29 - Principles of Local Anaesthesia

Question 1

How is a neuronal action potential generated?

Answer 1

-50-60mV = triggers opening of VGSCs

VGPCs also respond to depolarisation, but due to having different kinetics, they respond more slowly than VGSCs

Refractory Period = able to stimulate the neurone but need a greater stimulus to do so

All or nothing (not graded)

10-15 msecs per action potential

Question 2

Describe the chemical structures of different local anaesthetics

Answer 2

THREE MAIN REGIONS:

Aromatic Region

Ester or Amide Bond

• bridging group

Basic Amine Side-Chain

Cocaine - ester LA

Lidocaine - amide LA

Benzocaine - exception, doesn’t have an amine side chain but it has an alkyl side chain. Relatively weak LA, but good surface anaesthetic because it is lipid soluble

Question 3

Outline the interaction of local anaesthetics with sodium channels

Answer 3

HYDROPHILIC PATHWAY (MAIN MECHANISM OF ACTION)

Gives rise to use-dependency (works more effectively when neurones are firing rapidly, as the channels are open more)

LAs are weak bases

Equilibrium between the unionised and ionised forms of the LA

Only the unionised form can pass through the lipid membranes, connective tissue sheath and then the outer membrane of the sensory neurone

LAs must access the inside of the neurone in order to conduct its function

Converted to ionised form

The ionised (cationic) form is the one that blocks the VSSCs

Binds to the inside of the channels

Hinders the influx of sodium channel

Reduce the propagation of APs

HYDROPHOBIC PATHWAY

Highly lipid soluble LAs (e.g. benzocane)

Pass through outer membrane

Unionised form enters VSSCs

Then becomes ionised and blocks the channel in the normal way

The channels do not have to be open for this pathway to work

Question 4

What are the overall effects of local anaesthetics?

Answer 4

1. Prevent generation and conduction of APs
2. Do not influence resting membrane potential
3. May also influence channel gating

• VSSCs can exist in three states: resting, open, inactivated
• Some LAs may bind preferentially to the inactivated state
• Would prolong the refractory period, contributing to the anaesthetic action of the LAs

4. Selectively block:

• small diameter fibres (rather than bigger fibres)
• non-myelinated fibres (rather than myelinated fibres)

Question 5

Are local anaesthetics acidic or basic?

Answer 5

Local anaesthetics are weak bases (pKa 8-9)

Gives them a pH dependency of action

Are normally largely ionised at physiological pH

Question 6

What are the routes/methods of administration of local anaesthetics?

Answer 6

SURFACE ANAESTHESIA

Mucosal surface

• mouth
• bronchial tree

Spray or Powder

High concentrations

• systemic toxicity

INFILTRATION ANAESTHESIA

Directly into tissues

• sensory nerve terminals

Minor surgery

• just around site of surgery
• e.g. draining abcesses

Adrenaline co-injection

• not extremities

INTRAVENOUS REGIONAL ANAESTHESIA

I.V. distal to pressure cuff

Only time when local anaesthesia is intravenous

Limb surgery

Systemic toxicity of premature cuff release

• this occurs if you take the cuff off too soon
• bolus can travel to the heart and cause toxicity

NERVE BLOCK ANAESTHESIA

Close to nerve trunks

• e.g. dental nerves

Widely used

• low doses
• slow onset because the anaesthetic has to cross many membranes

Needs to be a very accurate injection

Vasoconstrictor co-injection

SPINAL ANAESTHESIA

Sub-arachnoid space

• spinal roots

Abdominal, pelvic, lower limb surgery

Low doses

Low blood pressure, therefore prolonged headache

Glucose, increases specific gravity

EPIDURAL ANAESTHESIA

Fatty tissue of epidural space

• spinal roots

Uses same as spinal anaesthesia and painless childbirth

Slower onset

Higher doses

More restricted action

• less effect on blood pressure

Question 7

Outline the pharmacokinetic properties of lidocaine and cocaine

Answer 7

Cocaine’s only therapeutic use is as a surface anaesthetic

Question 8

What are the unwanted effects of Lidocaine

Answer 8

These are the unwanted effects of the majority of local anaesthetics

Question 9

What are the unwanted effects of cocaine?

Answer 9

Question 10

Which on the the following statements about local anaesthetics is incorrect?

They:

A: Cause blockade of voltage-sensitive sodium channels

B: Block rapidly firing neurones more readily than more slowly firing neurones

C: Enhance action potential propagation

D: Are largely ionised at physiological pH

E: Have their durations of action increased if injected with adrenaline

Answer 10

Answer: C: They DO NOT enhance action potential propagation

Question 11

Define ‘Local Anaesthetics’

Answer 11

LOCAL ANAESTHETICS

Drugs which reversibly block neuronal conduction when applied locally