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β‐Blockade disappearance rate predicts β‐adrenergic hypersensitivity
Author(s) -
Reeves Richard A,
Boer Walther H,
DeLeve Laurie,
Leenen Frans H H
Publication year - 1989
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/clpt.1989.139
Subject(s) - nadolol , medicine , blockade , propranolol , heart rate , epinephrine , plasma renin activity , placebo , isoprenaline , discontinuation , blood pressure , catecholamine , anesthesia , endocrinology , stimulation , renin–angiotensin system , receptor , alternative medicine , pathology
We determined whether the β‐blockade disappearance rate would determine the degree of subsequent transient β‐adrenoceptor hyperresponsiveness after abrupt withdrawal of a β‐adrenoceptor drug. In a single‐blind randomized study, 10 healthy men took a placebo for 1 week and then took nadolol one time a day (t ½ , 18 to 24 hours) or propranolol three times a day (t ½ , 4 to 6 hours) in doses that were increased weekly for 4 weeks to reach 240 mg per day. β‐Receptor responsiveness was assessed before and repeatedly after abrupt drug withdrawal by infusion of isoproterenol and epinephrine and by ergometer exercise. In the 13 days after drug discontinuation, peak β‐receptor sensitivity correlated ( p < 0.05) with the disappearance rate of β‐blockade as assessed by heart rate responses to isoproterenol ( r = 0.68) and to submaximal exercise ( r = 0.62) and by diastolic blood pressure responses to isoproterenol ( r = 0.86) and epinephrine ( r = 0.86). Plasma catecholamine levels and renin activity showed no overshoot, β‐Blockers with long plasma t ½ values may prevent β‐blocker withdrawal syndromes by means of “self‐tapering.” Clinical Pharmacology and Therapeutics (1989) 46 , 279–290; doi: 10.1038/clpt.1989.139