Drugs

, Volume 20, Issue 4, pp 237–266 | Cite as

Ipratropium Bromide: A Review of its Pharmacological Properties and Therapeutic Efficacy in Asthma and Chronic Bronchitis

  • G. E. Pakes
  • R. N. Brogden
  • R. C. Heel
  • T. M. Speight
  • G. S. Avery
Evaluations on New Drugs

Abstract

Synopsis

Ipratropium bromide1 is an anticholinergic bronchodilator administered by inhalation. Although producing bronchodilation in most patients with obstructive airways disease, it is somewhat less effective than β2-adrenoceptor agonist drugs such as salbutamol or fenoterol in patients with asthma, but is at least as effective as these agents in bronchitis. As with the β2-adrenoceptor agonists, the onset of maximum effect with ipratropium (about 1.5 to 2 hours) is slower than with isoprenaline (although significant bronchodilation usually occurs within seconds or minutes of ipratropium inhalation), and the duration of effect (about 4 to 6 hours) is longer. Studies of concomitant use of ipratropium and other agents such as β2-adrenoceptor agonists, theophylline, or sodium cromoglycate, have usually shown a greater response in many patients than with single drug therapy, as might be expected from the different mechanisms of action of these groups of drugs. Usual inhaled doses of ipratropium were well tolerated in all studies.

Ipratropium thus appears to be a suitable alternative to β2-adrenoceptor agonist drugs in patients not fully responding to these agents, and combined therapy with ipratropium and other bronchodilating drugs may prove to be an important area of use in patients failing to respond adequately to a single drug regimen. (Nevertheless, in asthma patients in whom a ‘non-responsive’ state is developing, initiation of corticosteroid therapy should not be delayed). Ipratropium may also be useful in the occasional patient in whom side effects such as palpitations or tremor are troublesome with usual inhaled doses of β2-adrenoceptor agonists.

Pharmacodynamic Studies

Ipratropium is an anticholinergic agent which produces bron-chodilation probably by inhibiting cholinergic bronchomotor tone. In studies to measure the protective effect of ipratropium against experimental bronchospasm, it was most effective against cholinergic challenges (as might be expected), providing little protection against serotonin or histamine-induced bronchospasm, and moderate protection against bronchospasm induced by propranolol or common allergens. The protective effect against exercise-induced bronchospasm was variable, probably at least partially depending on the extent of cholinergic involvement in the disease process in individual patients. Although some bron-chodilator response occurs rapidly following ipratropium inhalation (50% of the eventual maximum response within the first few minutes), the onset of maximum effect is relatively slow (about 1.5 to 2 hours). The duration of significant bronchodilation is about 4 to 6 hours with usual doses. The maximum bronchodilator response occurs with a dose of 20 to 40 or 80μg, higher doses providing no increase in response in most studies. Neither mucociliary clearance nor the volume or viscosity of respiratory secretions were altered by usual doses of ipratropium in short term studies. As with usual doses of other inhaled bronchodilator drugs, the effects of bronchodilating doses of inhaled ipratropium are confined primarily to the respiratory tract. No cardiovascular changes have occurred following inhalation of usual doses in patients or after up to 280μg in healthy subjects; intravenous administration increases heart rate, arterial blood pressure, cardiac output and peripheral blood flow while decreasing central venous pressure. Oxygen saturation of arterial blood does not seem to be altered by ipratropium inhalation in usual dosage, but such studies have not been done in already severely hypoxic patients which comprise the ‘at risk’ population for this paradoxical effect which may occur with isoprenaline.

Pharmacokinetic Studies

About 30 % of an oral dose of ipratropium bromide is absorbed, and a lesser fraction when the drug is given by inhalation. Peak plasma concentrations are attained after both dosage forms at 3 hours; plasma concentrations with equi-effective (bronchodilation) doses are about 1000 times lower after inhalation than after oral administration. Inhaled ipratropium is metabolised to 8 metabolites, and is excreted in approximately equal proportions in the faeces and urine. The metabolites have little or no anticholinergic activity in vitro. The elimination half-life of ipratropium is 3.2 to 3.8 hours by all routes of administration.

Therapeutic Trials

Most trials with ipratropium have made reasonable attempts to minimise the effects of natural variability of obstructive airways disease through standard study design principles, but many studies did not clearly differentiate between asthma and bronchitic conditions. In single dose or short term studies ipratropium aerosol (usually 40 or 80μg) was an effective bronchodilator in most patients, but in patients with asthma its maximum bronchodilator effect on the whole was somewhat less than that achieved with usual inhaled doses of β2drenoceptor agonist drugs such as salbutamol or fenoterol. However, unlike the β2-adrenoceptor agonists, which may be most effective in atopic asthma, ipratropium had a similar effect in both atopic and nonatopic patients. In patients with chronic bronchitis ipratropium and β2-agonist drugs were usually about equally effective, although in a few studies ipratropium produced greater bronchodilation. As occurs with other inhaled bronchodilators, systemic corticosteroid requirements in steroid-dependent patients were usually reduced during ipratropium therapy. In a small number of longer term studies ipratropium remained effective during continuous administration for up to several years. Indeed, in some studies the response appeared to improve after several months of treatment. Ipratropium has been successfully used in children with obstructive airways diseases, but may be less effective than salbutamol in preventing exercise-induced bronchospasm in such patients. Studies of combined treatment with ipratropium and (β2-adrenoceptor agonists, or other agents such as theophylline or sodium cromoglycate, have generally found a greater response in many patients than with single drug treatment, but such differences were not always statistically significant. Further well designed studies are needed to confirm the apparent increased effect of combined therapy, and to identify those types of patients who might benefit most from such treatment.

Side Effects

Usual inhaled doses of ipratropium are well tolerated, and do not appear to exert important systemic effects. With the exception of transient local effects reported in about 20 to 30 % of patients in some studies (but not mentioned in most reports), such as dryness in the mouth, ‘scratching’ in the trachea, or a ‘bad’ taste in the mouth, no adverse effects have occurred.

Dosage

The recommended prophylactic inhaled dose of ipratropium in adults or children is 20 to 40μg (1 to 2 puffs of the metered aerosol) 3 times daily. For an acute attack of bronchospasm, 2 to 3 additional puffs may be inhaled. However, the relatively gradual onset and late peak of bronchodilation with ipratropium suggest that it is more suitable for regular prophylactic use than for rapid symptomatic relief of acute bronchospasm. As with other aerosol bronchodilators, the correct administration technique is most important; the physician and pharmacist should ensure that the patient clearly understands the method of administration.

Keywords

Asthma Salbutamol Chronic Bronchitis Sodium Cromoglycate Ipratropium 

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References

  1. Addis, C.J.; Barclay, J. and Chang, E.M.: Assessment of a combination of doses of fenoterol and ipratropium suitable for a single metered-dose aerosol. European Journal of Clinical Pharmacology 16: 97–100 (1979).PubMedGoogle Scholar
  2. Adlung, J.; Gohle, KD., Zeren, S. and Wahl, D.: Studies of pharmacokinetics and biotransformation of ipratropium in man. Arzneimittel-Forschung 26: 1005–1010 (1976).PubMedGoogle Scholar
  3. Ahonen, A.; Alanko, K. and Mattson, K.: Bronchodilator action of two different doses of ipratropium bromide (SCH 1000) compared with fenoterol and placebo. Current Therapeutic Research 24: 65–75 (1978).Google Scholar
  4. Ajewski, Z. and Popiak, B.: The relation between permanent administration of Atrovent and the dose of steroid in chronic bronchitis. Scandinavian Journal of Respiratory Diseases, Suppl. 103: 205 (1979).Google Scholar
  5. Alanko, K. and Poppius, H.: Anticholinergic blocking of prostaglandin F2 alpha-induced bronchoconstriction. Postgraduate Medical Journal (abstract 3/1) 51 (Suppl.7): 101 (1975).Google Scholar
  6. Allen, C.J. and Campbell, A.H.: Dose response of ipratropium bromide assessed by two methods. Thorax 35: 137–139 (1980).PubMedGoogle Scholar
  7. Anastasatu, C. and Dutu, S.: Effect of inhalation of an atropine derivative (SCH 1000) on airway resistance to flow and on specific conductance in patients with chronic obstructive bronchopneumopathy. Ftiziologic 23: 305–310 (1974).Google Scholar
  8. Anderson, S.D.; Seale, J.P.; Ferris, L.; Schoeffel, R. and Lindsay, D.A.: An evaluation of pharmacotherapy for exercise-induced asthma. Journal of Allergy and Immunology 64: 612–624 (1979).Google Scholar
  9. Assem, E.S.K. and Schild, H.D.: Inhibition by sympathomimetic amines of histamine release induced by antigen in passively sensitised human lung. Nature 224: 1028–1029 (1969).PubMedGoogle Scholar
  10. Baigelman, W. and Chodosh, S.: Bronchodilator action of the anticholinergic drug, ipratropium bromide (SCH 1000), as an aerosol in chronic bronchitis and asthma. Chest 71: 324–328 (1977).PubMedGoogle Scholar
  11. Barber, P.V.; Chatterjee, S.S. and Scott, R.: A comparison of ipratropium bromide, deptropine citrate and placebo in asthma and chronic bronchitis. British Journal of Diseases of the Chest 71: 101–104 (1977).PubMedGoogle Scholar
  12. Baronti, A. and Grieco, A.: A comparative trial of bronchodilator effects of fenoterol and SCH 1000 in chronic bronchitis. Bulletin Europeen de Physiopathologie Respiratoire 12: 533–543 (1976).Google Scholar
  13. Bauer, R.: Pharmacological relationship between the action of SCH 1000 on the airways and on other systems. Effects following different modes of administration. Postgraduate Medical Journal (abstract 1/2) 51 (Suppl.7): 91 (1975).Google Scholar
  14. Bauer, R. and Kummer, F.: Doppelblindstudie zum Vergleich der broncholytischen Wirkung eines neuen Fropasäure-Derivates mit Isoprenalin. International Journal of Clinical Pharmacology 8: 135–145 (1973).Google Scholar
  15. Bauer, R. and Kummer, F.: Zur Wirkung eines Tropasäure-Esters auf den Bronchospasmus. Doppelblindstudie zum Vergleich verschiedener Dosierungen mit Placebo. Wien Klinische Wochenschrift 87: 132–136 (1975).Google Scholar
  16. Bauer, R.; Püschmann, S. and Wick, H.: The effect of (8γ)-3α-hy-droxy-8-isopropyl-1 αH, 5αH-tropariumbromide-(±)-tropate (ipratropium bromide) on tracheobronchial spasm, bronchial and salivary secretions, ECG and heart rate. Arzneimittel-Forschung 26: 981–985 (1976).PubMedGoogle Scholar
  17. Beumer, H.M.: Antagonistic effect of several doses of inhaled SCH 1000 administered by metered dose inhaler (MDI) or a Bird respirator on acetylcholine-induced bronchospasm (abstract no. 3/2). Postgraduate Medical Journal 51 (Suppl. 7): 101–102 (1975).Google Scholar
  18. Bewtra, A.; Nain, N. and Townley, R.G.: Protection of SCH 1000 and metaproterenol against bronchoconstriction. Clinical Pharmacology and Therapeutics (abstract) 21: 98 (1977).Google Scholar
  19. Bleichert, A.: Effects of atropine sulphate MDI and SCH 1000 MDI in low and very high dosages on salivation and pulse rate in healthy volunteers (abstract no. 5/2). Postgraduate Medical Journal 51(Suppl. 7): 112 (1975a).Google Scholar
  20. Bleichert, A.: Effects on salivation and heart rate following intravenous injection of SCH 1000 and SCH 1000 MDI in healthy volunteers (abstract no. 1/3). Postgraduate Medical Journal 51(Suppl. 7): 92 (1975b).Google Scholar
  21. Bleichen, A.: Problem of side effects of anticholinergic drugs depending on the route of administration: inhalation versus intravenous injection of ipratropium bromide. Arzneimittel-Forschung 26: 1010–1013 (1976).Google Scholar
  22. Böhning, W. and Fabel, H.: Comparison of the onset of action of SCH 1000 and orciprenaline given by metered dose inhaler (MDI) (abstract no. 2/1). Postgraduate Medical Journal 51 (Suppl. 7): 95 (1975).Google Scholar
  23. Borum, P. and Mygind, N.: Ipratropium inhibition of hypersecretion in the nose. Journal of Allergy and Clinical Immunology 65: 187 (1980).Google Scholar
  24. Borum, P.; Larsen, F.S. and Mygind, N.: Nasal methacholine provocation and ipratropium therapy of perennial rhinitis. Acta Oto-Laryngologica (Stockholm) Suppl. 360: 35 (1979).Google Scholar
  25. Borut, T.C.; Tashkin, DP.; Fischer, T.J.; Katz, R.; Rachelefsky, G.; Siegel, S.C.; Lee, E. and Harper, C.: Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children. Journal of Allergy and Clinical Immunology 60: 127–133 (1977).PubMedGoogle Scholar
  26. Brinkmann, O.: The results of long-term treatment with SCH 1000 MDI on repeated measurements of FEV1.0, total airways resistance (Rt), haematological and biochemical tests in patients with chronic bronchitis and emphysema. Postgraduate Medical Journal (abstract 8/1) 51 (Suppl. 7): 130 (1975).Google Scholar
  27. Brittain, R.T.; Dean, C.M. and Jack, D.: Sympathomimetic bronchodilator drugs. Pharmacology and Therapeutics Bulletin 2: 423–462 (1976).Google Scholar
  28. Casali, L.; Grassi, C.; Rampulla, C. and Rossi, A.: Clinical pharmacology of a combination of bronchodilators. International Journal of Clinical Pharmacology and Biopharmacy 7: 277–280 (1979).Google Scholar
  29. Chan-Yeung, M.: The effect of SCH 1000 and disodium cromoglycate on exercise-induced asthma. Chest 71: 320–323 (1977).PubMedGoogle Scholar
  30. Chapman, T.T.: Effect of SCH 1000 MDI and salbutamol MDI on ventilatory function in patients with chronic bronchitis, assessed by spirometry (abstract no. 5/3). Postgraduate Medical Journal 51 (Suppl. 7): 112–113 (1975).Google Scholar
  31. Chervinsky, P.: Double-blind study of ipratropium bromide, a new anticholinergic bronchodilator. The Journal of Allergy and Clinical Immunology 59: 22–30 (1977).PubMedGoogle Scholar
  32. Coleman, A.J.; Leary, U.P. and Kaul, D.S.: Haemodynamic effects of SCH 1000 in normal subjects (abstract no. 6/1). Postgraduate Medical Journal 51 (Suppl. 7): 121 (1975).Google Scholar
  33. Cummiskey, J. and Keelan, P.: Study of SCH 1000 MDI used in therapeutic doses in patients with chronic bronchitis. Postgraduate Medical Journal (abstract 8/2) 51 (Suppl. 7): 130 (1975).Google Scholar
  34. Cummiskey, J.; Keelan, P.; Gray, P. and Cox, G.A.: Ipratropium bromide aerosol in chronic bronchitis. Journal of the Irish Medical Association 70: 445–447 (1977).PubMedGoogle Scholar
  35. Davies, D.S.: Pharmacokinetics of inhaled substances. Postgraduate Medical Journal 51 (Suppl. 7): 69–75 (1975).PubMedGoogle Scholar
  36. Deckers, W.: The chemistry of new derivatives of tropane alkaloids and the pharmacokinetics of a new quaternary compound. Postgraduate Medical Journal 51 (Suppl. 7): 76 (1975).PubMedGoogle Scholar
  37. De Vries, K.: Protective effect of inhaled SCH 1000 on bronchoconstriction induced by serotonin, histamine, acetylcholine and propranolol (abstract no. 3/12). Postgraduate Medical Journal 51 (Suppl. 7): 106 (1975).Google Scholar
  38. Dotevall, G. and Walan, A.: Long-term effect of ipratropium bromide on gastric secretion. Arzneimittel-Forschung 28: 2163–2165 (1978).PubMedGoogle Scholar
  39. Douglas, N.J.; Davidson, I.; Sudlow, M.F. and Flenley, D.C.: Bronchodilatation and the site of airway resistance in severe chronic bronchitis. Thorax 34: 51–56 (1979).PubMedGoogle Scholar
  40. Dry, J.; Pradalier, A.; Leynadier, F. and Herman, D.: Recherche d’une prévention de la bronchoconstriction induite par une épreuve d’efforts chez l’asthmatique par un atropinique de synthese: le SCH 1000. Thérapie 32: 181–188 (1977).PubMedGoogle Scholar
  41. Emirgil, C.; Dwyer, K.; Baskette, P. and Sobol, B.J.: A new parasympatholytic bronchodilator: a study of its onset of effect after inhalation. Current Therapeutic Research 17: 215–224 (1975).PubMedGoogle Scholar
  42. Engelhardt, A.: Pharmacology and toxicity of Atrovent. Scandinavian Journal of Respiratory Diseases (Suppl. 103): 110–115 (1979).Google Scholar
  43. Engelhardt, A. and Klupp, H.: The pharmacology and toxicology of a new tropane alkaloid derivative. Postgraduate Medical Journal 51 (Suppl. 7): 82–84 (1975).PubMedGoogle Scholar
  44. Fabel, H.; Hartmann, W. and Wettengel, R.: Effects on central haemodynamics and blood gas tensions following increasing doses of inhaled SCH 1000 MDI in patients with chronic obstructive lung disease (abstract no 6/2). Postgraduate Medical Journal 51 (Suppl. 7): 121 (1975).Google Scholar
  45. Fasske, E.; Juengst, G. and Themann, H.: The effect of a new parasympatholytic on the epithelium of the human bronchial mucosa: light and electron microscope investigations. Praxis der Pneumologie 27: 633 (1973).Google Scholar
  46. Förster, HJ.; Kramer, I.; Pook, K.-H. and Wahl, D.: Studies of pharmacokinetics and biotransformation of ipratropium bromide in rats and dogs. Arzneimittel-Forschung 26: 992–1005 (1976).PubMedGoogle Scholar
  47. Francis, R.A.; Thomson, M.L.; Pavia, D. and Douglas, R.B.: Ipratropium bromide: mucociliary clearance rate and airway resistance in normal subjects. British Journal of Diseases of the Chest 71: 173–178 (1977).PubMedGoogle Scholar
  48. Frith, P.A.; Ruffin, R.E.; Cockcroft, D.W. and Hargreave, F.E.: A comparison of the protective effect of SCH 1000 and fenoterol against bronchoconstriction induced by histamine and methacholine. Journal of Allergy and Clinical Immunology (abstract) 61: 175 (1978).Google Scholar
  49. Gamain, B.: Bronchoconstriction following inhalation of dust or acetylcholine and its reversibility by SCH 1000 MDI. Postgraduate Medical Journal (abstract 3/3) 51 (Suppl. 7): 102 (1975).Google Scholar
  50. Gayrard, P.; Orehek, J.; Charpin, J.: Effets bronchodilatateurs d’un atropinique de synthese: SCH 1000, aerosol-doseur. Revue Francaise des Maladies Respiratoires 1: 481–492 (1973).Google Scholar
  51. Gayrard, P.; Orehek, J.; Grimaud, Ch. and Charpin, J.: Bronchoconstriction due a l’inhalation de fumée de tabac: Effets comparés chez le sujet normal et l’asthmatique. Bulletin de Physio-Pathologie Respiratoire 10: 451–461 (1974).PubMedGoogle Scholar
  52. Grimaud, C.; Nicholi, M.M.; Delpiene, S. and Vanuxem, P.: Action of SCH 1000 M DI on blood gas tensions and alveolar ventilation in patients with chronic obstructive airways disease (COAD) (abstract no. 6/3). Postgraduate Medical Journal 51 (Suppl. 7): 121–123 (1975).Google Scholar
  53. Gross, N.J.: Dose-response study of the effect of SCH 1000 MDI on forced vital capacity (FVC), FEV1.0, maximal mid-expiratory flow (MMEF) and heart rate, ECG and blood pressure. Postgraduate Medical Journal (abstract 2/2) 51 (Suppl. 7): 95 (1975a).Google Scholar
  54. Gross, N.J.: SCH 1000: A new anticholinergic bronchodilator. American Review of Respiratory Disease 112: 823–828 (1975b).PubMedGoogle Scholar
  55. Günther, W. and Kamburoff, P.L.: The bronchodilator effect of a new anticholinergic drug, SCH 1000. Current Medical Research and Opinion 2: 281–287 (1974).PubMedGoogle Scholar
  56. Gutersohn, J.; Joos, H. and Herzog, H.: Effect of Raw on SCH 1000 MDI or fenoterol MDI and the combined administration of subthreshold dosages of both compounds (abstract no. 5/6). Postgraduate Medical Journal 51 (Suppl. 7): 113–114 (1975).Google Scholar
  57. Hamm, J.: Human pharmacologic and therapeutic results with Atrovent. Wiener Medizinische Wochenschrift 124 (Suppl. 20: 7 (1974).Google Scholar
  58. Hamm, J.: FEV1.0 and heart rate following administration of equal dosages of SCH 1000 as an intravenous injection and by metered dose inhaler (MDI) in patients with chronic obstructive airways disease (abstract no. 1/4). Postgraduate Medical Journal 51 (Suppl. 7): 93 (1975).Google Scholar
  59. Harnett, J. and Spector, S.L.: Blocking effect of SCH 1000, isoproterenol, and the combination on methacholine and histamine inhalations. Journal of Allergy and Clinical Immunology (abstract 174) 57: 261 (1976).Google Scholar
  60. Haslreiter, E.: Haematological and biochemical monitoring during long-term treatment with SCH 1000 MDI in patients with chronic bronchitis and emphysema (abstract no 8.3). Postgraduate Medical Journal 51 (Suppl. 7): 130–131 (1975).Google Scholar
  61. Haynes, R.L.; Ingram, R.H. Jr. and McFadden, E.R. Jr. The effect of SCH 1000 and disodium cromoglycate on exercise-induced asthma. American Review of Respiratory Disease (abstract) 113 (Pt. 2): 252 (1976).Google Scholar
  62. Heel, R.C.; Brogden, R.N.; Speight, T.M. and Avery, G.S.: Fenoterol: A Review of its Pharmacological Properties and Therapeutic Efficacy in Asthma. Drugs 15: 3–32 (1978).PubMedGoogle Scholar
  63. Heller, K.F.: Changes in total airways resistance (Rt) and thoracic gas volume (TGV) following SCH 1000 MDI or placebo. Multiple dose study over 12 hours. Postgraduate Medical Journal (abstract 2/3) 51 (Suppl. 7): 96 (1975).Google Scholar
  64. Hensley, M.J.; O’Cain, C.F.; McFadden, E.R. and Ingram, R.H.: Distribution of bronchodilatation in normal subjects: beta agonist versus atropine. American Journal of Physiology 45: 778–782 (1978).Google Scholar
  65. Hofmann, D. and Wönne, R.: Action of SCH 1000 MDI and fenoterol on bronchial obstruction induced by allergen challenge. Postgraduate Medical Journal (abstract 7/1) 51 (Suppl. 7): 126 (1975).Google Scholar
  66. Holst, P.E.; Gebbie, T.; Martin, P.D. and O’Donell, T.V.: A long-term trial of ipratropium bromide in asthmatic patients (abstract). Australian and New Zealand Journal of Medicine 6: 367–368 (1976).Google Scholar
  67. Hüther, W.: Comparison of the effect of SCH 1000 and or-ciprenaline MDI in asthmatic infants and school children (abstract no. 7.2). Postgraduate Medical Journal 51 (Suppl. 7): 126–129 (1975).Google Scholar
  68. Ingram, R.H. and McFadden, ER.: Localization and mechanisms of airway responses. New England Journal of Medicine 297: 596–600 (1977).PubMedGoogle Scholar
  69. Iravani, J.: Action of some bronchodilatory compounds on flicker activity with special attention to Berotec. International Journal of Clinical Pharmacology and Biopharmacy (Suppl. 4): 20 (1972).Google Scholar
  70. Iravani, J. and Morris-Melville, G.: Ciliary movement following various concentrations of different anticholinergic and adrenergic bronchodilator solutions in animals (abstract no. 4/3). Postgraduate Medical Journal 51 (Suppl. 7): 108 (1975).Google Scholar
  71. Irsigler, G.: Flow volume curves and changes in FEV1.0, forced vital capacity (VC), mid and slow vital capacity (Mid VC and SVC) in patients with bronchial asthma or chronic bronchitis and emphysema following increasing dosages of SCH 1000 MDI (abstract no. 2/4). Postgraduate Medical Journal 51 (Suppl. 7): 96 (1975).Google Scholar
  72. Ishizaka, T.; Ishizaka, K.; Orange, R.P. and Austen, K.F.: Pharmacologic inhibition of the antigen-induced release of histamine and slow reacting substances of anaphylaxis (SRSA) from monkey lung tissues mediated by human IgE1. Journal of Immunology 106: 1267–1273 (1971).Google Scholar
  73. Jaffé, G.V.; Grimshaw, J.J. and Cox, G.A.: A comparative trial of Atrovent and Ventolin in chronic bronchitis. Practitioner 224: 443–446 (1980).Google Scholar
  74. Jilg, J.: Long-term treatment with SCH 1000 MDI in outpatients with chronic bronchitis (abstract no. 8.4). Postgraduate Medical Journal 51 (Suppl. 7): 131 (1975).Google Scholar
  75. Jorde, W. and Schata, M.: Inhibitory effect of β-adrenergic stimulants on the histamine reaction in human skin. Arzneimittel-Forschung 26: 2103–2105 (1976).PubMedGoogle Scholar
  76. Kaik, G.: Comparative investigations of the setting in the intensity of the bronchodilation of SCH 1000 and Berotec in patients with obstructive airway diseases. Therapiewoche 23: 3260–3268 (1973).Google Scholar
  77. Kaik, G.: Kombinierte Anwendung von Ipratropiumbromid (SCH 1000) und Fenoterol bei Patienten mit chronisch obstruktiver Atemwegserkrankurg. Wiener Klinische Wochenschrift 87: 653–656 (1975a).PubMedGoogle Scholar
  78. Kaik, G.: Investigations with the new bronchodilator ipratropium bromide (SCH 1000, Atrovent®). Therapiewoche 25: 2428–2444 (1975b).Google Scholar
  79. Kaik, G.: Onset of action and maximum effect of bronchodilators administered by a metered dose inhaler. Clinical investigations with fenoterol, hexoprenaline, ipratropium bromide, isoprenaline, orciprenaline, salbutamol and terbutaline. Wiener Klinische Wochenschrift 88: 674–679 (1976).PubMedGoogle Scholar
  80. Kaik, G.: Bronchospasmolytika und Ihre Klinische Pharmacologie (Urban & Schwarzenberg, München, Wien, Baltimore 1980).Google Scholar
  81. Kaliner, M.: Human lung tissue and anaphylaxis. I. The role of cyclic GMP as a modulator of the immunologically induced secretory process. Journal of Allergy and Clinical Immunology 60: 204–211 (1977).PubMedGoogle Scholar
  82. Kersten, W.: Protective effect of Atrovent® druing allergen provocation. Wiener Medizinische Wochenschrift 124 (Suppl. 21): 19 (1974).Google Scholar
  83. Killiam, D.; Mellon, A. and Hargreave, F.E.: Protective effect of drugs on histamine-induced asthma. Journal of Allergy and Clinical Immunology (abstract) 57: 263 (1976).Google Scholar
  84. Konietzko, N.; Mueller, M.; Adam, W.E. and Matthys, H.: Untersuchungen zur mukociliaren Clearance nach Anwendung von Atrovent bei Gesunden und Patienten mit chronischer Bronchitis. Wien Medizinische Wochenschrift 124 (Suppl. 21): 15–19 (1974).Google Scholar
  85. Kosche, F. and Stemman, E.A.: Peak flow measurements following SCH 1000 MDI in children with reversible airways obstruction (abstract no. 7/3). Postgraduate Medical Journal 51 (Suppl. 7): 127 (1975).Google Scholar
  86. Kreisman, H.; Frank, H.; Wolkove, N. and Gent, M.: Anticholinergic therapy in bronchial asthma: Synergistic effect of ipratropium and theophylline. American Review of Respiratory Disease 117: 142 (1978).Google Scholar
  87. Krieger, E.: Effect of 2 different types of bronchodilators on FEV 1.0, vital capacity (VC), and clinical features of airways obstruction in patients with chronic obstructive airways disease (abstract no. 5/9). Postgraduate Medical Journal 51 (Suppl. 7): 115 (1975).Google Scholar
  88. Krieger, E. and Reitberger, U.: Sputum rheology following treatment with SCH 1000 MDI and orciprenaline MDI. Postgraduate Medical Journal (abstract 4/4) 51 (Suppl. 7): 108 (1975).Google Scholar
  89. Kummer, F.: Acute effect of an adrenergic and a parasympatholytic bronchodilator on obstructive lung disease as assessed by total airways resistance (Rt) in a double-blind study (abstract 5/10). Postgraduate Medical Journal 51 (Suppl. 7): 115 (1975).Google Scholar
  90. Kunkel, G.; Rudolph, R. and Stock, U.: Dose-titration and longterm studies in asthmatic children (abstract no. 7/4). Postgraduate Medical Journal 51 (Suppl. 7): 127 (1975).Google Scholar
  91. Kutz, K.; Schuler, G.; Brenner, U. and Miederer, S.E.: Comparative study on the effect of anticholinergic substances on basic gastric secretion as well as on gastric secretion stimulated by pentagastrin or hypoglycemia. Klinische Wochenschrift 54: 485–492 (1976).PubMedGoogle Scholar
  92. Lahdensuo, A.; Viljanen, A.A. and Muittari, A.: A comparative study on the effect of SCH 1000 MDI, salbutamol and placebo MDI in bronchial asthma. Postgraduate Medical Journal (abstract 5/11) 51 (Suppl. 7): 116 (1975).Google Scholar
  93. Laitinen, L.A.; Poppius, H. and Haahtela, T.: Comparison of ipratropium bromide and salbutamol in a long-term trial in asthmatic and bronchitic patients in a cold climate. Scandinavian J. Respiratory Diseases, Suppl. 103: 163–169 (1979).Google Scholar
  94. Leitcn, A.G.; Hopkin, J.M.M.; Elliss, D.A.; Merchant, S. and McHardy, G.J.R.: The effect of aerosol, ipratropium bromide and salbutamol on exercise tolerance in chronic bronchitis. Thorax 33: 711–713 (1978).Google Scholar
  95. Lightbody, I.M.; Ingram, CG.; Legge, J.S. and Johnston, R.N.: Ipratropium bromide, salbutamol and prednisolone in bronchial asthma and chronic bronchitis. British Journal of Diseases of the Chest 72: 181–186 (1978).PubMedGoogle Scholar
  96. Lin, M.T.; Lee-Hong, E. and Collins-Williams, C.: A clinical trial of the bronchodilatory effect of SCH 1000 aerosol in asthmatic children. Annals of Allergy 40: 326–332 (1978).PubMedGoogle Scholar
  97. Linehan, W.D.: Effect of SCH 1000 and terbutaline given as MDI on ventilatory function in patients with asthma as measured by spirometry (abstract no. 5/12). Postgraduate Medical Journal 51 (Suppl. 7): 116 (1975).Google Scholar
  98. Loddenkemper, R.: Dose- and time-response of SCH 1000 MDI on total (Rt) and expiratory (Re) airways resistance in patients with chronic bronchitis and emphysema. Postgraduate Medical Journal (abstract 2/7) 51 (Suppl. 7): 97 (1975).Google Scholar
  99. Loddenkemper, R.: Ipratropium bromide, an anticholinergic bronchodilator: effect on airways resistance after inhalation of different doses in patients with reversible airway obstruction. Arzneimittel-Forschung 26: 1017–1020 (1976).PubMedGoogle Scholar
  100. Logvinoff-Poidatz, M. and Geubelle, F.: Effects of SCH 1000 MDI on the lung function in asthmatic children. Postgraduate Medical Journal (abstract 7/5) 51 (Suppl. 7): 127 (1975).Google Scholar
  101. Lulling, J.; Delwiche, J.P.; Ledent, C. and Prignot, J.: Controlled trial of the effect of repeated administration of ipratropium bromide on ventilatory function of patients with severe chronic airways obstruction. British Journal of Diseases of the Chest 74: 135–141 (1980).PubMedGoogle Scholar
  102. Maesen, F.P.V.: Comparison of the effects of SCH 1000 MDI and fenoterol MDI in patients with bronchial asthma and chronic bronchitis (abstract no. 5/13). Postgraduate Medical Journal 51 (Suppl. 7): 116–117 (1975).Google Scholar
  103. Maesen, F. and Buytendijk, H.J.: Dose- and time-response curves of SCH 1000 MDI and placebo. Differential response in asthmatics and bronchitics as measured by FEV1.0, vital capacity, blood pressure and heart rate. Postgraduate Medical Journal (abstract 2/8) 51 (Suppl. 7): 97 (1975).Google Scholar
  104. Marcq, M. and Minette, A.: Effects of SCH 1000 inhalation on arterial blood gases in patients with reversible airway obstruction. Acta Tuberculosea et Pneumologica Belgica 66: 429–433 (1975).PubMedGoogle Scholar
  105. Marlin, G.E.; Berend, N. and Harrison, A.C.: Combined cholinergic antagonist and (β2-adrenoceptor agonist bronchodilator therapy by inhalation. Australian and New Zealand Journal of Medicine 9: 511–514 (1979).PubMedGoogle Scholar
  106. Marlin, G.E.; Bush, D.E. and Berend, N.: Comparison of ipratropium bromide and fenoterol in asthma and chronic bronchitis (letter). British Journal of Clinical Pharmacology 6: 547–549 (1978).PubMedGoogle Scholar
  107. Matthys, H.; Muller, M. and Konietzko, N.: Quantitative and selective bronchial clearance studies using 99mTC-sulfate particles. Scandinavian Journal of Respiratory Disease 55 (Suppl. 85): 33–45 (1974).Google Scholar
  108. May, CS. and Palmer, K.N.V.: Effect of aerosol ipratropium bromide (Sch 1000) on sputum viscosity and volume in chronic bronchitis (letter). British Journal of Clinical Pharmacology 4: 491–492 (1977).PubMedGoogle Scholar
  109. Minette, A.: Haematological and biochemical results during long-term treatment with Sch 1000 (abstract no. 8/5). Postgraduate Medical Journal 51 (Suppl. 7): 131–132 (1975).Google Scholar
  110. Minette, A. and Marcq, M.: Experience with Atrovent in coal miners. Scandinavian Journal of Respiratory Diseases, Suppl. 103: 192–199 (1979).Google Scholar
  111. Minette, A.; Marcq, M.; Bruninx, M.; Spass, B. and Van Hove, G.: Results of a study on ventilatory and side effects of SCH 1000 aerosol in 54 patients with reversible bronchoconstriction. Revenue de l’Institut d’Hygiene des Mines 28: 22–38 (1973).Google Scholar
  112. Molkenboer, J.F.W.M. and Lardenoye, J.G.: The effect of Atrovent in micturition function, double blind cross over study. Scandinavian Journal of Respiratory Diseases, Suppl. 103: 155–158 (1979).Google Scholar
  113. Morr, H.: Immunological release of histamine from human lung. II. Studies on acetylcholine and the anticholinergic agent ipratropium bromide. Respiration 38: 273–279 (1979).PubMedGoogle Scholar
  114. Mygind, N.; Borum, P. and Larsen, F.S.: Nasal methacholine challenge and ipratropium treatment (abstract). Allergy 33: 336 (1978).Google Scholar
  115. Nair, N.S.; Bewtra, A.K.; Watt, G.D.; Burke, K.M. and Townley, R.G.: Protection by SCH-1000 and metaproterenol against bronchoconstriction. American Review of Respiratory Disease 115 (Abstract): 68 (1977).Google Scholar
  116. Niggeschulze, A. and Palmer, A.K.: Reproductive toxicological investigations with ipratropium bromide. Arzneimittel-Forschung 26: 989–992 (1976).PubMedGoogle Scholar
  117. Nolte, D.: Physiologic and therapeutic aspects of reflex bronchoconstriction. Wiener Medizinische Wochenschrift 124 (Suppl. 21): 22 (1974).Google Scholar
  118. Nolte, D.: Action of SCH 1000 MDI on experimental bronchoconstriction induced by various types of non-specific and pharmacodynamic irritants in young asthmatics (abstract no. 3/7). Postgraduate Medical Journal 51 (Suppl. 7): 103 (1975).Google Scholar
  119. Offermeier, J.: In vitro action of SCH 1000 against various spasmogens (abstract no. 3/8). Postgraduate Medical Journal 51 (Suppl. 7): 103–105 (1975).Google Scholar
  120. Orehek, J.; Gayrard, P.; Grimaud, Ch. and Carpin, J.: The role of SCH 1000 MDI in preventing changes in SRaw following grass pollen challenge in allergie asthmatics. Postgraduate Medical Journal (abstract 3/9) 51 (Suppl. 7): 105 (1975).Google Scholar
  121. Otto, V.P.: Study on inhibition of gastric juice secretion in man by the atropine derivative N-isopropylnortropine-tropa-acid-ester-bromomethylate. Arzneimittel-Forschung 23: 1334–1336 (1973).PubMedGoogle Scholar
  122. Otto, A.J.: Comparison of ipratropium bromide and an oral anticholinergic drug in chronic bronchitis. Scandinavian Journal of Respiratory Diseases Suppl. 103: 151–153 (1979).Google Scholar
  123. Palmer, K.N.V. and Petrie, J.C.: Respiratory diseases; in Avery (Ed) Drug Treatment, 2nd Edition, p.767 (ADIS Press, Sydney and New York; Churchill-Livingstone, Edinburgh 1980).Google Scholar
  124. Pavia, D.; Bateman, J.R.M.; Sheahan, N.F. and Clarke, S.W.: Effect of ipratropium bromide on mucociliary clearance and pulmonary function in reversible airways obstruction. Thorax 34: 501–507 (1979).PubMedGoogle Scholar
  125. Petersen, B.N. and Weeke, E.: A comparative study of the bronchodilating effects of ipratropium and terbutaline inhaled with Monaghan IPPB-M515 by 19 patients with chronic obstructive airways disease. Scandinavian Journal of Respiratory Diseases Suppl. 103: 178–182 (1979).Google Scholar
  126. Petrie, G.R. and Palmer, K.N.V.: Comparative trial of SCH 1000 MDI and salbutamol MDI in chronic bronchitis and bronchial asthma (abstract 5/16). Postgraduate Medical Journal 51 (Suppl. 7): 117–118 (1975).Google Scholar
  127. Poppius, H. and Salorinne, Y.: Comparative trial of a new anticholinergic bronchodilator, SCH 1000, and salbutamol in chronic bronchitis. British Medical Journal 4: 134–136 (1973).PubMedGoogle Scholar
  128. Poppius, H.; Salorinne, Y. and Viljanen, A.A.: Inhalation of a new anticholinergic drug SCH 1000, in asthma and chronic bronchitis: effect on airway resistance, thoracic gas volume, blood gases and exercise-induced asthma. Bulletin de Physiopathologie Respiratoire 8: 643–652 (1972).Google Scholar
  129. Poppius, H.; Salorinne, Y. and Viljanen, A.A.: Role of SCH 1000 MDI in preventing exercise-induced asthma. Postgraduate Medical Journal (abstract 3/10) 51 (Suppl. 7): 105 (1975).Google Scholar
  130. Puchelle, E. and Uffholtz, H.: Sputum viscoelasticity following administration of SCH 1000 MDI. Postgraduate Medical Journal (abstract 4/7) 51 (Suppl. 7): 109 (1975).Google Scholar
  131. Rasmussen, F.V.; Madsen, L. and Bundgaard, A.: Combined effect of an anticholinergic drug ipratropium bromide and disodium cromoglycate in exercise induced asthma. Scandinavian Journal of Respiratory Diseases Suppl. 103: 159–162 (1979).Google Scholar
  132. Rebuck, A.S. and Marcus, H.I.: SCH 1000 in psychogenic asthma. Scandinavian Journal of Respiratory Diseases (Suppl. 103): 186–191 (1979).Google Scholar
  133. Ritter, V. and Koch, C.D.: Haematological and biochemical monitoring of healthy volunteers receiving SCH 1000 MDI 3 times per day for 6 months (abstract no. 8/5). Postgraduate Medical Journal 51 (Suppl. 7): 132 (1975).Google Scholar
  134. Rominger, K.L.: Chemistry and pharmacokinetics of ipratropium bromide. Scandinavian Journal of Respiratory Diseases (Suppl. 7): 116–129 (1979).Google Scholar
  135. Rosenthal, RR.; Bleeker, ER.; Beth-Lanbe, B.A.; Norman, P.S. and Permutt, S.: Cholinergic response to histamine challenge. Journal of Allergy and Clinical Immunology (abstract no. 36) 61: 139 (1978).Google Scholar
  136. Rufiin, R.E.; Fitzgerald, J.D. and Rebuck, A.S.: A comparison of the bronchodilator activity of SCH 1000 and salbutamol. Journal of Allergy and Clinical Immunology 59: 136–141 (1977).Google Scholar
  137. Ruffin, R.E. and Newhouse, MX: Ipratropium bromide (SCH 1000) monohydrate aerosol: Bronchodilator effect of three dose levels in asthmatics. Lung 155: 141–146 (1978).PubMedGoogle Scholar
  138. Ruffin, R.E.; Wolff, P.K.; Dolovich, M.B.; Rossman, C.M.; Fitzgerald, J.D. and Newhouse, M.T.: Aerosol therapy with SCH 1000. Short-term mucociliary clearance in normal and bronchitic subjects and toxicology in normal subjects. Chest 73: 501–600 (1978).PubMedGoogle Scholar
  139. Sackner, M.A.; Chapman, G.A. and Cougherty, R.D.: Effects of nebulized SCH 1000 and atropine sulfate in anaesthetized dogs (abstract). American Review of Respiratory Disease 113: 131 (1976).Google Scholar
  140. Sarafana, L.; Clark, G.C. and Stotzer, H.: Toxicological studies on ipratropium bromide. Arzneimittel-Forschung 26: 985–989 (1976).PubMedGoogle Scholar
  141. Scherberger, R.-R.; Kaess, H. and Bruckner, S.: Studies on the action of an anticholinergic in combination with a tranquilizer on gastric juice secretion in man. Arzneimittel-Forschung 25: 1460 (1975).PubMedGoogle Scholar
  142. Scheufler, G.: Ophthalmotonometry, pupil diameter and visual accommodation following repeated administration of SCH 1000 MDI in patients with glaucoma (abstract no. 8/7). Postgraduate Medical Journal 51 (Suppl. 7): 132 (1975).Google Scholar
  143. Schindl, R.: Controlled comparison of SCH 1000 MDI with salbutamol and placebo MDI (abstract no. 5/19). Postgraduate Medical Journal 51 (Suppl. 7): 119 (1975).Google Scholar
  144. Schlueter, D.P. and Neumann, J.L.: Double-blind comparison of acute bronchial and ventilation-perfusion changes of Atrovent® and isoproterenol. Chest 73 (Suppl): 982–983 (1978).PubMedGoogle Scholar
  145. Schultz, G.: Possible interrelations between calcium and cyclic nucleotides in smooth muscle; in Lichtenstein and Austen (eds) Asthma, Physiology, Immunopharmacology and Treatments (Academic Press, New York 1977).Google Scholar
  146. Sergysels, R.; Schandevyl, W.; Yernault, J.C. and Hennebert, A.: The complementary effects of an anticholinergic and sympathicomimetic drug inhalation in patients with severe chronic obstructive lung disease. Acta Tuberculosea et Pneumologica Belgica 67: 163–173 (1976).PubMedGoogle Scholar
  147. Sill, V.; Voelkel, N.; Siemssen, S. and Manvede, S.: Effects of SCH 1000 MDI on the pulmonary circulation under hypoxic conditions (abstract no. 6/8). Postgraduate Medical Journal 51 (Suppl. 7): 124 (1975).Google Scholar
  148. Sill, V.; Voelkel, N.; Lanser, K. and Manvede, S.: Bronchospasmolysis with Atrovent®. Munchener Medizinische Wochenschrift 118: 177–180 (1976).PubMedGoogle Scholar
  149. Simonsson, B.G.: Acute effects of ipratropium bromide (ITBR, SCH 1000, Atrovent): a review of previous studies. Scandinavian Journal of Respiratory Diseases Suppl. 103: 130–139 (1979).Google Scholar
  150. Simonsson, B.G.; Jonson, B. and Strom, B.: Bronchodilatory and circulatory effects of inhaling increasing doses of an anticholinergic drug, ipratropium bromide (SCH 1000). Scandinavian Journal of Respiratory Disease 56: 138–149 (1975).Google Scholar
  151. Sorenby, L.: The β-adrenoceptors of the lung mediating inhibition of antigen-induced histamine release. European Journal of Pharmacology 30: 140–147 (1975).PubMedGoogle Scholar
  152. Spector, S. and Ball, R.E. Jr.: Bronchodilating effects of aerosolized SCH 1000 and atropine sulfate in asthmatics. Chest 68: 426 (1975).Google Scholar
  153. Stemman, E.A. and Kosche, F.: Comparison of the effect of SCH 1000 MDI, sodium cromoglycate and beta-adrenergic drugs on exercise-induced asthma in children (abstract no. 3/11). Postgraduate Medical Journal 51 (Suppl. 7): 105–106 (1975).Google Scholar
  154. Stemman, E.A.; Muller, K.; Kosche, F.; Both, A. and Braun, S.H.: Lung function tests in the diagnosis and treatment of bronchial asthma in childhood. Praxis Pneumologie 29: 83–88 (1975).Google Scholar
  155. Storms, W.W.; DoPico, G.A. and Reed, C.E.: Aerosol SCH 1000: An anticholinergic bronchodilator. American Review of Respiratory Disease 111: 419 (1975).PubMedGoogle Scholar
  156. Stresemann, E.: Brief communication: measuring the effect of ipratropium bromide on bronchial secretion by rotation viscometry — a double-blind study. Arzneimittel-Forschung 26: 1013–1015 (1976a).PubMedGoogle Scholar
  157. Stresemann, E.: Time-response determinations from analysis of pulmonary function following ipratropium-bromide and isoprenaline. Arzneimittel-Forschung 26: 1015–1017 (1976b).Google Scholar
  158. Strietzel, G.: Ein atropinderivat zur Behandlung bronchospastischen Zustande (Doppeltblindversuch mit Lungenfunktionsprufung). Praxis der Pneumologie 28: 681–692 (1974)Google Scholar
  159. Su, C. and Bevan, J.A.: Pharmacology of pulmonary blood vessels. Pharmacology and Therapeutics (B) 2: 275–288 (1976).Google Scholar
  160. Thiessen, B. and Pedersen, O.F.: A double-blind crossover study of maximal expiration flows and arterial blood gas tensions in normals, asthmatics and bronchitics after salbutamol and ipratropium. Scandinavian Journal of Respiratory Diseases (Suppl. 103): 170–177 (1979).Google Scholar
  161. Thomson, N.C.; Patel, K.R. and Kerr, J.W.: Sodium cromoglycate and ipratropium bromide in exercise-induced asthma. Thorax 33: 694–699 (1978).PubMedGoogle Scholar
  162. Thumm, H.W.: Does Atrovent® manifest atropine-like side effects in the eye. Therapie der Gegenwart 115: 1244–1254 (1976).PubMedGoogle Scholar
  163. Ulmer, W.T.: Inhalation therapy with atropine derivatives. Medizinische Klinik 66: 326–329 (1971).PubMedGoogle Scholar
  164. Ulmer, W.T.: Repeated measurements of total airways resistance (Rt), intrathoracic gas volume (TGV), PaO2, PaCO2 and clinical features in patients with chronic obstructive lung disease during long-term treatment with SCH 1000 inhalations. Postgraduate Medical Journal (abstract 8/9) 51 (Suppl. 7): 133 (1975).Google Scholar
  165. Vastag, E.; Nagy, L. and Miskovitz, G.: Therapeutic value of anticholinergic agents in chronic obstructive pulmonary diseases. European Journal of Clinical Pharmacology 10: 201–208 (1976).Google Scholar
  166. Verstraeten, J.M.: L’association d’un atropinique (SCH 1000) et d’une substance sympathicomimétique peut-elle améliorer la bronchodilatation obtenue par un sympathicomimétique seul?. Acta Tuberculosea et Pneumologica Belgica 65: 395 (1974).PubMedGoogle Scholar
  167. Verstraeten, J.M.: Is there a selective indication for a parasympatholytic (Atrovent) and for a β-sympathomimetic (Berotec) in asthma and asthmatic bronchitis? Acta Tuberculosea et Pneumologic Belgica 67. 130–155 (1976).Google Scholar
  168. Verstraeten, J.M.: Bronchial response of asthmatic and bronchitic patients to fenoterol MDI with or without subsequent SCH 1000 MDI. Postgraduate Medical Journal (abstract 5/23) 51 (Suppl. 7): 120 (1975).Google Scholar
  169. Vlagopoulos, T.; Townley, R.G.; Ghazanshahi, S.; Bewtra, A. and Burke, K.: Comparison of the bronchodilating effects of SCH 1000 with isoproterenol in patients with bronchial asthma. Annals of Allergy 36: 223–230 (1976).PubMedGoogle Scholar
  170. Ward, R.M.; Singh, S. and Mirkin, B.L.: Fetal clinical pharmacology; in Avery (ed) Drug Treatment, 2nd Edition, pp. 77–96 (ADIS Press, Sydney; Churchill Livingstone, Edinburgh, 1980).Google Scholar
  171. Weinberg, E.G.: Experience with SCH 1000 MDI in the treatment of exercise-induced asthma in children. Postgraduate Medical Journal (abstract 7/7) 51 (Suppl. 7): 128 (1975).Google Scholar
  172. Wettengel, R.: Effects of SCH 1000 MDI in patients with mitral stenosis (abstract no. 6/10). Postgraduate Medical Journal 51 (Suppl. 7): 125 (1975).Google Scholar
  173. Wick, H.; Bauer, R. and Puschmann, S.: Atrovent, a new way in the treatment of chronic bronchial obstruction. Acta Tuberculosea et Pneumologie Belgica 67: 174–183 (1976).Google Scholar
  174. Wieser, O. and Konigshofer, R.: Dose-response study of SCH 1000 MDI on heart rate, ECG and blood pressure in healthy volunteers (abstract no. 6/11). Postgraduate Medical Journal 51 (Suppl. 7): 125 (1975).Google Scholar
  175. Wildbolz, U.; Kyd, K. and Scherrer, M.: Ipratropium in addition to theophylline-sustained betastimulation. Lung 154: 141–142 (1977).Google Scholar
  176. Wönne, R.; Kattan, M.; Orange, R.P. and Levison, H.: Bronchial hyperreactivity to histamine and methacholine in asthmatic children after inhalation of SCH 1000 and chlorphennamine maleate. Journal of Allergy and Clinical Immunology 62: 119–124 (1978).Google Scholar
  177. Wolkove, N.; Kreisman, H.; Frank, H. and Gent, M.: The effect of ipratropium on exercise-induced asthma. Journal of Allergy and Clinical Immunology (abstract no. 61) 63: 153 (1979).Google Scholar
  178. Wood, M.J. and Paterson, J.W.: Evaluation of cumulative doses of SCH 1000 in asthmatics (abstract no. 2/13). Postgraduate Medical Journal 51 (Suppl. 7): 100 (1975).Google Scholar
  179. Yeager, H. Jr.; Weinberg, R.H.; Kaufman, L.V. and Katz, S.: Asthma: comparative bronchodilator effects of ipratropium bromide and isoproterenol. Journal of Clinical Pharmacology 16: 198–204 (1976).PubMedGoogle Scholar
  180. Yernault, J.C.; Dejonghe, M.; Denaut, M.; Englert, M. and DeCoster, A.: Effects of SCH 1000 metered dose aerosol in patients with bronchial asthma and chronic bronchitis. Acta Tuberculosea et Pneumologie Belgica 66: 421–427 (1975).Google Scholar
  181. Yeung, R.; Nolan, G.M. and Levison, H.: Comparison of the effects of inhaled SCH 1000 and fenoterol on exercise-induced bronchospasm in children. Pediatrics 66: 109–114 (1980).PubMedGoogle Scholar
  182. Zeren, S.: Haematological and biochemical values in patients with chronic bronchitis and emphysema treated with SCH 1000 MDI over 3 months. Postgraduate Mediel Journal (abstract 8/11) 51 (Suppl. 7): 133–134 (1975).Google Scholar

Copyright information

© ADIS Press Australasia Pty Ltd. 1980

Authors and Affiliations

  • G. E. Pakes
    • 1
  • R. N. Brogden
    • 1
  • R. C. Heel
    • 1
  • T. M. Speight
    • 1
  • G. S. Avery
    • 1
  1. 1.Australasian Drug Information ServicesBirkenhead, Auckland 10New Zealand

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