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Hamostaseologie 1988; 08(02): 80-89
DOI: 10.1055/s-0038-1659866
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Schattauer GmbH

Kalziumantagonisten und Thrombozytenfunktion

G. Latta
1   Aggertalklinik für Gefäßkrankheiten, Engelskirchen, und Institut für Pharmakologie der Universität Düsseldorf
,
K. Schrör
1   Aggertalklinik für Gefäßkrankheiten, Engelskirchen, und Institut für Pharmakologie der Universität Düsseldorf
› Institutsangaben
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Publikationsdatum:
25. Juni 2018 (online)

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Zusammenfassung

Kalziumantagonisten zeigen neben ihren Wirkungen auf das Herz und den Gefäßtonus auch einen inhibitorischen Effekt auf die Thrombozyten-funktion. Dieser beinhaltet eine Hemmung von Aggregation und Sekretion sowie der Phospholipasenaktivierung und damit des thrombozytären Ara-chidonsäurestoffwechsels. Diese Wirkungen beruhen überwiegend auf einer Hemmung des transmembranären Ca++-Einstroms durch rezeptorabhängige Ca++-Kanäle. Außerdem beeinflussen Kalziumantagonisten wahrscheinlich auch die Ca++-Freisetzung aus intrazellulären Speicherstrukturen, sie zeigen dagegen keinen Effekt auf den . thrombozytären cAMP-Spiegel.

Eine Hemmung der Thrombozy-tenfunktion. durch Kalziumantagonisten in vitro beinhaltet neben den allen Substanzen gemeinsamen Wirkungen auf die zytosolische Ca++-Konzentration zusätzliche Mechanismen, die bei den verschiedenen Typen der Kalziumantagonisten unterschiedlich sind. Verapamil interferiert mit dem stimulatorischen Ob-Rezeptor der Thrombozytenmembran, Nifedipin und andere Dihydropyridine hemmen die thrombozytenstimulatorische Wirkung von TXA2. Diese Substanzen sowie Diltiazem stimulieren in vitro auch die vaskuläre PGI2-Bildung und hemmen synergistisch mit PGI2 die Thrombozytenfunktion.

Eine thrombozytenfunktionshem-mende Wirkung von Kalziumantagonisten wurde auch in bzw. ex vivo, vorzugsweise bei Patienten mit hyper-aggregablen Thrombozyten, gezeigt. Hyperreaktive Thrombozyten können durch Freisetzung vasoaktiver Substanzen (TXA2, Serotonin) zu Gefäßspasmen beitragen (instabile Angina pectoris, Prinzmetal-Angina, periphere Durchblutungsstörungen mit Ray-naud-Symptomatik, Migräne). Für die klinische Effektivität von Kalziumantagonisten bei diesen Krankheitsbildern wäre eine Thrombozytenfunktionshemmung nicht nur theoretisch interessant, sondern auch praktisch bedeutsam. Die Abklärung einer solchen Wirkkomponente erfordert allerdings weitere Untersuchungen. Dies gilt besonders für die Aussagekraft des aus technischen Gründen für Thrombozytenfunktionsuntersuchun-gen in vitro üblichen thrombozytenrei-chen Zitratplasmas mit einer Ca++-Konzentration von 40-50 μM.

 

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