Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1988 Nov;26(5):527–533. doi: 10.1111/j.1365-2125.1988.tb05292.x

Beta-adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

B J Lipworth 1, R A Clark 1, D P Dhillon 1, R A Brown 1, D G McDevitt 1
PMCID: PMC1386629  PMID: 2849969

Abstract

1. Fourteen asthmatics (mean +/- s.e. mean baseline FEV1 62 +/- 6% of predicted) were given cumulative doubling doses of salbutamol by metered-dose inhaler as follows: 100 micrograms, 200 micrograms, 500 micrograms, 1000 micrograms, 2000 micrograms, 4000 micrograms. 2. Airways, tremor, haemodynamic and cyclic AMP responses were measured at each dose increment (made every 20 min). 3. There was a linear log dose-response relationship for each airways parameter (FEV1, VC, sGaw, FEF 50%). The plateau in the dose-response curve was not reached within our dose range. These changes were also mirrored in cyclic AMP responses. 4. There was a wide range in maximum airways response expressed in terms of absolute increase over baseline (95% confidence intervals: delta FEV1 667-1483 ml; delta VC 689-1695 ml; delta sGaw 0.92-4.50 s-1 kPa-1; delta FEF 50% 0.94-2.15 l s-1). Patients with a lower baseline showed a greater response in terms of percent increase in FEV1 (r = -0.83, P less than 0.001). There was however, no correlation between baseline airway calibre and the dose required for maximum bronchodilatation. 5. There were objective increases (mean +/- s.e. mean) in both heart rate (maximum delta HR of 14 +/- 5 beats min-1 at 4000 micrograms) and tremor power (maximum delta Tr of 115 +/- 44% at 2000 micrograms). These were not dose limiting side-effects as subjective symptoms were infrequent at higher doses. 6. Higher than conventional doses of salbutamol given by metered-dose inhaler may produce a distinct improvement in airways response without significant side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF
531

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arnold J. M., McDevitt D. G. An assessment of physiological finger tremor as an indicator of beta-adrenoceptor function. Br J Clin Pharmacol. 1983 Aug;16(2):167–174. doi: 10.1111/j.1365-2125.1983.tb04981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arnold J. M., McDevitt D. G. Contribution of the vagus to the haemodynamic responses following intravenous boluses of isoprenaline. Br J Clin Pharmacol. 1983 Apr;15(4):423–429. doi: 10.1111/j.1365-2125.1983.tb01525.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arnold J. M., McDevitt D. G. Reflex vagal withdrawal and the hemodynamic response to intravenous isoproterenol in the presence of beta-antagonists. Clin Pharmacol Ther. 1986 Aug;40(2):199–208. doi: 10.1038/clpt.1986.164. [DOI] [PubMed] [Google Scholar]
  4. Bengtsson B., Fagerstrom P. O. Extrapulmonary effects of terbutaline during prolonged administration. Clin Pharmacol Ther. 1982 Jun;31(6):726–732. doi: 10.1038/clpt.1982.102. [DOI] [PubMed] [Google Scholar]
  5. Conolly M. E., Greenacre J. K. The lymphocyte beta-adrenoceptor in normal subjects and patients with bronchial asthma: the effect of different forms of treatment on receptor function. J Clin Invest. 1976 Dec;58(6):1307–1316. doi: 10.1172/JCI108586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DUBOIS A. B., BOTELHO S. Y., BEDELL G. N., MARSHALL R., COMROE J. H., Jr A rapid plethysmographic method for measuring thoracic gas volume: a comparison with a nitrogen washout method for measuring functional residual capacity in normal subjects. J Clin Invest. 1956 Mar;35(3):322–326. doi: 10.1172/JCI103281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DUBOIS A. B., BOTELHO S. Y., COMROE J. H., Jr A new method for measuring airway resistance in man using a body plethysmograph: values in normal subjects and in patients with respiratory disease. J Clin Invest. 1956 Mar;35(3):327–335. doi: 10.1172/JCI103282. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Finch J. S. Cardiovascular toxicity: clinical evaluation of albuterol, isoproterenol and placebo in rising dose tolerance trial. Ann Allergy. 1981 Nov;47(5 Pt 2):402–404. [PubMed] [Google Scholar]
  9. Harvey J. E., Tattersfield A. E. Airway response to salbutamol: effect of regular salbutamol inhalations in normal, atopic, and asthmatic subjects. Thorax. 1982 Apr;37(4):280–287. doi: 10.1136/thx.37.4.280. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jenne J. W., Chick T. W., Strickland R. D., Wall F. J. Subsensitivity of beta responses during therapy with a long-acting beta-2 preparation. J Allergy Clin Immunol. 1977 May;59(5):383–390. doi: 10.1016/0091-6749(77)90023-9. [DOI] [PubMed] [Google Scholar]
  11. Küng M., Croley S. W., Phillips B. A. Systemic cardiovascular and metabolic effects associated with the inhalation of an increased dose of albuterol. Influence of mouth rinsing and gargling. Chest. 1987 Mar;91(3):382–387. doi: 10.1378/chest.91.3.382. [DOI] [PubMed] [Google Scholar]
  12. Larsson S., Svedmyr N. Bronchodilating effect and side effects of beta2- adrenoceptor stimulants by different modes of administration (tablets, metered aerosol, and combinations thereof). A study with salbutamol in asthmatics. Am Rev Respir Dis. 1977 Nov;116(5):861–869. doi: 10.1164/arrd.1977.116.5.861. [DOI] [PubMed] [Google Scholar]
  13. Larsson S., Svedmyr N., Thiringer G. Lack of bronchial beta adrenoceptor resistance in asthmatics during long-term treatment with terbutaline. J Allergy Clin Immunol. 1977 Feb;59(2):93–100. doi: 10.1016/0091-6749(77)90209-3. [DOI] [PubMed] [Google Scholar]
  14. Marsden C. D., Foley T. H., Owen D. A., McAllister R. G. Peripheral beta-adrenergic receptors concerned with tremor. Clin Sci. 1967 Aug;33(1):53–65. [PubMed] [Google Scholar]
  15. Morris H. G., Rusnak S. A., Selner J. C., Barzens K., Barnes J. Comparative effects of ephedrine on adrenergic responsiveness in normal and asthmatic subjects. J Allergy Clin Immunol. 1978 May;61(5):294–302. doi: 10.1016/0091-6749(78)90050-7. [DOI] [PubMed] [Google Scholar]
  16. Nelson H. S., Raine D., Jr, Doner H. C., Posey W. C. Subsensitivity to the bronchodilator action of albuterol produced by chronic administration. Am Rev Respir Dis. 1977 Nov;116(5):871–878. doi: 10.1164/arrd.1977.116.5.871. [DOI] [PubMed] [Google Scholar]
  17. Newman S. P., Pavia D., Clarke S. W. Simple instructions for using pressurized aerosol bronchodilators. J R Soc Med. 1980 Nov;73(11):776–779. doi: 10.1177/014107688007301105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Newman S. P., Pavia D., Morén F., Sheahan N. F., Clarke S. W. Deposition of pressurised aerosols in the human respiratory tract. Thorax. 1981 Jan;36(1):52–55. doi: 10.1136/thx.36.1.52. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Plummer A. L. The development of drug tolerance to beta2 adrenergic agents. Chest. 1978 Jun;73(6 Suppl):949–957. doi: 10.1378/chest.73.6.949. [DOI] [PubMed] [Google Scholar]
  20. Prior J. G., Cochrane G. M. Assessment of optimum dose of inhaled terbutaline in patients with chronic asthma: the use of simple, cumulative dose-response curves. Br J Dis Chest. 1982 Jul;76(3):266–268. [PubMed] [Google Scholar]
  21. Repsher L. H., Miller T. D., Smith S. The lack of tachyphylaxis following prolonged therapy of asthma with inhaled albuterol aerosol. Ann Allergy. 1981 Nov;47(5 Pt 2):405–409. [PubMed] [Google Scholar]
  22. Spector S. L., Garza Gomez M. Dose-response effects of albuterol aerosol compared with isoproterenol and placebo aerosols: response to albuterol, isoproterenol, and placebo aerosols. J Allergy Clin Immunol. 1977 Apr;59(4):280–286. doi: 10.1016/0091-6749(77)90048-3. [DOI] [PubMed] [Google Scholar]
  23. Thiringer G., Svedmyr N. Evaluation of skeletal muscle tremor due to bronchodilator agents. Scand J Respir Dis. 1975 Aug;56(2):93–102. [PubMed] [Google Scholar]
  24. Tomashefski J. F. Pulmonary function and airways resistance studies on chronic stabilized asthma: comparison of acute and long-term effects of albuterol and isoproterenol aerosols. Ann Allergy. 1981 Nov;47(5 Pt 2):415–420. [PubMed] [Google Scholar]
  25. Walker S. R., Evans M. E., Richards A. J., Paterson J. W. The clinical pharmacology of oral and inhaled salbutamol. Clin Pharmacol Ther. 1972 Nov-Dec;13(6):861–867. doi: 10.1002/cpt1972136861. [DOI] [PubMed] [Google Scholar]
  26. Walters E. H., Cockroft A., Griffiths T., Rocchiccioli K., Davies B. H. Optimal dose of salbutamol respiratory solution: comparison of three doses with plasma levels. Thorax. 1981 Aug;36(8):625–628. doi: 10.1136/thx.36.8.625. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES