Comparison of the effects of two opioid antitussives, vadocaine hydrochloride, clobutinol and lidocaine on lung mechanics in guinea-pigs.
Intravenous administration of opioids, e.g. morphine and codeine, causes bronchoconstriction in animals and susceptible patients such as asthmatics. Therefore, the effects of two opioid antitussives (codeine and dextromethorphan), two non-opioid antitussives (vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) and clobutinol), and lidocaine on basal lung mechanics and methacholine (MeCh, 6 micrograms/kg i.v.)-induced airway obstruction were investigated in anaesthetized guinea-pigs. Intravenous administration of codeine (10-20 mg/kg) produced a dual response in the airways; initial bronchoconstriction was followed by attenuation of the MeCh-response. Dextromethorphan (10 and 15 mg/kg) caused bronchoconstriction only. Both the opioids affected dynamic lung compliance (CDyn) more than lung resistance (RL). At doses between 1 and 20 mg/kg i.v., vadocaine, clobutinol, and lidocaine had no obvious effect on the airways. Dextromethorphan and vadocaine, both at doses of 10 and 15 mg/kg, and clobutinol (15 and 20 mg/kg) caused irreversible bradycardia and hypotension, whereas codeine (5-20 mg/kg) increased blood pressure, and to a lesser extent heart rate. These results suggest that intravenous administration of an opioid antitussive influences the small peripheral airways more than the large airways, whether the opioid has euphoric analgesic properties or not. In contrast to this, non-opioid antitussives such as vadocaine and clobutinol are without effect. At large doses, all antitussives influence the cardiovascular system considerably.
Salonen
R O
RO
Department of Pharmacology and Toxicology, University of Helsinki, Finland.
D000605:Amino Alcohols / Q000494:pharmacology*; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology* / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008012:Lidocaine / Q000494:pharmacology* / Q000633:toxicity; D008168:Lung / Q000187:drug effects* / Q000502:physiology; D008688:Methacholine Compounds / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology* / Q000633:toxicity; D012129:Respiratory Function Tests
D000605:Amino Alcohols; D000996:Antitussive Agents; D008688:Methacholine Compounds; D010880:Piperidines; C017135:clobutinol; D008012:Lidocaine; C051410:vadocaine