Lecture 32: Local Anaesthetics

Question 1

Describe the conceptual operation of the voltage gated Na channel:

Answer 1

RMP
Threshold: With inner and outer gates open, Na influxes
Automatic deactivation: Inner gate closes
Recovering: Outer gate closes, inner gate opens, Back to RMP status

Question 2

Describe the basic ion flow of neural cell depolarisation:

Answer 2

Na influxes and threshold is reached. All Na channels open and cell depolarizes. K channels open, K effluxes and cell repolarizes.

Question 3

How do local anaesthetics work?

Answer 3

Local anaesthetic molecules block the Na channel, prevent voltage dependent increase in Na ion conductance.

Question 4

What is the structure of local anaesthetic molecules?

Answer 4

Aromatic group (Hydrophobic)
Amide or ester link
Amine (HYdrophilic)

Question 5

What is the structure activity relationship?

Answer 5

Ester or amide bonds determine site of metabolism and potential to produce allergic reactions

Esters are more rapidly metabolized (and shorter acting) and more allergenic.

Question 6

What are the important esters (LA)?

Answer 6

Cocaine
Procaine
Benzocaine
Tetracaine

Question 7

What are the important amides (LA)?

Answer 7

Prilocaine

Most commonly used LA:
Lignocaine
Bupivocaine
Ropivacaine

Question 8

Describe the relationship between acid base status and LA activity:

Answer 8

ALL LOCAL ANAESTHETICS ARE WEAK BASES

• ONLY FREE BASES (non ionised) CAN CROSS MEMBRANES

Therefore, the amount of free base present at physiological pH depends on the pKa of the drug.

More free base = faster onset of action

Question 9

High pKa vs low pKa, what is better?

Answer 9

High pKa = Ionized from

Low pKa = Free based, i.e faster diffusion, ie quicker onset

Question 10

Order the 7 common La in rank of onset speed:

Answer 10

Slower i.e higher pKa:

Procaine
Tetracaine
Bupivacaine
Ropivacaine
Prilocaine
Lignocaine

Faster i.e lower pKa

Question 11

Explain why La arent effective as a block in acidic infected tissue

Answer 11

LAs with pKa closest to physiological pH have fastest onset of action

This explains poor quality of block when LA injected into acidic infected tissue.

Question 12

What increases the solubility of LAs? Rank 4

Answer 12

Lengthening alkyl chain increases lipid solubility. In general: More lipid soluble = more potent

Most lipid soluble:
Bupivicaine
Lignocaine
Prilocaine
Procaine
Least:

Question 13

What influences the duration of LA? Rank 4:

Answer 13

Protein binding, the more protein binding the more duration of action

Most:
Bupivicaine
Ropivacaine
Lignocaine
Prilocaine
Least:

Question 14

What breaks down LA?

Answer 14

Esters: Plasma cholinesterases

Amides (And some cocaine): Liver metabolism

Question 15

Write some notes on Lignocaine/Lidocaine:

Answer 15

AMIDE (standard agent to which others compared)

Potency -> Low lipid solubility, Low potency
Onset -> Lower pKa, non-ionised, FAST ONSET
Duration -> Low protein binding, Short Duration of action

Ideal for short surgical procedures i.e dental or mole removal

Question 16

Write some notes on bupivocaine:

Answer 16

AMIDE

Potency -> High lipid solubility, More potent that ligno
Onset -> High pKa, slower onset that ligno
Duration -> High protein binding, Longer Duration of action that ligno

Ideal for nerve blocks for prolonged anaesthesia (peripheral nerve block)

Question 17

Write some notes on cocaine:

Answer 17

Ester, topical to nose, vasoconstrictor

Question 18

Write some notes on prilocaine:

Answer 18

Amide, SAFEST agent, used in IV regional anaesthesia (Lowest CV toxicity)

Question 19

Write some notes on Ropivacaine:

Answer 19

Amide, slow onset, long acting like bupivacaine, but less cardiac toxicity.

Question 20

How can LA be toxic?

Answer 20

• Allergic reactions (rare amides)
• Dose dependent CNS toxicity i.e seizures, tinnitus
• Dose dependent CV toxicity i.e heart block, Vfib, both more likely and dangerous with bupivacaine
• CC-CNS ratio:ratio dose required to cause cardiac VS CNS toxicity i.e Lignocaine 7, bupivicaine 3 i.i.e Takes 3x the dose of bupivicaine to cause cardiac vs CNS toxicity
• Usually inadvertant IV administration

Question 21

Write some notes of LA use topical to skin:

Answer 21

EMLA (Eutectic mixture of LAs)

- Mixture of lignocaine and prilocaine as an oil prep (more free base and can cross skin)

Question 22

Write some notes of LA use topical to mucous membranes:

Answer 22

• Cocaine (also vasocon adv)

- Lignocaine spray and viscous preps (Instrumentation of the nose/mouth/pharynx/urethra

Question 23

Write some notes on the soft tissue infiltration of LAs:

Answer 23

Soft tissue infiltration

• For minor interventions i.e mole removal (fast acting, short duration agent)
• For post operative pain relief in surgical wounds (Slow acting, long duration agent)

Question 24

Where can a nerve block be placed?

Answer 24

• Peripheral NB

- Neuroaxial (spine) NB

Question 25

Write some notes on a peripheral nerve block:

Answer 25

Peripheral nerve block

• LA is infiltrated around a specific nerve i.e brachial plexus for surgery on the arm
• A mixed nerve, smaller sensory more susceptible, but motor can be affected
• For surgery without GA, or post op pain releif

Question 26

Write some notes on neuralaxial blockade specifically a spinal block:

Answer 26

Spinal anesthesia

• LA injected into the INTRATHECAL space (ONLY BELOW L2) where SC terminates
• Profound distal motor and sensory blockade
• i.e major surgery of knee, hip, C section IN AWAKE Pt

Question 27

Write some notes on neuroaxial blockade specifically an epidural anaesthesia:

Answer 27

Epidural anesthesia

• Small catheter inserted into epidural space and LA infused. Bathes spinal nerves passing through space. can be done at any level
• Distal sensory +/- motor blockade
• Excellent post op or labor analgesia if inserted at correct level.