Hämostasestörungen durch Analgetika, Antiphlogistika und Antirheumatika

Th. Hohlfeld

doi:10.1055/s-0037-1619501

Hämostaseologie, Table of Contents

Hamostaseologie 2001; 21(01): 22-29
DOI: 10.1055/s-0037-1619501

Original article

Schattauer GmbH

Hämostasestörungen durch Analgetika, Antiphlogistika und Antirheumatika

Hemostatic side effects of analgesic, antiphlogistic and antirheumatic drugs

Th. Hohlfeld

Abstract

Zusammenfassung

Nichtsteroidale Antiphlogistika/Analgetika wie Azetylsalizylsäure (ASS), Indometazin, Diclofenac, Naproxen und Piroxicam hemmen die thrombozytäre Thromboxansynthese und damit die Thrombozytenfunktion. Auch in therapeutischer Dosierung können diese Verbindungen daher zu Blutungskomplikationen führen. Wohl am besten untersucht ist hier das Risiko gastrointestinaler Blutungen, welches bei Behandlung mit Metamizol, Propyphenazon und Paracetamol vergleichsweise gering, unter Indometazin, Diclofenac, Naproxen und Azetylsalizylsäure (ASS) höher und bei Piroxicam relativ gesehen am höchsten ist. Eine direkte Schädigung der Magen- und Duodenalschleimhaut trägt bei diesen Substanzen zum gastrointestinalen Blutungsrisiko bei. Selektive Inhibitoren der induzierbaren Zyklooxygenase (COX-2), wie Celecoxib und Rofecoxib, haben nach bisheriger Erfahrung nur selten zu gastrointestinalen Blutungen geführt. Glukokortikoide beeinflussen in mehrfacher Weise die Hämostase. Zunächst ist hier eine Stimulation der hepatischen Synthese verschiedener Gerinnungsfaktoren (I, II, V, VII, VIII, IX, XI, XII) bekannt. Darüber hinaus können Glukokortikoide auch eine Hypofibrinolyse bewirken, wahrscheinlich infolge erhöhter Aktivität von Inhibitoren der Fibrinolyse (PAI-1, α₂-Antiplasmin). Im Rahmen einer Behandlung mit antirheumatischen Basistherapeutika (darunter Goldsalze, Penicillamin, Methotrexat) ist vor allem auf nicht ganz seltene Thrombozytopenien immunologischer oder myelotoxischer Genese zu achten. Von praktischer Bedeutung sind auch Arzneimittelinteraktionen, wie z.B. eine Steigerung des Blutungsrisikos durch Antikoagulanzien (Warfarin-Derivate, Heparine) bei gleichzeitiger Behandlung mit nichtsteroidalen Antiphlogistika und Analgetika, wozu neben der synergistischen Wirkung auf Thrombozyten und das plasmatische Gerinnungssytem auch pharmakokinetische Mechanismen beitragen können.

Summary

Non-steroidal antiinflammatory drugs like acetylsalicyclic acid, indomethacin, diclofenac, naproxen and piroxicam suppress platelet thromboxane formation and are inhibitors of platelet function. Bleeding complications may occur at therapeutic (analgesic and antiinflammatory) dosages. The relative risk of gastrointestinal bleeding is different according to the individual compound. It is relatively low for paracetamol, metamizol and propyphenazon and higher for indomethacin, diclofenac and mefenamic acid. Piroxicam appears to be associated with a rather high risk, possibly due to its long half life and the potential to accumulate. In addition to platelet inhibition, a toxic action on gastric and duodenal mucosa contributes to the increased risk of gastrointestinal bleeding. Selective inhibitors of the inducible isoform of cyclooxygenase (COX-2), including celecoxib and rofecoxib, appear to be rather safe with respect to gastrointestinal and other bleeding complications. Glucocorticoids have several effects on hemostasis. First, the hepatic synthesis of a number of coagulation factors (I, II, V, VII, VIII, IX, XI, XII) is increased. Second, corticosteroids inhibit endogenous fibrinolysis, probably by an increased activity of antifibrinolytic proteins, such as PAI-1 and α₂-antiplasmin. The main hemostatic risk of the disease modifying antirheumatic drugs (DMARDs), such as gold compounds, penicillamine and methotrexate, is thrombocytopenia. Both, immunological and myelotoxic mechanisms may be involved. Relevant drug interactions exerted by co-administration of non-steroidal antiinflammatory compounds with anticoagulant drugs (warfarin derivatives, heparins) include an increased risk for bleeding, resulting from a synergistic inhibition of both clot formation and platelet activation. In addition, pharmacokinetic interactions may also be involved.

Schlüsselwörter

Zyklooxigenase - Glukokortikoide - Gerinnungsfaktoren - antirheumatische Basistherapeutika

Keywords

Cyclooxygenase - glucocorticoids - coagulation factors - antirheumatic drugs

Full Text

References

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