Anticholinergic Bronchodilators

  • Nicholas J. Gross


Anticholinergic agents are among the oldest known bronchodilators. They have been used for many centuries in the Indian subcontinent in the form of the leaves of Datura stramonium [1]. The active ingredients were identified by German chemists in the mid-19th century as the alkaloids, atropine and scopolamine, among others. These naturally occurring anticholinergic agents were widely used throughout Europe until they were replaced by adrenergic agents and methylxanthines in the early 20th century. In part, their disappearance was due to their rapid absorption from mucosal surfaces and the skin, which caused undesirable side effects.


Chronic Obstructive Pulmonary Disease Ipratropium Bromide Anticholinergic Agent Stable Chronic Obstructive Pulmonary Disease Tiotropium Bromide 
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References and Recommended Reading

  1. 1.
    Gandevia B: Historical review of the use of parasympatholytic agents in the treatment of respiratory disorders. Postgrad Med J 1975, 51(suppl):13–20PubMedGoogle Scholar
  2. 2.
    Gross NJ, Skorodin SM: Anticholinergic, antimuscarinic bronchodilators. Am Rev Respir Dis 1984, 129:856–870.PubMedGoogle Scholar
  3. 3.
    Richardson JB: The innervation of the lung. Eur J Respir Dis 1982, 117(suppl):13–31.Google Scholar
  4. 4.
    Widdicombe JG: The parasympathetic nervous system in airways disease. Scand J Respir Dis 1979, 103(suppl):38–43.Google Scholar
  5. 5.
    Nadel JA: Autonomic regulation of airway smooth muscle. In Physiology and Pharmacology of the Airways. Edited by Nadel JA. New York: Marcel Dekker; 1980:217–257.Google Scholar
  6. 6.
    Shah PK, Lakhotia M, Mehta S, et al.: Clinical dysautonomia in patients with bronchial asthma: study with seven autonomic function tests. Chest 1990, 98:1408–1413.PubMedCrossRefGoogle Scholar
  7. 7.
    Gross NJ, Co E, Skorodin MS: Cholinergic bronchomotor tone in COPD: estimates of its amount in comparison with that in normal subjects. Chest 1989, 96:984–987.PubMedCrossRefGoogle Scholar
  8. 8.
    Gross NJ, Barnes PJ: A short tour around the muscarinic receptor. Am Rev Respir Dis 1988, 138:765–767.PubMedCrossRefGoogle Scholar
  9. 9.
    Fryer AD, Jacoby DB: Parainfluenza virus infection damages inhibitory M2 muscarinic receptors on pulmonary parasympathetic nerves in the guinea-pig. Br J Pharmacol 1991, 102:267–271.PubMedCrossRefGoogle Scholar
  10. 10.
    Fryer AD, Jacoby DB: Effect of inflammatory cell mediators on M2 muscarinic receptors in the lungs. Life Sci 1993, 52:529–536.PubMedCrossRefGoogle Scholar
  11. 11.
    O’Connor BJ, Towse LJ, Barnes PJ: Prolonged effect of tiotropi-um bromide on methacholine-induced bronchoconstriction in asthma. Am J Respir Crit Care Med 1996, 154(4 pt 1):876–880.PubMedCrossRefGoogle Scholar
  12. 12.
    Maesen FP, Smeets JJ, Sledsens TJ, et al.: Tiotropium bromide, a new long-acting antimuscarinic bronchodilator: a pharmacodynamic study in patients with chronic obstructive pulmonary disease (COPD): Dutch Study Group. Eur Respir J 1995, 8:1506–1513.PubMedGoogle Scholar
  13. 13.
    Barnes PJ, Belvisi MG, Mak JC, et al.: Tiotropium bromide (Ba 679 BR), a novel long-acting muscarinic antagonist for the treatment of obstructive airways disease. Life Sci 1995, 56:853–859.PubMedCrossRefGoogle Scholar
  14. 14.
    Gross NJ, Skorodin MS: Massive overdose of atropine methoni-trate with only slight untoward effects [letter]. Lancet 1985, 2:386.PubMedCrossRefGoogle Scholar
  15. 15.
    Van Noord JA, Bantje TA, Eland ME: A randomised controlled comparison of triotropium and ipratropium in the treatment of chronic obstructive pulmonary disease. Thorax 2000, 55:289–294. This is an informative introduction into the properties and actions of this important new anticholinergic agent.PubMedCrossRefGoogle Scholar
  16. 16.
    Gross NJ, Skorodin M: Anticholinergic agents. In Drug Therapy. Edited by Jenne JW, Murphy S. New York: Marcel Dekker; 1987:615–668.Google Scholar
  17. 17.
    Gross NJ, Petty TL, Friedman M, et al.: Dose response to ipratropium as a nebulized solution in patients with chronic obstructive pulmonary disease: a three-center study. Am Rev Respir Dis 1989, 139:1188–1191.PubMedCrossRefGoogle Scholar
  18. 18.
    Bollert FG, Matusiewicz SP, Dewar MH, et al.: Comparative efficacy and potency of ipratropium via Turbuhaler and pressurized metered-dose inhaler in reversible airflow obstruction. Eur Respir J 1997, 10:1824–1828.PubMedCrossRefGoogle Scholar
  19. 19.
    Littner MR, Ilowite JS, Tashkin DP, et al.: Long-acting bronchodilation with once-daily dosing of tiotropium in stable chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000, 161:1136–1142. This is an informative introduction into the properties and role of this new anticholinergic agent in clinical practice.PubMedCrossRefGoogle Scholar
  20. 20.
    Ayala LE, Ahmed T: Is there loss of protective muscarinic receptor mechanism in asthma? Chest 1989, 96:1285–1291.PubMedCrossRefGoogle Scholar
  21. 21.
    Azevedo M, da Costa JT, Fontes P, et al.: Effect of terfenadine and ipratropium bromide on ultrasonically nebulized distilled water-induced asthma. J Int Med Res 1990, 18:37–49.PubMedGoogle Scholar
  22. 22.
    Ayala LE, Choudry NB, Fuller RW: LTD4-induced bronchocon-striction in patients with asthma: lack of a vagal reflex. Br J Clin Pharmacol 1988, 26:110–112.PubMedCrossRefGoogle Scholar
  23. 23.
    Ruffin RE, Fitzgerald JD, Rebuck AS: A comparison of the bronchodilator activity of Sch 1000 and salbutamol. J Allergy Clin Immunol 1977, 59:136–141.PubMedCrossRefGoogle Scholar
  24. 24.
    Ullah MI, Newman GB, Saunders KB: Influence of age on response to ipratropium and salbutamol in asthma. Thorax 1981, 36:523–529.PubMedCrossRefGoogle Scholar
  25. 25.
    Vichyanond P, Sladek WA, Sur S, et al: Efficacy of atropine methylnitrate alone and in combination with albuterol in children with asthma. Chest 1990, 98:637–642.PubMedCrossRefGoogle Scholar
  26. 26.
    Jolobe OM: Asthma vs. non-specific reversible airflow obstruction: clinical features and responsiveness to anticholinergic drugs. Respiration 1984, 45:237–242.PubMedCrossRefGoogle Scholar
  27. 27.
    Rebuck AS, Chapman KR, Abboud R, et al.: Nebulized anticholinergic and sympathomimetic treatment of asthma and chronic obstructive airways disease in the emergency room. Am J Med 1987, 82:59–64.PubMedCrossRefGoogle Scholar
  28. 28.
    Stoodley RG, Aaron SD, Dales RE: The role of ipratropium bromide in the emergency management of acute asthma exacerbation: a meta-analysis of randomized clinical trials. Ann Emerg Med 1999, 34:8–18.PubMedCrossRefGoogle Scholar
  29. 29.
    Brophy C, Ahmed B, Bayston S, et al.: How long should Atrovent be given in acute asthma? Thorax 1998, 53:363–367.PubMedCrossRefGoogle Scholar
  30. 30.
    Beck R, Robertson C, Galdes-Sebaldt M, Levison H: Combined salbutamol and ipratropium bromide by inhalation in the treatment of severe acute asthma. J Pediatr 1985, 107:605–608.PubMedCrossRefGoogle Scholar
  31. 31.
    Reisman J, Galdes-Sebalt M, Kazim F, et al.: Frequent administration by inhalation of salbutamol and ipratropium bromide in the initial management of severe acute asthma in children. J Allergy Clin Immunol 1988, 81:16–20.PubMedCrossRefGoogle Scholar
  32. 32.
    Ducharme FM, Davis GM: Randomized controlled trial of ipratropium bromide and frequent low doses of salbutamol in the management of mild and moderate acute pediatric asthma. J Pediatr 1998, 133:479–485.PubMedCrossRefGoogle Scholar
  33. 33.
    Schuh S, Johnson DW, Callahan S, et al.: Efficacy of frequent nebulized ipratropium bromide added to frequent high-dose albuterol therapy in severe childhood asthma. J Pediatr 1995, 126:639–645.PubMedCrossRefGoogle Scholar
  34. 34.
    Zorc JJ, Pusic MV, Ogborn CJ, et al.: Ipratropium bromide added to asthma treatment in the pediatric emergency department. Pediatrics 1999, 103(4 pt l):748–752.PubMedCrossRefGoogle Scholar
  35. 35.
    Qureshi F, Pestian J, Davis P, Zaritsky A: Effect of nebulized ipratropium on the hospitalization rates of children with asthma. N Engl J Med 1998, 339:1030–1035.PubMedCrossRefGoogle Scholar
  36. 36.
    Plotnick L, Ducharme F: Should inhaled anticholinergics be added to β2 agonists for treating acute childhood and adolescent asthma? A systematic review. Br Med J 1998, 317:971–977.CrossRefGoogle Scholar
  37. 37.
    Warner JO, Gotz M, Landau LI, et al.: Management of asthma: a consensus statement. Arch Dis Child 1989, 64:1065–1079.PubMedCrossRefGoogle Scholar
  38. 38.
    Hargreave FE, Dolovich J, Newhouse MT: The assessment and treatment of asthma: a conference report. J Allergy Clin Immunol 1990, 85:1098–1111.PubMedCrossRefGoogle Scholar
  39. 39.
    Thiessen B, Pedersen OF: Maximal expiratory flows and forced vital capacity in normal, asthmatic and bronchitic subjects after salbutamol and ipratropium bromide. Respiration 1982, 43:304–316.PubMedCrossRefGoogle Scholar
  40. 40.
    Passamonte PM, Martinez AJ: Effect of inhaled atropine or metaproterenol in patients with chronic airway obstruction and therapeutic serum theophylline levels. Chest 1984, 85:610–615.PubMedCrossRefGoogle Scholar
  41. 41.
    Gross NJ, Skorodin MS: Role of the parasympathetic system in airway obstruction due to emphysema. N Engl J Med 1984, 311:421–425. This study shows that optimal dosage of an anticholinergic agent provides all the available bronchodilation in COPD.PubMedCrossRefGoogle Scholar
  42. 42.
    Siafakas NM, Vermeire P, Pride NB, et al.: Optimal assessment and management of chronic obstructive pulmonary disease (COPD): the European Respiratory Society Task Force. Eur Respir J 1995, 8:1398–1420.PubMedCrossRefGoogle Scholar
  43. 43.
    American Thoracic Society: Standards for the diagnosis and care of patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1995, 152(5 pt 2):S77–121. This is the current document on optimal management of COPD in the United States. It provides specific recommendations that are still appropriate. Google Scholar
  44. 44.
    Anthonisen NR, Connett JE, Kiley JP, et al.: Effects of smoking intervention and the use of an inhaled anticholinergic bronchodilator on the rate of decline of FEV1: the Lung Health Study. JAMA 1994,272:1497–1505. This is the definitive study on the importance of smoking cessation in COPDy its effect on subsequent airflow, and the lack of long-term benefit of iratropium.PubMedCrossRefGoogle Scholar
  45. 45.
    Rennard SI, Serby CW, Ghafouri M, et al.: Extended therapy with ipratropium is associated with improved lung function in patients with COPD: a retrospective analysis of data from seven clinical trials. Chest 1996, 110:62–70.PubMedCrossRefGoogle Scholar
  46. 46.
    Martin RJ, Bucher-Bartleson BL, Smith P, et al.: Effect of ipratropium bromide treatment on oxygen saturation and sleep quality in COPD. Chest 1999, 115:1338–1345.PubMedCrossRefGoogle Scholar
  47. 47.
    Karpel JP, Pesin J, Greenberg D, Gentry E: A comparison of the effects of ipratropium bromide and metaproterenol sulfate in acute exacerbations of COPD. Chest 1990, 98:835–839.PubMedCrossRefGoogle Scholar
  48. 48.
    Patrick DM, Dales RE, Stark RM, et al.: Severe exacerbations of COPD and asthma: incremental benefit of adding ipratropium to usual therapy. Chest 1990, 98:295–297.PubMedCrossRefGoogle Scholar
  49. 49.
    Koutsogiannis Z, Kelly A: Does high dose ipratropium bromide added to salbutamol improve pulmonary function for patients with chronic obstructive airways disease in the emergency department? Aust NZJ Med 2000, 0:38–40.CrossRefGoogle Scholar
  50. 50.
    British Thoracic Society: Guidelines for the management of chronic obstructive pulmonary disease. Thorax 1996, 52(suppl):1–28.Google Scholar
  51. 51.
    Petty TL: In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent alone: an 85-day multicenter trial: Inhalation Aerosol Study Group. Chest 1994, 105:1411–1419.CrossRefGoogle Scholar
  52. 52.
    Ikeda A, Nishimura K, Koyama H, Izumi T: Bronchodilating effects of combined therapy with clinical dosages of ipratropium bromide and salbutamol for stable COPD: comparison with ipratropium bromide alone. Chest 1995, 07:401–405.CrossRefGoogle Scholar
  53. 53.
    The COMBIVENT Inhalation Solution Study Group: Routine nebulized ipratropium and albuterol together are better than either alone in COPD. Chest 1997, 112:1514–1521.CrossRefGoogle Scholar
  54. 54.
    Friedman M, Serby CW, Menjoge SS, et al.: Pharmacoeconomic evaluation of a combination of ipratropium plus albuterol compared with ipratropium alone and albuterol alone in COPD. Chest 1999, 115:635–641.PubMedCrossRefGoogle Scholar
  55. 55.
    Gross N, Tashkin D, Miller R, Oren J, et al.: Inhalation by nebulization of albuterol-ipratropium combination (Dey combination) is superior to either agent alone in the treatment of chronic obstructive pulmonary disease. Respiration 1998, 65:354–362.PubMedCrossRefGoogle Scholar
  56. 56.
    Gross NJ: Ipratropium bromide. N Engl J Med 1988, 319:486–494.PubMedCrossRefGoogle Scholar
  57. 57.
    Watson WT, Shuckett EP, Becker AB, Simons FE: Effect of nebulized ipratropium bromide on intraocular pressures in children. Chest 1994, 105:1439–1441.PubMedCrossRefGoogle Scholar
  58. 58.
    Pavia D, Bateman JR, Sheahan NF, Clarke SW: Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction. Thorax 1979, 34:501–507.PubMedCrossRefGoogle Scholar
  59. 59.
    Tobin MJ, Hughes JA, Hutchison DC: Effects of ipratropium bromide and fenoterol aerosols on exercise tolerance. Eur J Respir Dis 1984, 65:441–446.PubMedGoogle Scholar
  60. 60.
    Chapman KR, Smith DL, Rebuck AS, Leenen FH: Haemodynamic effects of inhaled ipratropium bromide, alone and combined with an inhaled beta 2-agonist. Am Rev Respir Dis 1985, 132:845–847.PubMedGoogle Scholar
  61. 61.
    Ashutosh K, Dev G, Steele D: Nonbronchodilator effects of pirbuterol and ipratropium in chronic obstructive pulmonary disease. Chest 1995, 107:173–178.PubMedCrossRefGoogle Scholar
  62. 62.
    Gross NJ, Bankwala Z: Effects of an anticholinergic bronchodilator on arterial blood gases of hypoxaemic patients with chronic obstructive pulmonary disease: comparison with a beta-adrenergic agent. Am Rev Respir Dis 1987, 36:1091–1094.CrossRefGoogle Scholar
  63. 63.
    Koukhaz G, Gross NJ: Effects of salmeterol on arterial blood gases in patients with stable chronic obstructive pulmonary disease: comparison with albuterol and ipratropium. Am J Respir Crit Care Med 1999, 160:1028–1030.CrossRefGoogle Scholar
  64. 64.
    Leak A, O’Connor T: High dose ipratropium bromide: is it safe? Practitioner 1988, 232:9–10.PubMedGoogle Scholar
  65. 65.
    Samter M, Beers RF Jr: Intolerance to aspirin. Clinical studies and consideration of its pathogenesis. Ann Intern Med 1968, 68(5):975–983.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media New York 2003

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  • Nicholas J. Gross

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