Pharmacokinetics and pharmacodynamics of alprenolol in the treatment of hypertension

Abstract

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.

Concentration‐effect relationships for oxprenolol in patients with essential hypertension.

“…Our inability to define the relationship between plasma oxprenolol concentrations and post exercise BP is likely to reflect the multiplicity of mechanisms which control BP and the complexity of the overall response to ,B-adrenoceptor antagonism (Israili, 1979). Although correlation between reduction in BP and plasma concentrations of 13-adrenoceptor antagonists have been reported occasionally in acute studies uncomplicated by adaptive changes (Martin et al, 1978), in chronic studies, relationships are much less clear (Collste et al, 1976;Esler et al, 1978). Furthermore, during exercise the reduction in systolic BP induced by 13-adrenoceptor antagonists is not enhanced while their action on diastolic BP may actually be reversed (Leenen et al, 1980) indicating that the sympathetic nervous system may not play a major role in controlling BP during exercise and/or that it can be easily overcome.…”

“…Although correlation between reduction in BP and plasma concentrations of 13-adrenoceptor antagonists have been reported occasionally in acute studies uncomplicated by adaptive changes (Martin et al, 1978), in chronic studies, relationships are much less clear (Collste et al, 1976;Esler et al, 1978).…”

“…Since the heart rate response to submaximal exercise is a marker of endogenous sympathetic activity (Robinson et al, 1966), reduction in exercise heart rate (EHR) is a valid measure of P-adrenoceptor blockade (Israili, 1979). Although systolic blood pressure (BP) on moderate exertion is also influenced by adrenergic tone, its modification during ,B-adrenoceptor blockade is less consistent (Collste et al, 1976;Esler et al, 1978;Israili, 1979;Martin etal., 1978). Hitherto, plasma concentration-effect relationships for EHR and BP have been described mainly in terms of a loglinear model (Brunner et al, 1975;Israili, 1979;McAinsh et al, 1978;McDevitt, 1977;Martin et al, 1978;Mason & Winer, 1976) but this approach has limitations (Holford & Sheiner, 1981), and as it depends on mean results, no allowance is made for variability in responses.…”