Effects on exercise tachycardia during forty-eight hours of a series of doses of atenolol, sotalol, and metoprolol

Abstract

Beta adrenoceptor blockers differ mainly in their plasma elimination half-lives (t 1/2 s). It has been assumed that drugs with longer t 1/2 will have a longer duration of effect on exercise tachycardia. Several factors may influence the duration of action of beta blockers; we have investigated the contribution of plasma elimination t 1/2 and dose by comparing the effects on an exercise tachycardia in healthy subjects of placebo, 25, 50, 100, and 200 mg of atenolol and of sotalol, and 50, 100, 200, and 400 mg metoprolol. Subjects exercised before and at 2, 3, 6, 8, 24, 33, and 48 hr after oral doses of each drug. Plasma samples for measurement of drug concentration were drawn before each exercise period. Twenty-four hours after 50, 100, and 200 mg atenolol and 50, 100, 200, and 400 mg sotalol there were reductions in an exercise tachycardia; at this time reductions were greater after the larger doses. The plasma elimination t 1/2s of atenolol were between 7.2 +/0 1.0 hr. Although 50, 100, and 200 mg metoprolol induced the same reductions in an exercise tachycardia 2 hr after drug as 25, 50, and 100 mg atenolol and 50, 100, and 200 mg sotalol, these doses were without effect at 24 hr. Metoprolol 400 mg reduced exercise tachycardia at 24 hr but the effect was less than that of the three largest doses of atenolol and sotalol. The plasma elimination t 1/2 for metoprolol was between 3.6 +/- 0.6 and 5.0 +/- 1.8 hr. These results show that duration of cardiac beta blocking of cardiac beta blocking activity of atenolol, sotalol, and metoprolol is determined by the elimination t 1/2 and dose.

Comparison of the haemodynamic effects of bucindolol, propranolol and pindolol in healthy volunteers.

“…In man the degree of P-adrenoceptor antagonism can be determined by the use of a standardized isoprenaline sensitivity test (Cleaveland et al, 1972;George et al, 1972) or by the degree of inhibition of an exercise tachycardia (Brick etal., 1968;Carruthers etal., 1974;Harron et al, 1981 Harron et al, 1981). In the present study propranolol (160 mg) reduced an exercise tachycardia by 25.8%.…”

The β1 and β2‐adrenoceptor affinity and β1‐blocking potency of S‐ and R‐metoprolol

“…For the fl-selective blocker metoprolol it is clear from this study that the fl-adrenoceptor blocking effect of the racemic compound, at therapeutically effective plasma concentrations (50-300nM) (Harron et al, 1981;Ryden et al, 1988) resides solely in the S-enantiomer (KD = 20 nM). The R-form is much less active as a fl-adrenoceptor antagonist (KD= 10,000nM) than the Senantiomer.…”

CNS‐related subjective symptoms during treatment with beta 1‐ adrenoceptor antagonists (atenolol, metoprolol): two double‐blind placebo controlled studies.

“…With the dosages used the 01-adrenoceptor blockade at peak is considered to be of the same magnitude, while at 8 and 24 h the effect of atenolol is more pronounced (Harron et al, 1981).…”