The effect of bucindolol on the airway function of asthmatics

Abstract

The airway and cardiovascular effects of separate single oral doses of 50, 100 and 200 mg of bucindolol were compared to those of placebo in a double-blind trial in 16 patients with mild to moderately severe asthma. Heart rate (HR), blood pressure (BP), forced vital capacity (FVC), forced expired volume in one second (FEV1), maximum expiratory flow at 50% of vital capacity (FEF50) and maximum expiratory flow at 75% of expired vital capacity (FEF75) were measured before and at intervals for 4h, when salbutamol (200 micrograms) was inhaled and the measurements repeated 15 min later. There was an interval of at least 4 days between each drug treatment day. Four of the 16 patients developed clinically significant bronchoconstriction with 50 mg (3) or 100 mg (1) of bucindolol and were withdrawn from the study. The remaining patients showed impaired bronchodilator response to salbutamol for each bucindolol dose as compared to placebo. No significant BP or HR effects were measured. Two patients withdrew because of circumstances unrelated to bucindolol induced bronchoconstriction. The development of bucindolol induced bronchoconstriction in this group of mild to moderate asthmatics was not predicted by the level of baseline pulmonary function, or the level of histamine responsiveness. However, there was a weak relationship between bucindolol induced bronchoconstriction and salbutamol induced bronchodilation. There are no definitive asthmatic characteristic to predict the likelihood of significant bucindolol induced bronchoconstriction in this asthmatic population.

Bucindolol: A Pharmacogenomic Perspective on its Use in Chronic Heart Failure

“…This study showed a 25% incidence of bronchoconstriction with bucindolol use 20. In addition, the remainder of patients demonstrated an impaired bronchodilator response to salbutamol, independent of baseline pulmonary function and consistent with a traditional dose-response relationship 20. The early bucindolol heart failure trials were carried out in small and heterogeneous populations.…”

Comparative effects of dilevalol and atenolol on lung function and airway response to methacholine in hypertensive subjects.

“…With the development of new ,B-adrenoceptor antagonists with intrinsic sympathomimetic activity (ISA) it was hoped that the adverse effects of these drugs on airways could be minimized. Studies on pindolol, a drug with ISA, showed that it had less influence on resting airway function than propranolol, a non-selective 3-adrenoceptor antagonist, or atenolol, a 11adrenoceptor selective antagonist but without ISA (Ruffin et al, 1982(Ruffin et al, , 1986. However, accord-ing to the current literature, no drug with 1adrenoceptor blocking properties can be considered safe in patients with airflow obstruction.…”

The applied pharmacology of beta-adrenoceptor antagonists (beta blockers) in relation to clinical outcomes

“…The availability of effective alternative antihypertensive and antianginal agents leads to the conclusion that beta blockers as a class should be avoided in patients with a current or past history of asthma [57]. It is noteworthy that even the newer beta 1-selective antagonists, such as bucindolol [58] and celiprolol [54], which have both partial agonism and nonadrenoceptor smooth muscle inhibitory properties, can cause adverse bronchial effects.…”