Lecture 30: Local Anaesthetics

Question 1

Describe the 4 steps of V gated Na+ channels

Answer 1

1. At resting potential (-90) the gate is closed to prevent Na+ coming in from outside, but the inner gate is open
2. At threshold depolarisation the outside gate opens allowing Na+ to enter the cell
3. After short time there is automatic deactivation: Inner gate shuts
4. Recovering, the gates return to original resting position

Question 2

What is the mechanism of action of local anaesthetics

Answer 2

The ionised form of the Anaesthetic physically block voltage gated Na+ channels at the node of ranvier from the inside of the cell to prevent Na+ inflow triggering depolarisation of the cell and transmission of AP.

Question 3

what is the structure of local anaesthetic and how does it affect

2. its site of metabolism and allergenicity,
3. onset of effect,
4. potency and
5. duration of action

Answer 3

1. Structure is hydrophobic aromatic group linked to hydrophillic amine group by amide or ester link
2. Ester bond: rapidly metabolised by plasma cholinesterases, shorter acting and more allergenic than Amide bonds
3. The onset of action is related to the amount of free base (LA) in proportion to ionised form LAH+. This is because only the nonionised form can cross membranes and enter cells to the target site.

LA with pKA closest to Physiological pH have fastest onset of action (lower pKa)

4. Potency is proportional to the length of the alkyl chain: the increased lipid solubility.
5. duration of action proportional to protein binding.

Question 4

Compare the uses for LA lignocaine and Bupivacaine with their pk properties - both soft tissue infiltration

Answer 4

Both are amides, however
Lignocaine is good to cover short surgical procedures because it has low potency, low pKA so fast onset, and low protein binding so short duration.

Bupivacaine is good for nerve blocks for analgesia as it has high potency, high pKA: slow onset, high protein binding: long effect

Question 5

What forms of toxicity do LA cause

Answer 5

-Esters cause allergic reactions
Dose dependent toxicity caused by inadvertent IV administration

1stly Dose dependent CNS toxicity: Perioral paresthesia, tinnitus and seizurse
2nd: Dose dependent CVS toxicity: heart block, ventricular fibrillation

the dose ratio of getting CVS symptoms after CNS helps to show the risk of toxicity- bupivacaine = 3 so 3x dose needed to go from CNS symptoms to CVS.

Question 6

What are the two uses of topical LA and which compounds are used

Answer 6

1. topical to skin: cream + bandage for insertion of IV cannulae into children.
   This is a mixture of lignocaine and prilocaine as an oil to allow crossing the skin
2. topical to mucous membranes: cocaine, lignocaine spray for instrumentation of nose , mouth, pharynx, urethra

Question 7

Compare the Peripheral nerve block, Spinal anaesthesia and Epidural anaesthesia uses, administration and effects

Answer 7

PNB: Used to avoid general anaesthetic in patients with comorbities + post op pain relief. LA infiltrated around specific nerve/plexus affecting mostly sensory but also motor.

SpA: Used for major surgery in awake patient (C section, hip replacement) for distal motor and sensory.
La in subarachnoid space below L2 in the CSF

EpA: Used for post op/ labour anaesthesia which can be left in for couple of days. Catheter inserted into epidural space affecting spinal nerves passing through that space at any level