Question 12

Outline the pharmacology of an opioid injected into the spinal intrathecal space.

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College Answer

Though it would be unusual for patients to receive spinal opioids whilst they are in intensive care, the complications of spinal opioids are not an uncommon reason for admission to intensive care thus it is important candidates understand their pharmacology. Answers generally lacked structure. Outlining pharmacology should include pharmacokinetics, pharmacodynamics and side effects (both common and dangerous). An explanation of the effect of lipid solubility was expected. Following a structure will ensure a more complete answer.

Reference: Neural Blockade. 3rd edition Cousins and Bridenbaugh


Domain Epidural opioid pharmacokinetics: Intrathecal opioid pharmacokinetics:
Absorption into target site

Rate of diffusion into CSF is slower, and depends on Fick's Law of Diffusion (volume, i.e.  surface area of available meninges, concentration, protein binding and free fraction, as well as CSF flow rate/turbulence)

Rate of diffusion into target tissue is rapid: high CSF concentration, short diffusion distance (2-4mm)


Epidural spaces are irregular, segmental, and the injected material encircles the dural sack.

Depends on baricity (density of injectate relative to CSF)
Systemic distribution

Two-compartment model: Rapid early distribution (into epidural fat) and then slowly back out.

Slow absorption; increased half life

Pharmaceutics Some opioid formulations cannot be administered intrathecally or via epidural because of specific excipients, eg. remifentanyl comes as a lyophilized powder with a glycine buffer, and IV morphine comes with preservatives
Lipid solubility

The effect of the lipid solubility of opioids on their spinal and epidural effect:

  • High lipid solubility (eg. fentanyl)
    • More rapid onset of effect
    • More rapid offset of effect
    • More rapid uptake into capillaries, and therefore faster clearance from the CNS spaces
  • Lower lipid solubility (eg. morphine)
    • Slower onset of effect
    • Slower offset of effect
    • Slow clearance from the CNS, and prolonged clinical effect
      (eg. hypotension). 
Metabolism and elimination Because of the haemodynamic effects of spinal (anaesthetic) drugs, the perfusion of liver and kidneys may be decreased, which could delay clearance. 

Intrathecal opioids affect spinal μ-opioid receptors as well as being redistributed to the brainstem. Epidural opioids are also absorbed systemically to have an effect similar to IV administration

  • Hypotension
  • Pruritis
  • Urinary retention
  • Unexpectedly prolonged action
  • Respiratory depression with higher spinal levels


Dahlström, B. E. N. G. T. "Pharmacokinetics and pharmacodynamics of epidural and intrathecal morphine." International anesthesiology clinics 24.2 (1986): 29-42.

Bernards, Christopher M. "Understanding the physiology and pharmacology of epidural and intrathecal opioids." Best Practice & Research Clinical Anaesthesiology 16.4 (2002): 489-505.