28. Principles of local anaesthesia

Question 1

What pH are local anaesthetics?

Answer 1

High - all LAs are weak bases, so are pH dependent to have an effect

Question 2

What do LAs generally do?

Answer 2

Block sodium ion channels - preventing neuronal depolarisation

Question 3

What 3 structures do all LAs have in common?

Answer 3

• Aromatic region (benzene)
• Basic amine side chain (tertiary)
• Linked by ester or amide bond

Question 4

What are the 2 different groups of LAs and give examples?

Answer 4

• Esther LA - cocaine
• Amide LA - lidocaine

2 different linking of benzene and amine gives rise to these groups

Question 5

Which LA is an exception to the general structure of LAs and why, and what is it used for?

Answer 5

Benzocaine
• Doesn’t have the basic amine side chain
• Has an alkyl group instead
• Still has weak LA properties and is lipid soluble

• Used as surface anaesthetic
• Useful in throat lozenges

Question 6

How does LA go from being injected close to sensory pain-conducting neurones, to blocking their effect?

Answer 6

• Unionised (lipid-soluble) form passes through the connective tissue sheath
• Passes through the lipid bilayer and gains access inside the sensory axon
• LA becomes ionised (polar) inside axon, due to acid (physiological) environment
• Ionised form has anaesthetic properties, and binds to the inside of the of VGSC
• VGSC has to be open

Hydrophilic pathway - uses use -dependency

Question 7

How is the hydrophobic pathway of LAs different to the hydrophilic?

Answer 7

• More important for the more lipid-soluble LAs
• As the unionised form cross the axonal membrane, some can convert into the cation ionised form and block the ion channel
• Can drop into a closed channel as well as an open channel

Question 8

Do LAs influence the resting membrane potential?

Answer 8

No

Question 9

Do LAs influence channel gating?

Answer 9

Yes

Question 10

How does an LA having a higher affinity for the inactivated state of the channel affect the refractory period?

Answer 10

Prolongs it

Question 11

What type of fibres do LAs selectively block?

Answer 11

• Smaller diameter fibres

* Non-myelinated fibres e.g. pain C-fibres

Question 12

How is using an LA on infected tissue different and why?

Answer 12

• More difficult

* Tend to be acidic, so more LA becomes ionised and harder to enter axon

Question 13

What are the different routes of LA administration?

Answer 13

• Surface
• Infiltration
• IV regional
• Nerve block
• Spinal
• Epidural

Question 14

Can surface LA lead to systemic toxicity?

Answer 14

Yes, at high concentrations

Question 15

How is infiltration anaesthesia administered?

Answer 15

• Subcutaneously
• Co-injected with adrenaline, as it causes vasoconstriction (apart from extremities to prevent ischaemic damage)
• This increases duration and reduces incidence of systemic effects

Question 16

When and how is IV regional anaesthesia administered?

Answer 16

• Limb surgery?
• Administered distal to pressure cuff
• Cuff should be kept on for 20mins minimum
• LA diffuses from vein into tissue
• Premature cuff release can cause systemic toxicity

Question 17

What is nerve block anaesthesia and how is it administered?

Answer 17

• LA injected close to nerve trunks e.g. dental nerve trunks
• Slow onset - many membranes to cross
• Co-injection with vasoconstrictor

Question 18

Describe spinal anaesthesia, and when is it used?

Answer 18

• LA injected into sub-arachnoid space
• Action on spinal roots (intrathecal)
• Can be mixed with glucose to increase specific gravity - control
• Abdominal, pelvic and lower limb surgery
• LA mixes with CSF (injected at L3/4)

Question 19

Describe the side effects of spinal anaesthesia

Answer 19

• Decreased BP - LA acting on small-diameter pre-ganglionic sympathetic neurones - bradycardia and vasodilation
• Prolonged headache - accesses the brain

Question 20

How is the onset and dose of epidural different to spinal anaesthesia?

Answer 20

• Slower onset

* Higher doses required

Question 21

What is the advantage of epidural anaesthesia compared to spinal?

Answer 21

• More restricted action

* Less effects on BP

Question 22

How is lidocaine and cocaine metabolised?

Answer 22

• Lidocaine - hepatic N-dealkylation

* Cocaine - hepatic and plasma metabolism by non-specific esterases

Question 23

Do amides or esters have a longer duration of action and why?

Answer 23

Amides as they are more resistant to metabolism

Question 24

Why is Bupivacaine used for and what is it’s duration of action?

Answer 24

Epidural anaesthesia (half-life: 6 hours - long)

Question 25

What are the unwanted effects of cocaine?

Answer 25

Sympathetic
• CNS: euphoria, excitation (slow NA re-uptake)
• CVS: increase CO, vasoconstriction, increased BP, cardia arrhythmias

Question 26

What are the unwanted effects of lidocaine?

Answer 26

• CNS: stimulation, restlessness, confusion (GABAergic neurones are sensitive to LA - paradoxical, then depressive symptoms)
• CVS: myocardial depression, vasodilation, decreased BP (NA channel blockade)