1 The effects on heart rate and blood pressure after single and multiple dosing (1 month) of a long acting formulation of propranolol 160 mg daily, and conventional propranolol, 80 mg twice daily, or 160 mg daily were compared in 11 moderately hypertensive subjects previously shown to respond to propranolol.2 After acute dosing all three treatments produced significant reduction in blood pressure. After multiple dosing all three treatments maintained significant reductions in lying, standing and exercise heart rate and blood pressure throughout the 24 h. At24 h, after multiple dosing, the fall in resting and standing systolic BP was significantly greater with LA propranolol than with conventional propranolol 80 mg twice daily or conventional propranolol 160 mg once daily (P at least < 0.05). 3 The plasma propranolol concentration time curve after LA propranolol showed slowed absorption, and the area under the curve was significantly lower than after conventional propranolol (acute dosing; LA propranolol 160 mg 560 mg ml-l h, conventional propranolol 80 mg twice daily 1135 mg ml-l h, conventional propranolol 160 mg daily 1414 mg ml-l h).

1 To compare the haemodynamic effects of secondary characteristics of beta‐adrenoceptor blockers with an angiotensin converting enzyme inhibitor forty patients with previously untreated mild to moderate hypertension were prescribed either atenolol 50‐100 mg day‐1, labetalol 200‐800 mg day‐1, pindolol 10‐30 mg day‐1 or captopril 25‐100 mg day‐1 and observed for 6 months. 2 Over this period: (a) All four drugs produced similar reductions in blood pressure at rest (P less than or equal to 0.01) and after exercise (P less than or equal to 0.01). (b) All four drugs significantly decreased resting forearm (P less than or equal to 0.01) and calf blood flow (P less than or equal to 0.01). They all also caused a significant reduction in the increased calf blood flow following exercise (P less than or equal to 0.01). (c) No drug produced a change in resting forearm vascular resistance, while resting calf vascular resistance was decreased by captopril and pindolol, unaltered by labetalol and increased by atenolol. Post‐exercise calf vascular resistance was increased by atenolol, labetalol and pindolol but unaltered by captopril. (d) Although all four drugs produced a fall in resting heart rate this was significantly greater for atenolol and labetalol (P less than or equal to 0.01). All four treatments however significantly reduced the increase in heart rate following exercise (P less than or equal to 0.01). (e) No drug produced any significant change in resting and post‐exercise stroke volume/ejection fraction. 3 It is concluded that despite differing modes of action all four drugs reduce limb blood flow. This primarily appears to be a consequence of reduced perfusion pressure associated with limited autoregulation of skeletal muscle circulation. The reduction in arterial vascular resistance produced by captopril and pindolol is inconsistent and does not appear of major benefit in preserving limb blood flow. The reduction in perfusion with the agents studied may in part be related to a fall in cardiac output associated with decreased heart rate. This suggests that captopril may exert antisympathetic activity when used as an antihypertensive agent.

1 Labetalol is an effective agent in essential hypertension as documented in open studies and controlled studies in which its efficacy has been compared with both placebo and a variety of other anti‐ hypertensive drugs. 2 Labetalol given by mouth lowers blood pressure rapidly. There is no evidence of tolerance to its anti‐hypertensive action. 3 Adverse effects include excessive hypotension, but only when the drug is given in large doses. Epigastric discomfort and scalp tingling have been documented especially after intravenous administration. 4 From a pharmacokinetic and pharmacodynamic point of view, labetalol can be given once daily, but postural hypotension after large (greater than 1 g) single doses may limit the usefulness of once daily regimes. Twice daily administration appears an acceptable compromise.

The kinetics of alprenolol, in relation to its effect on blood pressure and plasma renin activity, have been studied in sixteen patients. A within-patient comparison was made between therapy for six weeks with placebo or alpronolol 200 mg thrice daily. Thirteen patients responded to alprenolol by a signoficant fall in blood pressure. In three other patients treatment did not lower blood pressure. In the group as a whole there was no significant correlation between the fall in systolic, diastolic or mean blood pressure, and the steady-state plasma alprenolol concentration, renin status, or degree of beta blockade. However, the thirteen responsive patients showed a significant relationship (p less than 0.05 - 0.001) between the log mean steady-state plasma alprenolol concentration and the hypotensive response.

1 Labetalol caused a fall in blood pressure within 2 h or oral doses of 100, 200 and 400 mg in six hypertensive patients. 2 This fall which was dose‐related was maximal by 3 h and was sustained when the drug was given in doses of 100 mg 8 hourly, 200 mg 8 hourly and 400 mg 8 hourly. 3 This rapid fall in pressure when labetalol is given by mouth which contrasts to that seen on administration of pure beta‐adrenoceptor blocking agents is a valuable therapeutic property.