Opioids have been used for spinal
analgesia for more than a century, and their injection epidurally and intrathecally has a key role in the control of
postoperative pain. Since the discovery of the endogenous
opioid system, 3 decades ago, their use has become more generalized in
obstetric analgesia, the management of chronic
pain, and
acute postoperative pain. To use
opioids effectively for this type of
analgesia, it is important to understand the pharmacokinetics and clinical pharmacology of these drugs, specifically those that produce
analgesia by an intrinsic spinal mechanism. Evidence from animal and human experiments indicates that hydrophilic
opioids (such as
hydromorphone and
morphine) bind more strongly to specific receptors within the dorsal horn of the spinal cord than lipophilic
opioids (such as
alfentanil,
fentanyl, and
sufentanil). This can be understood by considering the spinal cord selectivity and bioavailability of these
opioids. This difference is attributable to differences in the pharmacokinetic and pharmacodynamic properties of the 2 groups. It is more difficult for lipophilic
opioids to reach and remain at sufficiently high concentrations at the site of action due to their sequestration in epidural fat and rapid plasma clearance from both epidural and intrathecal spaces, resulting in
analgesia with a limited spread and duration, as well as the appearance of early supraspinal side effects. In contrast,
morphine has very different properties, including greater spinal bioavailability and therefore administered neuraxially, it is suitable choice for the treatment of
acute postoperative pain. However, when using
morphine, a greater incidence of adverse effects can be expected, and it requires careful patient selection.