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

+++++