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Measurement of pharmacological antagonism produced by atropine in bronchi of normal and asthmatic subjects.
Eur Respir J. 1988 Jan; 1(1):27-33.ER

Abstract

The bronchial response of six normal and six asthmatic subjects to increasing concentrations of methacholine aerosol was measured by serial measurements of specific airways conductance (sGaw) in a body plethysmograph. On separate days, the subjects were premedicated with 0.9% NaCl, inhaled atropine at four different doses, or intravenous atropine at two different doses. Cumulative log dose-response curves were constructed. The provocative dose of methacholine needed to cause a 35% fall in sGaw was measured from each curve (PD35). The antagonism produced by a given atropine dose was quantified as the dose ratio, which was defined as the ratio of PD35 after atropine to PD35 after saline. In normal subjects, approximately equal amounts of atropine given by the inhaled or intravenous routes produced mean dose ratios of almost identical value. However, in asthmatic subjects inhaled atropine (1.28 mg, 4.4 mumol) produced a mean dose ratio 7.5 times greater than the mean value seen with intravenous atropine (1.0 mg, 3.46 mumol). Intravenous atropine (1.0 mg, 3.46 mumol) produced a mean dose ratio of 18.3 for all subjects, compared to a value of 26 predicted from in vitro experiments. The slope of the regression line for the relationship of log (dose ratio -1) vs -log atropine dose (Schild plot) for all subjects was -0.99. The actions we have observed are compatible with the main actions of atropine being that of a competitive antagonist at the muscarinic receptor. The greater blocking effect of inhaled atropine in some asthmatics suggests that a higher concentration of atropine is achieved at the muscarinic receptor by the inhaled route in these subjects.

Authors+Show Affiliations

Department of Medicine, Charing Cross and Westminster Medical School, London, UK.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

3366235

Citation

Gillett, M K., and P D. Snashall. "Measurement of Pharmacological Antagonism Produced By Atropine in Bronchi of Normal and Asthmatic Subjects." The European Respiratory Journal, vol. 1, no. 1, 1988, pp. 27-33.
Gillett MK, Snashall PD. Measurement of pharmacological antagonism produced by atropine in bronchi of normal and asthmatic subjects. Eur Respir J. 1988;1(1):27-33.
Gillett, M. K., & Snashall, P. D. (1988). Measurement of pharmacological antagonism produced by atropine in bronchi of normal and asthmatic subjects. The European Respiratory Journal, 1(1), 27-33.
Gillett MK, Snashall PD. Measurement of Pharmacological Antagonism Produced By Atropine in Bronchi of Normal and Asthmatic Subjects. Eur Respir J. 1988;1(1):27-33. PubMed PMID: 3366235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Measurement of pharmacological antagonism produced by atropine in bronchi of normal and asthmatic subjects. AU - Gillett,M K, AU - Snashall,P D, PY - 1988/1/1/pubmed PY - 1988/1/1/medline PY - 1988/1/1/entrez SP - 27 EP - 33 JF - The European respiratory journal JO - Eur Respir J VL - 1 IS - 1 N2 - The bronchial response of six normal and six asthmatic subjects to increasing concentrations of methacholine aerosol was measured by serial measurements of specific airways conductance (sGaw) in a body plethysmograph. On separate days, the subjects were premedicated with 0.9% NaCl, inhaled atropine at four different doses, or intravenous atropine at two different doses. Cumulative log dose-response curves were constructed. The provocative dose of methacholine needed to cause a 35% fall in sGaw was measured from each curve (PD35). The antagonism produced by a given atropine dose was quantified as the dose ratio, which was defined as the ratio of PD35 after atropine to PD35 after saline. In normal subjects, approximately equal amounts of atropine given by the inhaled or intravenous routes produced mean dose ratios of almost identical value. However, in asthmatic subjects inhaled atropine (1.28 mg, 4.4 mumol) produced a mean dose ratio 7.5 times greater than the mean value seen with intravenous atropine (1.0 mg, 3.46 mumol). Intravenous atropine (1.0 mg, 3.46 mumol) produced a mean dose ratio of 18.3 for all subjects, compared to a value of 26 predicted from in vitro experiments. The slope of the regression line for the relationship of log (dose ratio -1) vs -log atropine dose (Schild plot) for all subjects was -0.99. The actions we have observed are compatible with the main actions of atropine being that of a competitive antagonist at the muscarinic receptor. The greater blocking effect of inhaled atropine in some asthmatics suggests that a higher concentration of atropine is achieved at the muscarinic receptor by the inhaled route in these subjects. SN - 0903-1936 UR - https://www.unboundmedicine.com/medline/citation/3366235/Measurement_of_pharmacological_antagonism_produced_by_atropine_in_bronchi_of_normal_and_asthmatic_subjects_ L2 - https://medlineplus.gov/asthma.html DB - PRIME DP - Unbound Medicine ER -