Document Detail

Comparison of hypersensitivity to adrenergic stimulation after abrupt withdrawal of propranolol and nadolol: influence of half-life differences.
MedLine Citation:
PMID:  2389694     Owner:  NLM     Status:  MEDLINE    
To test whether a beta-blocker's pharmacokinetics has an effect on the development of the beta-blocker withdrawal syndrome, we compared response to exercise and isoproterenol after abrupt withdrawal of two beta-blockers, one with a short half-life (propranolol) and one with a long half-life (nadolol). Eight normal males participated in the randomized cross-over trial. They took propranolol, 40 mg every 6 hours for 6 days, and nadolol, 80 mg daily for 7 days. Exercise- and isoproterenol-induced changes in heart rate and pulse pressure were significantly less than control values during treatment with both drugs (p less than 0.05). Significant hypersensitivity of heart rate response was seen on days 2, 3, and 7 after propranolol withdrawal (p less than 0.05) and on day 6 after nadolol withdrawal (p less than 0.005). Hypersensitive responses to isoproterenol were seen after propranolol withdrawal; no evidence of hypersensitivity to isoproterenol was seen after nadolol withdrawal. The area under the heart rate response, time curve after nadolol withdrawal was significantly less than that after propranolol withdrawal (20.3 beats/ vs 44.9 beats/, respectively, (p less than 0.05). There was a significant inverse correlation between the degree of hypersensitivity and nadolol pharmacokinetic half-life (r = -0.80, p less than 0.02). We conclude that abrupt withdrawal of a beta-blocker with a long half-life may protect against the development of the beta-blocker withdrawal syndrome.
J J Krukemyer; H Boudoulas; P F Binkley; J J Lima
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Publication Detail:
Type:  Clinical Trial; Comparative Study; Journal Article; Randomized Controlled Trial; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American heart journal     Volume:  120     ISSN:  0002-8703     ISO Abbreviation:  Am. Heart J.     Publication Date:  1990 Sep 
Date Detail:
Created Date:  1990-09-27     Completed Date:  1990-09-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0370465     Medline TA:  Am Heart J     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  572-9     Citation Subset:  AIM; IM    
University of Tennessee, Department of Clinical Pharmacy, College of Pharmacy, Memphis 38163.
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MeSH Terms
Blood Pressure / drug effects
Heart Rate / drug effects
Isoproterenol / pharmacology*
Nadolol / adverse effects*,  pharmacokinetics
Propranolol / adverse effects*,  pharmacokinetics
Pulse / drug effects
Substance Withdrawal Syndrome / physiopathology*
Grant Support
Reg. No./Substance:
42200-33-9/Nadolol; 525-66-6/Propranolol; 7683-59-2/Isoproterenol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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