The effect on blood pressure of beta‐adrenoceptor blocking drugs administered once daily and their duration of action when therapy is ceased.

1. Eleven hypertensive patients were studied in a double‐blind comparison of acebutolol, a beta‐adrenoceptor blocker, and placebo. 2. Optimum dosage defined in an open assessment varied from 200–600 mg twice daily. 3. Blood pressure and pulse rate fell significantly while patients were lying, standing and after exercise. 4. Blood pressure remained as well controlled on each patient's optimum daily dose when taken once daily, and assessed 24 h post dose. 5. There was no correlation between blood pressure reduction and changes in heart rate. On once daily therapy while blood pressure remained unchanged at 24 h post dose there was a signficant reduction in beta‐adrenoceptor blockade as measured by percentage reduction in exercise tachycardia. 6. There was no significant change in urinary catecholamine excretion or echocardiographically estimated cardiac output. 7. A correlation was found between the change in plasma renin activity (log transformed) and blood pressure reduction.

Section: Discussionmentioning

confidence: 99%

Acebutolol in hypertension‐double‐blind trial against placebo.

Martin¹,

Phillips²,

Smith³

1978

“…As the beneficial effects of propranolol in angina pectoris and cardiac arrhythmias result from blockade of cardiac f3-adrenoceptors (Shanks, 1976) Studies have already shown that once daily administration of conventional propranolol is effective in controlling raised arterial pressure throughout a 24 h period (Wilson et al, 1976;Douglas-Jones et al, 1978). However it has been suggested that use of this formulation may be associated with a higher incidence of adverse effects (Ross and Baber-quoted by Douglas-Jones et al, 1978).…”

Section: Discussionmentioning

confidence: 99%

“…Although observations in patients with hypertension have shown that satisfactory control of arterial pressure can be obtained throughout a 24 h period with twice daily administration (Berglund, Anderson, Habssen & Olander, 1973) and even once daily administration of propranolol (Wilson, Morgan & Morgan, 1976;Douglas-Jones, Baber & Lee, 1978), this may not be an effective regime for other 0306-5251/80/010033-08 $01.00 conditions such as angina or cardiac arrhythmias where the therapeutic effect may be more directly related to cardiac JJ-adrenoceptor blockade which is not maintained over 24 h after single dose of 100 mg propranolol (Aellig, 1976). Although a therapeutic effect with propranolol may be obtained in hypertension by giving the total daily amount as a single dose once per day, high plasma levels will occur shortly after administration which may produce adverse effects.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the efficacy and pharmacokinetics of conventional propranolol and a long acting preparation of propranolol.

Leahey¹,

Neill²,

Varma³

et al. 1980

1 Plasma levels of propranolol were measured at intervals after the oral administration of 160 mg propranolol and 160 mg L.A. propranolol in ten subjects who received both drugs on separate occasions.2 Mean peak plasma concentration of propranolol occurred 2 h after propranolol and 10 h after the L.A. formulation; the peak concentration with the former was four times that with the latter. At 24 h the plasma level was significantly higher after L.A. propranolol. 3 Observations were made in nine healthy volunteers who exercised before and at intervals after the oral administration of 160 mg propranolol and 160 mg L.A. propranolol.4 Propranolol produced a maximum reduction (27.84 + 2.4%) in the exercise tachycardia at 3 h and L.A. propranolol a maximum reduction (22.00 + 1.73%) at 6 h. The effects at 24 h were 9.24 + 1.55 and 16.79 + 2.16% respectively.5 Five subjects were given 160 mg propranolol as a single dose daily for 8 days and on a separate occasion similar treatment with L.A. propranolol. Subjects were exercised and blood samples were taken before and 3 h after each dose on days 1 to 5 and on day 8. propranolol were 12.5 to 17.5 (trough values) and 18.4 to 50.0 (peak values) ng/ml. 8 These observations show that the new long acting formulation of propranolol produces a significant reduction of an exercise tachycardia throughout a 24 h period without a very high initial effect during single and multiple dosing. This formulation should be suitable for once a day administration.

“…Attention has been paid recently to the administration of the total daily dose of f3-adrenoceptor blocking drugs as a single dose. The administration of propranolol as a single dose each 24 h has been shown to control arterial pressure throughout this period (Wilson, Morgan & Morgan, 1976;Douglas-Jones, Baber & Lee, 1978) but at the end of the dose interval, the degree of cardiac /8-adrenergic receptor blockade will probably be small (Leahey et al, 1980a).…”

Section: Discussionmentioning

confidence: 99%

Observation on the efficacy and pharmacokinetics of betaxolol (SL 75212), a cardioselective beta‐adrenoceptor blocking drug.

Balnave¹,

Neill²,

Russell³

et al. 1981

1 Observations were made in five subjects who exercised before and at 2, 3, 6, 8, 24, 33 and 48 h after the oral administration of placebo and 5, 10,20 and 40 mg betaxolol. 2 The exercise heart rate remained constant at all times after the placebo. All doses of betaxolol significantly reduced the exercise tachycardia at all times. The maximum effect (34.4 + 2.2%) occurred after 40 mg.3 There was a small decline in effect from the peak to 24 h when 40 mg produced a 23.3+2.7% reduction and a further decline to 48 h when there was a 14.6 + 1.8% reduction. 4 Plasma levels of betaxolol were measured in these studies. The peak plasma concentration occurred between 3 and 8 h with different doses. The plasma elimination half-lives after 10, 20 and 40 mg were 11.4 + 2.5, 15.9 + 4.9 and 15.1 + 3.1 h. 5 The effects of 40 mg betaxolol, 200 mg atenolol, 160 mg propranolol, 160 mg oxprenolol, 400 mg sotalol and placebo on an exercise tachycardia were compared in five subjects who received all treatments in random order. 6 There was no significant difference in the maximum reduction produced in an exercise tachycardia by the different drugs. 7 The effect of all drugs decreased with time. The effect of oxprenolol had worn off at 24 h but at 48 h only atenolol and betaxolol produced significant reductions in the exercise tachycardia. 8 Plasma concentrations of the different drugs were measured and plasma elimination half-lives determined. The half-life for betaxolol was 24.5 h which was longer than that for any of the other drugs. 9 These observations show that betaxolol is a potent f-adrenoceptor antagonist with a long duration of effect on an exercise tachycardia and a long plasma elimination half-life.