Effects of nadolol β-blockade on blood pressure in hypertension

Abstract

Nadolol, a nonselective beta adrenoceptor antagonist, was evaluated in 9 normal sybjects with essential hypertension for ability to inhibit exercise-induced changes in double-product (systolic pressure x heart rate). Propranolol and placebo were included as positive and negative controls. The beta antagonists were administered orally in single doses at 10, 20, 40, and 80 mg on a crossover basis. Both nadolol and propranolol induced comparable dose-related inhibition of double-product. Duration of beta receptor blockade was greater with nadolol than with propranolol; significant inhibition of double-product occurred 24 hr after a single 80-mg dose of nadolol. The antihypertensive effect of nadolol was evaluated in another series of 46 subjects with essential hypertension. The dose of nadolol ranged from 80 to 320 mg once daily. Consistent decreases in supine heart rate (20%) and diastolic blood pressure (9%) from baseline were observed. During steady state, the oral daily dose of nadolol was proportional to the minimum steady-state serum concentration (Cmin) of nadolol (r = 0.75, p less than 0.001) obtained just before the next dose of nadolol. Statistically significant correlation was observed between the antihypertensive effect and the Cmin for nadolol (r = 0.45, p less than 0.05).

Nadolol in thyrotoxicosis.

“…We have been unable to relate steady state drug levels to clinical response or reduction in serum T3 nor were Murchison et al (1979), although a significant correlation between steady state propranolol levels, weight change, reduction in therapeutic index and reduction in serum T3 has been shown (Feely et al, 1980). In hypertensive patients serum nadolol concentration was related to change in double product and to reduction in blood pressure (Duchin et al, 1980). The present study has shown a modest but significant fall in serum T3 (7%) and a rise in rT3 levels (13%) while the serum T4 was unchanged.…”

Effects of single green tea ingestion on pharmacokinetics of nadolol in healthy volunteers

“…Although we did not find significant differences in the AUEC 0–8 for PR, SBP and DBP between groups partly due to the small sample size, those pharmacodynamic responses to nadolol tended to decline with concomitant ingestion of brewed green tea. It has been reported that nadolol exerts dose‐related decreases of heart rate and SBP as indexed by double product, which is calculated by heart rate × SBP, 16 and therefore it is assumed that the decrease in plasma concentration of nadolol could result in the reduction of its β‐blocking effect. However, it should be noted that we only recorded the acute response to nadolol after single oral administration.…”

Nadolol, A Once Daily Treatment for Hypertension Multi‐Centre Clinical Evaluation

“…The investigator's estimation of the clinical response of the patients both on nadolol alone and on nadolol plus diuretic at stabilisation of blood pressure is shown in Table V. 3,864 (91.45%) of patients on nadolol alone were rated excellent or good, as were 2,090 (90.80%) patients on nadolol plus diuretic.…”

“…Following oral administration, peak serum levels are attained in 2‐4 hours, absorption not being affected by food. Maximal beta‐receptor inhibition occurring 5‐8 hours after the first dose 3 . Steady state serum levels occur after 6‐9 days 4 , accumulation has not been shown 5 .…”

“…Excretion is mainly via the renal (70%) and biliary systems. These factors have been shown to contribute to a significant relationship between oral doses and steady state serum levels, which have been shown to correlate to anti‐hypertensive effect 3 .…”