Studies of cardioselectivity and partial agonist activity in beta‐ adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise.

Self Cite

Treatment of angina pectoris with beta‐adrenoceptor antagonists and verapamil in combination is effective and increasingly common. The study reported here was designed to show whether the pharmacokinetics of verapamil are influenced by concurrent treatment with three different beta‐adrenoceptor blockers, and whether there is any pharmacodynamic interaction between these drugs. Twelve healthy volunteers (eight men, four women) aged 21‐25 years and weighing 48‐82 kg consented to participate in the study. They received verapamil 50 mg three times daily for four 1‐week periods, each separated by a 1 week ‘washout’ period. During three of the four treatment periods, the subjects took either atenolol 100 mg once daily, metoprolol 100 mg twice daily or propranolol 80 mg twice daily; in the remaining period they took verapamil alone. The concentration/time curve and plasma elimination half‐life of verapamil and norverapamil, its major metabolite, were not influenced by 1 weeks co‐administration atenolol, metoprolol or propranolol. As expected, co‐administration of each of the beta‐adrenoceptor blockers significantly reduced exercise heart rate when compared with verapamil alone.

Section: Discussionsupporting

confidence: 81%

Pharmacokinetics and pharmacodynamics of verapamil in combination with atenolol, metoprolol and propranolol.

Warrington¹,

Holt²,

Johnston³

et al. 1984

Self Cite

“…Our experiments potentially explain the discrepancies noted when exercise-induced changes in respiratory measurements are used to attempt to demonstrate cardioselectivity in man (McDevitt, 1977). Further support for our suggestions comes from earlier work (Woods et al, 1979;Oh et al, 1978). Both of these groups found a tendency for all P-adrenoceptor blocking drugs except those possessing partial agonist activity to diminish exercise-induced increases in peak expiratory flow rate.…”

Section: Discussionsupporting

confidence: 71%

Beta 1‐selective and non‐selective beta‐adrenoceptor blockade, anaerobic threshold and respiratory gas exchange during exercise.

McLeod¹,

Knopes²,

Shand³

et al. 1985

1 The effect of oral doses of the pl-selective adrenoceptor antagonist atenolol (50 mg), the non-selective antagonist propranolol (40 mg) and placebo was investigated during exercise in a crossover comparison in six healthy but untrained subjects. Descriptors of ventilation, respiratory gas exchange, and arterialized blood lactate and glucose were obtained during steady state bicycle ergometric exercise at 20% and 60% of the subjects' previously determined maximal oxygen uptake (Vo2 max). 2 At these work intensities, the previously reported increase of respiratory exchange ratio (RER) during non-selective 3-adrenoceptor blockade was found to be trivial (placebo = 0.96 ± 0.03 s.e. mean; propranolol = 0.97 + 0.01; atenolol = 0.97 + 0.04; 60% Vo2 max, 10 min exercise) and only present during the early minutes of effort.Oxygen uptake and carbon dioxide production did not differ between treatments. 3 Both drugs produced highly significant falls in peak expiratory flow (PEF) rates and tidal volume (VT) which were compensated by an increase in respiratory rate. PEF, 60% Vo2 max: placebo = 3.8 + 0.3 l/s; propranolol 3.6 + 0.3 1/s (P < 0.03); atenolol 3.1 + 0.3 1/s (P < 0.01). VT, 60% Vo2 max: placebo 2.0 + 0.1 1; propranolol 1.8 + 0.2 1 (P < 0.05); atenolol 1.7 ± 0.1 1 (P < 0.01). 4 Arterialized lactate was significantly elevated during work at 20% and 60% Vo2 max, but rose progressively at the 60% Vo2 max load. Ventilation, oxygen uptake and ventilatory equivalent for carbon dioxide also rose progressively at this workload. Ventilatory equivalent for oxygen showed no significant rise. There were no treatment differences, either at the aerobic or anaerobic workloads. During steady state exercise, previously described determinants of anaerobic threshold (RER, 02 ventilatory equivalent) appear not to be valid. 5 We conclude that normoglycaemic aerobic or anaerobic work is associated with a I3l-adrenoceptor response which reduces airway resistance. Despite antagonism of lipolysis and hepatic glycogenolysis, ,B-adrenoceptor blockade does not appear to alter the pattern of substrate utilization.

“…It is also difficult to measure selectivity quantitatively in patients with asthma where airways obstruction is unstable and the patient may be taking other treatment. Recent studies have used the post exercise increase in peak expiratory flow rate (PEFR) in normal subjects and compared the extent to which different,-adrenoceptor blocking drugs antagonize this effect but the increases in PEFR are small (Kumana, Marlin, Kaye & Smith, 1974;Kumana, Kaye, Leighton, Turner & Hamer, 1975;Oh, Kaye, Warrington, Taylor & Wadsworth, 1978) and the effects difficult to quantitate.…”

Section: Introductionmentioning

confidence: 99%

Quantitative assessment of bronchial beta‐adrenoceptor blockade in man.

Gribbin¹,

Baldwin²,

Tattersfield³

1979

I We describe a method for assessing bronchial ,B-adrenoceptor blockade quantitatively in man. Specific airway conductance is measured after increasing doses of inhaled salbutamol and the extent to which the dose-response curve is displaced to the right after f-adrenoceptor blocking drugs is used to assess bronchial ,B-adrenoceptor blockade. 2 Salbutamol dose-response curves were plotted for six normal subjects by measuring sGaw 15 min after increasing doses of inhaled salbutamol. Salbutamol produced a 30-70% increase in sGaw. 3 Salbutamol dose response curves were obtained 2 h after oral practolol (100 mg and 200 mg) and oral propranolol (40 mg and 80 mg) on separate days and were displaced to the right. 4 The mean dose ratios for practolol 100mg and 200mg were 1.2 and 2.1 and for propranolol 40 mg and 80mg they were 21 and 61 respectively.