Exhibit 3-6Opioid Rotation

When an opioid is ineffective, becomes ineffective, or produces intolerable side effects, it is common practice to rotate opioids. This practice is based on the observation that particular opioids affect people differently, primarily because of intraindividual and interindividual variability among opiate receptors, so-called mu-receptor polymorphism. Although most opioid analgesics are mu agonists, they affect some mu receptors differently from others. A Cochrane review (Quigley, 2004) looked at the evidence supporting the replacement of an opioid to which an individual has developed analgesic tolerance with a different opioid. The conclusion was that although evidence is scant, the practice appears to be efficacious. The most common opioid rotation, and most studied, is from morphine to methadone.