Principles of local anaesthesia

Question 1

Define “local anaesthetic”

Answer 1

Drug which reversibly blocks neuronal conduction when applied locally

Question 2

Describe the chemical structure of local anaesthetics

Answer 2

Aromatic region
Tertiary amine side chain
2 regions either bound by ester or amide bond

Question 3

Give examples of a local anaesthetic drug for both ester- and amide-bound aromatic and amide groups in their structures

Answer 3

Ester bond: cocaine

Amide bond: lidocaine

Question 4

What is the trade name of lidocaine?

Answer 4

Xylocaine

Question 5

Give one example of a local anaesthetic that does not share the normal structure of local anaesthetics and describe how it differs

Answer 5

Benzocaine

No tertiary amine side chain

Question 6

What is the main use of benzocaine and why?

Answer 6

Surface local anaesthetic

Pretty weak

Question 7

Describe the pH of local anaesthetic drugs

Answer 7

Weakly basic

pKa 8-9

Question 8

What barriers must the local anaesthetic drug pass through to affect a neuron, and in what state must this occur?

Answer 8

Connective tissue sheath and axon membrane

Unionised

Question 9

Recall the 2 possible MOAs of local anaesthetics and which of these is the main one

Answer 9

Hydrophillic (main one) and hydrophobic

Question 10

Recall the hydrophillic MOA of local anaesthetics

Answer 10

1. Enters neuron
2. Forms cation
3. Binds WITHIN the sodium channels
4. Stereochemically inhibits Na+ pasage

Question 11

Why does the hydrophillic MOA of local anaesthetics give rise to use-dependency?

Answer 11

Bind within the channels so the channel has to be open in order for the drug to bind

Question 12

Recall the hydrophobic MOA of local anaesthetics

Answer 12

1. Enters neuron
2. Drop straight into the ion channel due to high lipophilicity, without first ionising
3. Become ionised within the channel, blocking it

Question 13

Describe the effect of local anaesthetics on neuronal membranes

Answer 13

1. Prevents AP generation
2. Influences channel-gating
3. DO NOT influence resting potential

Question 14

How do local anaesthetics influence channel gating in neuronal membranes?

Answer 14

They bind preferentially to Na+ channels in the inactive state, holding them in this configuration for longer

Question 15

Which elements of local anaesthetic selectivity make them show preference for nociceptive fibres?

Answer 15

Selective for small diameter fibres - like A-delta and C fibres
Selective for non-myelinated fibres - like C fibres

Question 16

Why is it more difficult to anaesthetise infected tissue?

Answer 16

Infected tissue tends to be acidic, which pushed local anaesthetics towards their ionised state

Question 17

Recall the 6 possible routes of local anaesthetic administration

Answer 17

SIRENS
Surface 
Infiltration 
Regional IV
Epidural
Nerve-block
Spinal

Question 18

To where is surface anaesthesia applied? Give examples

Answer 18

Mucosae
Mouth
Eyes
Bronchial tree

Question 19

What is the main risk associated with surface anaesthesia?

Answer 19

High concentrations can cause systemic toxicity

Question 20

How is infiltration anaesthesia applied?

Answer 20

Injected straight into tissue you want to anaesthetise

Question 21

What is the main use of infiltration anaesthesia?

Answer 21

Minor surgery

Question 22

What is co-administered with infiltration anaesthesia and why?

Answer 22

Adrenaline to keep anaesthetic at site of injection

Question 23

In which routes of administration should adrenaline be co-administered?

Answer 23

Infiltration, nerve-block

Question 24

Describe the method for IV regional administration of local anaesthesia

Answer 24

1. Add pressure cuff
2. Insert IV line distally
3. Leave cuff for 20 mins to ensure administration does not become systemic
4. Remove cuff when LA has diffused into tissues

Question 25

What is the main indication for administering local anaesthetic using the IV regional route?

Answer 25

Limb surgery

Question 26

Which route of administration is used in dental surgery?

Answer 26

Nerve-block

Question 27

Where do you inject in nerve-block anaesthesia?

Answer 27

Close to nerve trunks eg dental trunks

Question 28

Recall an advantage and a disadvantage of nerve-block anaesthesia

Answer 28

Advantage: can use low doses
Disadvantage: Slow onset (mins)

Question 29

Where is spinal anaesthesia injected?

Answer 29

Intrathecally at L34 - into the subarachnoid space

Question 30

What are the side effects associated with spinal anaesthesia?

Answer 30

Sudden hypotension

Prolonged headache

Question 31

What is the cause of hypotension in spinal anaesthesia?

Answer 31

Sensitive pre-ganglionic SNS neurons with a small diameter are triggered to up SNS outflow and thus vasodilate

Question 32

How can spinal anaesthesia be localised to one place?

Answer 32

Mix with glucose to increase its specific gravity

Question 33

Where is epidural anaesthesia administered

Answer 33

Outside all of the layers of mater

Question 34

Recall 2 advantages and 2 disadvantages of epidural anaesthesia compared to spinal anaesthesia

Answer 34

Advantages:
Less likely to...
1) diffuse up spinal cord
2) Affect BP
Disadvantages:
1) Higher doses
2) Slower onset

Question 35

Recall the main type of reaction involved in lidocaine metabolism

Answer 35

Hepatic N-dealkylation

Question 36

Compare the plasma half life of cocaine and lidocaine

Answer 36

Cocaine: 1 hour
Lidocaine: 2 hours

Question 37

Recall and EXPLAIN the side effects of lidocaine

Answer 37

On the CNS:
Restlessness, confusion, tremor
Explanation: GABA neurons are more sensitive to the anaesthetic than CNS neurons
On the CVS: myocardial depression, vaodilation, hypotension
Explanation: Na+ channel blockade

Question 38

Compare the site of metabolism of lidocaine and cocaine

Answer 38

Cocaine = plasma and liver
Lidocaine = liver only

Question 39

Recall and EXPLAIN the side effects of cocaine

Answer 39

On the CNS: euphoria and excitation
On the CVS: Opposite to lidocaine
increased CO, vasoconstriction, hypertension
Explanation: actions on the SNS