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.

Inhaled beta 2‐adrenoceptor agonists in asthma: help or hindrance?

“…In this respect fenoterol also causes greater hypokalaemia in comparison with inhaled salbutamol (Crane et al, 1989b;Deenstra et al, 1988;Scheinin et al, 1987). Thus, inhaled fenoterol would appear to cause greater P2-mediated systemic effects (heart rate and hypokalaemia).…”

“…This infers either that systemic absorption of fenoterol is greater in comparison with salbutamol, or that fenoterol exhibits a greater potency at systemic 132-receptors. Since systemic absorption appears to be due to lung rather than gut absorption (Collier et al, 1980;Kung et al, 1987;Lipworth et al, 1989d), the greater lipophilicity of fenoterol (Deenstra et al, 1988;Jeppsson et al, 1989) could result in a greater propensity for absorption across the lung-vascular bed. There is evidence in vitro that fenoterol has a greater potency for 132-receptors compared with salbutamol, at equimolar concentrations (O'Donnell & Wanstall, 1978).…”

Electrolyte disturbances associated with commonly prescribed medications in the intensive care unit

“…The major extracellular cation in the body is sodium, which is normally kept at a serum concentration of [135][136][137][138][139][140][141][142][143][144][145] mmol/L (5). It accounts for Ͼ85% of fluid osmolality and is responsible for maintaining tonicity, hence controlling water movement across cell membranes and regulating extracellular fluid volume (5,6).…”

Risks Versus Benefits of Inhaled ??2-Agonists in the Management of Asthma

“…Dose-response curves for inhaled salbutamol show that systemic effects are not present until after the 500ILg dose, and then occur in linear dose-dependent fashion. Systemic absorption occurs primarily across the lung-vascular bed (Collier et al 1980;Kung et al 1987;Lipworth et al 1 989d), and hence compounds which are more lipophilic, such as fenoterol, are absorbed to a greater degree (Deenstra et al 1988;Jeppsson et al 1989). …”