Principles of Local Anaesthesia

Question 1

Describe the generation of a neuronal action potential

Answer 1

Depolarisation occurs, NA channels open, Na influx causing depolarisation till around +40mV then Na channels close, VGKC open, K efflux causing repolarisation till about -90mV, VGKC and channels shut

Question 2

What determines resting potential of a neuronal cell?

Answer 2

K+ efflux down concentration gradient and K+ influx down electrochemical gradient (although membrane is slightly permeable to other ions too, hence why RP is -70mV not -92mV)

Question 3

Definition of a local anaesthetic

Answer 3

Drug which reversibly blocks neuronal conduction when applied locally

Question 4

2 groups of LA?

Answer 4

ester LAs, amide LAs

Question 5

Example of ester anaesthetic?

Answer 5

Cocaine

Question 6

Example of amide anaesthetic?

Answer 6

Lidocaine

Question 7

Saying to remember a type of LA?

Answer 7

Ester smokes cocaine

Question 8

What is the pKa of all LA?

Answer 8

Weak bases, pKa 8-9

Question 9

What’re the 2 MOA of LAs called?

Answer 9

The hydrophilic pathway and hydrophobic pathway

Question 10

Explain the hydrophilic pathway of LA MOA

Answer 10

• Once the unionized LA gets inside the neurone, the cationic form (BH+) of the LA is formed inside
• This can only bind with the sodium channel when it is open because the binding site is inside the channel
• Once inside the channel, it stereo-chemically inhibits the passage of sodium ions from the outside to the inside of the cell

Question 11

Where must the LA be for the hydrophilic pathway

Answer 11

inside the neurone

Question 12

Explain the use-dependency of the LA

Answer 12

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

Question 13

Selectivity of LA? what impact does this have

Answer 13

• They are not super selective so they will inhibit motor neurons as well as nociceptive

Question 14

Explain the hydrophobic MOA of LA

Answer 14

• LA passes into the membrane of the neurone in the unionized form
• Some highly lipid soluble LAs can drop straight into the sodium channel
• They then become ionized in the sodium channel and block the channel

Question 15

Effects of LA (4)

Answer 15

1. Prevent generation and conduction of APs
2. Do NOT influence resting membrane potential
3. May also influence channel gating (they have preference to bind to the inactivated state)
4. Selectively block small diameter fibres and non-myelinated fibres

Question 16

What type of fibre do LA have selectivity for

Answer 16

small diameter fibres and non-myelinated fibres

Question 17

What problems does infected tissue pose re. GA?

Answer 17

Tends to be acidic so a higher proportion of the LA will be ionised so harder to treat infected tissue with LA

Question 18

6 ROA of LA?

Answer 18

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

Question 19

Surface anaesthesia: type of surface? How is drug administered? Risk?

Answer 19

• Mucosal surface (mouth, bronchial tree)
• Spray (or powder)
• High concentrations systemic toxicity

Question 20

Infiltration anaesthesia: where? Used for? Coinjected with…? Why coinjected with X?

Answer 20

• Directly into tissues sensory nerve terminals
• Minor surgery
• Adrenaline co-injection (vasoconstrictor so the anaesthetic will be held at the site of action so lower doses can be used and won’t cause systemic toxicity) (NOT do in extremities as can cause ischaemia)

Question 21

Intravenous regional anaesthesia: how? Used for? Risk?

Answer 21

• Use a pressure cuff
• I.V. distal to pressure cuff
• Limb surgery
• Systemic toxicity of premature cuff release

Question 22

Nerve block anaesthesia: where? speed of onset? size of dosage? Coinjected with? Why coinjection?

Answer 22

• Close to nerve trunks e.g. dental nerves
• Widely used – low doses – slow onset
• Vasoconstrictor co-injection (adrenaline - anaesthetic will be held at the site of action so lower doses can be used and won’t cause systemic toxicity)

Question 23

Spinal anaesthesia: where? Used for what? Side effect, caused by what? Why does this side effect occur? Coinjected with, why?

Answer 23

• Sub-arachnoid space – floods around spinal roots
• Abdominal, pelvic, lower limb surgery
• Decrease BP  prolonged headache, this is because preganglionic sympa fibres are narrow and unmyelinated so sympa outflow can be blocked too
• Mix it with glucose (to increase specific gravity)

Question 24

Epidural anaesthesia: where? Used for? Onset speed? Risk? Dosage? Effect on BP?

Answer 24

• Fatty tissue of epidural space – spinal roots
• Uses as for spinal anaesthesia and painless childbirth
• Slower onset – higher doses are needed because you’re injecting outside of the spinal cord, this increases risk of systemic toxicity
• More restricted action – less effect on BP

Question 25

Effect of spinal anaesthesia on BP? Why?

Answer 25

• Decrease BP  prolonged headache, this is because preganglionic sympa fibres are narrow and unmyelinated so sympa outflow can be blocked too

Question 26

Where is spinal anaesthesia injected?

Answer 26

Sub-arachnoid space

Question 27

PP binding of lidocaine vs cocaine?

Answer 27

cocaine 90% bound lidocaine 70%

Question 28

Metabolism of lidocaine

Answer 28

Hepatic N-dealkylation

Question 29

Metabolism of cocaine

Answer 29

Liver and plasma by non-specific esterases

Question 30

Plasma 1/2 life of lidocaine

Answer 30

2hr

Question 31

Plasma 1/2 life of cocaine

Answer 31

1hr

Question 32

Unwanted effects of cocaine?

Answer 32

CNS – sympathetic actions:
-	Euphoria, excitation (sympathetically blocks reuptake of noradrenaline)
CVS – sympathetic actions:
-	Increased C.O.
-	Vasoconstriction
-	Increased BP

Question 33

Unwanted effects of lidocaine?

Answer 33

CNS – paradoxical:
-	Stimulation
-	Restlessness, confusion
-	Tremor
CVS – caused by Na+ channel blockade:
-	Myocardial depression
-	Vasodilatation
-	Decreased BP