Influence of cardioselectivity and respiratory disease on pulmonary responsiveness to beta-blockade

Abstract

The effects on ventilation of the non-selective beta-blocker propranolol, and the relatively cardioselective beta-blocker, metoprolol, were compared in a randomized single-blind crossover study in 16 patients with asthma, bronchitis and emphysema (American Thoracic Society criteria). Group I had "fixed" airways disease with less than 20% improvement in FEV1 following inhaled salbutamol 5 mg by nebuliser. Group II had "reversible" obstruction, greater than 20% improvement. Bronchodilator therapy was withheld for 24 h with the exception of aerosols which were permitted until 12 h before study. After control observations on each of 2 study days, each patient received cumulative doses of propranolol (maximum 170 mg) and metoprolol (maximum 187.5 mg). Ventilatory function (FEV1, FVC, FEV1%) was assessed at 0, 2, 4, 6 and 8 h. In Group I, 2 patients were unable to complete the study. One patient became dizzy with propranolol 70 mg but tolerated metoprolol 187.5 mg. One patient developed wheeze with propranolol 15 mg but tolerated metoprolol 187.5 mg. Metoprolol was tolerated in all 8 patients with "fixed" disease, although FEV1 was reduced by more than 30% in 1 patient. Three patients in Group II did not complete the study because of wheezing following propranolol 10 mg, metoprolol 37.5 mg; propranolol 17.5 mg, metoprolol 37.5 mg; propranolol 45 mg, tolerated metoprolol 187.5 mg respectively. Wheezing responded in all cases to inhaled isoprenaline. The response to either propranolol or metoprolol was unpredictable in patients with "reversible" disease. When wheezing occurred in this group, it developed following small, potentially subtherapeutic doses of each drug. Although metoprolol was better tolerated, the practical benefit of cardioselectivity in those patients with reversible airways disease was negligible.

β-Blockers, heart disease and COPD: current controversies and uncertainties

“…Furthermore in the general population, FEV 1 increased in those who stopped taking β-blockers during the study. Other studies in patients with COPD report a fall in lung function and wheeze with propranolol and metoprolol 44 45. A study directly examining β-blocker tolerability in patients with concomitant heart disease and carefully documented airways disease, found that β-blockers were tolerated by 84% of the COPD patients (but only 50% with asthma) 46…”

Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Cardiovascular Links

“…The use of β blockers in patients with COPD has been a contentious issue since older generations of β blockers were shown to be intolerable by patients with obstructive airways disease, by precipitating bronchoconstriction [161], reducing FEV1, or lowering the methylcholine challenge threshold [162]. As a result, β blockers have been prescribed less to COPD patients, likely due to a concern that these side effects outweighed any cardiovascular benefit [11, 20, 21, 25].…”

Beta-Blockers after Myocardial Infarction: Do Benefits Ever Outweigh Risks in Asthma?

“…Metoprolol has been studied in varying doses in patients with asthma in at least 16 trials [17, 18, 26, 27, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40]. In virtually all of these studies, metoprolol caused some decrease in pulmonary function.…”

“…These authors also mentioned that 2 subjects with moderately severe asthma (not reported in the trial) had prolonged and severe bronchospasm associated with propranolol administration. Subsequent trials verified that nonspecific β-blockers should be avoided in patients with asthma [18, 26, 27, 28, 29, 30]. Table 1 offers examples of β 1 -blockers and nonspecific β-blockers.…”