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

Abstract

SUMMARY The possibility of j-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 (gg/m'), 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 i-adrenoreceptor-mediated responses was not demonstrated after sudden withdrawal of oxprenolol SR.

Acebutolol-Induced Decrease of Mononuclear Leukocyte β-Adrenoceptors in Hypertension

“…Very interestingly, no signs of withdrawal syndrome were observed in sub jects treated with the (3-blocker oxprenolol. a partial |3-agonist like acébutolol [14], The par allelism observed between receptor up-regu lation and P-adrenergic hypersensitivity fol lowing antagonist treatment on the one hand and between the lack of receptor up-regulation and the absence of P-adrenergic hyper sensitivity after treatment with partial ago nists on the other, strongly supports the view that the increase in receptor density may me diate clinical effects.…”

beta‐Adrenoceptor hypersensitivity after stopping oxprenolol: discrepant findings not attributable to methodology.

“…They show also that rebound hypersensitivity is similarly present after stopping the slow-release formulation of oxprenolol: this is as expected because the peak of this rebound effect occurs 2-3 days after stopping either slow release or conventional oxprenolol, when plasma levels are negligible in each case (Bolli et al, 1981). We therefore failed to confirm the negative findings reported by Bolli et al (1981) after slow release oxprenolol.…”

“…Our subjects were given oxprenolol only for 2 weeks but we have previously shown that the phenomenon is manifest after as little as 1 week's treatment (Ross et al, 1981). It may be relevant that Bolli et al (1981) studied hypertensive patients aged 27-53 years whereas we used younger normotensive subjects in the present study : Bertel et al (1980) have reported that the CD25 of the chronotropic response to isoprenaline is slightly depressed both by age and by the presence of hypertension. This seems unlikely though to provide the whole explanation for the lack of rebound hypersensitivity observed by Bolli etal.…”

“…Absence of f-adrenoceptor antagonist withdrawal hypersensitivity following slow-release oxprenolol was recently reported (Bolli et al, 1981), leading to the suggestion that the phenomenon does not occur after /8-adrenoceptor antagonists possessing partial agonist activity. A similar lack of withdrawal hypersensitivity has been reported in some studies with pindolol (Rangno & Langlois, 1982;Szecsi etal., 1982) and in particular a down regulation of human lymphocyte f-adrenoceptor density has been noted with this drug and attributed to its partial agonist activity (Molinoff et al, 1982).…”

Abrupt withdrawal of beta-blockade therapy in patients with myocardial infarction: effects on infarct size, left ventricular function, and hospital course.

“…25,11,[13][14][15][16][17][18][19][20][21][22][23][24] Moreover, accurate clinical evaluation of the syndrome is confounded by an inability to distinguish between reemergence of symptoms after cessation of effective therapy and true rebound phenomena. It is reasonable, however, to postulate that rebound /3-adrenergic hypersensitivity is most likely to be unmasked during acute myocardial infarction, a condition characterized by marked elevation of both plasma25-27 and local myocardial catecholamine levels.…”