Journal of pain and symptom management
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The effects of opioids usually parallel the plasma concentrations but with a temporal shift. This temporal shift differs between opioids. It is small with alfentanil or remifentanil and very long with the active metabolite of morphine, morphine-6-glucuronide (M6G). ⋯ PK/PD modeling has advanced the understanding of the time course of the clinical effects of opioids after various dosing regimens. It may provide a rational basis for the selection of opioids in clinical circumstances. PK/PD modeling of opioids may also be employed for the design and the interpretation of experiments addressing clinical effects of opioids.
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Fentanyl, a potent lipid-soluble opioid which was first synthesized more than 40 years ago, is still the most popular opioid used in the perioperative period throughout the world. Fentanyl's introduction, versatility, and popularity have resulted in its use in many acute and chronic pain conditions and a multitude of novel delivery systems in the last two decades. In spite of the development of more potent, safer, faster onset, and both shorter and longer lasting alternative opioids, fentanyl remains the mainstay of anesthesiologists and Certified Registered Nurse Anesthetists in the perioperative period, and for many pain physicians throughout the world.
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Pain is the cancer-related event that is most disruptive to the cancer patient's quality of life. Although bone cancer pain is one of the most severe and common of the chronic pains that accompany breast, prostate, and lung cancers, relatively little is known about the mechanisms that generate and maintain this pain. Recently, we developed a mouse model of bone cancer pain. ⋯ Humans suffering from bone cancer pain generally require significantly higher doses of morphine as compared to individuals with inflammatory pain and in the mouse model the doses of morphine required to block bone cancer pain-related behaviors were 10 times that required to block peak inflammatory pain behaviors of comparable magnitude induced by hindpaw injection of complete Freund's adjuvant (CFA; 1-3 mg/kg). As these animals were treated acutely, there was not time for morphine tolerance to develop and the rightward shift in analgesic efficacy observed in bone cancer pain versus inflammatory pain suggests a fundamental difference in the underlying mechanisms that generate bone cancer versus inflammatory pain. These results indicate that this model will be useful in defining drug therapies that are targeted for complex bone cancer pain syndromes.
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Opioids provide excellent pain relief in most patients. Yet the responses of patients to individual opioids can vary markedly, even among the mu opioids. Understanding this variability would greatly enhance our ability to treat patients appropriately. ⋯ These variants all show the same selectivity for mu opioids, confirming their classification as mu opioid receptors. Yet, they differ in their functional activation by opioids as well as in their localization within cells and regions in the brain. These multiple mu opioid receptors may help explain the range of responses seen clinically among patients for the various opioid drugs.