Lecture 12: local anaesthetics

Question 1

General mechanism of action of local anaesthetics?

Answer 1

They become non-ionized and travel into the neuron before becoming re-ionized where they block Na⁺ channels on membranes from the inside stopping AP travelling.

Question 2

General structure of local anaesthetics and the implications of this?

Answer 2

Ester bond or amide bond between an aromatic and a amine group

The ester bonds are more rapidly metabolised (shorter acting) and more likely to give an allergic reaction - not used as much these days

Question 3

Structure-activity relationship?

Answer 3

They are all weak bases so exist in an ionized and non-ionized (free base) and this ratio is determined by pKa of the drug. A low pKa will therefore have more free base so work faster.

Lengthening the alkyl chain also increases their lipid solubilty so they are more potent.

Question 4

Explain why anaesthetics injected into infected areas are less fast acting?

Answer 4

Because the infected area is acidic and so the pH is lower and thus further away from the pKa of the weak base anaesthetic leading to less free base being available.

Question 5

What does duration of action vary with?

Answer 5

Protein binding

Question 6

Lignocaine structure, properties, ideal use?

Answer 6

• Amide
• Low lipid solubility = low potency
• low pKa = fast onset
• low protein binding = short duration
• ideal to cover short surgical procedures (eg. dental or mole removal)

Question 7

Bupivacaine structure, properties and ideal use?

Answer 7

• Amide
• High lipid solubility = more potent
• High pKa = slower acting
• High protein binding = Longer duration of action
• Ideal for nerve blocks for analgesia

Question 8

3 other alternative anaesthetics?

Answer 8

Cocaine - ester, topical to nose, vasoconstricts

Prilocaine - Amide, very safe, IV regional anaesthesia -(using cuff = Bier’s block)

Roprivocaine - Amide, slow onset, long acting, low cardiac toxicity

Question 9

LA toxicity?

Answer 9

1. Allergic reactions - very rare with amides
2. Dose dependent CNS toxicity -(seizure)
3. Dose dependent cardiac toxicity -(cardiac arrest)
4. Dose dependent toxicity from accidental IV administration but can be just too much in tissue.

CC:CNS ratio is how much you have to give to induce a cardiac arrest vs a seizure. A bigger number the best chance of not messing up accidentally. If someone has a seizure then STOP.

Question 10

topical administrtion and uses of LAs?

Answer 10

1. Topical to skin​
   - EMLA - eutectic mixture of LAs
   - Mixture of lignocaine and prilocaine in an oil to allow it all to be free base.
   - used for insertion of IV cannulae to children.
2. Topical to mucus membranes

- Cocaine

• lignocaine spray and viscous preparations for nose/mouth/pharynx/urethra

Question 11

soft tissue administration and use?

Answer 11

• for minor interventions like mole removal they are fast acting and short lasting
• For post opertative pain relief around the wound

Question 12

types of nerve blocks?

Answer 12

1. Peripheral nerve block
2. Neuraxial blockade

Question 13

Peripheral nerve block?

Answer 13

LA is infiltrated around a specific nerve

Sensory fibres more susceptable but motor fibres can be affected as well

Good for surgery without GA or for post-op pain

Question 14

Neuraxial blockades?

Answer 14

1. Spinal Anaesthesia
   - LA is injested onto the intrathecal space below L2
   - Profound distal motor and sensory blockade from level down
2. Epidural anaesthesia
   - Small catheter inserted into epidural space using loss of resistance technique
   - creates a band on numbness at that spinal level for up to 2/3 days if catheter is left in and continual anaesthetic release.