Enhanced muscarinic receptor blockade with atropine in the asthmatic tracheobronchial tree. Evidence for increased drug delivery.

We measured the competitive antagonistic effect of atropine in bronchi of 8 normal and 15 asthmatic subjects. Classic pharmacologic theory states that the degree of competitive antagonism depends only upon (1) antagonist concentration at the receptor and (2) receptor affinity. Delivery and affinity also influence agonist responsiveness, but measurement of bronchial antagonism allows study of these factors in isolation. Bronchial responsiveness to methacholine was measured as the cumulative dose required to produce a 35% fall in specific airway conductance (PD35). On different days three measurements of control PD35 were made on each subject. On 2 days PD35 was measured after inhalation of 0.14 mg atropine and, on another day, after intravenous injection of 0.32 mg atropine. The antagonist effect of atropine was measured as dose ratio - 1 (DR - 1), where DR = PD35 after atropine/control PD35. Geometric mean DR - 1 with inhaled atropine in asthmatic subjects (11.7) was 6.3 times that of normal subjects (1.9) (p less than 0.001), and DR - 1 with intravenous atropine in asthmatic subjects (8.0) was 5.6 times that of normal subjects (1.4) (p less than 0.001). In conclusion, there is enhanced muscarinic blockade from inhaled and intravenously administered atropine in asthmatic bronchi. We suggest that this is due to increased access of the drug to bronchial muscarinic receptors.