Codeine and cough: an ineffective gold standard

Abstract

We propose that these differences, as well as results from animal models, can be explained by the existence of a complex hierarchical control system that regulates the expression of coughing. This system, known as a holarchy, is composed of regulatory elements known as 'holons' that interact with one another to regulate cough. Based on work in animal models, codeine is proposed to act on an intermediate order holon that may not be critical for coughing under some situations in humans. Testing of this hypothesis and further elucidation of the control system for cough will represent an important direction for future research in this area.

Antitussive Drugs—Past, Present, and Future

“…Although still one of the most widely used and prescribed antitussives, codeine has repeatedly been found to be poorly effective in clinical studies, leading some authors to question this widespread practice, particularly in children (Herbert and Brewster, 2000;Bolser and Davenport, 2007;Goldman, 2010;Chang et al, 2012;Paul, 2012). In cough evoked by capsaicin, codeine (30 and 60 mg p.o.)…”

Endogenous central suppressive mechanisms regulating cough as potential targets for novel antitussive therapies

“…However, arguably the neuroanatomical organisation and physiology of the endogenous central suppressive circuits regulating airway afference and cough are not known in sufficient detail at present to effectively target such circuits and bring about selective effects on cough (rather than general central neural inhibition, as is the case with opioid therapies). In this regard, it is also interesting that while morphine and other opioids have been shown to suppress cough in many experimental studies, the efficacy of opioid therapies for providing clinical relief in some patients with chronic cough has been debated [38,39]. Furthermore, GABA receptor agonists (such as baclofen) have been shown to suppress cough in some clinical cohorts (e.g.…”

Gabapentin as a Potential Treatment for Cough Syncope

“…However, multiple trials have demonstrated that it is poorly effective in controlling cough. 19,20 The mechanisms by which histone H1 antagonists and dextromethorphan affect cough remain unclear. There have been no placebo-controlled trials for levodropropizine to date.…”