S1-3 Three examples of science translation to practice: opioid rotation, management of breakthrough pain, role of methadone

Opiate analgesics continue to be the most effective drugs for management of cancer-related pain. These mainly work by binding mu opioid receptor in multiple areas along central nervous system. For many years, clinical pain using opiate involved dose escalation. This was primarily due fact that all opiates were perceived as sharing same mechanism action and site. It therefore considered—unnecessary change from one another. Our team initially observed patients with developed opiate-induced neurotoxicity, changing type associated a rapid dramatic reduction neurotoxicity. also became clear that, paradoxically, who underwent rotation required lower achieve or better analgesia. initial findings confirmed other groups later followed research showing there is considerable heterogeneity receptors, opioid-induced hyperalgesia, neurotoxic metabolites. Breakthrough has been described presence brief periods uncontrolled otherwise have good control on regular analgesic. The included use only needed. emergence extended-release changed practice order maintain constant blood level. Findings our studies led understanding combination plus an intermittent immediate-release necessary, since majority experience breakthrough Further found 90% are able excellent oral analgesics, making need opioids such transmucosal, buccal, intranasal fentanyl unnecessary vast patients. Methadone old synthetic agonist combines NMDA antagonist properties. Initial attempts methadone analgesic during 1960s 1970s failed, severe toxicity when replaced at excessively high equal dosages. started carefully selected cases refractory inpatient palliative care unit setting. daily titrations allowed us learn while ratio agonists linear flat, case progressively more potent received higher MEDD previous opioid. knowledge safer titration methadone, resulting