Genetic polymorphisms of multiple metabolic pathways are significant issues, particularly in the setting of the use of controlled-release preparations, such as slow-release tablets or dermal patches, where attempts to circumvent the controls or individual variability in metabolism can lead to toxicity. This same genetic polymorphism can be an issue with oxycodone, which is partially metabolized by CYP2D6 into the even more potent opioid, oxymorphone. 12 An FDA review of codeine use in children following surgery (typically tonsillectomy and/or adenoidectomy) resulted in the issuing of a “black box warning” in February 2013 13 restricting use in that setting. Food and Drug Administration (FDA) to recommend caution in the use of codeine alone or in combination products for nursing mothers. The potential for significant opiate toxicity from the latter situation has led the U.S. On the other hand, in those individuals with ultra-functioning CYP2D6, excessive amounts of morphine may be generated by codeine metabolism, leading to altered mental status and respiratory depression. In those individuals with the poor metabolizer phenotype for CYP 2D6, codeine causes only nausea and vomiting and has no analgesic effects. 10,11 The conversion of codeine into its active opiate morphine is dependent on the activity of cytochrome P450 2D6 (CYP2D6). Individual genetic polymorphisms, with a population frequently as high as 10%, also come into play with opioid use. Individual variability in response and toxicity 8 Although all ages are affected, the increase in use of nonmedical analgesics is most prominent in teenagers and young adults, suggesting that the problem will continue to increase. In 2008, for the first time, deaths attributable to drugs (about half being opioid-related) equaled the number of traffic fatalities in the United States. 7 Death rates vary greatly among states, with those that have higher nonmedical use also having both higher substance abuse treatment admission rates and death rates. Recently, the ready availability of high dosage products and circumventable, controlled-release mechanisms has resulted in a significant increase in accidental fatal overdoses. The traditional “street dealer” is a source only 16% of the time. Indeed, most of the non-prescribed use is accessed by being given (70%) or taking (22%) another person’s prescribed medication. It has often been said that although there is not a drug dealer on every corner of rural and suburban America, there is usually a pharmacy.
5 The Monitoring the Future study (an annual telephone-based survey of more than 45,000 eighth, tenth, and twelfth graders in 400 private and public secondary schools throughout the U.S.) indicates that 8% to 10% of adolescents are using prescription opioids without a valid medical reason or prescription. While Americans comprise less than 5% of the world’s population, they account for more than 80% of the prescription opioid use worldwide, and more than 99% of the hydrocodone (e.g., Vicodin) use.
Some statistics regarding opioid use in the U.S. 4 These efforts have had unintended consequences, as it is now clear that over-prescription and inappropriate prescription of narcotics is a growing problem. 1-3 Pain scales became the norm, and they have become a Joint Commission on Accreditation of Healthcare Organizations standard. This was particularly true in the assessment of abdominal pain.ĭuring the 1990s the recognition of the problem of undertreatment of patients with acutely painful conditions led the American Pain Society, the Veterans Administration, and others to promulgate pain as the “fifth vital sign” in an effort to increase physician attention to undertreated pain. Emergency Department physicians, surgeons, and others often withheld pain medication for fear of obscuring a progressive condition or interfering with clinical assessment. History is rife with examples of early promotion of a “new, non-addicting pain reliever” which was promoted to avoid the complications of the previous pain reliever (which had once been heralded the same way). These drugs have been considered both a panacea for the ills and injuries of life and a path to self-destruction due to the rapid onset of tolerance and the potential for addiction. The opiates, along with their semi-synthetic opioid derivatives (heroin, hydrocodone, hydromorphone, nalbuphine, oxycodone, oxymorphone) and the increasing number of completely synthetic opioids (propoxyphene, levorphanol, meperidine, diphenoxylate, butorphanol, methadone, fentanyl derivatives, tramadol, buprenorphine, tapentadol) have a long and checkered history in medicine.
The naturally occurring opiates (morphine, codeine, and thebaine) can be extracted from the opium poppy, Papaver somniferum, along with a number of other alkaloid compounds.