Codeine, cough and upper respiratory infection.

Codeine is generally accepted as a standard or reference antitussive against which new antitussive medications can be compared. However there are very few studies which have investigated the antitussive efficacy of codeine using cough associated with upper respiratory tract infection (URTI) and there is little if any evidence to support the antitussive efficacy of codeine in this model. This paper discusses the mechanism of cough in man and describes some clinical investigations on the effects of codeine on cough associated with URTI. The recent clinical investigations do not provide any evidence to support an antitussive action of codeine in the treatment of cough associated with URTI yet there is evidence in the literature which indicates that codeine inhibits fictive cough in animal models and also has antitussive activity against both induced and chronic cough models in man. In order to explain these different effects of codeine on the different models of cough, a hypothesis is put forward that there are two cough pathways in man. A voluntary pathway associated with cough related to URTI which is not affected by codeine, and a reflex pathway associated with induced and chronic cough which is inhibited by codeine.