Local anaesthetics

Question 1

What are local anaesthetics?

Answer 1

Drugs which reversibly blocks neuronal conduction when applied locally

Question 2

What three main regions do all local anaesthetics have?

Answer 2

Aromatic region
Basic amino acid side chain
Ester or Amide bond

Question 3

What is the basis for classification of local anaesthetics?

Answer 3

Type of bond that links the aromatic group and basic amino acid side chain:
Ester- e.g. cocaine
Amide- Lidocaine

Question 4

Why is benzocaine the odd one out?

Answer 4

Doesn’t have a tertiary amine group, it just has an alkyl group- means that it is relatively weak but highly lipid soluble

Question 5

How do all local anaesthetics exist?

Answer 5

As weak bases

Question 6

When can a local anaesthetic pass through the connective tissue sheath and through the axon membrane?

Answer 6

When it is unionised

Question 7

When can a cationic local anaesthetic bind with sodium channel?

Answer 7

Only with the sodium channel when it is open because the binding site is inside the channel

Question 8

What effect do local anaesthetics have once inside?

Answer 8

They stereochemically inhibit the passage of sodium ions from the outside to the inside of the cell

Question 9

What is the blockage of sodium passage by local anaesthetic known as?

Answer 9

Hydrophilic pathway- main mechanism of action

Question 10

The hydrophilic pathway gives rise to the use dependency of local anaesthetics, what is use dependency?

Answer 10

The more active the cell is, the more frequently its sodium channel will be open and more it will be blocked

Question 11

Why is use dependency a useful feature?

Answer 11

It gives a greater degree of selectivity for nociceptive neurones- when conducting pain, they fire more rapidly

Question 12

What is the other mechanism of action of local anaesthetics?

Answer 12

The hydrophobic pathway- 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 13

What are the effects of local anaesthetics?

Answer 13

Prevent generation and conduction of action potentials
Do not influence resting membrane potential
Channel gating- bind more to inactivated state of sodium channel and hold it causing analgesic effect because it increases refractory period and reduces activation and propagation of action potentials
Surface tension

Question 14

What is the selectivity block of local anaesthetics?

Answer 14

They have a preference for small diameter axons which is good because A-delta and C-neurones have small diameter axons. They tend to block non-myelinated axons

Question 15

What does the fact all local anaesthetics are weak bases influence?

Answer 15

It means that at physiological pH, a relatively small proportion of drug is unionised and can gain access to the neurones
Infected tissue tends to be more difficult to anaesthetise because it is more acidic

Question 16

What are the main methods of administration of local anaesthetics?

Answer 16

Surface 
Infiltration
Intravenous regional
Nerve block
Spinal 
Epidural

Question 17

What does surface anaesthesia involve?

Answer 17

Mucosal surface (mouth, bronchial tree)
Spray (or powder)
High concentrations -> systemic toxicity

Question 18

What does infiltration anaesthesia involve?

Answer 18

Directly into tissues -> sensory nerve terminals
Minor surgery
Adrenaline co-injection
Sometimes felypressin (V1 agonist) used

Question 19

What does intravenous regional anaesthesia involve?

Answer 19

IV distal to pressure cuff
Limb surgery
Systemic toxicity of premature cuff release

Question 20

Why is adrenaline used when administering local anaesthetic?

Answer 20

It causes vasoconstriction and will keep local anaesthetic at site for longer and will reduce amount going into systemic circulation so reduces likelihood of systemic toxicity
Adrenaline also reduces bleeding from wound

Question 21

What does nerve block anaesthesia involve?

Answer 21

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

Question 22

What does spinal anaesthesia involve?

Answer 22

Sub-arachnoid space- spinal roots
Abdominal, pelvic, lower limb surgery
Decreased b.p. and prolonged headache
Glucose- increased specific gravity

Question 23

What does epidural anaesthesia involve?

Answer 23

Fatty tissue of epidural space- spinal roots
Uses as for 5) and painless childbirth
Slower onset- higher doses
More restricted action- less effect on b.p.

Question 24

What can spinal anaesthesia cause and how?

Answer 24

It can cause a drop in blood pressure because it is injected into CSF- preganglionic sympathetic neurones are very susceptible to block by local anaesthetic. :If they get blocked, you get reduced sympathetic outflow to the heart and vasculature. This leads to a drop in blood pressure

Question 25

How can spinal anaesthesia cause prolonged headaches?

Answer 25

The local anaesthetic is mixing in with CSF and can diffuse towards brain

Question 26

What is the trick for controlling the level of spinal anaesthesia?

Answer 26

Giving some glucose with LA- will increase its specific gravity so local anaesthetic stays more or less in one place and can be moved by tilting the patient rather than freely diffusing through CSF

Question 27

How do cocaine and lidocaine compare in pharmacokinetic properties- Absorption, plasma protein binding, metabolism and plasma t 1/2?

Answer 27

Lidocaine:
Absorption- good
Plasma protein binding- 70%
Metabolism- hepatic N-dealkylation
Plasma t 1/2 2h

Cocaine:
Absorption-  good
Plasma protein binding- 90%
Metabolism- Liver and plasma, non-specific esterase's
Plasma t 1/2 1h

Question 28

What are the unwanted effects of lidocaine?

Answer 28

CNS (paradoxical):
Stimulation
Restlessness
Tremor
CVS (Na+ channel blockade):
Myocardial depression
Vasodilatation
Decreased bp

Question 29

What are the unwanted effects of cocaine?

Answer 29

CNS:
Euphoria, excitation
CVS:
Increased C.O
Vasoconstriction 
Increased bp

Question 30

Why are the effects of lidocaine on CNS paradoxical?

Answer 30

You would think that something that blocks nerve transmission would be a CNS depressant but GABA system is very sensitive to local anaesthetics