Propafenone shows class Ic and class II antiarrhythmic effects.

AIMS: Propafenone is a well-known Class Ic antiarrhythmic agent. It has the typical chemical structure of a beta-blocker, but human studies on its beta-blocking effects revealed conflicting results. METHODS AND RESULTS: Twelve healthy males received single oral doses of 600 mg propafenone and placebo according to a randomized, double-blind, placebo-controlled, cross-over protocol. Four hours following drug intake, heart rate and blood pressure were measured, and plasma concentrations of propafenone were determined at rest, during exercise and after recovery. At exercise, propafenone significantly decreased heart rate (-6%, P < 0.05), systolic blood pressure (-6%, P < 0.05), and the rate-pressure product (-11%, P < 0.05). Plasma concentrations of propafenone increased during exercise (+23%, P < 0.05) and decreased during recovery (-33%, P < 0.05). CONCLUSION: Both effects on heart rate and blood pressure as well as the changes of plasma concentrations of propafenone during exercise represent two particular features of beta-blockers. Therefore, we conclude that propafenone is both a Class Ic and a Class II antiarrhythmic agent, and 600 mg propafenone, i.e. the dose recommended in current guidelines for cardioversion of paroxysmal atrial fibrillation, cause clinically significant beta-blockade. Thus, single oral doses of 600 mg propafenone appear also suitable for cardioversion of paroxysmal atrial fibrillation in patients with structural heart disease since beta-blockers are explicitly indicated in the treatment of both coronary artery disease and heart failure.

Unpredicted lack of effect of exercise on plasma concentrations of carvedilol.

In vitro studies have shown that beta-blockers are taken up into and released from adrenergic cells together with epinephrine and norepinephrine. Consequently, studies in humans revealed an increase in plasma concentrations of propranolol and atenolol during physical exercise. However, carvedilol has not been investigated in a similar fashion. Eleven hypertensive patients on long-term treatment (4 months) with carvedilol followed an exercise regimen. Plasma concentrations of carvedilol were determined at rest (9.7 +/- 3.4 ng/ml), during exercise (9.0 +/- 3.2 ng/ml), and after 15 min of recovery (9.1 +/- 2.7 ng/ml). Contrary to predictions, exercise had no effect on plasma concentrations of carvedilol, a finding that is in contrast to other beta-blockers. We conclude that carvedilol is not taken up into and released from adrenergic nerves during exercise, a feature that clearly distinguishes carvedilol from all other beta-adrenergic antagonists so far investigated.