Codeine-induced bronchoconstriction and putative bronchial opiate receptors in asthmatic subjects.
To determine whether a mu opiate agonist can constrict the human airways, the dose of codeine (C) or histamine (H) producing a 40% decrease (PD40) in specific airway conductance (SGAW) was measured in 17 asthmatic and 14 normal subjects. Then, the subjects were skin tested with C and H, and the effect of naloxone (N) and chlorpheniramine (CP) on PD40-C was assessed. In five asthmatic subjects responding to less than 5 mg (16.6 mumol) inhaled C, SGAW was also recorded after oral administration (30 mg) and pharyngeal spraying (5 mg) of C. PD40-C could be determined in 11 of the 17 asthmatics but in none of the normal subjects. This constrictor effect lasted less than 15 min, was unrelated to resting airway caliber, and required a relatively high bronchial sensitivity to H (PD40-H usually less than 0.2 mumol) and high doses of C (11.93 +/- 12.0 mumol). However, in C responders, PD40-C and PD40-H were unrelated. C-induced bronchoconstriction was blunted by N in a dose-dependent fashion and to a mild and inconsistent degree, by CP. Pharyngeal spraying or oral challenge with C failed to change SGAW. Skin sensitivity to H and C was similar in C-responders and non-responders. In conclusion, large doses of inhaled C constrict the airways of asthmatic subjects highly sensitive to H. This effect seems mediated through (mu?) opiate receptors located bronchially rather than centrally, pharyngeally or in the skin. In C-induced bronchoconstriction H liberation plays a contributory but minor role. Skin and bronchial sensitivity to C are unrelated.
Popa
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Pulmonary Clinic, Veterans Administration Clinic, Sacramento, California, USA.
D000293:Adolescent; D000328:Adult; D001249:Asthma / Q000188:drug therapy*; D001980:Bronchi / Q000187:drug effects*; D016084:Bronchoconstriction / Q000187:drug effects; D016085:Bronchoconstrictor Agents / Q000494:pharmacology*; D003061:Codeine / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D009270:Naloxone / Q000494:pharmacology; D017450:Receptors, Opioid, mu / Q000187:drug effects*; D013997:Time Factors
D016085:Bronchoconstrictor Agents; D017450:Receptors, Opioid, mu; D009270:Naloxone; D006632:Histamine; D003061:Codeine