LA

Question 1

Types of local anaesthetics (2)

Answer 1

1. Esters
   - Procaine
   - Tetracaine
2. Amides
   - Lidocaine
   - Mepivacaine
   - Bupivacaine (cardiotoxicity)

Question 2

Stages of voltage-gated Na+ channels (4)

Answer 2

1. Closed
2. Activated
3. Inactivated
4. Deactivated

Question 3

Inactivated vs Deactivated Na+ channels

Answer 3

Inactivated

• channel open
• gate closed

Deactivated

• channel closed
• gate closed

Question 4

MOA of LA

Answer 4

• block Na+ channel in axonal membrane intracellularly
• at appropriate dose
• locally

(( prevent depolarisation ))

Question 5

Use-dependency

Answer 5

Depth of LA nerve block increases with action potential frequency (increase transition between the various stages of channel) cos

• gain access to the channel more readily when channel is open
• have higher affinity for inactivated than closed channels

hence, increasing pain, frequency of action potential increases, increasing LA action

Question 6

Selectivity of LA

Answer 6

• non-selective

Question 7

Methods to minimise systemic absorption of LA

Answer 7

1. Apply locally to minimise blocking of action potentials in all neurons
2. Use of epinephrine to constrict blood vessels

Question 8

Factors affecting LA actions (6)

Answer 8

1. Size (small > large)
2. Myelination
3. Frequency of firing : high(sensory) > low(motor)
4. Position of nerve (circumferential > deep)
5. pH (intracellularly & extracellularly)
   eg inflammation
6. Lipid solubility of LA

Question 9

Types of nerve fibres

Answer 9

Type A
- least sensitive to LA block
- but most myelinated
Type B
- most sensitive to LA block
- smaller size
Type C
- most sensitive to LA block
- smallest size

Question 10

Why pH can affect LA action?

Answer 10

• LA pKa 8-9 (weak bases)
• at low pH, LA ionised to positively charged, reduce amount available to cross membrane
• LA bind intracellularly to block Na+ channels

Question 11

pH and LA relationship

Answer 11

Low pH (acidic) - low activity
High pH (alkaline) - high activity

Question 12

How LA causes anaesthesia?

Answer 12

1. Unionised LA passes through lipophilic membrane intracellularly
2. Ionisation of LA
3. Binding of LA to the inner end of the sodium channel (activated/inactivated)

Question 13

Esters LA (2)

Answer 13

1. Procaine
   - short acting
2. Tetracaine
   - long acting

Question 14

Amides LA (3)

Answer 14

1. Lidocaine
   - moderate acting
2. Mepivacaine
   - moderate acting
3. Bupivacaine
   - long acting

Question 15

Incidence of LA allergies (esters vs amides)

Answer 15

Esters

• low
• due to metabolism to p-aminobezoic acid (PABA)

Amide
- very low

Question 16

Metabolism of LA (esters vs amides)

Answer 16

Esters
- plasma/tissue non-specific esterase

Amide
- hepatic enzymes

Question 17

Distribution phases of LA

Answer 17

2.
Phase l - highly perfused tissues
- steep decline
- heart, liver, kidney, lungs

Phase ll - less perfused tissues

• less steep, assume nearly linear
• GI, muscles

Question 18

Causes of LA toxicity (2)

Answer 18

1. Incidental administration of LA IV/intra-arterial
2. Overdosage lead to systemic absorption

Hence, combine with epinephrine to prevent systemic distribution of LA from site of action

Question 19

LA toxicity (4)

Answer 19

1. bupivacaine (cardiotoxicity)
2. cocaine (constricts blood vessels -> hypertension)
3. o-toluidine (metabolite of prilocaine, causes methaemoglobin)
4. esters LA (metabolised to p-aminobenzoic acid which trigger allergies)

Question 20

Methods of local anaesthesia

Answer 20

1. Surface anaesthesia (not for skin)
2. Infiltration anaesthesia
3. Nerve-block anaesthesia (close to nerve trunks)
4. Epidural anaesthesia (epidural space)

Question 21

Choice of LA (2)

Answer 21

1. Duration of action

2. Site of action

Question 22

Patients with liver dysfunction

Answer 22

Esters LA

- cannot give amide LA cos it decrease metabolism, increase duration of action

Question 23

Patients with PABA allergies

Answer 23

Amide LA

- very low chance of triggering allergy

Question 24

Treatment for Methaemaglobin

Answer 24

IV methylene blue or ascorbic acid

Question 25

Lipid solubility of LA

Answer 25

More hydrophobic (TEB)

• Tetracaine
• Etidocaine
• Bupivacaine

Less hydrophobic (LPM)

• Lidocaine
• Procaine
• Mepivacaine

Question 26

High frequency of activation of action potentials

Answer 26

Sensory neurons

Question 27

Low frequency of activation of action potentials

Answer 27

Motor neurons

Question 28

How does lipid solubility of LA affects its action?

Answer 28

Increase lipid solubility increase LA action

• permeation through membrane
• permeation through myelin sheath

Question 29

How does application of LA on inflamed wound affect its action?

Answer 29

Inflammation

• more acidic extracellularly
• more positive ionisation of LA
• decrease permeation across membrane
• decrease LA blocking of Na+ channels intracellularly

Question 30

Hierarchy of the factors affecting LA action

size vs myelination

Answer 30

size > myelination

small myelinated > small non-myelinated > large myelinated

Question 31

What kind of transmission is blocked first? (2)

Answer 31

• Nociceptive transmission

- Sympathetic transmission

Question 32

Why is pH important in affecting LA action?

Answer 32

pH plays a critical role in LA penetration of nerve sheath and axon membrane to reach inner end of the Na+ channels (which is LA binding site)

Hence, LA action is strongly dependent on pH

Question 33

pKa of LA

Answer 33

pKa 8-9 (weak bases)

- mainly ionised (but not completely) at physiological pH of 7.4