Codeine has been in existence since 1920, although as a derivative of opium its history goes back to the 18th century.
Activation of opioid receptors results in inhibition of synaptic neurotransmission in the central nervous system (CNS). The physiological effects of opioids are mediated principally through receptors in the CNS. The effects of these receptors include analgesia, euphoria, respiratory depression, sedation and meiosis (cell division without exact chromosome copying).
Peak plasma concentration generally is reached within 90 minutes with the oral route. Following therapeutic doses, most absorption occurs in the small intestine. Toxic doses may have delayed absorption because of delayed gastric emptying and slowed gut motility.
The conversion of codeine to morphine occurs in the liver and is catalysed by the P-450 enzyme system. The morphine is then metabolized by conjugation in the liver to inactive compounds that are excreted in the urine. All opioids have a prolonged duration of action in patients with liver disease (e.g., cirrhosis) because of impaired liver function or prolonged strain on the P-450 enzyme system due to drugs or alcohol. This may lead to drug accumulation and opioid toxicity.