Death codeine

Ferner RE. Did the drug cause death Codeine and breastfeeding. Lancet 2008 372 606-8. 

The answer is c. (Hardman, pp 528-537.) Morphine is a pure agonist opioid drug with agonist activity toward all the opioid subtype receptor sites. In high doses, deaths associated with morphine are related to the depression of the respiratory center in the medulla. Morphine has a high addiction potential related to the activity of heroin or dihydromorphine. Codeine has a significantly lower addiction potential. 

Propoxyphene (dextropropoxyphene Darvon) is structurally related to methadone but is much less potent as an analgesic. Compared with codeine, propoxyphene is approximately half as potent and is indicated for the treatment of mild pain. It is not antipyretic or antiinflammatory like aspirin and is less useful than aspirin in most cases of mild pain. Toxicity from propoxyphene, especially in combination with other sedatives, such as alcohol, has led to a decrease in its use. Death following ingestion of alcohol in combination with propoxyphene can occur rapidly (within 20 minutes to 1 hour). The drug is not indicated for those with histories of suicide or depressive illnesses. 

Propoxyphene is chemically related to methadone but has low analgesic activity. Various studies have reported its potency at levels ranging from no better than placebo to half as potent as codeine that is, 120 mg propoxyphene = 60 mg codeine. Its true potency probably lies somewhere between these extremes, and its analgesic effect is additive to that of an optimal dose of aspirin or acetaminophen. However, its low efficacy makes it unsuitable, even in combination with aspirin, for severe pain. The increasing incidence of deaths associated with its use and misuse has caused it to be scheduled as a controlled substance. Moreover, banning its use in the United States is under consideration. 

The opioid derivatives most commonly used as antitussives are dextromethorphan, codeine, levopropoxyphene, and noscapine (levopropoxyphene and noscapine are not available in the USA). They should be used with caution in patients taking monoamine oxidase inhibitors (see Table 31-5). Antitussive preparations usually also contain expectorants to thin and liquefy respiratory secretions. Importantly, due to increasing reports of death in young children taking dextromethorphan in formulations of over-the-counter "cold/cough" medications, its use in children less than 6 years of age has been banned by the FDA. Moreover, due to variations in the metabolism of codeine, its use for any purpose in young children is being reconsidered. 

Dextromethorphan is the dextrorotatory stereoisomer of a methylated derivative of levorphanol. It is purported to be free of addictive properties and produces less constipation than codeine. The usual antitussive dose is 15-30 mg three or four times daily. It is available in many over-the-counter products. Dextromethorphan has also been found to enhance the analgesic action of morphine and presumably other -receptor agonists. However, abuse of its purified (powdered) form has been reported to lead to serious adverse events including death. 

Use of benzodiazepines with narcotics, such as meperidine (Demerol), oxycodone (Percodan), codeine, morphine, or pentazocine (Talwin), increase their sedative effects. Combining these agents can lead to serious reductions in breathing rate, and even death. These two types of drugs should never be taken together. 

Codeine is a Schedule HI drug. These drugs have less potential for abuse than Schedule I or II drugs, an accepted medical use in the United States, and the likelihood of moderate or low physical dependence if abused. Federal trafficking penalties for a first offense of a Schedule III substance is not more than five years and fines of up to 250,000 for individuals and one million dollars for organizations. A second offense carries a maximum of 30 years to life if a death is involved and fines up to two and 10 million dollars. 

Ciszkowski C, Madadi P, Phillips MS, Lauwers AE, Koren G (2009) Codeine, ultrarapid-metabolism genotype, and postoperative death. N Engl J Med 361(8) 827—828... 

IMATINIB ANALGESICS-OPIOIDS May cause t plasma concentrations, with a risk of toxic effects of codeine, dextromethorphan, hydroxycodone, methadone, morphine, oxycodone, pethidine and tramadol Inhibition of CYP2D6-mediated metabolism of these opioids Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise or anorexia. Measure amylase and lipase levels if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts, and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider 1 dose. Methadone may cause Q-T prolongation the CHM has recommended that patients with heart and liver disease who are on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG as they may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily and thus an t in plasma concentrations necessitates close monitoring of cardiac and respiratory function... 

Toxicity. The estimated minimum lethal dose is 800, mg, but codeine is much less toxic than morphine and death directly attributable to codeine is rare in most fatalities involving codeine, other drugs and/or alcohol are also present. Drug addicts may use doses up to 10 times normal before showing toxic effects, whilst children may show toxicity with only l/20th of the dose. 

Codeine ultrarapid-metabolism genotype and postopertative death. N Engl J Med 361 827-828... 

Friedrichsdorf SJ, Nugent AP, Strobl AQ (2013) Codeine-associated pediatric deaths despite using recommended dosing guidelines three case reports. J Opioid Manag 9 151-155... 

Codeine, which has only one-quarter of the toxicity of morphine, is sometimes used as a suicidal agent (2), probably because it is easy to obtain, but as the majority of such suicides are caused by tablets in which the codeine is compounded with other substances such as aspirin or phenacetin, it is difficult to say if it is really the cause of death. 

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