Summary
A double-blind, balanced and randomised study in 8 healthy volunteers examined the effects of relatively high versus low single doses of practolol on heart rate and ventilation at rest and during standardised exercise. Practolol 1 and 4 mg/kg, a typically non-selective drug propranolol 0.2 mg/kg, and placebo were given intravenously at weekly intervals. Cardiac beta-adrenoceptor blockade was measured by the reduction in exercise heart rate >160 beats/min, and bronchial beta-adrenoceptor blockade by the reduction in exercise peak expiratory flow rate (PEFR) up to 4 h after each treatment. Results were assessed by analysis of co-variance. All three active treatments reduced exercise heart rate markedly, practolol 4 mg/kg causing most reduction. Exercise PEFR was significantly reduced by propranolol 0.2 mg/kg compared with both practolol 1 mg/kg and placebo at all times of measurement, and by practolol 4 mg/kg compared with practolol 1 mg/kg and placebo at most times. Mean plasma concentrations after practolol 4 mg/kg were 3.5 to 4.5 times higher than after 1 mg/kg. Practolol may lose its ‘cardioselectivity’ and cause airflow obstruction at relatively high plasma concentrations above about 2 µg/ml.
Similar content being viewed by others
References
Bodem, G., Bramwell, H. L., Weil, J. V., Chidsey, C. A.: Pharmacodynamic studies of beta adrenergic antagonism induced in man by propranolol and practolol. J. Clin. Invest.52, 747–754 (1973)
Bonn, J. A., Turner, P., Hicks, D. C.: Beta-adrenergic-receptor blockade with practolol in treatment of anxiety. Lancet1972/I, 814–815
Fairbairn, A. S., Fletcher, C. M., Tinker, C. M., Wood, C. H.: A comparison of spirometric and peak expiratory flow measurements in man with and without chronic bronchitis. Thorax17, 168–174 (1962)
George, C. F., Nagle, R. E., Pentecost, B. L.: Practolol in treatment of angina pectoris. A double-blind trial. Br. Med. J.1970/II, 402–404
Harms, H. H.: Isoproterenol antagonism of cardioselective beta adrenergic receptor blocking agents: a comparative study of human and guinea-pig cardiac and bronchial beta adrenergic receptors. J. Pharmacol. Exp. Ther.199, 329–335 (1976)
Harms, H. H., Spoelstra, A. J. G.: Cardiac and bronchial β-adrenoreceptor blocking potencies of atenolol, metoprolol, acebutolol, practolol, propranolol and pindolol in the anaesthetized dog. Clin. Exp. Pharmacol. Physiol.5, 53–59 (1978)
Johnsson, G., Svedmyr, N., Thiringer, R.: Effects of intravenous propranolol and metoprolol and their interaction with isoprenaline on pulmonary function, heart rate and blood pressure in asthmatics. Eur. J. Clin. Pharmacol.8, 175–180 (1975)
Jones, R. S., Wharton, M. J., Buston, M. H.: The place of physical exercise and bronchodilator drugs in the assessment of the asthmatic child. Arch. Dis. Child.38, 539–545 (1963)
Kumana, C. R., Marlin, G. E., Kaye, C. M., Smith, D. M.: New approach to assessment of cardioselectivity of beta blocking drugs. Br. Med. J.1974/IV, 444–447
Kumana, C. R., Kaye, C. M., Leighton, M., Marlin, G. E.: An investigation of ‘absolute plasma level effect relationships’ and ‘absolute cardioselectivity’ with respect to beta-adrenoceptor blockade. Eur. J. Clin. Pharmacol.12, 7–13 (1977)
Lertora, J. J. L., Mark, A. L., Johannsen, U. J., Wilson, W. R., Abboud, F. M.: Selective beta-1 receptor blockade with oral practolol in man: a dose-related phenomenon. J. Clin. Invest.56, 719–724 (1975)
McDevitt, D. G.: The assessment of β-adrenoceptor blocking drugs in man. Br. J. Clin. Pharmacol.4, 413–425 (1977)
McDevitt, D. G.: β-adrenoceptor antagonists and respiratory function. Br. J. Clin. Pharmacol.5, 97–99 (1978)
Oh, V. M. S., Kaye, C. M., Warrington, S. J., Taylor, E. A., Wadsworth, J.: Studies of cardioselectivity and partial agonist activity in β-adrenoceptor blockade comparing effects on heart rate and peak expiratory flow rate during exercise. Br. J. Clin. Pharmacol.5, 107–120 (1978)
Parker, C. W., Smith, J. W.: Alterations in cyclic adenosine monophosphate metabolism in human bronchial asthma. 1. Leukocyte responsiveness to β-adrenergic agents. J. Clin. Invest.52, 48–59 (1973)
Perks, W. H., Chatterjee, S. S., Croxson, R. S., Cruickshank, J. M.: Comparison of atenolol and oxprenolol in patients with angina or hypertension and co-existent chronic airways obstruction. Br. J. Clin. Pharmacol.5, 101–106 (1978)
Powles, R., Shinebourne, E., Hamer, J.: Selective cardiac sympathetic blockade as an adjunct to bronchodilator therapy. Thorax24, 616–618 (1969)
Shand, D. G., Nuckolls, E. M., Oates, J. A.: Plasma propranolol levels in adults with observations in four children. Clin. Pharmacol. Ther.11, 112–120 (1970)
Skrabal, F., Czaykowska, W., Dittrich, P., Braunsteiner, H.: Immediate plasma renin response to propranolol: differentiation between essential and renal hypertension. Br. Med. J.1976/II, 144–147
Turner, P., Burman, J., Hicks, D. C., Cherrington, N. K., MacKinnon, J., Waller, T., Woolnough, M.: A comparison of the effects of propranolol and practolol on forced expiratory volume and resting heart rate in normal subjects. Arch. Int. Pharmacodyn. Ther.191, 104–110 (1971)
Ziskind, M., Weill, H., Bailey, W., Jackson, H., Houser, J.: Special study of the effects of propranolol and practolol on forced expiratory volume and resting heart rate in normal subjects. Clin. Pharmacol. Ther.14, 137 (1973)
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Oh, V.M.S., Taylor, E.A., Wadsworth, J. et al. Relationship between bronchial effects and plasma practolol concentration in man. Eur J Clin Pharmacol 15, 91–96 (1979). https://doi.org/10.1007/BF00609870
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00609870