Skip to main content
NCBI home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1989 Jul;28(1):95–102. doi: 10.1111/j.1365-2125.1989.tb03510.x

Assessment of airways, tremor and chronotropic responses to inhaled salbutamol in the quantification of beta 2-adrenoceptor blockade.

B J Lipworth 1, R A Brown 1, D G McDevitt 1
PMCID: PMC1379975  PMID: 2570601

Abstract

1. The purpose of the study was to assess and compare the effects of inhaled salbutamol on heart rate (HR), finger tremor (Tr) and specific airways conductance (sGaw) in the measurement of beta 2-adrenoceptor blockade in normal subjects. 2. Five healthy volunteers were given oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40) or identical placebo (P1) in a single-blind crossover design. 3. Three hours after drug ingestion, dose-response curves were constructed using cumulative doses of inhaled salbutamol: 200 micrograms, 700 micrograms, 1700 micrograms, 3200 micrograms, 6200 micrograms. HR, Tr and sGaw were measured at each dose increment, made every 20 min. 4. Increasing doses of atenolol were associated with progressive reduction in salbutamol induced beta-adrenoceptor responses. The greatest attenuation occurred with propranolol. These effects on beta-adrenoceptor responses were similar for HR, Tr and sGaw. Geometric mean dose ratios (compared with placebo) for A50, A100, A200 and P40 were as follows HR: 1.98, 2.75, 4.29; Tr: 1.60, 3.78, 6.34, 80.50; sGaw: 1.08, 4.35, 12.30, 66.0 (no dose ratio was obtained for HR with P40). 5. These results showed that atenolol and propranolol attenuated the effects of salbutamol on HR to a similar degree as Tr and sGaw. Furthermore, the variability was least in the measurement of chronotropic responses, suggesting that this may be used to quantify beta 2-adrenoceptor antagonism. The beta 1-adrenoceptor selectivity of atenolol was a dose-dependent phenomenon, although the beta 2-adrenoceptor blockade of A200 was much less than with P40.

Full text

PDF
95

Selected References

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

  1. Anderson E. G., Calcraft B., Jariwalla A. G., Al-Zaibak M. Persistent asthma after treatment with beta-blocking agents. Br J Dis Chest. 1979 Oct;73(4):407–408. [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. Enhancement of physiological finger tremor by intravenous isoprenaline infusions in man: evaluation of its role in the assessment of beta-adrenoceptor antagonists. Br J Clin Pharmacol. 1984 Aug;18(2):145–152. doi: 10.1111/j.1365-2125.1984.tb02446.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Arnold J. M., McDevitt D. G. Heart rate and blood pressure responses to intravenous boluses of isoprenaline in the presence of propranolol, practolol and atropine. Br J Clin Pharmacol. 1983 Aug;16(2):175–184. doi: 10.1111/j.1365-2125.1983.tb04982.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arnold J. M., O'Connor P. C., Riddell J. G., Harron D. W., Shanks R. G., McDevitt D. G. Effects of the beta 2-adrenoceptor antagonist ICI 118,551 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man. Br J Clin Pharmacol. 1985 May;19(5):619–630. doi: 10.1111/j.1365-2125.1985.tb02689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Aström H. Comparison of the effects on airway conductance of a new selective beta-adrenergic blocking drug, atenolol, and propranolol in asthmatic subjects. Scand J Respir Dis. 1975;56(6):292–296. [PubMed] [Google Scholar]
  7. Benson M. K., Berrill W. T., Cruickshank J. M., Sterling G. S. A comparison of four beta-adrenoceptor antagonists in patients with asthma. Br J Clin Pharmacol. 1978 May;5(5):415–419. doi: 10.1111/j.1365-2125.1978.tb01647.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Brown H. C., Carruthers S. G., Johnston G. D., Kelly J. G., McAinsh J., McDevitt D. G., Shanks R. G. Clinical pharmacologic observations on atenolol, a beta-adrenoceptor blocker. Clin Pharmacol Ther. 1976 Nov;20(5):524–534. doi: 10.1002/cpt1976205524. [DOI] [PubMed] [Google Scholar]
  9. Cleaveland C. R., Rangno R. E., Shand D. G. A standardized isoproterenol sensitivity test. The effects of sinus arrhythmia, atropine, and propranolol. Arch Intern Med. 1972 Jul;130(1):47–52. doi: 10.1001/archinte.130.1.47. [DOI] [PubMed] [Google Scholar]
  10. Conway F. J., Fitzgerald J. D., McAinsh J., Rowlands D. J., Simpson W. T. Human pharmacokinetic and pharmacodynamic studies on the atenolo (ICI 66,082), a new cardioselective beta-adrenoceptor blocking drug. Br J Clin Pharmacol. 1976 Apr;3(2):267–272. doi: 10.1111/j.1365-2125.1976.tb00602.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Ellis M. E., Sahay J. N., Chatterjee S. S., Cruickshank J. M., Ellis S. H. Cardioselectivity of atenolol in asthmatic patients. Eur J Clin Pharmacol. 1981;21(3):173–176. doi: 10.1007/BF00627916. [DOI] [PubMed] [Google Scholar]
  14. Fitzgerald J. D., Ruffin R., Smedstad K. G., Roberts R., McAinsh J. Studies on the pharmacokinetics and pharmacodynamics of atenolol in man. Eur J Clin Pharmacol. 1978 May 17;13(2):81–89. doi: 10.1007/BF00609750. [DOI] [PubMed] [Google Scholar]
  15. Gribbin H. R., Baldwin C. J., Tattersfield A. E. Quantitative assessment of bronchial beta-adrenoceptor blockade in man. Br J Clin Pharmacol. 1979 Jun;7(6):551–556. doi: 10.1111/j.1365-2125.1979.tb04641.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Gribbin H. R., Mackay A. D., Baldwin C. J., Tattersfield A. E. Bronchial and cardiac beta-adrenoceptor blockade--a comparison of atenolol, acebutolol and labetalol. Br J Clin Pharmacol. 1981 Jul;12(1):61–65. doi: 10.1111/j.1365-2125.1981.tb01855.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lertora J. J., Mark A. L., Johannsen J., Wilson W. R., Abboud F. M. Selective beta-1 receptor blockade with oral practolol in man. A dose-related phenomenon. J Clin Invest. 1975 Sep;56(3):719–724. doi: 10.1172/JCI108143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Löfdahl C. G., Svedmyr N. Cardioselectivity of atenolol and metoprolol. A study in asthmatic patients. Eur J Respir Dis. 1981 Dec;62(6):396–404. [PubMed] [Google Scholar]
  19. MCNEILL R. S. EFFECT OF A BETA-ADRENERGIC-BLOCKING AGENT, PROPRANOLOL, ON ASTHMATICS. Lancet. 1964 Nov 21;2(7369):1101–1102. doi: 10.1016/s0140-6736(64)92617-0. [DOI] [PubMed] [Google Scholar]
  20. Mackay A. D., Gribbin H. R., Baldwin C. J., Tattersfield A. E. Assessment of bronchial beta blockade after oral bevantolol. Clin Pharmacol Ther. 1981 Jan;29(1):1–6. doi: 10.1038/clpt.1981.1. [DOI] [PubMed] [Google Scholar]
  21. McDevitt D. G. The assessment of beta-adrenoceptor blocking drugs in man. Br J Clin Pharmacol. 1977 Aug;4(4):413–425. doi: 10.1111/j.1365-2125.1977.tb00756.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Oh V. M., Taylor E. A., Wadsworth J., Turner P. Relationship between bronchial effects and plasma practolol concentration in man. Eur J Clin Pharmacol. 1979 Mar 26;15(2):91–96. doi: 10.1007/BF00609870. [DOI] [PubMed] [Google Scholar]
  24. 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. 1978 Feb;5(2):101–106. doi: 10.1111/j.1365-2125.1978.tb01608.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Perucca E., Pickles H., Richens A. Effect of atenolol, metoprolol, and propranolol on isoproterenol-induced tremor and tachycardia in normal subjects. Clin Pharmacol Ther. 1981 Apr;29(4):425–433. doi: 10.1038/clpt.1981.59. [DOI] [PubMed] [Google Scholar]
  26. Pringle T. H., Riddell J. G., Shanks R. G. A comparison of the cardioselectivity of five beta-adrenoceptor blocking drugs. J Cardiovasc Pharmacol. 1987 Aug;10(2):228–237. doi: 10.1097/00005344-198708000-00014. [DOI] [PubMed] [Google Scholar]
  27. Raine J. M., Palazzo M. G., Kerr J. H., Sleight P. Near-fatal bronchospasm after oral nadolol in a young asthmatic and response to ventilation with halothane. Br Med J (Clin Res Ed) 1981 Feb 14;282(6263):548–549. doi: 10.1136/bmj.282.6263.548. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Sinclair D. J. Comparison of effects of propranolol and metoprolol on airways obstruction in chronic bronchitis. Br Med J. 1979 Jan 20;1(6157):168–168. doi: 10.1136/bmj.1.6157.168. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Skinner C., Gaddie J., Palmer K. N. Comparison of effects of metoprolol and propranolol on asthmatic airway obstruction. Br Med J. 1976 Feb 28;1(6008):504–504. doi: 10.1136/bmj.1.6008.504. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Vilsvik J. S., Schaanning J. Effect of atenolol on ventilatory and cardiac function in asthma. Br Med J. 1976 Aug 21;2(6033):453–455. doi: 10.1136/bmj.2.6033.453. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES