β blockers for asthma: a double-edged sword

Response to salbutamol in patients with mild asthma treated with nadolol

“…Seven out of the 10 subjects were able to be escalated to 40 mg, one tolerated a 10-mg daily dose and one tolerated a 5-mg daily dose. One subject was excluded from the study because of an asthma exacerbation early in the study while on a dose of 1.25 mg. As demonstrated in our first study [8], we were able to show a significant effect on airway hyperresponsiveness with chronic nadolol dosing ( fig. 1) with geometric mean¡SEM PC20 at baseline and at final visit of 1.04¡1.54 and 3.61¡1.52, respectively, and a doubling dose change¡SEM of 1.79¡0.44 (p50.004).…”

“…We demonstrated that nadolol produced a dose-dependent increase in the PC20 (provocative dose causing a 20% fall in forced expiratory volume in 1 s (FEV1)) methacholine when administered over 11 weeks. However, a concern that remained is whether these subjects treated with nadolol can still respond to short-acting b 2 -ADR agonists for rescue of bronchospasm [8]. In fact, one concern is that nadolol ''may block bronchodilation produced by endogenous or exogenous catecholamine stimulation of b 2 receptors'' (Corgard1 product insert; King Pharmaceuticals, Inc., Bristol, TN, USA).…”

Obstructive lung diseases and beta-blockers: Where do we stand?

“…Taken together, these observations suggest that ß-blockers may have independent beneficial effects in obstructive lung diseases. One possibility is that up-regulation of ß2AR by chronic ß-blockade may improve the effectiveness of ß2-agonists [5,7]. In this regard, no adverse effect was observed with the addition of ß-blockers to treatment regimens that included long-acting ß-agonists [5].…”

“…Moreover, co-administration of long-acting anti-muscarinic drugs may be beneficial to prevent ß-blocker induced bronchoconstriction. This would suggest a rationale for using tiotropium when prescribing a ß-blocker for a patient with obstructive pulmonary disease [5,7].…”

Of mice and men—the curious tale of β blockers in asthma

“…It has been proposed that switching off β2ADR (thereby lowering cAMP) with an inverse β2-agonist such as nadolol might paradoxically result in improved in airway AHR and associated control 5 . This concept was supported by data from knockout mice devoid of β2ADR who when exposed to antigen did not develop airway hyper-responsiveness (AHR) or other cardinal inflammatory features of the asthma phenotype, while the same phenomenon also occurred with nadolol treatment in wild type mice expressing β2ADR 6 .…”