Isoetharine versus albuterol for acute asthma: greater immediate effect, but more side effects.

PURPOSE: To compare the magnitudes of the immediate effects of the nebulized beta-agonists isoetharine and albuterol in the treatment of acute severe asthma. PATIENTS AND METHODS: Fifty-one adults presenting with severe asthma exacerbations (forced expiratory volumes in the first second of exhalation [FEV1] <40% of predicted) to the emergency department were randomized (double-blind) to receive hourly inhaled nebulization treatment with either isoetharine (5 mg) or albuterol (2.5 mg). The FEV1 was measured immediately before and after each nebulized treatment. Any side effects were recorded. RESULTS: Immediately after the first nebulized treatment, the isoetharine group improved its mean FEV1 (+/-SEM) by a significantly greater amount than did the albuterol group: 60% +/- 11% versus 39% +/- 5%, respectively (P <0.05). One hour later the mean FEV1 were equivalent. This pattern repeated itself after the second hourly treatment. The two groups did not differ in any outcome parameters (FEV1 at discharge, number of nebulized treatments required, the number of inpatient admissions, number of clinical relapses after discharge). More patients treated with isoetharine had side effects (36% versus 4% for albuterol, P <0.01), 1 of whom required discontinuation from the study. CONCLUSIONS: Both medications were equally effective in alleviating bronchospasm. The immediate effect of isoetharine was significantly greater, but equalized that of albuterol within an hour after treatment. There were more side effects with isoetharine.

A randomized, controlled comparison of isoetharine and albuterol in the treatment of acute asthma.

STUDY OBJECTIVE: To determine whether treatment of acute asthma with repeated doses of nebulized albuterol leads to greater bronchodilation and lower hospital admission rate than treatment with nebulized isoetharine. DESIGN: Randomized, double-blinded, controlled trial of albuterol and isoetharine. TYPE OF PARTICIPANTS: Patients between 18 and 50 years old presenting with acute asthma. Patients were excluded if they had a history of sensitivity to the study drugs, had congestive heart failure or chronic-obstructive pulmonary disease, or were unable to perform spirometry. One hundred three patients were entered into the study. INTERVENTIONS: All patients received oxygen and methylprednisolone in addition to administration of either isoetharine or albuterol. The nebulized aerosol was given at hourly intervals for a total of three doses. MEASUREMENTS AND MAIN RESULTS: Spirometry was performed before treatment and again at 90 and 180 minutes. Initial forced expiratory volume at one minute (FEV1) was 38.1% of predicted normal for the albuterol group and 36.0% of predicted normal for the isoetharine group. At 180 minutes, FEV1 was 55.6% of predicted normal for the albuterol group and 57.1% of predicted for the isoetharine group (NS). Twenty-eight percent of the albuterol group required admission compared with 26% of the isoetharine group (NS). There was no difference in occurrence of side effects between the two groups. CONCLUSION: Repeated doses of albuterol do not lead to a greater improvement in pulmonary function or a lower hospital admission rate than treatment with isoetharine.

An exaggerated response to beta-adrenergics.

Beta-adrenergics are used frequently in the management of asthma. Tremor has been found to be a limiting side effect with the oral or the inhaled forms. We describe one child who developed gross tremors necessitating an extensive neurologic evaluation to eliminate any other cause. With the results of a normal work-up and the reappearance of tremor when challenged again, the diagnosis of increased sensitivity to the tremorogenic effect of beta-adrenergics was made.

Hypokalemia induced by inhaled bronchodilators.

Since parenteral beta 2-adrenergic stimulation can induce hypokalemia, we postulated that administration of beta 2 adrenoreceptor agonists by inhalation could induce the same. We administered the usual clinical doses of three commonly used bronchodilators to each of six subjects receiving assisted mechanical ventilation in line with the ventilator: two beta 2-adrenoreceptor agonists, metaproterenol, 5 percent solution, and isoetharine, 1 percent solution; and the anticholinergic agent atropine as a control. Each bronchodilator was nebulized over 10 to 15 minutes in random order, four hours apart, and given to every subject. Plasma potassium was measured at five-minute intervals and arterial blood gases at 15-minute intervals, for a total of 50 minutes after administration of each bronchodilator. Following administration of each drug, plasma potassium showed an average decline. The mean decline in plasma potassium from baseline was statistically significant for metaproterenol (p = 0.04) and atropine (p = 0.001) but not for isoetharine (p = 0.09). Although there were no statistically significant differences among the declines in plasma potassium induced by the three drugs, metaproterenol caused the greatest decline (-0.6 mEq/L).

Hypomania related to phenelzine and isoetharine interaction in one patient.

A case is reported of a man with apparent unipolar depression that was responsive to treatment with phenelzine who became hypomanic when isoetharine was added to treat his chronic obstructive pulmonary disease. The role of beta-adrenergic receptors in affective illness is reviewed in light of this case.

A study of isoetharine mesylate in patients with chronic bronchial asthma.

We performed a double-blind, random crossover study to investigate the respiratory effects of a single dose isoetharine mesylate (IM), administered by a metered aerosol canister in 19 subjects with mild, stable asthma. In addition, we studied the influence of the dose (number of actuations) and the mode of administration (delay between actuations) on these respiratory effects. The protocol consisted of a screening day and four test days: (1) one inhalation IM (2) two inhalations IM (3) one inhalation placebo (P), and (4) two inhalations P. In addition, the first nine asthmatics paused one minute between inhalations whereas the last ten paused five minutes between inhalations. Lung function was assessed using maximal and partial expiratory flow volume curves. Measurements were taken prior to aerosol delivery and for six hours after aerosol. Significant differences between IM and P were seen for up to two hours. The maximum effect was observed at 15 minutes, corresponding to a 23% and 25% increase in FEV1 from baseline with one and two puffs, respectively (P less than .001). The differences between one and two actuations were, in general, not significant. No significant differences were observed between individuals who waited one versus five minutes between inhalations. We conclude that IM aerosol results in significant improvement compared with placebo for two hours. Differences between one and two inhalations and the interval between two inhalations did not, in general, lead to enhanced effectiveness of this drug in the group of asthmatics studied.

Comparison of bronchodilator effectiveness of fenoterol and isoetharine.

The present study was undertaken to compare efficacy and duration of action of fenoterol and isoetharine in patients who subjectively required urgent therapy. Analysis of the resulting data showed that in this population fenoterol had a longer duration of action and was more effective at the later time periods.

Atropine nebulization--simple and safe.

Ten children with chronic perennial asthma received a single dose of atropine at approximately 0.075 mg/kg. The drug was compared to isoetharine and was delivered by a simple nebulizing system. Both drugs were noted to be effective bronchodilators as determined by FEV1 and MMEF responses. While isoetharine demonstrated an initial overall better effect at 30 minutes, atropine had a more sustained bronchodilatory action at three hours. No adverse effects were noted with either drug.

Clinical study of broncholytic effect and side-effects of isoetharine ('Numotac').

In thirty-nine adult asthmatics a clinical trial was carried out with 10 mg slow-release tablets of isoetharine ('Numotac', 3M Riker) at two dose levels: 10 mg and 20 mg four times a day. The trial was double-blind with crossover after six weeks. Twenty-three patients reported a positive effect on their respiratory symptoms when isoetharine had replaced their previous treatment; negative effect was reported by one patient while twelve patients were undecided. Tremor was a common side-effect but except in three cases it was slight. There was no difference in side-effects between the high and the low doses if the initial dose was low. However, there were significantly more side-effects when the trial was started with the high dose.