Method for differentiating in humans the direct effects of anti-arrhythmic drugs from those mediated by the autonomic nervous system. Effects of quinidine and propafenone
Paparella, N.; Pirani, R.; Cappato, R.; Candini, G.C.; Alboni, P.
Giornale Italiano di Cardiologia 16(9): 762-769
1986
ISSN/ISBN: 0046-5968 PMID: 3803798 Document Number: 274631
We have set up a method which investigates the different modes of action of an antiarrhythmic drug in man, in particular the direct effects of the drug and those mediated by the autonomic nervous system (ANS). The electrophysiological study (ES) is performed twice in each patient. In the first study the parameters of sinus and A-V nodal functions are evaluated both in the basal state and after pharmacological autonomic blockade (AB) (propranolol 0.2 mg/kg and atropine 0.04 mg/kg). Subsequently, the antiarrhythmic drug is administered per os until a steady-state has been achieved and the ES is then repeated with the same method. By comparing the data obtained in the two studies in the basal state, before and after drug administration, we can evaluate the overall effect, and by comparing those obtained after pharmacological AB we can assess the direct action of the drug. From the comparison of the percentage changes in the examined parameters in the basal state and following AB we can evaluate whether the drug, besides having a possible direct action, also has another one which is mediated by the ANS. This method can be adapted to the way of administration and to the pharmacodynamics of the drug. If the drug does not induce important hemodynamic effect, it can be studied also after intravenous administration. In this case during the first study we can evaluate the overall effect and during the second study the direct effect. The electrophysiological parameters are then compared with the above mentioned method.