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