Decrease of plasma potassium due to inhalation of beta-2-agonists: absence of an additional effect of intravenous theophylline

Abstract

The effect on the plasma potassium concentration of inhalation of the beta-2-agonists fenoterol, salbutamol (albuterol), and terbutaline from metered-dose inhalers was studied in normal volunteers. All three drugs caused a significant, dose-dependent decrease, more pronounced for fenoterol and salbutamol than for terbutaline. Relative to the bronchodilating potency (one puff of fenoterol 0.2 mg is considered to be equivalent to two puffs of salbutamol 2 x 0.1 mg, or two puffs of terbutaline 2 x 0.25 mg), fenoterol had a more pronounced effect on plasma potassium than salbutamol or terbutaline. The systemic effect on plasma potassium seems to be related to the structure of the drugs: the more lipophilic the drug (fenoterol) the sooner the systemic symptoms appear and the more pronounced they are. The effects of theophylline alone, and combined with fenoterol, were also studied. The intravenous infusion of theophylline (after placebo inhalation; maximal mean plasma concentration 14.9 +/- 2.2 mg l-1) caused a small but significant decrease of plasma potassium. There was no additive or synergistic effect when theophylline was added to fenoterol. It is concluded that inhalation of beta-agonists induces a decrease of plasma potassium, that this effect is relatively more pronounced for fenoterol than either salbutamol or terbutaline, and that it is not enhanced by the concomitant use of theophylline. Theophylline by itself causes a slight decrease in plasma potassium concentration.