ABSTRACT
This chapter describes the most widely used and clinically relevant strong opioid analgesics in palliative medicine. M3G has no analgesic effect; however, it has been reported to antagonize morphine analgesia and produce side effects including hyperalgesia, while M6G has been reported to produce higher analgesic effect than morphine. Further, it was suggested that prolonged analgesia may be due to attenuated brain penetration of M6G, its retention in the extracellular fluid, and consequently slower rate of elimination from the brain compared to morphine. Despite the weak evidence, five randomized controlled trials compared low and higher doses of methadone with oral morphine and transdermal fentanyl and found similar analgesic and side effects between those drugs. Therefore, buprenorphine was suggested as a fourth-line option compared to morphine, oxycodone, and fentanyl.
