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Hamostaseologie 1998; 18(04): 161-170
DOI: 10.1055/s-0038-1655349
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Schattauer GmbH

Azetylsalizylsäure und Thromboxaninhibitoren

T. Hohlfeld
1   Institut für Pharmakologie Heinrich-Heine-Universität Düsseldorf
,
K. Schrör
1   Institut für Pharmakologie Heinrich-Heine-Universität Düsseldorf
› Author Affiliations
Further Information

Publication History

Publication Date:
27 June 2018 (online)

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Zusammenfassung

Azetylsalizylsäure (ASA) ist seit über 100 Jahren Standardtherapeutikum zur Behandlung von Schmerzen und Entzündungen und seit etwa 40 Jahren Standardsubstanz als Plättchenfunktionshemmer. Grundlage dieser vielfältigen Wirkungen von ASA ist die Hemmung der Fettsäure-Cyclooxygenase (COX). Diese beruht auf einer irreversiblen Acetylierung des Serin 530 im Cyclooxygenasemolekül und nachfolgender sterischer Hinderung des Zutritts des Substrates Arachidonsäure zum katalytischen Zentrum des Enzyms. Die Antiplättchenwirkung von ASA beinhaltet ausschließlich eine Hemmung der thrombozytären Thromboxansynthese nach Inhibition der COX-1. Andere Mechanismen der Plättchenaktivierung werden nicht beeinflußt. Nebenwirkungen von ASA, z. B. Magen-Darm-Blutungen, werden ebenfalls entscheidend durch die Hemmung der Prostaglandinsynthese bestimmt. Daher wurde versucht, eine selektive Hemmung der Thromboxansynthese, Blockade von Thromboxanrezeptoren oder beides zu erreichen. Dazoxiben, Picotamide und Terbogrel sind Referenzsubstanzen für diese Entwicklungen. Die vorliegenden klinischen Daten für Dazoxiben sind weniger überzeugend, für Picotamid wurde bei Patienten mit peripherer Verschlußkrankheit eine nur tendenzielle Senkung der Reverschlußrate gezeigt. Eine größere klinische Studie mit dem kombinierten Inhibitor Terbogrel ist derzeit in Vorbereitung. Insgesamt wird ASA seinen Stellenwert als Basistherapeutikum zur Verhinderung thromboembolischer Gefäßverschlüsse sicher behalten, wobei neuere Antiplättchensubstanzen wie Abciximab bei schweren akuten Koronarsyndromen oder eine Kombination mit Thienopyridinen bei akuten Koronarinterventionen die Wirkung verstärkt. Der therapeutische Stellenwert von selektiven Thromboxaninhibitoren in der antithrombotischen Therapie ist noch zu definieren.

Schlüsselwörter

Azetylsalizyläure - Thromboxan-Synthesehemmer - Thromboxan-Rezeptorantagonist - klinische Studien
 

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