Metabolic effects of inhaled fenoterol in normal subjects

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Date: Oct. 1992
From: Chest(Vol. 102, Issue 4)
Publisher: Elsevier B.V.
Document Type: Article
Length: 2,988 words

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Although the hypokalemic effect of inhaled [[unkeyable].sup.2]-adrenergic agonists has been well documented, little is known as to their effect on plasma magnesium. We therefore examined in ten healthy young volunteers the effect of the inhalation of 2 mg of nebulized fenoterol on plasma potassium (Kpl), plasma magnesium (Mgpl), and intraerythrocytic magnesium (MgIE) levels, as well as on plasma insulin and C peptide concentrations, measured before and serially up to 110 min after fenoterol inhalation. In all subjects, fenoterol inhalation caused a reversible reduction in Kpl (range, 0.2 to 1.1 mEq/L), which was progressive, reaching a statistically significant nadir 30 to 60 min following fenoterol inhalation (largest dip in Kpl, 0.55 [+ or -] 0.29 mEq/L; p<0.05). The nadir in Kpl levels was preceded by a peak in plasma insulin levels in all subjects. No significant changes in Mgpl or MgIE were observed in any of the subjects. We conclude that feoterol inhaled at a dosage used in clinical practice significantly reduces Kpl but not Mgpl nor MgIE levels in healthy subjects, indicating a lower sensitivity of Mg++ ions to [[unkeyable].sub.2]-adrenergic stimulation than K+ ions. [Beta.sub.2]-adrenergic-induced insulin secretion probably contributes to the hypokalemic effect of inhaled fenoterol.

(Chest 1992; 102:1099-1103)

Stimulation of [[unkeyable].sub.2]-adrenergic receptors plays a role in the regulation of plasma potassium (Kpl)[1,2] and plasma magnesium (Mgpl)[3] levels, leading to intrecellular uptake of both ions, predominantly in liver and muscle cells. Hypokalemia is a well-known side effect of non-[[unkeyable].sub.1]-selective adrenergic drugs, having been reported as a result of the parenteral administration of epinephrine,[4-6] albuterol (salbutamol),[7] and terbutaline.[8-10] Hypokalemia has also been reported following the inhalation of albuterol, isoproterenol (isoprenaline), or fenoterol.[11-19] Hypokalemia induced by [[unkeyable].sub.2]-adrenergic drugs may be potentially harmful, predisposing to cardiac arrhythmias and respiratory muscle weakness. These potential hazards are particularly relevant during acute exacerbations of asthma, when high doses of [[unkeyable].sub.2]-adrenergic drugs are utilized and other circumstances may exist that predispose to hypokalemia (such as respiratory alkalosis and previous or concomitant steroid, theophylline, or diuretic therapy) and to cardiac arrhythmias (such as hypoxemia).

A [[unkeyable].sub.2]-adrenergic agonist-induced fall in Mgpl, which might then further increase the risk for cardiac arrhythmias and respiratory muscle weakness, has also been reported to occur following intravenous administration of albuterol and epinephrine;[3,20] however, only few data are available on the effects of inhaled [[unkeyable].sup.2]-adrenergic agonists on Mgpl.[21] We therefore examined whether the inhalation of 2 mg of nebulized fenoterol, a dose capable of causing hypokalemia,[15] is also capable of inducing significant changes in Mgpl and intraerythrocytic magnesium (MgIE) in healthy volunteers. We also serially measured plasma insulin and C peptide levels in an attempt to contribute to the understanding of the mechanism behind the hypokalemia induced by [[unkeyable].sub.2]-adrenergic agonists.

MATERIALS AND METHODS

Ten healthy young subjects (eight men and two women; mean age [+ or - SD], 26 [+ or -] 3 yr) consented to participate in the study, which was approved by the ethics committee of our hospital. The subjects were not taking any medication.

On the day of the study, the...

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Gale Document Number: GALE|A12738192