4.7 Intrathecal Opioids Flashcards
Q7 — Intrathecal opioids
a) What are the sites of action of intrathecal (IT) opioids?
● Intrathecal opioids bind to
G-protein coupled receptors @
presynaptic and postsynaptic areas
in the lamina 1 and 2
of the dorsal horn of the spinal cord.
● The number of receptors are much higher
in the presynaptic areas
compared with the postsynaptic areas
b) What are the intracellular and extracellular mechanisms of
analgesic effect within the spinal cord following the
administration of IT opioids?
Complex mechanisms exist for the actions
of intrathecal opioids.
1 At the presynaptic level:
● G-protein coupled receptor activation leads to
potassium channel opening and
calcium channel closure thereby
reducing intracellular calcium.
● This causes a reduction of excitatory neurotransmitters (glutamate and substance P)
from the C-fibres (presynaptic)
thereby leading to reduced nociceptive transmission.
-
2 At the postsynaptic level:
● Opioids bind to postsynaptic receptors
of the dorsal horn of the spinal cord causing
potassium channel opening and
activation of descending pathways causing analgesia
-
Other theories of mechanism of actions include:
3 ● Reduction of release of GABA and glycine
(inhibitory neurotransmitters)
from the dorsal horns in the inhibitory pathways
leading to a reduction in nociceptive transmission.
-
4 ● Increase in CSF adenosine activity.
Adenosine causes hyperpolarisation
through increased potassium transmission into the
cells causing a reduction in the activity of neurones
c) List the principal side effects of IT opioids.
More common:
● Nausea and vomiting.
● Respiratory depression (most feared).
● Pruritis.
Others:
● Sweating.
● Sedation.
● Delayed gastric emptying.
● Urinary retention.
Note: intrathecal opioids have much
lower side effects compared with
other systemic administration routes.
d) List the factors that may increase the risk of postoperative
respiratory depression following the administration of IT
opioids.
The risk of respiratory depression is increased by:
● A high dose of opioids.
● Low-dose lipophilic opioids —
early respiratory depression (~1 hour).
● Low-dose hydrophilic opioids —
late respiratory depression (up to 24 hours).
● Increasing age.
● Concomitant use of other sedatives.
● Co-administration of opioids in the first 24
hours after intrathecal administration.
● Positive pressure ventilation and
coexisting respiratory disease such as COPD.
e) What is the role of antihistamines in opioid-induced pruritis?
● There is no role for antihistaminics in pruritis
if it is opioid-induced.
● The likely mechanism is through modulation
of C-fibres centrally,
which may be responsible for the itch response
f) How would you manage opioid-induced pruritis?
● Naloxone low-dose continuous infusion at less than 2mg/kg/hr.
g Damo q extension
A 63 year old man has had an elective laparotomy and removal of intestinal tumour in an enhanced recovery setting. He has had a single shot spinal with an intrathecal (IT) opioid.
a) What other methods could be used to control postoperative pain in this patient? (3 marks
not a text book answer - mine
Simple analgesics
Regular paracetamol 1g qds
Consider NSAID - renal function permits/ no oter c/i
Regional
Thoracic epidral - opioid free infusion may not be most appropriate in eras setting unless ambulatory epidural emplyed
Blocks - Tap blocks and rectus sheath blocks and catheters
adjuvant analgesics - clonidine / ketamine / mgso4
