β‐Blockade disappearance rate predicts β‐adrenergic hypersensitivity

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 (t½, 18 to 24 hours) or propranolol three times a day (t½, 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 t½ 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