paracetamol. Am J Ther, 12: 56–66, 2005
Reinhardt N, Jantos R, Sinning C, et al. Renaissance eines Analgetikums. Pharmazeutische Zeitschrift, 32, 2006 (online)
Campos C, de Gregorio R, Garcia-Nieto R, et al. Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol, 378: 339–347, 1999
Verspohl EJ. Analgetika mit antipyretischer und antiphlogistischer Wirkungskomponente. In: Ammon HPT (Hrsg) Arzneimittelneben- und -wechselwirkungen. 4. Auflage, WVG: Stuttgart, pp 420–424, 2001
Fachinformation Novalgin®, August 2004. Aventis Pharma
Levy M. Risks of agranulocytosis and aplastic anaemia: the international agranulocytosis and aplastic anaemia study. J Am Med Assoc, 256: 1749–1757, 1986
Arzneimittelkommission der dt. Ärzteschaft, Arzneiverordnungen. 21. Auflage, pp 214–216, 2006
Saussele T, Burk O, Blievernicht JK, et al. Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther, 83: 265–274, 2007
Enggaard Th, Poulsen L, Arendt-Nielsen L, et al. The analgesic effect of tramadol after intravenous injection in healthy volunteers in relation to CYP2D6. Anesth Analg, 102: 146–150, 2006
Dayer P, Desmeules J, Collart L. Pharmacology of tramadol. Drugs, 53(Suppl 2): 18–24, 1997
Opioids+benzodiazepines, stockleys drug interactions, medicines complete. In: Baxter K (ed) London, UK: RPS Publishing, http://www.medicinescomplete.com/mc, 01/08/2008
Serotonin reuptake inhibitors/tramadol. In: Tatro DS (ed) Drug Interaction Facts, Facts and Comparisons 4.0. St. Louis, MI, USA: Wolters Kluwer Health Inc., http://online.factsandcomparisons.com, 14/05/2009
Kesavan S, Sobala GM. Serotonin syndrome with fluoxetine plus tramadol. J R Soc Med, 92: 474–475, 1999
Boyd IW. Tramadol and seizures. Med J Aust, 182: 595–596, 2005
Pisani F, Oteri G, Costa C, et al. Effects of psychotropic drugs on seizure threshold. Drug Saf, 25: 91–110, 2002
Desmeules JA. The tramadol option. Eur J Pain, 4(Suppl A): 15–21, 2000
Hedges D, Jeppson K, Whitehead P. Antipsychotic medication and seizures: a review. Drugs Today, 39: 551–557, 2003
Potschka H, Friderichs E, Loscher W. Anticonvulsant and proconvulsant effects of tramadol, its enantiomers and its M1 metabolite in the rat kindling model of epilepsy. Br J Pharmacol, 131: 203–212, 2000
Tramadol Hydrochloride, American Hospital Formulary Service Drug Information, Medicines Complete. In: McEvoy GK (ed) London, UK: RPS Publishing, http://www.medicinescomplete.com/mc, 07/07/2008
Opioids+Antiepileptics; Enzyme-inducing, Stockleys Drug Interactions, Medicines Complete. In: Baxter K (ed) London, UK: RPS Publishing, http://www.medicinescomplete.com/mc, 15/12/2008
Arcioni R, della Rocca M, Romanò S, et al. Ondansetron inhibits the analgesic effects of tramadol: a possible 5-HT(3) spinal receptor involvement in acute pain in humans. Anesth Analg, 94: 1553–1557, 2002
De Witte JL, Schoenmaekers B, Sessler DI, et al. The analgesic efficacy of tramadol is impaired by concurrent administration of ondansetron. Anesth Analg, 92: 1319–1321, 2001
Hedenmalm K, Lindh JD, Sawe J, et al. Increased liability of tramadol-warfarin interaction in individuals with mutations in the cytochrome P450 2D6 gene. Eur J Clin Pharmacol, 60: 369–372, 2004
Sabbe JR, Sims PJ, Sims MH. Tramadol-warfarin interaction. Pharmacotherapy, 18: 871–873, 1998
Penning-van Beest F, Erkens J, Petersen KU, et al. Main comedications associated with major bleeding during anticoagulant therapy with coumarins. Eur J Clin Pharmacol, 61: 439–444, 2005
Rang ST, Field J, Irving C. Serotonin toxicity caused by an interaction between fentanyl and paroxetine. Can J Anaesth, 55: 521–525, 2008
Ailawadhi S, Sung KW, Carlson LA, et al. Serotonin syndrome caused by interaction between citalopram and fentanyl. J Clin Pharm Ther, 32: 199–202, 2007
Won A, Lapane KL, Vallow S, et al. Long-term effects of analgesics in a population of elderly nursing home residents with peristent nonmalignant pain. J Gerontol A Biol Sci Med Sci, 61: 165–169, 2006
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Gosch, M., Böhmdorfer, B., Benvenuti-Falger, U. et al. Polypharmazie und Schmerztherapie. Wien Med Wochenschr 160, 286–292 (2010). https://doi.org/10.1007/s10354-010-0788-z
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DOI: https://doi.org/10.1007/s10354-010-0788-z