Principles of local anaesthesia

Question 1

Define LA

Answer 1

Drugs which reversibly block neuronal conduction when applied locally

Question 2

Describe the generation of a neuronal action potential

Answer 2

1) Resting Na+ Channels open Na+ enters cells (resting membrane potential -70mV). Depolarisation at -50mV
2) Na+ channels close (stay open for a 10-15 msec inactivation) K+ Channels open, K+ leaves cell. Repolarisation
3) Na+ channels restored to resting state but K+ channels still open therefore cell refractory period
4) Na+ and K+ channels restored to resting state therefore cell will respond normally to further to depolarizing stimulus

All or nothing potential
See slide 2 for diagram

Question 3

Describe the basic structure of LAs?

Answer 3

Aromatic region - Ester or amide bond - Basic amine side chain

Cocaine (ester bridge)
Lidocaine (amide bridge)

Question 4

What are the effects of LAs? Describe the interaction of LAs with sodium channels

Answer 4

LAs are weak bases (pKa 8-9). Physiological pH is 7.4. This means LAs are largely ionized at physiological pH.

IMPORTANT: Hydrophilic pathway - Only the unionzed form can pass through lipid membranes. The LA must gain access to the inside of the neurone for it work. It is the cationized form of the LA which blocks the Na+ channel blocking sodium influx = reducing generation and propagation of AP. LAs turn into their cationized form once inside the cell. It can only bind to open Na+ channels (binding site is inside the channel) = use dependency. This property means there is a greater degree of selectivity for nociceptive neurones.

Hydrophobic pathway - The local anaesthetic passes into the membrane of the neurone in the unionised form. Some highly lipid soluble local anaesthetics can drop straight into the sodium channel. They then become ionised in the sodium channel and block the channel

Question 5

What are 6 methods/routes of administration and describe each route?

Answer 5

Surface anaesthesia

• Mucosal surface (mouth, bronchial tree)
• Spray (or powder)
• High concentrations for its effects → systemic toxicity can be a problem

Infiltration anaesthesia

• Directly into tissues → sensory nerve terminals
• Minor surgery (small areas)
• Adrenaline co-injection (NOT extremities). This is so it holds the LA at the site of action + prevent systemic toxicity + reducing bleeding at the site

Intravenous regional anaesthesia

• i.v. distal to pressure cuff
• Limb surgery
• Systemic toxicity of premature cuff release. You don’t want the LA to go hit the heart.

Nerve block anaesthesia

• Close to nerve trunks e.g. dental nerves
• Widely used – low doses – slow onset.
• Vasoconstrictor co-injection

Spinal anaesthesia

• Sub-arachnoid space – floods around the spinal roots. Essentially injecting it into the CSF
• Abdominal, pelvic, lower limb surgery
• Low doses
• ↓ b.p (can block sympathetic system); prolonged headache
• Mix with glucose (↑ specific gravity). Increases density of solution. You can adjust the angle of the table to move the LA up and down the spinal cord.

Epidural anaesthesia

• Fatty tissue of epidural space – spinal roots
• Uses as for 5) and painless childbirth
• Slower onset compared to spinal anaesthesia– higher doses = likely to get systemic toxicity.
• More restricted action – less effect on b.p because it is outside the spinal cord.

Question 6

Compare the pharmacokinetic properties of lidocaine and cocaine

Answer 6

Lidocaine (amide):
Absorption (mucous membranes) = good, means they can be used as surface anaesthetics
Plasma protein binding = 70%
Metabolism = Hepatic, N-dealkylation
Plasma t1/2 = 2 hours

Cocaine (ester):
Absorption (mucous membranes) = good
Plasma protein binding = 90%
Metabolism = Liver and plasma, Non-specific esterases
Plasma t1/2 = 1 hour

Bupivicane (doa ~6hr; epidural anaesthesia)

Question 7

What are the unwanted effects of lidocaine?

Answer 7

These are at high concentrations (toxic) of Lidocaine

CNS: paradoxical increased CNS excitability. The inhibitory GABA neurones are sensitive to LAs = reduced GABA signalling.

• stimulation
• restlessness, confusion
• tremor

CVS: Na+ channel blockade

• myocardial depression
• vasodilatation
• ↓ b.p.

Question 8

What are the unwanted effects of cocaine?

Answer 8

This is in high dose effects (toxic) of cocaine

CNS: sympathetic actions. Blocks re-uptake of NA, dopamine and serotonin
- euphoria, excitation

CVS: sympathetic actions

• ↑ C.O.
• vasoconstriction
• ↑ b.p.