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Inhaled β2-Adrenoceptor Agonists

Cardiovascular Safety in Patients with Obstructive Lung Disease

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Abstract

Although large surveys have documented the favourable safety profile of β2-adrenoceptor agonists (β2-agonists) and, above all, that of the long-acting agents, the presence in the literature of reports of adverse cardiovascular events in patients with obstructive airway disease must induce physicians to consider this eventuality. The coexistence of β1- and β2-adrenoceptors in the heart clearly indicates that β2-agonists do have some effect on the heart, even when they are highly selective. It should also be taken into account that the β2-agonists utilised in clinical practice have differing selectivities and potencies. β2-agonist use has, in effect, been associated with an increased risk of myocardial infarction, congestive heart failure, cardiac arrest and sudden cardiac death. Moreover, patients who have either asthma or chronic obstructive pulmonary disease may be at increased risk of cardiovascular complications because these diseases amplify the impact of these agents on the heart and, unfortunately, are a confounding factor when the impact of β2-agonists on the heart is evaluated. Whatever the case may be, this effect is of particular concern for those patients with underlying cardiac conditions. Therefore, β2-agonists must always be used with caution in patients with cardiopathies because these agents may precipitate the concomitant cardiac disease.

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Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Pauwels RA, Buist AS, Calverley PM, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: NHLBI/WHO Global Initiative for Chronic Obstructive Lung Disease (GOLD) workshop summary. Am J Respir Crit Care Med 2001; 163: 1256–76

    PubMed  CAS  Google Scholar 

  2. Bennett A, Tattersfield AE. Time course and relative dose potency of systemic effects from salmeterol and salbutamol in healthy subjects. Thorax 1997; 52: 458–64

    Article  PubMed  CAS  Google Scholar 

  3. Lipworth BJ, McDevitt DG. Inhaled β2-adrenoceptor agonists in asthma: help or hindrance? Br J Clin Pharmacol 1992; 33: 129–38

    Article  PubMed  CAS  Google Scholar 

  4. Wong CS, Pavord ID, Williams J, et al. Bronchodilator, cardiovascular, and hypokalaemic effects of fenoterol, salbutamol, and terbutaline in asthma. Lancet 1990; 336: 1396–9

    Article  PubMed  CAS  Google Scholar 

  5. Jouven X, Desnos M, Guerot C, et al. Predicting sudden death in the population: the Paris Prospective Study I. Circulation 1999; 99: 1978–83

    Article  PubMed  CAS  Google Scholar 

  6. de Bruyne MC, Hoes AW, Kors JA, et al. QTc dispersion predicts cardiac mortality in the elderly: the Rotterdam Study. Circulation 1998; 97: 467–72

    Article  PubMed  Google Scholar 

  7. Manttari M, Oikarinen L, Manninen V, et al. QT dispersion as a risk factor for sudden cardiac death and fatal myocardial infarction in a coronary risk population. Heart 1997; 78: 268–72

    PubMed  CAS  Google Scholar 

  8. Copie X, Hnatkova K, Staunton A, et al. Predictive power of increased heart rate versus depressed left ventricular ejection fraction and heart rate variability for risk stratification after myocardial infarction: results of a two-year follow-up study. J Am Coll Cardiol 1996; 27: 270–6

    Article  PubMed  CAS  Google Scholar 

  9. Siegel D, Hulley SB, Black DM, et al. Diuretics, serum and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men. JAMA 1992; 267: 1083–9

    Article  PubMed  CAS  Google Scholar 

  10. Olsson SB. Nature of cardiac arrhythmias and electrolyte disturbances: role of potassium in atrial fibrillation. Acta Med Scand Suppl 1981; 647: 33–7

    PubMed  CAS  Google Scholar 

  11. Fisch C. Relation of electrolyte disturbances to cardiac arrhythmias. Circulation 1973; 47: 408–19

    Article  PubMed  CAS  Google Scholar 

  12. Bristow MR. β-Adrenergic receptor blockade in chronic heart failure. Circulation 2000; 101: 558–69

    Article  PubMed  CAS  Google Scholar 

  13. Brodde OE. β1- and β2-adrenoceptors in the human heart: properties, function and alterations in chronic heart failure. Pharmacol Rev 1991; 43: 203–42

    PubMed  CAS  Google Scholar 

  14. Bristow MR, Ginsburg R, Umans V, et al. β1- and β2-adrenergic-receptor subpopulations in nonfailing and failing human ventricular myocardium: coupling of both receptor subtypes to muscle contraction and selective β1-receptor down-regulation in heart failure. Circ Res 1986; 59: 297–309

    Article  PubMed  CAS  Google Scholar 

  15. Xiao RP, Cheng H, Zhou YY, et al. Recent advances in cardiac β2-adrenergic signal transduction. Circ Res 1999; 85: 1092–100

    Article  PubMed  CAS  Google Scholar 

  16. Rodefeld MD, Beau SL, Schuessler RB, et al. β-adrenergic and muscarinic cholinergic receptor densities in the human sinoatrial node: identification of a high β2-adrenergic receptor density. J Cardiovasc Electrophysiol 1996; 7: 1039–49

    Article  PubMed  CAS  Google Scholar 

  17. Newton GE, Parker JD. Acute effects of β1-selective and non-selective β-adrenergic receptor blockade on cardiac sympathetic activity in congestive heart failure. Circulation 1996; 94: 353–8

    Article  PubMed  CAS  Google Scholar 

  18. Brodde OE, Michel MC. Adrenergic and muscarinic receptors in the human heart. Pharmacol Rev 1999; 51: 651–90

    PubMed  CAS  Google Scholar 

  19. Xiao RP, Zhu W, Zheng M, et al. Subtype-specific β-adrenoceptor signaling pathways in the heart and their potential clinical implications. Trends Pharmacol Sci 2004; 25: 358–65

    Article  PubMed  CAS  Google Scholar 

  20. Clark RB, Knoll BJ, Barber R. Partial agonists and G protein-coupled receptor desensitization. Trends Pharmacol Sci 1999; 20: 279–86

    Article  PubMed  CAS  Google Scholar 

  21. Hanania NA, Sharafkhaneh A, Barber R, et al. β-Agonist intrinsic efficacy: measurement and clinical significance. Am J Respir Crit Care Med 2002; 165: 1353–8

    Article  PubMed  Google Scholar 

  22. Qing F, Rahman SU, Rhodes CG, et al. Pulmonary and cardiac β-adrenoceptor density in vivo in asthmatic subjects. Am J Respir Crit Care Med 1997; 55: 1130–4

    Google Scholar 

  23. Johnson M. Salmeterol. Med Res Rev 1995; 15: 225–57

    Article  PubMed  CAS  Google Scholar 

  24. Johnson M, Butchers PR, Coleman RA, et al. The pharmacology of salmeterol. Life Sci 1993; 52: 2131–43

    Article  PubMed  CAS  Google Scholar 

  25. Grønnerød TA, von Berg A, Schwabe G, et al. Formoterol via Turbuhaler gave better protection than terbutaline against repeated exercise challenge for up to 12 hours in children and adolescents. Respir Med 2000; 94: 661–7

    Article  PubMed  Google Scholar 

  26. Pönicke K, Heinroth-Hoffmann I, Brodde O-E. Role of β1- and β2-adrenoceptors in hypertrophic and apoptotic effects of noradrenaline and adrenaline in adult rat ventricular cardiomyocytes, Naunyn-Schmiedebergs. Arch Pharmacol 2003; 367: 592–9

    Article  CAS  Google Scholar 

  27. Brodde OE, Leineweber K. Autonomic receptor systems in the failing and aging human heart: similarities and differences. Eur J Pharmacol 2004; 500: 167–76

    Article  PubMed  CAS  Google Scholar 

  28. Sato N, Vatner SF, Shen YT, et al. Effects of cardiac denervation on development of heart failure and catecholamine desensitization. Circulation 1997; 95: 2130–40

    Article  PubMed  CAS  Google Scholar 

  29. Lakatta EG, Gerstenblith G, Angell CS, et al. Diminished inotropic response of aged myocardium to catecholamines. Circ Res 1975; 36: 262–9

    Article  PubMed  CAS  Google Scholar 

  30. Fleg JL, Tzankoff SP, Lakatta EG. Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males. J Appl Physiol 1985; 59: 1033–9

    PubMed  CAS  Google Scholar 

  31. White M, Roden R, Minobe W, et al. Age-related changes in β-adrenergic neuroeffector systems in the human heart. Circulation 1994; 90: 1225–38

    Article  PubMed  CAS  Google Scholar 

  32. Xiao RP, Tomhave ED, Wang DJ, et al. Age-associated reductions in cardiac β1- and β2-adrenergic responses without changes in inhibitory G proteins or receptor kinases. J Clin Invest 1998; 101: 1273–82

    Article  PubMed  CAS  Google Scholar 

  33. Maesen FPV, Costongs R, Smeets JJ, et al. The effect of maximal doses of formoterol and salbutamol from a metered dose inhaler on pulse rates, ECG, and serum potassium concentrations. Chest 1991; 99: 1367–73

    Article  PubMed  CAS  Google Scholar 

  34. Lemaitre RN, Siscovick DS, Psaty BM, et al. Inhaled β2 adrenergic receptor agonists and primary cardiac arrest. Am J Med 2002; 113: 711–6

    Article  PubMed  CAS  Google Scholar 

  35. Au D, Lemaitre R, Curtis J, et al. The risk of myocardial infarction associated with inhaled β-adrenoceptor agonists. Am J Respir Crit Care Med 2000; 161: 827–30

    PubMed  CAS  Google Scholar 

  36. Coughlin SS, Metayer C, McCarthy EP, et al. Respiratory illness, β-agonists, and risk of idiopathic dilated cardiomyopathy: the Washington, DC, Dilated Cardiomyopathy Study. Am J Epidemiol 1995; 142: 395–403

    PubMed  CAS  Google Scholar 

  37. Martin R, Dunn N, Freemantle S, et al. Risk of non-fatal cardiac failure and ischaemic heart disease with long acting β2-agonists. Thorax 1998; 53: 558–62

    Article  PubMed  CAS  Google Scholar 

  38. Newhouse MT, Chapman KR, McCallum AL, et al. Cardiovascular safety of high doses of inhaled fenoterol and albuterol in acute severe asthma. Chest 1996; 110: 595–603

    Article  PubMed  CAS  Google Scholar 

  39. Palmqvist M, Ibsen T, Mellen A, et al. Comparison of the relative efficacy of formoterol and salmeterol in asthmatic patients. Am J Respir Crit Care Med 1999; 160: 244–9

    PubMed  CAS  Google Scholar 

  40. Jartti T, Kaila T, Tahvanainen K, et al. The acute effects of inhaled salbutamol on the beat-to-beat variability of heart rate and blood pressure assessed by spectral analysis. Br J Clin Pharmacol 1997; 43: 421–8

    Article  PubMed  CAS  Google Scholar 

  41. Kaya D, Barutcu I, Esen AM, et al. Comparison of the effects of ipratropium bromide and salbutamol on autonomie heart rate control. Europace 2004; 6: 602–7

    Article  PubMed  Google Scholar 

  42. Salpeter SR, Ormiston TM, Salpeter EE. Cardiovascular effects of β-agonists in patients with asthma and COPD: a meta-analysis. Chest 2004; 125: 2309–21

    Article  PubMed  CAS  Google Scholar 

  43. Sears MR. Adverse effects of β-agonists. J Allergy Clin Immunol 2002; 110 (6 Suppl.): S322–8

    Article  PubMed  CAS  Google Scholar 

  44. Bennett JA, Smyth ET, Pavord ID, et al. Systemic effects of salbutamol and salmeterol in patients with asthma. Thorax 1994; 49: 771–4

    Article  PubMed  CAS  Google Scholar 

  45. Braden GL, Germain MJ, Mulhern JG, et al. Hemodynamic, cardiac, and electrolyte effects of low-dose aerosolized terbutaline sulfate in asthmatic patients. Chest 1998; 114: 380–7

    Article  PubMed  CAS  Google Scholar 

  46. Braun SR, Levy SF. Comparison of ipratropium bromide and albuterol in chronic obstructive pulmonary disease: a three-center study. Am J Med 1991; 91: 28S-32S

    Article  Google Scholar 

  47. Buch J, Bundgaard A. Cardiovascular effects of intramuscular or inhaled terbutaline in asthmatics. Acta Pharmacol Toxicol (Copenh) 1984; 54: 183–8

    Article  CAS  Google Scholar 

  48. Burgess C, Ayson M, Rajasingham S, et al. The extrapulmonary effects of increasing doses of formoterol in patients with asthma. Eur J Clin Pharmacol 1998; 54: 141–7

    Article  PubMed  CAS  Google Scholar 

  49. Burggraaf J, Westendorp RGJ, in’t Veen JCCM, et al. Cardiovascular side effects of inhaled salbutamol in hypoxic asthmatic patients. Thorax 2001; 56: 567–9

    Article  PubMed  CAS  Google Scholar 

  50. Chan CK, Loke J, Snyder PE, et al. Oral terbutaline augments cardiac performance in chronic obstructive pulmonary disease. Am J Med Sci 1988; 296: 33–8

    Article  PubMed  CAS  Google Scholar 

  51. Marlin GE, Bush DE, Berend N. Comparison of ipratropium bromide and fenoterol in asthma and chronic bronchitis. Br J Clin Pharmacol 1978; 6: 547–9

    Article  PubMed  CAS  Google Scholar 

  52. Vathenen AS, Britton JR, Ebden P, et al. High-dose inhaled albuterol in severe chronic airflow limitation. Am Rev Respir Dis 1988; 138: 850–5

    Article  PubMed  CAS  Google Scholar 

  53. Riding WD, Dinda P, Chatterjee SS. The bronchodilator and cardiac effects of five pressure-packed aerosols in asthma. Br J Dis Chest 1970; 64: 37–45

    Article  PubMed  CAS  Google Scholar 

  54. Bremner P, Woodman K, Burgess C, et al. A comparison of the cardiovascular and metabolic effects of formoterol, salbutamol and fenoterol. Eur Respir J 1993; 6: 204–10

    PubMed  CAS  Google Scholar 

  55. Bremner P, Burgess C, Beasley R, et al. Nebulized fenoterol causes greater cardiovascular and hypokalaemic effects than equivalent bronchodilator doses of salbutamol in asthmatics. Respir Med 1992; 86: 419–23

    Article  PubMed  CAS  Google Scholar 

  56. Tandon MK. Cardiopulmonary effects of fenoterol and salbutamol aerosols. Chest 1980; 77: 429–31

    Article  PubMed  CAS  Google Scholar 

  57. Gray BJ, Frame MH, Costello JF. A comparative double-blind study of the bronchodilator effects and side effects of inhaled fenoterol and terbutaline administered in equipotent doses. Br J Dis Chest 1982; 76: 341–50

    Article  PubMed  CAS  Google Scholar 

  58. Crane J, Burgess C, Beasley R. Cardiovascular and hypokalaemic effects of inhaled salbutamol, fenoterol, and isoprenaline. Thorax 1989; 44: 136–40

    Article  PubMed  CAS  Google Scholar 

  59. Lipworth BJ, McDevitt DG. β-Adrenoceptor responses to inhaled salbutamol in normal subjects. Eur J Clin Pharmacol 1989; 36: 239–45

    Article  PubMed  CAS  Google Scholar 

  60. Lipworth BJ, Struthers AD, McDevitt DG. Tachyphylaxis to systemic but not to airway responses during prolonged therapy with high dose inhaled salbutamol in asthmatics. Am Rev Respir Dis 1989; 140: 586–92

    PubMed  CAS  Google Scholar 

  61. Lipworth BJ, Clark RA, Dhillon DP, et al. β-Adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma. Br J Clin Pharmacol 1988; 26: 527–33

    Article  PubMed  CAS  Google Scholar 

  62. Paterson JW, Connolly ME, Davies DS, et al. Isoprenaline resistance and the use of pressurised aerosols in asthma. Lancet 1968; II: 426–9

    Article  Google Scholar 

  63. Lipworth BJ, Clark RA, Dhillon DP, et al. Comparison of the effects of prolonged treatment with low and high doses of inhaled terbutaline on β-adrenoceptor responsiveness in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1990; 142: 338–42

    PubMed  CAS  Google Scholar 

  64. Nemec J, Hejlik JB, Shen WK, et al. Catecholamine-induced T-wave lability in congenital long QT syndrome: a novel phenomenon associated with syncope and cardiac arrest. Mayo Clin Proc 2003; 78: 40–50

    Article  PubMed  Google Scholar 

  65. Chao CL, Chen WJ, Chen MF, et al. Torsade de pointes in a patient using usual dose of beta agonist therapy. Int J Cardiol 1996; 57: 295–6

    Article  PubMed  CAS  Google Scholar 

  66. Lipworth B. Revisiting interactions between hypoxaemia and β2-agonists in asthma. Thorax 2001; 56: 506–7

    Article  PubMed  CAS  Google Scholar 

  67. Finn AF, Thompson CM, Banov CH, et al. β2-Agonist induced ventricular dysrhythmias secondary to hyperexcitable conduction system in the absence of a long QT syndrome. Ann Allergy Asthma Immunol 1997; 78: 230–2

    Article  PubMed  CAS  Google Scholar 

  68. Kiely DG, Cargill RI, Grove A, et al. Abnormal myocardial repolarisation in response to hypoxaemia and fenoterol. Thorax 1995; 50: 1062–6

    Article  PubMed  CAS  Google Scholar 

  69. Jackson CM, Lipworth B. Benefit-risk assessment of long-acting β2-agonists in asthma. Drug Saf 2004; 27(4): 243–70

    Article  PubMed  CAS  Google Scholar 

  70. Cazzola M, Donner CF. Long-acting β2 agonists in the management of stable chronic obstructive pulmonary disease. Drugs 2000; 60(2): 307–20

    Article  PubMed  CAS  Google Scholar 

  71. Ostrom NK. Tolerability of short-term, high-dose formoterol in healthy volunteers and patients with asthma. Clin Ther 2003; 25: 2635–46

    Article  PubMed  CAS  Google Scholar 

  72. Lecaillon JB, Kaiser G, Palmisano M, et al. Pharmacokinetics and tolerability of formoterol in healthy volunteers after a single high dose of Foradil dry powder inhalation via Aerolizer. Eur J Clin Pharmacol 1999; 55: 131–8

    Article  PubMed  CAS  Google Scholar 

  73. Guhan AR, Cooper S, Oborne J, et al. Systemic effects of formoterol and salmeterol: a dose-response comparison in healthy subjects. Thorax 2000; 55: 650–6

    Article  PubMed  CAS  Google Scholar 

  74. Kemp JP, Bierman CW, Cocchetto DM. Dose-response study of inhaled salmeterol in asthmatic patients with 24-hour spirometry and Holter monitoring. Ann Allergy 1993; 70: 316–22

    PubMed  CAS  Google Scholar 

  75. Tunaoglu FS, Turktas I, Olgunturk R, et al. Cardiac side effects of long acting β-2 agonist salmeterol in asthmatic children. Pediatr Int 1999; 41: 28–31

    Article  PubMed  CAS  Google Scholar 

  76. Tranfa CME, Pelaia G, Grembiale RD, et al. Short-term cardiovascular effects of salmeterol. Chest 1998; 113: 1272–6

    Article  PubMed  CAS  Google Scholar 

  77. Chervinsky P, Goldberg P, Galant S, et al. Long-term cardiovascular safety of salmeterol powder pharmacotherapy in adolescent and adult patients with chronic persistent asthma. Chest 1999; 115: 642–8

    Article  PubMed  CAS  Google Scholar 

  78. Maesen FP, Costongs R, Smeets SJ, et al. Formoterol as dry powder inhalation: a dose finding study in comparison with formoterol metered dose inhaler and placebo. Chest 1992; 101: 1376–81

    Article  PubMed  CAS  Google Scholar 

  79. Totterman KJ, Huhti L, Sutinen E, et al. Tolerability to high doses of formoterol and terbutaline via Turbuhaler for 3 days in stable asthmatic patients. Eur Respir J 1998; 12(3): 573–9

    Article  PubMed  CAS  Google Scholar 

  80. Lanes SF, Lanza LL, Wentworth III CE. Risk of emergency care, hospitalization, and ICU stays for acute asthma among recipients of salmeterol. Am J Respir Crit Care Med 1998; 158: 857–61

    PubMed  CAS  Google Scholar 

  81. Malolepszy J, Böszörményi Nagy G, Selroos O, et al. Safety of formoterol Turbuhaler at cumulative dose of 90 μg in patients with acute bronchial obstruction. Eur Respir J 2001; 18: 928–34

    Article  PubMed  CAS  Google Scholar 

  82. Therapeutic Products Directorate: TPD-Web [online]. Available from URL: http://www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt/serevent_prof_e.html [Accessed 2005 Feb 20]

  83. Shih HT, Webb CR, Conway WA, et al. Frequency and significance of cardiac arrhythmias in chronic obstructive lung disease. Chest 1998; 94: 44–8

    Article  Google Scholar 

  84. Goldkorn A, Diotto P, Burgess C, et al. The pulmonary and extra-pulmonary effects of high-dose formoterol in COPD: a comparison with salbutamol. Respirology 2004; 9: 102–8

    Article  PubMed  Google Scholar 

  85. Ferguson GT, Funck-Brentano C, Fischer T, et al. Cardiovascular safety of salmeterol in COPD. Chest 2003; 123: 1817–24

    Article  PubMed  CAS  Google Scholar 

  86. Cazzola M, Imperatore F, Salzillo A, et al. Cardiac effects of formoterol and salmeterol in patients suffering from COPD with pre-existing cardiac arrhythmias and hypoxemia. Chest 1998; 114: 411–5

    Article  PubMed  CAS  Google Scholar 

  87. Cazzola M, D’Amato M, Califano C, et al. Formoterol as dry powder oral inhalation in comparison with salbutamol metered dose inhaler in acute exacerbations of chronic obstructive pulmonary disease. Clin Ther 2002; 24: 595–604

    Article  PubMed  CAS  Google Scholar 

  88. Cazzola M, Califano C, Di Perna F, et al. Acute effects of higher than customary doses of salmeterol and salbutamol in patients with acute exacerbation of COPD. Respir Med 2002; 96: 790–5

    Article  PubMed  CAS  Google Scholar 

  89. Cazzola M, Matera MG, D’Amato M, et al. Long-acting β2 agonists in the treatment of acute exacerbations of COPD. Clin Drug Invest 2002; 22: 369–76

    Article  CAS  Google Scholar 

  90. Cazzola M, Santus P, Matera MG, et al. A single high dose of fomoterol is as effective as the same dose administered in a cumulative manner in patients with acute exacerbation of COPD. Respir Med 2003; 97: 458–62

    Article  PubMed  CAS  Google Scholar 

  91. Meier CR, Jick SS, Derby LE, et al. Acute respiratory-tract infections and risk of first-time acute myocardial infarction. Lancet 1998; 351: 1467–71

    Article  PubMed  CAS  Google Scholar 

  92. Au DH, Curtis JR, Every NR, et al. Association between inhaled β-agonists and the risk of unstable angina and myocardial infarction. Chest 2002; 121: 846–51

    Article  PubMed  CAS  Google Scholar 

  93. Willich SN, Linderer T, Wegscheider K, et al. Increased morning incidence of myocardial infarction in the ISAM study: absence with prior beta-adrenergic blockade. ISAM Study Group. Circulation 1989; 80: 853–8

    CAS  Google Scholar 

  94. Tanaka S, Momose Y, Tsutsui M, et al. Quantitative estimation of myocardial fibrosis based on receptor occupancy for β2-adrenergic receptor agonists in rats. J Toxicol Sci 2004; 29: 179–86

    Article  PubMed  CAS  Google Scholar 

  95. Mason DA, Moore JD, Green SA, et al. A gain-of-function polymorphism in a G-protein coupling domain of the human β1-adrenergic receptor. J Biol Chem 1999; 274: 12670–4

    Article  PubMed  CAS  Google Scholar 

  96. Iwai C, Akita H, Kanazawa K, et al. Arg389Gly polymorphism of the human β1-adrenergic receptor in patients with nonfatal acute myocardial infarction. Am Heart J 2003; 146: 106–9

    Article  PubMed  CAS  Google Scholar 

  97. Rossinen J, Partanen J, Stenius-Aarniala B, et al. Salbutamol inhalation has no effect on myocardial ischaemia, arrhythmias and heart-rate variability in patients with coronary artery disease plus asthma or chronic obstructive pulmonary disease. J Intern Med 1998; 243: 361–6

    Article  PubMed  CAS  Google Scholar 

  98. Suissa S, Assimes T, Ernst P. Inhaled short acting β agonist use in COPD and the risk of acute myocardial infarction. Thorax 2003; 58: 43–6

    Article  PubMed  CAS  Google Scholar 

  99. Hole DJ, Watt GCM, Davey-Smith G, et al. Impaired lung function and mortality risk in men and women: findings from the Renfrew and Paisley prospective population study. BMJ 1996; 313: 711–5

    Article  PubMed  CAS  Google Scholar 

  100. Au DH, Udris EM, Curtis JR, et al. Association between chronic heart failure and inhaled β-2-adrenoceptor agonists. Am Heart J 2004; 148: 915–20

    Article  PubMed  CAS  Google Scholar 

  101. Sengstock DM, Obeidat O, Pasnoori V, et al. Asthma, β-agonists, and development of congestive heart failure: results of the ABCHF study. J Card Fail 2002; 8: 232–8

    Article  PubMed  CAS  Google Scholar 

  102. Brodde OE. β-Adrenoceptors in cardiac disease. Pharmacol Ther 1993; 60: 405–30

    Article  PubMed  CAS  Google Scholar 

  103. Bohm M. Alterations of β-adrenoceptor-G-protein-regulated adenylylcyclase in heart failure. Mol Cell Biochem 1995; 147: 147–60

    Article  PubMed  CAS  Google Scholar 

  104. Poller U, Fuchs B, Gorf A, et al. Terbutaline-induced desensitization of human cardiac β2-adrenoceptor-mediated positive inotropic effects: attenuation by ketotifen. Cardiovasc Res 1998; 40: 211–22

    Article  PubMed  CAS  Google Scholar 

  105. Schafers RF, Adler S, Daul A, et al. Positive inotropic effects of the β2-adrenoceptor agonist terbutaline in the human heart: effects of long-term β1-adrenoceptor antagonist treatment. J Am Coll Cardiol 1994; 23: 1224–33

    Article  PubMed  CAS  Google Scholar 

  106. Liggett SB, Wagoner LE, Craft LL, et al. The Ile164 β2-adrenergic receptor polymorphism adversely affects the outcome of congestive heart failure. J Clin Invest 1998; 102: 1534–9

    Article  PubMed  CAS  Google Scholar 

  107. Brode OE, Buscher R, Tellkamp R, et al. Blunted cardiac responses to receptor activation in subjects with Thr164Ile β2-adrenoceptors. Circulation 2001; 103: 1048–50

    Article  Google Scholar 

  108. Wagoner LE, Craft LL, Singh B, et al. Polymorphisms of the β2-adrenergic receptor determine exercise capacity in patients with heart failure. Circ Res 2000; 86: 834–40

    Article  PubMed  CAS  Google Scholar 

  109. Mahon NG, McKenna WJ. Genes and acquired disease: β-adrenoceptor polymorphisms and heart failure. Eur Heart J 2000; 21: 1810–2

    Article  PubMed  CAS  Google Scholar 

  110. Murray DR, Prabhu SD, Chandrasekar B. Chronic β-adrenergic stimulation induces myocardial proinflammatory cytokine expression. Circulation 2000; 101: 2338–41

    Article  PubMed  CAS  Google Scholar 

  111. Pagani FD, Baker LS, Hsi C, et al. Left ventricular systolic and diastolic dysfunction after infusion of tumor necrosis factor-α in conscious dogs. J Clin Invest 1992; 90: 389–98

    Article  PubMed  CAS  Google Scholar 

  112. Yokoyama T, Vaca L, Rossen RD, et al. Cellular basis of the negative inotropic effects of tumor necrosis factor-α in the adult mammalian heart. J Clin Invest 1993; 92: 2302–12

    Article  Google Scholar 

  113. Gulick T, Chung MK, Pieper SJ, et al. Interleukin 1 and tumor necrosis factor inhibit cardiac myocyte β-adrenergic responsiveness. Proc Natl Acad Sci U S A 1989; 86: 6753–7

    Article  PubMed  CAS  Google Scholar 

  114. Ng TM, Munger MA, Lombardi WL, et al. Chronically inhaled salmeterol improves pulmonary function in heart failure. J Cardiovasc Pharmacol 2002; 40: 140–5

    Article  PubMed  CAS  Google Scholar 

  115. Chapman KR, D’Urzo AD, Druck MN, et al. Cardiovascular response to acute airway obstruction and hypoxia. Am Rev Respir Dis 1989; 140: 1222–7

    Article  PubMed  CAS  Google Scholar 

  116. Zimmer G, Dahinten A, Fitzner A, et al. β-Agonistic bronchodilators: comparison of dose/response in working rat hearts. Chest 2000; 117: 519–29

    Article  PubMed  CAS  Google Scholar 

  117. De Bruin ML, Hoes AW, Leufkens HG. QTc-prolonging drugs and hospitalizations for cardiac arrhythmias. Am J Cardiol 2003; 91: 59–62

    Article  PubMed  Google Scholar 

  118. Sakamaki F, Satoh T, Nagaya N, et al. Abnormality of left ventricular sympathetic nervous function assessed by 123I-metaiodobenzylguanidine imaging in patients with COPD. Chest 1999; 116: 1575–81

    Article  PubMed  CAS  Google Scholar 

  119. MacNee W. Pulmonary circulation, cardiac function and fluid balance. In: Calverley P, Pride N, editors. Chronic obstructive pulmonary diseases.London: Chapman & Hall, 1995: 243–91

    Google Scholar 

  120. Mador MJ, Tohin MJ. Acute respiratory failure. In: Calverley P, Pride N, editors. Chronic obstructive pulmonary diseases. London: Chapman & Hall, 1995: 461–95

    Google Scholar 

  121. Stewart AG, Waterhouse JC, Howard P. The QTc interval, autonomie neuropathy and mortality in hypoxemic COPD. Respir Med 1995; 89: 79–84

    Article  PubMed  CAS  Google Scholar 

  122. Shah L, Wilson AJ, Gibson PG, et al. Long acting β-agonists versus theophylline for maintenance treatment of asthma. Cochrane Database Syst Rev 2003; (3): CD001281

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Acknowledgements

This paper has not been supported by any funding.

M. Cazzola has received fees for speaking and consulting and/or financial support for attending meetings from Abbott, Altana, AstraZeneca, Boehringer Ingelheim, Chiesi Farmaceutici, GlaxoSmithKline, Manarini Farmaceutici, Novartis, Valeas and Pfizer. M.G. Matera has received fees for consulting from Boehringer Ingelheim and financial support for attending meetings from AstraZeneca, GlaxoSmithKline and Pfizer. C. Donner has received fees for speaking and consulting and/or financial support for attending meetings from GlaxoSmithKline, Pfizer, Boehringer Ingelheim, Novartis, Angelini and AstraZeneca.

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Correspondence to Claudio F. Donner.

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Cazzola, M., Matera, M.G. & Donner, C.F. Inhaled β2-Adrenoceptor Agonists. Drugs 65, 1595–1610 (2005). https://doi.org/10.2165/00003495-200565120-00001

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