Beta-blockade disappearance rate predicts beta-adrenergic hypersensitivity.
We determined whether the beta-blockade disappearance rate would determine the degree of subsequent transient beta-adrenoceptor hyperresponsiveness after abrupt withdrawal of a beta-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 (t1/2, 18 to 24 hours) or propranolol three times a day (t1/2, 4 to 6 hours) in doses that were increased weekly for 4 weeks to reach 240 mg per day. beta-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 beta-receptor sensitivity correlated (p less than 0.05) with the disappearance rate of beta-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. beta-Blockers with long plasma t1/2 values may prevent beta-blocker withdrawal syndromes by means of "self-tapering."
Reeves
R A
RA
Department of Medicine, Toronto Western Hospital, Ontario, Canada.
Boer
W H
WH
DeLeve
L
L
Leenen
F H
FH
D000328:Adult; D002986:Clinical Trials as Topic; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000008:administration & dosage; D008297:Male; D009248:Nadolol / Q000009:adverse effects / Q000493:pharmacokinetics*; D011433:Propranolol / Q000009:adverse effects / Q000493:pharmacokinetics*; D011897:Random Allocation; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000378:metabolism*
D011943:Receptors, Adrenergic, beta; D009248:Nadolol; D011433:Propranolol; D007545:Isoproterenol