β-Adrenercic Subsensitivity Induced by Chronic Administration of Terbutaline

Abstract

The effect of 6-day courses of terbutaline and ephedrine on the metablic and hemodynamic responses to a 4-hour epinephrine infusion were compared in the same five individuals. Terbutaline suppressed the subsequent lactate response to epinephrine more than ephedrine did. The suppression of blood glucose response to epinephrine was similar for the two drugs. Ephedrine profoundly altered the hemodynamic responses to epinephrine causing significantly higher systolic and diastolic blood pressures and slower pulse. Terbutaline did not alter the systolic blood pressure during subsequent epinephrine infusion, and had less effect than ephedrine on the diastolic pressure and heart rate during the infusion. The effect of terbutaline on physiologic responses to exercise was studied, employing both brief strenuous and prolonged moderate treadmill exercice. Following 6 days of terbutaline the blood glucose and lactate levels during and following exercise were consistently but not markedly reduced. There was no effect on hemodynamic responses or on blood levels of free fatty acids, nor did exercise tolerance appear to be reduced. The 6-day course of terbutaline did not alter the bronchial sensitivity to inhaled methacholine as measured by spirometry. We conclude that subsensitivity is a characteristic response in most tissues to chronic exogenous adrenergic stimulation. The failure to demonstrate altered methacholine sensitivity may indicate that the adrenergic receptors of the bronchial smooth muscles are an exception to this rule, or, more likely, may reflect the difficulty in demonstrating partial bronchial adrenergic blockade in normal individuals.

Airway and Metabolic Responsiveness to Intravenous Salbutamol in Asthma: Effect of Regular Inhaled Salbutamol

“…Impairment of the glucose response to fJ-adrenoceptor agonists has, in general, occurred more readily than impairment of the response to other metabolites such as glycerol and non-esterified fatty acids (Lockey et al, 1967;Nelson, Raine, Branch & Kalisker, 1976). It has been particularly difficult to demonstrate the development of resistance in the airways despite doses of fJ-adrenoceptor agonists which have caused impaired tremor, lymphocyte cyclic AMP or metabolic responses (Larsson, Svedmyr & Thiringer, 1977;Morris, Rusnak, Selner, Barzens & Barnes, 1978).…”