Principles of local anaesthesia

Question 1

Define Local Anaesthetic.

Answer 1

Drugs that reversibly block neuronal conduction when applied locally

Question 2

What is the rapid depolarisation stage of the action potential caused by?
What is the re-polarisation initially caused by?

Answer 2

Opening of Voltage-gated sodium channels => influx of Na+

Inactivation of Voltage-gated sodium channels and opening of K+ channels

Question 3

What are the three structural components that make up all local anaesthetic molecules?

Answer 3

Aromatic region
Basic amine side-chain
Amide or ester link (in the middle)

Question 4

Give an example of a local anaesthetic with an amide link and one with an ester link

Answer 4

Ester = COCAINE
Amide = LIDOCAINE

Question 5

Name a local anaesthetic that doesn’t fit the structure of all other local anaesthetics. State why.
What does this structural difference mean for its chemical properties?

Answer 5

Benzocaine – it has an alkyl group rather than the basic amine side chain
This means that it is a relatively weak anaesthetic but highly lipid soluble (good for surface anaesthesia e.g. lozenges)

Question 6

What are the two pathways of local anaesthesia, important in explaining their mechanism of action? State which one is more important.

Answer 6

1. HYDROPHILIC – most important

2. Hydrophobic

Question 7

Describe the hydrophilic pathway.

Answer 7

• Unionised LA from the blood crosses the axon membrane and gets into the axon
• Within the axon it becomes the cation form of the LA
• Then binds to the inside of the voltage-gated sodium channels (when they open) and block sodium entry
  => This blocks action potential conduction

Question 8

What feature of local anaesthetics helps make it more selective for nociceptive neurones (which are rapidly firing)?

Answer 8

Use-dependency

Question 9

Describe the hydrophobic pathway.

Answer 9

Some very lipophilic local anaesthetics will move into the cell membrane (in unionised form) and then drop straight into the sodium channel (i.e. without needing to enter the axon)
It will then become the cation form in the sodium channel
And it will block sodium influx

Question 10

What effect do local anaesthetics have on resting membrane potential?

Answer 10

No effect on resting membrane potential

Question 11

Explain the effect of local anaesthetics on channel gating.

Answer 11

There is some suggestion that local anaesthetics bind more strongly to the sodium channels in their inactive state
Once bound to the sodium channel, it then holds it in the inactive stage for longer thus increasing the refractory period and reducing the frequency of action potentials

Question 12

Explain the effect of local anaesthetics on surface tension.

Answer 12

They lodge into the plasma membrane and reduce surface tension of the membrane
This leads to non-selective expansion of the lipid membrane and leads to non-specific inhibition of ion channels

Question 13

Describe the selectivity of local anaesthetics for different types of nerve fibres.

Answer 13

Selectively block small diameter axons (e.g. nociception neurones)

Selectively block non-myelinated axons

Question 14

Describe the pKa of all local anaesthetics. What are all local anaesthetics?

Answer 14

8-9

All local anaesthetics are WEAK BASES

Question 15

Explain why it is difficult to anaesthetise infected tissue.

Answer 15

Infected tissue is ACIDIC

So there will be less anaesthetic that is unionised

Question 16

What are the 6 methods of administration of local anaesthetics?

Answer 16

1. Surface anaesthesia
2. Infiltration anaesthesia
3. Intravenous regional anaesthesia
4. Nerve block anaesthesia
5. Spinal anaesthesia
6. Epidural anaesthesia

Question 17

What are the consequences of using high doses in local anaesthesia?

Answer 17

It can cause systemic toxicity

Question 18

What is infiltration anaesthesia? When might it be used?

Answer 18

Injection of anaesthetic directly into the tissue near the sensory nerve terminals

It is used for minor surgery

Question 19

What is often coadministered with infiltration anaesthesia and what are the benefits of this?

Answer 19

Adrenaline – this causes vasoconstriction and increases the duration of action of the anaesthetic meaning that a lower dose can be used
It also slows bleeding at the site of injection and reduces the amount of local anaesthetic going into the systemic circulation
NOTE: felypressin (V1 agonist) can also be used

Question 20

What is intravenous regional anaesthesia and how can this cause systemic toxicity?

Answer 20

Pressure cuff is used to cut off the blood supply downstream of it
Anaesthetic is administered intravenously
Removing the pressure cuff too early can lead to a bolus of anaesthetic entering the systemic circulation

Question 21

What is nerve block anaesthesia? Describe the dosage and onset.

Answer 21

Inject anaesthetic close to the nerve trunks

Low doses and slow onset

Question 22

What is coadministered with nerve block anaesthesia?

Answer 22

A vasoconstrictor e.g. adrenaline

Question 23

What is another name given to spinal anaesthesia?

Answer 23

Intrathecal

Question 24

Where is the anaesthetic inserted in spinal anaesthesia?

Answer 24

Into the subarchnoid space (into the CSF)

Question 25

Which parts of the body can be anaesthetised effectively with spinal and epidural anaesthesia?

Answer 25

Abdomen, pelvis, lower limbs

Question 26

How does spinal anaesthesia affect blood pressure and why does it have this effect?

Answer 26

It can cause a drop in blood pressure because it anaesthetises the nerve roots and the preganglionic sympathetic nerves are particularly sensitive to blockade by local anaesthetics
This leads to reduced sympathetic output and hence a drop in blood pressure

Question 27

What trick can anaesthetists do to get better control over the location of the spinal anaesthesia?

Answer 27

Add glucose to the anaesthetic mixture
This increases the specific gravity of the local anaesthetic meaning that the patient can be tilted to move the bolus of anaesthetic to the right place

Question 28

Surface anaesthesia

• where
• in what form

Answer 28

Mucosal surface (mouth, bronchial tree)
Spray (or powder)

Question 29

How does Epidural anaesthesia compare with spinal anaesthesia

Answer 29

Fatty tissue of epidural space – spinal roots
Uses as for spinal anaesthesia and for painless childbirth
Slower onset – higher doses
Less effect on BP

e.g. Bupivacaine

Question 30

Describe the difference in metabolism of lidocaine and cocaine.

Answer 30

Lidocaine – hepatic – N-dealkylation

Cocaine – hepatic and plasma by non-specific cholinesterases

Question 31

What are the CNS side-effects of lidocaine? Explain why it has these effects.

Answer 31

CNS stimulation
Restlessness
Confusion
Tremor
This is because the GABA system (inhibitory effect on CNS) is very sensitive to local anaesthetics

Question 32

What are the CVS side-effects of lidocaine?

Answer 32

Myocardial depression
Vasodilation
Decrease in blood pressure
All because of sodium channel blockade

Question 33

What are the CNS side-effects of cocaine?

Answer 33

Euphoria and excitation

Because of blockade of monoamine transporters

Question 34

What are the CVS side effects of cocaine? Explain why it has these effects.

Answer 34

Increased cardiac output
Vasoconstriction
Increased blood pressure
Due to increased sympathetic drive caused by blockade of monoamine transporters