MAGNITUDE AND TIME COURSE OF BETA-ADRENERGIC ANTAGONISM DURING ORAL AMIODARONE THERAPY

To examine the presence and time course of betaadrenergic antagonism produced by amiodarone, the heart rate, QT interval and arrhythmia frequency in response to graded doses of isoproterenol were evaluated in eight patients treated with oral amiodarone for sustained ventricular tachycardia. Measurements were made before and every 2 days after beginning oral amiodarone therapy (600 mg twice daily). Isoproterenol was given in doses of 12.5, 25 and 50 ng/kg body weight per min. The mean heart rate at rest decreased from 73.1 ± 17.8 beats/min on day 0 to 57.8 ± 15.0 beats/min after 12 days of amiodarone therapy. A significant linear decline in heart rate at rest was observed until day 6 (p < 0.05 for all comparisons). On all days isoproterenol produced a progressive increase in heart rate that reached 115.5 ± 20.2 beats/min on day 0 and 94.2 ± 18.5 beats/min on day 12. Amiodarone blunted the heart rate increase produced by isoproterenol on days 2 to 12 (p < 0.05 versus day 0). This effect was present by day 2 and did not change significantly thereafter. The mean corrected QT (QTc) interval increased from 430 ± 30 ms on day 0 to 449 ± 63 ms on day 12. A significant linear increase in QTc interval was observed until day 6 (p < 0.05 for all comparisons). There was no systematic effect of isoproterenol on the QTc interval. Five of eight patients had a significant number of isoproterenol-induced premature ventricular complexes. Ventricular ectopic activity in response to isoproterenol was abolished after 4 days of amiodarone therapy. It is concluded that 1) attenuation of the chronotropic and proarrhylhmic effects of isoproterenol by amiodarone provides in vivo evidence of beta-adrenergic antagonism by orally administered amiodarone; and 2) adrenergic antagonism occurs within 2 days after the onset of amiodarone therapy and may be responsible for some of this drug's early efficacy. © 1990.