Lack of beta-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy with oxprenolol.

Abstract

The possibility of beta-adrenoreceptor hypersensitivity after abrupt withdrawal of long-term therapy (8-18 months) with the slow-release (SR) formulation of oxprenolol (160-320 mg/day) was assessed in six patients with uncomplicated essential hypertension. The chronotropic dose 25 of isoproterenol (the dose that increases the resting heart rate by 25 beats/min), plasma concentration of catecholamines, triiodothyronin and thyroxin, plasma renin activity and aldosterone, hemoglobin, hematocrit and oxyhemoglobin dissociation were measured on the last day of oxprenolol SR intake and 1, 2, 3, 6 and 13 days after abrupt replacement by identical placebo tablets. The chronotropic dose 25 of isoproterenol (microgram/m2), which was greater than 25.6 in all patients on the last day of oxprenolol SR, fell to 4.83 +/- 2.03 on the second day and to 3.50 on the third day after its abrupt withdrawal and reached a minimal value on the thirteenth day (2.78 +/- 0.30). Throughout the study, plasma concentrations of catecholamines, triiodothyronin and thyroxin and oxyhemoglobin dissociation remained unchanged. Plasma renin activity and plasma aldosterone, which were suppressed during oxprenolol administration, rose significantly during placebo, coinciding with a significant fall in hematocrit and hemoglobin. No major subjective symptoms were reported by the patients. Thus, hypersensitivity of beta-adrenoreceptor-mediated responses was not demonstrated after sudden withdrawal of oxprenolol SR.