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Kardiale Elektrophysiologie von Na+- und Ca2+-Kanal-Inhibitoren

  • U. Borchard
  • D. Hafner
Conference paper

Zusammenfassung

Chinidin und Lidocain unterscheiden sich im wesentlichen bezüglich der Frequenzabhängigkeit ihrer Hemmwirkung auf den schnellen Na+-Kanal der Myokardzellmembran. Lidocain bewirkt eine schnell einsetzende Na+-Kanal-Blockade und eine schnelle Wiedererholung, während nach Chinidin die Blockbildung sehr langsam einsetzt und die Wiedererholung stark verzögert abläuft. Mit Hilfe der Theorie vom modulierten Rezeptor läßt sich die Na+-Kanal-Inhibition für beide Antiarrhythmika auf ein einheitliches Wirkprinzip zurückführen, wobei die substanzspezifischen Unterschiede in der Entstehung und Rückbildung des Blocks auf Unterschiede in der Assoziations-und Dissoziationskinetik am Kanalrezeptor basieren. Hieraus lassen sich wichtige Konsequenzen für die Therapie ableiten: Arrhythmieformen, die vor allem von einzelnen frühzeitig einfallenden Extrasystolen geprägt sind, werden durch Lidocain effektiver unterdrückt, während tachykarde Formen geeigneter durch Chinidin zu therapieren sind.

In Analogie zu den Na+-Kanal-Inhibitoren läßt sich auch fur die Kalziumantagonisten Nifedipin und Verapamil ein Unterschied in der Frequenzabhängigkeit der Ca2+-Kanal-Blockade nachweisen. Ähnlich wie unter Lidocain tritt die Blockierung der lonenkanäle unter Nifedipin im Unterschied zu Verapamil erst bei sehr hohen Herzfrequenzen auf. Dieser Wirkunterschied läßt sich u. a. als Erklärung für die fehlende antiarrhythmische Wirkung von Nifedipin heranziehen.

Die Kombination von Na+- und Ca2+-Kanal-Inhibitoren (Chinidin und Verapamil) erweist sich in bezug auf die antiarrhythmische Wirkung als besonders günstig, da sich die Wirksamkeit auf den gesamten Membranpotentialbereich erstreckt (−90 mV bis −60 mV: Na+-System, oberhalb −60 mV: Ca2+-System).

Summary

The prime difference between quinidine and lidocaine is found in their rate-dependent inhibitory effect on the fast Na+ channel of the myocardial cell membrane. Lidocaine causes a rapid onset of Na+ channel blockade and a rapid recovery while quinidine induces block very slowly and markedly delays recovery. Based on the theory of the modulated receptor the Na+ channel inhibition of both antiarrhythmic drugs can be attributed to one principle of action, which they both have in common. The substance-specific differences in the formation and regression of the block are due to differences in association and dissociation kinetics at the channel receptor. The following therapeutic consequences of great value can be derived: lidocaine is more effective in suppressing arrhythmias which are characterized by single premature extrasystoles while quinidine is more effective for the treatment of tachyarrhythmias.

As with the Na+ channel inhibitors a difference regarding rate dependency of the Ca2+ channel blockade can be demonstrated for the calcium antagonists nifedipine and verapamil. Unlike verapamil and similar to lidocaine, nifedipine blocks the ion channels only at very high heart rates. This difference in action is one explanation for the missing antiarrhythmic effect of nifedipine.

The combination of Na+ and Ca2+ channel inhibitors (quinidine and verapamil) proves to have a particularly favourable antiarrhythmic action as it is effective in the whole membrane potential range (−90 mV to −60 mV: Na+ system, above −60 mV: Ca2+ system).

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Copyright information

© Dr. Dietrich Steinkopff Verlag, GmbH & Co. KG, Darmstadt 1985

Authors and Affiliations

  • U. Borchard
    • 1
  • D. Hafner
  1. 1.Institut für PharmakologieUniversität DüsseldorfDüsseldorfDeutschland

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