2021B06 Explain how local anaesthetics prevent the conduction of action potentials within a major peripheral nerve.

 

List:

·     Nerve physiology

·     Mechanism of action

·     Differential effects

 

Nerve physiology:

Sodium channel

 

 

Activation gate

Inactivation gate

Resting

Closed

Open

Activated

Open

Open

Inactivated

Open

Closed

Action potential

 

Mechanism of action:

Target

·      Voltage-dependent Na+ channel (VDNaC)

·      Less active at VDKC, VDCaC

Entry

·      Spread across three consecutive nodes of Ranvier (if myelinated)

·      Diffusion across connective tissue and cell membrane
(N.B. examiner appears to request a discussion of pharmacokinetics)

·      Major: unionised form enters cell -> ionised form enters active receptor

·      Minor: ionised form enters active receptor from outside

Binding

·      Rate of binding ∝ time in active state ∝ rate of cycling ∝ nerve activity

·      Affinity: inactive > resting > activated

Effect

·      Reduced rate of cycling -> no action potential -> no signal propagation

·      No change to resting potential

·      Initial blockade: incomplete, tonic

·      Repeated blockade: complete, phasic

Differential effect

·      ↑ Sensitivity if

o   Unmyelinated

o   Small

o   Active

·      Hence analgesia (C, Aδ) > sensory (Aβ) > motor (Aα)

 

 

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Appendix: differential effects:

Type

Function

Size (μm)

Conduction velocity (m/s)

Myelination

LA sensitivity

Aα

Motor

Proprioception

12-20

70-120

Heavy

+

Aβ

Light touch

Vibration

5-12

30-70

Heavy

++

Aγ

Tone

Spindles

3-6

15-30

Heavy

+++

Aδ

Sharp pain

Cold temperature

2-5

12-30

Heavy

++++

B

Pre-ganglionic:

SNS and PSNS

<3

3-15

Light

++++++

C-polymodal

Dull pain

Warm temperature

0.4-1.2

0.5-2.3

None

+++++

C-SNS

Post-ganglionic:

SNS vasomotor

0.3-1.3

0.7-2.3

None

+++++