2009A05 Outline the effect of an opioid injected into the spinal intrathecal space.

Aims

·   Surgical anaesthesia (synergistic with LA; elevates and prolongs block)

·   Post-op analgesia (e.g. intrathecal morphine for Whipple’s procedure)

Mechanism of opioid action

·   Activate G_i protein-coupled receptor

·   ↓Guanylyl cyclase activity -> ↓cAMP

·   Inhibit VDCC

·   ↑K⁺ efflux

·   Hyperpolarisation, ↓action potential

Preservative-free

·   i.e. no remifentanil
(glycine additive is an inhibitory neurotransmitter)

Drugs and doses

·   Tiny dose because:

oNear effect site

oLow volume of CSF

oRelatively slow reabsorption

·   Morphine:

o0.5mg (range 0.2-1mg)

oIT:IV potency 300:1

·   Fentanyl:

o15mcg (range 10-25mg)

oIT:IV potency 20:1

·   Other:

oDiacetylmorphine

oPethidine (can be a sole intrathecal agent)

oSufentanil (local anaesthetic effect at high dose)

If highly lipid soluble (fentanyl)

·   Rapid onset (5 mins?)

·   Rapid offset (1 hour?)

·   ↓ Effect from central spread via CSF due to faster diffusion out of it

·   ↑ Effect from systemic absorption

If poorly lipid soluble (morphine)

·   Slower onset (4-6 hours)

·   Slower offset (12-24 hours

·   ↑Effect from central spread via CSF due to slower diffusion out of it

·   ↓Effect from systemic absorption

Spinal cord segments (++++)

·   Diffuse across pia mater into dorsal horn (fentanyl fast, morphine slow)

·   Height ∝ dose

·   Pre-synaptic inhibition of 1° afferent nociceptors especially layer 2 -> ↓Release of excitatory neurotransmitters (glutamate, ACh, substance P)

·   Some post-synaptic inhibition

Brain (++)

·   Circulate via CSF bulk flow due to arterial pulsation
(morphine yes, fentanyl minimal)

·   PAG and RVMM: inhibition of OFF cell -> disinhibition of ON cell -> ↑descending modulation (NAd > 5HT) -> pre-synaptic inhibition

·   ? Some post-synaptic inhibition

Systemic (+)

·   Absorption via epidural venous plexus

·   Very low peak plasma concentration

·   Effect on brainstem, spinal cord, GIT, etc

Receptors

·   M, D

Location

·   Respiratory centre in the medulla

Highly lipid soluble (fentanyl)

·   Peak at 30 mins due to systemic absorption

Poorly lipid soluble (morphine)

·   Peak at 6-12 hours due to central spread of CSF