18.7 Intrathecal Opioids

Question 1

a) What are the site of action and the intra and extracellular mechanisms of analgesic effect within the
spinal cord following the administration of intrathecal (IT) opioids? (6 marks)

Answer 1

potassium channel opening (DOP and MOP),

> > MOP (μ), DOP (δ) and KOP (κ) receptors
are G protein linked receptors.

> > Present in laminae I and II of dorsal horn.

> > Found presynaptically on primary afferent
C and Aδ fibres and
postsynaptically to a lesser extent.

> > Presynaptic stimulation causes

inactivation of voltage sensitive calcium
channels (VSCC) (KOP) or

resulting in hyperpolarisation of the cell and so reduced release of excitatory neurotransmitters glutamate and substance P.

> > Postsynaptic activation of opioid receptors
causes potassium channel
opening and indirect activation of
descending inhibitory pathways from
brainstem.

> > Intrathecal opioids spread caudally

(pumped upwards by effect of respiration and pulsation of brain with heartbeat) to cause central effects:

stimulation of receptors in nucleus raphe magnus
and periaqueductal grey (PAG) results in reduced GABAergic tone on the descending
inhibitory pathways,

thus allowing them to exert an
antinociceptive effect
at spinal level.

> > Lipid soluble opioids may behave
like local anaesthetics due to similar
pKa, molecular weight, and partition coefficients.

Question 2

b) List the principal side effects of IT opioids. (7 marks)

Answer 2

> > Nausea and vomiting.

> > Respiratory depression.

> > Pruritis.

> > Sedation.

> > Delayed gastric emptying.*

> > Urinary retention.*

> > Sweating.*

Question 3

c) What factors may increase the risk of postoperative respiratory depression following administration
of IT opioids? (7 marks)

Answer 3

> > Hydrophilic opioid use:
lipophilic opioids rapidly partition to receptor
and non-receptor sites,
i.e. epidural fat, myelin, white matter. CSF
concentration reduces rapidly, and so the peak in plasma concentration occurs rapidly.

Therefore, centrally mediated respiratory depression and that mediated by decreased sensitivity of peripheral chemoreceptors
happens early.

Hydrophilic opioids maintain a high CSF concentration for longer,

allowing more drug to spread caudally with time,
and for the peak plasma concentration
to occur much later.

> > Increasing age.

> > Concomitant use of long-acting sedatives.

> > Co-existing respiratory disease.

> > Positive pressure ventilation