SUBSENSITIVITY OF BETA RESPONSES DURING THERAPY WITH A LONG-ACTING BETA-2 PREPARATION

[摘要] The question of whether some tolerance or subsensitivity of various .beta. receptors develops during therapy with long-acting oral .beta.-2 agents has practical and theoretical importance. A strong .beta.-2 stimulus (terbutaline, 5.0 mg orally) was given at weekly intervals for up to 3 wk in 19 stable asthmatics and bronchitics while commencing 5.0 mg terbutaline 3 times daily. The evening dose was omitted before each morning challenge. Challenges were continued at 1 and 2 wk off terbutaline in some patients to test return of .beta. function. Patients received no ephedrine for 2 wk before the study but were allowed aminophylline or isoproterenol inhalations up to 18 and 4 h before challenges, respectively. Pulmonary function, pulse and blood pressure were monitored at 0, 60, 120 and 180 min, and metabolic parameters measured at 0 and 180 min. There was significant drug tolerance in the drop and minimum diastolic pressure reached, rise in lactate, cyclic AMP and blood glucose, and a drop in eosinophils. Peak FEV1 [forced expiratory volume in 1 s] and V50 dropped slightly, but vital capacity and minimal airway resistance did not change significantly. During continuous therapy this slight bronchial subsensitivity is probably obscured by elevated baseline function. This might assume importance during periods of excessive inhaler use or abrupt drug withdrawal.