Analgesia codeine

Desmeules J, Gascon MP, Dayer P, Magistris M. 1991. Impact of environmental and genetic factors on codeine analgesia. Eur J Clin Pharmacol 41 23-26. 

Madadi P, Koren G (2008) Pharmacogenetic insight into codeine analgesia implications to pediatric codeine use. Pharmacogenomics 9 1267-1284... 

Desmeules J, Dayer P, Gascon M-P, Magistris M. Impact of genetic and environmental factors on codeine analgesia. Clin Pharmacol (1989) 45,122. 

Codeine, hydrocodone, morphine, methadone, and oxycodone are substrates of the cytochrome P-450 isoenzyme CYP2D6.47 Inhibition of CYP2D6 results in decreased analgesia of codeine and hydrocodone due to decreased conversion to the active metabolites (e.g., morphine and hydromorphone, respectively) and increased effects of morphine, methadone, and oxycodone. Methadone is also a substrate of CYP3A4, and its metabolism is increased by phenytoin and decreased by cimetidine. CNS depressants may potentiate the sedative effects of opiates. 

Oxycodone is nearly 10 times as strong as codeine, with absorption equal to that of orally administered morphine. Neither hydromorphone nor oxycodone is approved for use in children, and hydromorphone is contraindicated in obstetrical analgesia and in asthmatics. 

The problem, and the intrigue, with placebos is that they work through their meaning. Though actually pharmacodynamic blanks, they have been shown to be 55%-60% as effective in analgesia as codeine and as-... 

The word analgesia is from the Greek an-, meaning not or without, + algesis, sense of pain. Codeine is more potent than other pain-relieving medications, such as aspirin and ibupro-fen, but less potent than the really serious painkillers—morphine, oxycodone -I- acetaminophen, hydromorphone. When a... 

Oxidation CYP2D6 Codeine (analgesic) Reduced analgesia... 

Codeine,oxycodone, dihydrocodeine, and hydrocodone are all somewhat less efficacious than morphine (they are partial agonists) or have adverse effects that limit the maximum tolerated dose when one attempts to achieve analgesia comparable to that of morphine. 

Codeine, as noted, has a useful antitussive action at doses lower than those required for analgesia. Thus, 15 mg are usually sufficient to relieve cough. 

Summation - different mechanisms of action are involved with the same effects for each. Analgesia can be achieved by stimulating opiate receptors (codeine) and blocking prostaglandin synthesis (aspirin). 

Cleary, J., Mikus, G., Somogyi, A., Bochner, F. The influence of pharmacogenetics on opioid analgesia studies with codeine and oxycodone in the Sprague-Dawley/Dark Agouti rat model, J. Pharmacol. Exp. Ther. 1994, 271, 1528-1534. 

Dimethoxanate [477-93-0] (47) and pipazethate [2167-85-3] (48) are related phenothiazine derivatives that have shown antitussive activity. Unlike many phenothiazines, these do not produce central nervous system depression or analgesia at therapeutic doses. They are both somewhat less potent than codeine. It has been suggested that the unique side chain that is similar to, but shorter than, the one on benzonatate, may be at least pardy responsible for the antitussive effects. Both dimethoxanate and pipazethate are the result of molecular modifications of classical phenothiazines, such as promethazine [60-87-7], which possess antitussive activity in addition to central nervous system depressant activity. Dimethoxanate can be prepared by the reaction of phenothiazine- 10-carboxylic acid chloride with p-dimethylaminoethoxyethanol (66). 

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