Summary
The aim of the present study was to quantify and compare the airways and systemic beta-adrenoceptor responses to inhaled salbutamol in normal subjects. Seven non-atopic, normal subjects were given cumulative doubling doses of inhaled salbutamol (100 µg to 4000 µg) or placebo in a single-blind cross-over design. Airways (sGaw, FEF 50%, FEF 25%), tremor, haemodynamic and metabolic responses were measured at each dose increment.
There were dose-related changes in sGaw, FEF 50% and FEF 25% up to a plateau at 1.0 mg. Analysis of individual responses showed that most subjects required either 1.0 or 2.0 mg for maximum bronchodilatation, independent of the parameter of airflow. There was no correlation between maximum response and baseline airway calibre. In contrast to airways effects, systemic beta-adrenoceptor responses did not occur until 500 µg, and a ceiling in the dose-response curve was not reached.
Therer were significant correlations between air-ways, tremor and haemodynamic responses, and between different metabolic variables. The intraindividual variability was greatest for tremor and sGaw, although this was small in comparison to the size of maximum change with salbutamol. The converse applied to the hypomagnesaemic response.
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References
Lipworth BJ, Clark RA, Dhillon DP, Brown RA, McDevitt DG (1988) Beta-adrenoceptor responses to high doses of inhaled salbutamol in patients with asthma. Br J Clin Pharmacol 26: 527–533
Lipworth BJ, Clark RA, Dhillon DP, Fraser CG, McDevit DG (1988) Metabolic effects of cumulative doses of salbutamol from a metered-dose inhaler in bronchial asthma. Br J Clin Pharmacol 25: 667p-668p
Newman SP, Pavia D, Clarke SW (1980) Simple instructions for using pressurised aerosol bronchodilators. J Roy Soc Med 73: 776–779
Dubois AB, Botelho SY, Bedell GN, Marshall R, Comroe JH Jr (1956a) A rapid plethysmographic method for measuring thoracic gas volume: A comparison with nitrogen-washout method for measuring functional residual capacity in normal subjects. J Clin Invest 35: 322–326
DuBois AB, Botelho SY, Comroe JH Jr (1956b) A new method for airway resistance in man using a body plethysmograph: Values in normal subjects and in patients with respiratory disease. J Clin Invest 35: 327–335
Barnes PJ, Gribbin HR, Osmanliev D, Pride NB (1981) Partial flow-volume curves to measure bronchodilator dose-response curves in normal humans. J Appl Physiol 50: 1193–1197
Tattersfield AE, Keeping IM (1979) Assessing change in airway calibre — measurement of airway resistance. Br J Clin Pharmacol 8: 307–319
Holgate ST, Baldwin CJ, Tattersfield AE (1977) Beta-adrenergic agonist resistance in normal human airways. Lancet 1: 375–377
Harvey JE, Tattersfield AE (1982) Airway response to salbutamol, effect of regular salbutamol inhalations in normal, atopic and asthmatic subjects. Thorax 37: 280–287
Pride NB (1983) Physiology (normal airway physiology). In: Clark TJH, Godfrey S (eds) Asthma. Chapman and Hall, London, pp 12–56
Tashkin DP, Trevor E, Chopra SK, Taplin GV (1980) Sites of airway dilatation in asthma following inhaled versus subcutaneous terbutaline: Comparison of physiologic tests with radionuclide lung images. Am J Med 68: 14–26
Davies DS (1975) Pharmacokinetics of inhaled substances. Postgrad Med J 51 [Suppl 7]: 69–75
Newman SP, Pavia D, Moren F, Sheahan NE, Clarke SW (1981) Deposition of pressurised aerosols in the human respiratory tract. Thorax 36: 52–55
Kung M, Croley SW, Phillips BA (1987) Systemic cardiovascular and metabolic effects associated with the inhalation of an increased dose of albuterol. Influence of mouth rinsing and gargling. Chest 91: 382–387
Davies DS (1984) The fate of inhaled terbutaline. eur J Respir Dis 65 [Suppl 134]: 141–147
Haalboom JRE, Deenstra M, Struyvenburg A (1985) Hypokalaemia induced by inhalation of fenoterol. Lancet 1: 1125–1127
Scheinin M, Koulu M, Laurikainen E, Allonen H (1987) Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: A placebo-controlled dose-response study in healthy volunteers. Br J Clin Pharmacol 24: 645–653
Whyte KF, Addis GJ, Whitesmith R, Reid JL (1987) Adrenergic control of plasma magnesium in man. Clin Sci 72: 135–138
Bos WJW, Postma DS, Van Doormaal JJ (1988) Magnesiuric and calciuric effects of terbutaline in man. Clin Sci 74: 595–597
Levine BS, Coburn JW (1984) Magnesium, the mimic/antagonist of calcium. N Engl J Med 310: 1253–1254
Quamme GA, Dirks JH (1986) The physiology of renal magnesium handling. Renal Physiol 9: 270–278
Whyte KF, Addis GJ, Whitesmith R, Reid JL (1987) The mechanism of salbutamol-induced hypokalaemia. Br J Clin Pharmacol 23: 65–71
Struthers AD, Reid JL, Whitesmith R, Rodger JC (1987) The effects of cardioselective and non-selective beta-adrenoceptor blockade on the hypokalaemic and cardiovascular responses to adrenomedullary hormones in man. Clin Sci 65: 143–147
Conolly ME, Greenacre JK (1976) The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma. J Clin Invest 58: 307–316
Nelson HS, Raine DJR, Doner HC, Posey WC (1977) Subsensitivity to the bronchodilator action of albuterol produced by chronic administration. Am Rev Respir Dis 116: 871–877
Morris HG, Rusnak SA, Selner JC, Barzens, Barnes JB (1978) Comparative effects of ephedine on adrenergic responsiveness in normal and asthmatic subjects. J Allergy Clin Immunol 61: 294–302
Harvey JE, Baldwin CJ, Wood PJ, Alberti KGM, Tattersfield AE (1981) Airway and metabolic responsiveness to intravenous salbutamol in asthma: Effect of regular inhaled salbutamol. Clin Sci 60: 579–585
Bengstsson B, Fagerstrom PO (1982) Extrapulmonary effects of terbutaline during prolonged administration. Chest 31: 726–732
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Parts of this paper have been presented in abstract form to the British Pharmacological Society: Liverpool UK (Spring Meeting, April 1988) and Dublin, Eire (Summer Meeting, July 1988)
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Lipworth, B.J., McDevitt, D.G. Beta-adrenoceptor responses to inhaled salbutamol in normal subjects. Eur J Clin Pharmacol 36, 239–245 (1989). https://doi.org/10.1007/BF00558154
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DOI: https://doi.org/10.1007/BF00558154