The effects of lower than conventional doses of oral nadolol on relative beta 1/beta 2-adrenoceptor blockade.
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)
Wheeldon
N M
NM
University Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland, UK.
McDevitt
D G
DG
Lipworth
B J
BJ
D000284:Administration, Oral; D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000328:Adult; D000420:Albuterol / Q000009:adverse effects / Q000097:blood; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D015444:Exercise; D005260:Female; D006801:Humans; D006947:Hyperkalemia / Q000139:chemically induced; D008297:Male; D009248:Nadolol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology* / Q000627:therapeutic use; D016037:Single-Blind Method; D013610:Tachycardia / Q000188:drug therapy / Q000209:etiology; D014202:Tremor / Q000188:drug therapy
D058671:Adrenergic beta-1 Receptor Antagonists; D058672:Adrenergic beta-2 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D009248:Nadolol; D000420:Albuterol