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Neuraxial opioids: lipophilicity

Opioids are probably the second most common class of medication used for neuraxial analgesia. Like all drugs, their pharmacokinetics are governed by their specific pharmacologic properties. One of these properties, the degree of lipid solubility, will be quickly reviewed.

In general, lipophilic opioids (e.g., fentanyl) have a more rapid onset and shorter duration of action than hydrophilic opioids (e.g., morphine) when injected into either the epidural or intrathecal space. They also display less spread throughout the CSF, therefore resulting in a narrower band of segmental analgesia (i.e., near the site of injection). All of this is due to the fact that lipophilic opioids can more readily cross the lipid membranes of cells which therefore leads to increased uptake into surrounding neural tissue and fat as well as equally rapid systemic uptake and redistribution (thus terminating effect).

Hydrophilic opioids on the other hand result in a larger CSF distribution (when injected intrathecally) with slower tissue penetration. Therefore, this larger CSF spread may result in analgesia at areas further away from the site of injection. Furthermore, because hydrophilic opioids have more time to spread throughout the CSF, delayed respiratory depression may result when injected intrathecally as the opioid ascends the spinal column and reaches the brain stem.

It should be noted though that although lipophilic opioids do not typically ascend the CSF like hydrophilic opioids do when injected intrathecally, if used epidurally, they are much more likely to redistribute through surrounding tissues and into the blood eventually reaching the brainstem which can have unwanted side effects (e.g., respiratory depression).