The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.

Abstract

1. The aim of the present study was to evaluate the relative beta 1/beta 2 antagonist selectivity of the beta-adrenoceptor blocker nadolol, in lower than conventional clinical doses. 2. Eight normal volunteers received single oral doses of either placebo (PL), nadolol 5 mg (N5), 20 mg (N20) or 80 mg (N80) in a single-blind, randomised crossover design. beta 1-adrenoceptor antagonism was assessed by attenuation of exercise tachycardia, and beta 2-adrenoceptor blockade by effects on salbutamol-induced chronotropic, hypokalaemic and finger tremor responses. The relative percentage attenuation of beta 2 and beta 1-mediated responses was calculated and expressed as beta 2:beta 1 selectivity ratios. 3. Nadolol produced dose-related reductions in exercise tachycardia in keeping with increasing beta 1-adrenoceptor blockade; mean % reduction (95% CI) compared with placebo: N5 10.7 (6.6 to 14.8), N20 21.4 (17.3 to 25.4), N80 38.9 (34.8 to 42.9). However, even the lowest dose of nadolol (5 mg) produced almost complete blunting of beta 2-mediated effects and significantly increase exercise hyperkalaemia; peak exercise hyperkalaemia (mmol l-1) (means and 95% CI): PL 4.88 (4.68 to 5.07), N5 5.36 (5.17 to 5.55), N20 5.48 (5.28 to 5.67), N80 5.42 (5.22 to 5.61). beta 2:beta 1 selectivity ratios significantly increased as the dose of nadolol was reduced. 4. These data suggest that whereas in the clinical dose range nadolol behaves as a non-selective beta-adrenoceptor antagonist, as the dose is reduced this drug demonstrates an increasing degree of selectivity for the beta 2-adrenoceptor.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: N M Wheeldon, D G McDevitt, B J Lipworth
• Journal: British journal of clinical pharmacology (Br J Clin Pharmacol) Vol. 38 Issue 2 Pg. 103-8 (Aug 1994) ISSN: 0306-5251 [Print] England
• PMID: 7981009 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Randomized Controlled Trial)

Chemical References

• Adrenergic beta-1 Receptor Antagonists
• Adrenergic beta-2 Receptor Antagonists
• Adrenergic beta-Antagonists
• Nadolol
• Albuterol

Topics

• Administration, Oral
• Adrenergic beta-1 Receptor Antagonists
• Adrenergic beta-2 Receptor Antagonists
• Adrenergic beta-Antagonists (administration & dosage, pharmacology, therapeutic use)
• Adult
• Albuterol (adverse effects, blood)
• Cross-Over Studies
• Dose-Response Relationship, Drug
• Exercise
• Female
• Humans
• Hyperkalemia (chemically induced)
• Male
• Nadolol (administration & dosage, blood, pharmacology, therapeutic use)
• Single-Blind Method
• Tachycardia (drug therapy, etiology)
• Tremor (drug therapy)