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Protective effect of oral oxyphenonium bromide, terbutaline and theophylline against the bronchial obstructive effects of inhaled histamine, acetylcholine and propranolol

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Summary

The protective effects of oxyphenonium bromide, terbutaline and theophylline were compared in 8 asthmatic patients by determination of the degree of non-specific airway reactivity after 1 week of oral treatment according to a fixed dose scheme in a double-blind random order: oxyphenonium bromide 3×10 mg; terbutaline 3×5 mg; theophylline 2×300 mg and placebo. Controlled, standardized inhalation provocation tests were carried out with histamine, acetylcholine and propranolol. The study was monitored by measuring blood concentrations of the 3 drugs, and their effect on the plasma cAMP concentration was also determined. Significant protection by oxyphenonium bromide against the bronchial obstructive effects of acetylcholine and propranolol was observed, but not against the effect of inhaled histamine. The other two drugs provided no significant protection against the inhaled agents. The absence of any protective effect of terbutaline and theophylline might have resulted from too low a blood concentration. The observed differences in protection could not be explained by changes in pulmonary function. The study suggests dissociation between the bronchodilating effect of a drug and its protective effect against inhaled substances.

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References

  • Bandouvakis J, Cartier A, Roberts R, Ryan G, Hargreave F (1981) The effect of ipratropium bromide and fenoterol on methacholine- and histamine-induced bronchoconstriction. Br J Dis Chest 75: 295–305

    Google Scholar 

  • Berg van den W, Leferink JG, Tabingh Suvermondt W, Kreukniet J, Maes RAA, Serra R, Bruynzeel PLB (1982) Terbutaline serum concentrations related to different lung function parameters and beta-receptor function. Clin Pharmacol Ther 21 [1] 24–30

    Google Scholar 

  • Berg van den W, Leferink JG, Fokkens JG, Kreukniet J, Maes RAA, Bruynzeel PLB (1982) Clinical implications of drug-induced desensitization of the beta-receptor after continuous oral use of terbutaline. J Allergy Clin Immunol, 69 [5] 410–417

    Google Scholar 

  • Bergstrand H (1980) Phosphodiesterase inhibition and theophylline. Eur J Respir Dis 61 [Suppl 109] 37–44

    Google Scholar 

  • Boody-Noord H, Quanjer PH, Vries de K (1972) Protective effect of Berotec in provocation tests using inhalation of specific allergens and histamine. Int J Clin Pharmacol Ther 4: 69–72

    Google Scholar 

  • Bork van LE, Jonkman JHG, Greving JE, Orie NGM, Peset R, Vries de K, Zeeuw de RA (1983) Effects of three anticholinergics in the receptor compartment of the lung and the heart. Eur J Respir Dis (in press)

  • Campbell JA, Middleton WG, McHardy GJR, Shotter MV, McKenzie R, Kay AB (1977) Interaction between isoprenaline and aminophylline in asthma. Thorax 32: 424–428

    Google Scholar 

  • Casterline CL, Evans R, Ward GW (1976) The effect of atropine and albuterol aerosols on the human bronchial response to histamine. J Allergy Clin Immunol 58 [5]: 607–613

    Google Scholar 

  • Chatham M, Bleecker ER, Smith PL, Rosenthal RR, Mason P, Norman PS (1982) A comparison of histamine, methacholine and exercise airway reactivity in normal and asthmatic subjects. Am Rev Respir Dis 126: 235–240

    Google Scholar 

  • Cockcroft DW, Killian DN, Mellon JJA, Hargreave FE (1977) Protective effect of drugs on histamine-induced asthma. Thorax 32: 329–337

    Google Scholar 

  • Fagerberg E, Tegner KB (1972) Effects of oral terbutaline in asthmatic patients. A dose response study. Scand J Respir Dis 53: 3–9

    Google Scholar 

  • Ferron GA, Kerrebijn KF, Weber J (1976) Properties of aerosols produced with nebulizers commonly used in medicine. Am Rev Respir Dis 114: 899–908

    Google Scholar 

  • Greving JE (1981) Bioanalysis and pharmacokinetics of oxyphenonium bromide. Thesis. Groningen, published by the “Nederlands Astma Fonds”. Geuschen. The Netherlands

    Google Scholar 

  • Hargreave FE, Ryan G, Thomson NC, O'Byrne PM, Latimer K, Juniper EF, Dolovich J (1981) Bronchial responsiveness to histamine or methacholine in asthma: measurement and clinical significance. J Allergy Clin Immunol 68: 347–355

    Google Scholar 

  • Holtzman MJ, Sheller JR, Wimeo M, Nadel JA, boushey MA (1980) Effect of ganglion blockade on bronchial reactivity in atopie subjects. Am Rev Respir Dis 122: 17–25

    Google Scholar 

  • Jonkman JHG, Schoenmaker R, Greving JE, Zeeuw de RA (1980) Rapid and selective theophylline serum and saliva assay by means of high pressure liquid chromatography. Pharm Weekbl [Sci], 2: 49–53

    Google Scholar 

  • Juniper EF, Frith PA, Hargreave FE (1981) Airway responsiveness to histamine and metacholine: relationship to minimum treatment to control symptoms of asthma. Thorax 36: 575–579

    Google Scholar 

  • Koëter GH, Jonkman JHG, Vries de K, Schoenmaker R, Greving JE, Zeeuw de RA (1981) Pharmacokinetics of sustained release theophylline in low and high multidose regimens. Br J Clin Pharmacol 12: 647–651

    Google Scholar 

  • Koëter GH, Meurs H, Monchy de JGR, Vries de K (1982) Protective effect of disodium cromoglycate on propranolol challenge. Allergy 37: 587–590

    Google Scholar 

  • Koëter GH, Meurs H, Kauffman HF, Monchy de JGR, Sluiter HJ, Vries de K (1983) Changes in the beta-adrenergic system in bronchial asthma induced by terbutaline. In: Morley J, Rainsford KD (eds) Agents and Actions Supplements, vol 13, Pharmacology of Asthma. Birkhäuser, Basel

    Google Scholar 

  • Kolbeck RC, Speir WA, Carrier GO, Brandsome ED (1979) Apparent irrelevance of cyclic nucleotides to the relaxation of tracheal smooth muscle induced by theophylline. Lung 156: 173–183

    Google Scholar 

  • Leferink JG, Wagemaker-Engels I, Maes RAA, Lamont H, Pauwels R, Straeten van der M (1977) Qualitative analysis of terbutaline in serum and urine at therapeutic levels using gas chromatography mass spectrometry. J Chromatogr 143: 299–305

    Google Scholar 

  • MacDonald AG, Ingram CG, McNeill RS (1967) The effect of propranolol on airway resistance. Br J Anaesth 39: 919–926

    Google Scholar 

  • Mitenko PA, Ogilvie RJ (1973) Rational intravenous doses of theophylline. N Engl J Med 289: 600–603

    Google Scholar 

  • Meurs H, Kauffman HF, Koëter GH, Vries de K (1980) Extraction of cyclic AMP for the determination in the competitive protein binding assay. Clin Chim Acta 106: 91–97

    Google Scholar 

  • O'Bryne PM, Ryan G, Morris M, McCormack D, Jones NL, Morse JLC, Hargreave FE (1982) Asthma induced by cold air and its relation to non-specific bronchial responsiveness to methacholine. Am Rev Respir Dis 125: 281–285

    Google Scholar 

  • Salomé CM, Schaeffel RE, Woolcock AJ (1981) Effect of aerosol and oral fenoterol on histamine and methacholine challenge in asthmatic subjects. Thorax 36: 580–584

    Google Scholar 

  • Tiffeneau R (1958) Hypersensibilité cholinergo-histaminique pulmonaire de l'asthmatique. Relations avec l'hypersensibilité allergenique. Acta Allergol [Suppl 5] 187–221

    Google Scholar 

  • Vries de K, Koëter GH, Gökemeyer JDM (1982) Some aspects of the regulation of the bronchial tree in obstructive lung disease. Eur J Respir Dis 63 [Suppl 121]: 60–63

    Google Scholar 

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Koëter, G.H., Meurs, H., Jonkman, J.H.G. et al. Protective effect of oral oxyphenonium bromide, terbutaline and theophylline against the bronchial obstructive effects of inhaled histamine, acetylcholine and propranolol. Eur J Clin Pharmacol 26, 435–441 (1984). https://doi.org/10.1007/BF00542137

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  • DOI: https://doi.org/10.1007/BF00542137

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