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Erschienen in: Der Schmerz 6/2014

01.12.2014 | Übersichten

Metamizol: Wirkmechanismen, Interaktionen und Agranulozytoserisiko

verfasst von: Prof. Dr. C. Lampl, R. Likar

Erschienen in: Der Schmerz | Ausgabe 6/2014

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Zusammenfassung

Metamizol ist als Vertreter der Pyrazolone ein Nichtopioidanalgetikum mit starker analgetischer sowie antipyretischer und spasmolytischer Wirkung. Aufgrund einer geringen Zahl von Agranulozytosen wurde die Substanz in manchen Ländern vom Markt genommen, in anderen Ländern wurde der Gebrauch stark eingeschränkt. Die vorliegende Arbeit diskutiert die Sicherheitsaspekte von Metamizol und zieht Vergleiche mit anderen Substanzen aus dem gleichen Indikationsgebiet.
Literatur
1.
Zurück zum Zitat Abbate R, Gori AM, Pinto S et al (1990) Cyclooxygenase and lipoxygenase metabolite synthesis by polymorphonuclear neutrophils: in vitro effect of dipyrone. Prostaglandins Leukot Essent Fatty Acids 41:89–93PubMedCrossRef Abbate R, Gori AM, Pinto S et al (1990) Cyclooxygenase and lipoxygenase metabolite synthesis by polymorphonuclear neutrophils: in vitro effect of dipyrone. Prostaglandins Leukot Essent Fatty Acids 41:89–93PubMedCrossRef
2.
Zurück zum Zitat Abbott FV, Hellemans KG (2000) Phenacetin, acetaminophen and dipyrone: analgesic and rewarding effects. Behav Brain Res 112:177–186PubMedCrossRef Abbott FV, Hellemans KG (2000) Phenacetin, acetaminophen and dipyrone: analgesic and rewarding effects. Behav Brain Res 112:177–186PubMedCrossRef
3.
Zurück zum Zitat Ajgaonkar VS, Marathe SN, Virani AR (1988) Dipyrone versus paracetamol: a double-blind study in typhoid fever. J Int Med Res 16:225–230PubMed Ajgaonkar VS, Marathe SN, Virani AR (1988) Dipyrone versus paracetamol: a double-blind study in typhoid fever. J Int Med Res 16:225–230PubMed
4.
Zurück zum Zitat Alves D, Duarte I (2002) Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive effect induced by dipyrone. Eur J Pharmacol 444:47–52PubMedCrossRef Alves D, Duarte I (2002) Involvement of ATP-sensitive K(+) channels in the peripheral antinociceptive effect induced by dipyrone. Eur J Pharmacol 444:47–52PubMedCrossRef
5.
Zurück zum Zitat Andres E, Maloisel F (2008) Idiosyncratic drug-induced agranulocytosis or acute neutropenia. Curr Opin Hematol 15:15–21PubMedCrossRef Andres E, Maloisel F (2008) Idiosyncratic drug-induced agranulocytosis or acute neutropenia. Curr Opin Hematol 15:15–21PubMedCrossRef
6.
7.
Zurück zum Zitat Beirith A, Santos AR, Rodrigues AL et al (1998) Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin and glutamate tests. Study of the mechanism of action. Eur J Pharmacol 345:233–245PubMedCrossRef Beirith A, Santos AR, Rodrigues AL et al (1998) Spinal and supraspinal antinociceptive action of dipyrone in formalin, capsaicin and glutamate tests. Study of the mechanism of action. Eur J Pharmacol 345:233–245PubMedCrossRef
8.
Zurück zum Zitat Bigal ME, Bordini CA, Speciali JG (2002) Intravenous dipyrone for the acute treatment of episodic tension-type headache: a randomized, placebo-controlled, double-blind study. Braz J Med Biol Res 35:1139–1145PubMedCrossRef Bigal ME, Bordini CA, Speciali JG (2002) Intravenous dipyrone for the acute treatment of episodic tension-type headache: a randomized, placebo-controlled, double-blind study. Braz J Med Biol Res 35:1139–1145PubMedCrossRef
9.
Zurück zum Zitat Bigal ME, Bordini CA, Speciali JG (2001) Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic tension-type headache – a placebo-controlled study. Cephalalgia 21:90–95PubMedCrossRef Bigal ME, Bordini CA, Speciali JG (2001) Intravenous metamizol (Dipyrone) in acute migraine treatment and in episodic tension-type headache – a placebo-controlled study. Cephalalgia 21:90–95PubMedCrossRef
10.
Zurück zum Zitat Campos C, De Gregorio R, Garcia-Nieto R et al (1999) Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol 378:339–347PubMedCrossRef Campos C, De Gregorio R, Garcia-Nieto R et al (1999) Regulation of cyclooxygenase activity by metamizol. Eur J Pharmacol 378:339–347PubMedCrossRef
11.
Zurück zum Zitat Coates TD, Boxer LA, Tirnauer JS (2014) Drug-induced neutropenia and agranulocytosis. UpToDate 22.2 – C22.60:Version 20.20 Coates TD, Boxer LA, Tirnauer JS (2014) Drug-induced neutropenia and agranulocytosis. UpToDate 22.2 – C22.60:Version 20.20
12.
Zurück zum Zitat Craig DG, Ford AC, Hayes PC et al (2010) Systematic review: prognostic tests of paracetamol-induced acute liver failure. Aliment Pharmacol Ther 31:1064–1076PubMed Craig DG, Ford AC, Hayes PC et al (2010) Systematic review: prognostic tests of paracetamol-induced acute liver failure. Aliment Pharmacol Ther 31:1064–1076PubMed
13.
Zurück zum Zitat Cruz P, Garutti I, Diaz S et al (2002) Metamizol versus propacetamol: comparative study of the hemodynamic and antipyretic effects in critically ill patients. Rev Esp Anestesiol Reanim 49:391–396PubMed Cruz P, Garutti I, Diaz S et al (2002) Metamizol versus propacetamol: comparative study of the hemodynamic and antipyretic effects in critically ill patients. Rev Esp Anestesiol Reanim 49:391–396PubMed
14.
Zurück zum Zitat Edwards JE, Meseguer F, Faura C et al (2002) Single dose dipyrone for acute renal colic pain. Cochrane Database Syst Rev CD003867 Edwards JE, Meseguer F, Faura C et al (2002) Single dose dipyrone for acute renal colic pain. Cochrane Database Syst Rev CD003867
15.
Zurück zum Zitat Eldor A, Polliack G, Vlodavsky I et al (1983) Effects of dipyrone on prostaglandin production by human platelets and cultured bovine aortic endothelial cells. Thromb Haemost 49:132–137PubMed Eldor A, Polliack G, Vlodavsky I et al (1983) Effects of dipyrone on prostaglandin production by human platelets and cultured bovine aortic endothelial cells. Thromb Haemost 49:132–137PubMed
16.
Zurück zum Zitat Flower RJ, Vane JR (1972) Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature 240:410–411PubMedCrossRef Flower RJ, Vane JR (1972) Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature 240:410–411PubMedCrossRef
17.
Zurück zum Zitat Geisslinger G, Peskar BA, Pallapies D et al (1996) The effects on platelet aggregation and prostanoid biosynthesis of two parenteral analgesics: ketorolac tromethamine and dipyrone. Thromb Haemost 76:592–597PubMed Geisslinger G, Peskar BA, Pallapies D et al (1996) The effects on platelet aggregation and prostanoid biosynthesis of two parenteral analgesics: ketorolac tromethamine and dipyrone. Thromb Haemost 76:592–597PubMed
18.
Zurück zum Zitat Gladtke E (1983) Use of antipyretic analgesics in the pediatric patient. Am J Med 75:121–126PubMedCrossRef Gladtke E (1983) Use of antipyretic analgesics in the pediatric patient. Am J Med 75:121–126PubMedCrossRef
19.
Zurück zum Zitat Gozzoli V, Treggiari MM, Kleger GR et al (2004) Randomized trial of the effect of antipyresis by metamizol, propacetamol or external cooling on metabolism, hemodynamics and inflammatory response. Intensive Care Med 30:401–407PubMedCrossRef Gozzoli V, Treggiari MM, Kleger GR et al (2004) Randomized trial of the effect of antipyresis by metamizol, propacetamol or external cooling on metabolism, hemodynamics and inflammatory response. Intensive Care Med 30:401–407PubMedCrossRef
20.
Zurück zum Zitat Graff J, Arabmotlagh M, Cheung R et al (2007) Effects of parecoxib and dipyrone on platelet aggregation in patients undergoing meniscectomy: a double-blind, randomized, parallel-group study. Clin Ther 29:438–447PubMedCrossRef Graff J, Arabmotlagh M, Cheung R et al (2007) Effects of parecoxib and dipyrone on platelet aggregation in patients undergoing meniscectomy: a double-blind, randomized, parallel-group study. Clin Ther 29:438–447PubMedCrossRef
21.
Zurück zum Zitat Hernandez-Delgadillo GP, Cruz SL (2004) Dipyrone potentiates morphine-induced antinociception in dipyrone-treated and morphine-tolerant rats. Eur J Pharmacol 502:67–73PubMedCrossRef Hernandez-Delgadillo GP, Cruz SL (2004) Dipyrone potentiates morphine-induced antinociception in dipyrone-treated and morphine-tolerant rats. Eur J Pharmacol 502:67–73PubMedCrossRef
22.
Zurück zum Zitat Hernandez N, Vanegas H (2001) Antinociception induced by PAG-microinjected dipyrone (metamizol) in rats: involvement of spinal endogenous opioids. Brain Res 896:175–178PubMedCrossRef Hernandez N, Vanegas H (2001) Antinociception induced by PAG-microinjected dipyrone (metamizol) in rats: involvement of spinal endogenous opioids. Brain Res 896:175–178PubMedCrossRef
23.
Zurück zum Zitat Hohlfeld T, Zimmermann N, Weber AA et al (2008) Pyrazolinone analgesics prevent the antiplatelet effect of aspirin and preserve human platelet thromboxane synthesis. J Thromb Haemost 6:166–173PubMedCrossRef Hohlfeld T, Zimmermann N, Weber AA et al (2008) Pyrazolinone analgesics prevent the antiplatelet effect of aspirin and preserve human platelet thromboxane synthesis. J Thromb Haemost 6:166–173PubMedCrossRef
24.
Zurück zum Zitat Ibanez L, Vidal X, Ballarin E et al (2005) Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol 60:821–829PubMedCrossRef Ibanez L, Vidal X, Ballarin E et al (2005) Agranulocytosis associated with dipyrone (metamizol). Eur J Clin Pharmacol 60:821–829PubMedCrossRef
25.
Zurück zum Zitat Kaufman DW, Kelly JP, Jurgelon JM et al (1996) Drugs in the aetiology of agranulocytosis and aplastic anaemia. Eur J Haematol Suppl 60:23–30PubMed Kaufman DW, Kelly JP, Jurgelon JM et al (1996) Drugs in the aetiology of agranulocytosis and aplastic anaemia. Eur J Haematol Suppl 60:23–30PubMed
26.
Zurück zum Zitat Kaufman DW, Kelly JP, Levy M et al (1986) Risks of agranulocytosis and aplastic anemia: a first report of their relation to drug use with special reference to analgesics. JAMA 256:1749–1757CrossRef Kaufman DW, Kelly JP, Levy M et al (1986) Risks of agranulocytosis and aplastic anemia: a first report of their relation to drug use with special reference to analgesics. JAMA 256:1749–1757CrossRef
27.
Zurück zum Zitat Maj S, Centkowski P (2004) A prospective study of the incidence of agranulocytosis and aplastic anemia associated with the oral use of metamizole sodium in Poland. Med Sci Monit 10:PI93–PI95PubMed Maj S, Centkowski P (2004) A prospective study of the incidence of agranulocytosis and aplastic anemia associated with the oral use of metamizole sodium in Poland. Med Sci Monit 10:PI93–PI95PubMed
28.
Zurück zum Zitat Messmann H, Andus T (Hrsg) (2012) Klinische Gastroenterologie: das Buch für Fort- und Weiterbildung; plus DVD mit über 1400 Befunden; 312 Tab. Thieme, Stuttgart Messmann H, Andus T (Hrsg) (2012) Klinische Gastroenterologie: das Buch für Fort- und Weiterbildung; plus DVD mit über 1400 Befunden; 312 Tab. Thieme, Stuttgart
29.
Zurück zum Zitat Pakulska W, Czarnecka E (2002) Influence of mianserin on the antinociceptive effect of morphine, metamizol and indomethacin in mice. Pharmacol Res 46:415–423PubMedCrossRef Pakulska W, Czarnecka E (2002) Influence of mianserin on the antinociceptive effect of morphine, metamizol and indomethacin in mice. Pharmacol Res 46:415–423PubMedCrossRef
30.
Zurück zum Zitat Park BK, Pirmohamed M, Kitteringham NR (1992) Idiosyncratic drug reactions: a mechanistic evaluation of risk factors. Br J Clin Pharmacol 34:377–395PubMedCentralPubMedCrossRef Park BK, Pirmohamed M, Kitteringham NR (1992) Idiosyncratic drug reactions: a mechanistic evaluation of risk factors. Br J Clin Pharmacol 34:377–395PubMedCentralPubMedCrossRef
31.
Zurück zum Zitat Poveda R, Planas E, Pol O et al (2003) Interaction between metamizol and tramadol in a model of acute visceral pain in rats. Eur J Pain 7:439–448PubMedCrossRef Poveda R, Planas E, Pol O et al (2003) Interaction between metamizol and tramadol in a model of acute visceral pain in rats. Eur J Pain 7:439–448PubMedCrossRef
32.
Zurück zum Zitat Prado J, Daza R, Chumbes O et al (2006) Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial. Sao Paulo Med J 124:135–140PubMedCrossRef Prado J, Daza R, Chumbes O et al (2006) Antipyretic efficacy and tolerability of oral ibuprofen, oral dipyrone and intramuscular dipyrone in children: a randomized controlled trial. Sao Paulo Med J 124:135–140PubMedCrossRef
33.
Zurück zum Zitat Reiner M, Massera E, Magni E (1984) Nimesulide in the treatment of fever: a double-blind, crossover clinical trial. J Int Med Res 12:102–107PubMed Reiner M, Massera E, Magni E (1984) Nimesulide in the treatment of fever: a double-blind, crossover clinical trial. J Int Med Res 12:102–107PubMed
34.
Zurück zum Zitat Saussele T, Burk O, Blievernicht JK et al (2007) Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther 82:265–274PubMedCrossRef Saussele T, Burk O, Blievernicht JK et al (2007) Selective induction of human hepatic cytochromes P450 2B6 and 3A4 by metamizole. Clin Pharmacol Ther 82:265–274PubMedCrossRef
35.
Zurück zum Zitat Shimada SG, Otterness IG, Stitt JT (1994) A study of the mechanism of action of the mild analgesic dipyrone. Agents Actions 41:188–192PubMedCrossRef Shimada SG, Otterness IG, Stitt JT (1994) A study of the mechanism of action of the mild analgesic dipyrone. Agents Actions 41:188–192PubMedCrossRef
36.
Zurück zum Zitat Siebel JS, Beirith A, Calixto JB (2004) Evidence for the involvement of metabotropic glutamatergic, neurokinin 1 receptor pathways and protein kinase C in the antinociceptive effect of dipyrone in mice. Brain Res 1003:61–67PubMedCrossRef Siebel JS, Beirith A, Calixto JB (2004) Evidence for the involvement of metabotropic glutamatergic, neurokinin 1 receptor pathways and protein kinase C in the antinociceptive effect of dipyrone in mice. Brain Res 1003:61–67PubMedCrossRef
37.
Zurück zum Zitat Tortorici V, Vasquez E, Vanegas H (1996) Naloxone partial reversal of the antinociception produced by dipyrone microinjected into the periaqueductal gray of rats. Possible involvement of medullary off- and on-cells. Brain Res 725:106–110PubMedCrossRef Tortorici V, Vasquez E, Vanegas H (1996) Naloxone partial reversal of the antinociception produced by dipyrone microinjected into the periaqueductal gray of rats. Possible involvement of medullary off- and on-cells. Brain Res 725:106–110PubMedCrossRef
38.
Zurück zum Zitat Van Der Klauw MM, Goudsmit R, Halie MR et al (1999) A population-based case-cohort study of drug-associated agranulocytosis. Arch Intern Med 159:369–374CrossRef Van Der Klauw MM, Goudsmit R, Halie MR et al (1999) A population-based case-cohort study of drug-associated agranulocytosis. Arch Intern Med 159:369–374CrossRef
39.
Zurück zum Zitat Vazquez E, Hernandez N, Escobar W et al (2005) Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats. Brain Res 1048:211–217PubMedCrossRef Vazquez E, Hernandez N, Escobar W et al (2005) Antinociception induced by intravenous dipyrone (metamizol) upon dorsal horn neurons: involvement of endogenous opioids at the periaqueductal gray matter, the nucleus raphe magnus, and the spinal cord in rats. Brain Res 1048:211–217PubMedCrossRef
40.
Zurück zum Zitat Verspohl EJ (2001) Analgetika mit antipyretischer und antiphlogistischer Wirkungskomponente. In: Ammon HPT (Hrsg) Arzneimittelneben- und -wechselwirkungen. W.V.G., Stuttgart Verspohl EJ (2001) Analgetika mit antipyretischer und antiphlogistischer Wirkungskomponente. In: Ammon HPT (Hrsg) Arzneimittelneben- und -wechselwirkungen. W.V.G., Stuttgart
41.
Zurück zum Zitat Weithmann KU, Alpermann HG (1985) Biochemical and pharmacological effects of dipyrone and its metabolites in model systems related to arachidonic acid cascade. Arzneimittelforschung 35:947–952PubMed Weithmann KU, Alpermann HG (1985) Biochemical and pharmacological effects of dipyrone and its metabolites in model systems related to arachidonic acid cascade. Arzneimittelforschung 35:947–952PubMed
Metadaten
Titel
Metamizol: Wirkmechanismen, Interaktionen und Agranulozytoserisiko
verfasst von
Prof. Dr. C. Lampl
R. Likar
Publikationsdatum
01.12.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Der Schmerz / Ausgabe 6/2014
Print ISSN: 0932-433X
Elektronische ISSN: 1432-2129
DOI
https://doi.org/10.1007/s00482-014-1490-7

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