Neuraxial opioids: mechanism

Advanced, Clinical Subspecialties

Spinal selectivity: liposolubility is inversely proportional to their spinal selectivity, which is higher for the most water-soluble drug, morphine, than for other more lipophilic drugs, such as fentanyl and sufentanil Lipophilic drugs (Fentanyl) diffuse intravascularly quickly and then reach brainstem via systemic circulation. Hydrophilic drugs (morphine) remain in CSF and circulate with CSF to brainstem receptors over 12-24 hours.

Epidural vs Intrathecal: opioids in the epidural space have farther to diffuse to reach target site. Epidural space contains fat and epidural venous plexus, which can absorb opioids or divert them to systemic circulation, respectively. Therefore, dosing for epidural administration is higher than for intrathecal.

All intrathecally administered opioids can produce brainstem-mediated side effects (euphoria, respiratory depression) due to vascular reabsorption to systemic circulation, but only hydrophilic opioids (morphine) produce these effects via spread within the CSF. This spread can take up to 12 hours to reach brainstem.


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Emmad Kabil, MD