Local anaesthetics

Question 1

What do local anaesthetics exist as?

Answer 1

All LAs are weak bases; existing in unionised (B) and ionised (BH+) forms.

Question 2

How do local anaesthetics reach the target site and act?

Answer 2

They diffuse across the lipid cell membrane in their unionised form, where they are ionised by the (more) acidic intracellular cytosol and bind/block the VGSC from the inside.

Question 3

What forms can LAs derived from cocaine exist in, and what enzymes metabolise them?

Answer 3

Amide and ester variants:
Amides: metabolised by liver amidases (implication for liver failure)
Esters: metabolised by cholinesterase

Question 4

Are LAs more ionised or unionised at physiological pH?

Answer 4

LAs are more ionised at physiological pH (7.4) than unionised; all pKa values are greater than 7.4.

Question 5

What pKa is preferable for LAs to act, and what does a more pKa mean for the drug action?

Answer 5

As close to a pKa of 7.4 as possible (where there’d be 50% 1:1 ratio ionised/unionised due to pH 7.4); Lidocaine has pKa 7.9 = 25% unionised, Bupivacaine has pKa 8.1 = 15% unionised; Lidocaine thus has a more rapid onset of action (passing through lipid cell membrane more).

Question 6

Can the ionised LA pass back through the membrane back to the extracellular fluid?

Answer 6

Not readily; its ionised state means it is ‘trapped’, thus increasing the length it is bound and blocking VGSC’s exerting their therapeutic effect.

Question 7

What type of nerve fibres are LAs most efficacious for/are the target for?

Answer 7

C fibres (slow pain) are most sensitive; myelinated and thicker axons (e.g. Aα, Aβ, Aγ, Aδ) are more difficult to penetrate for LAs than thin, unmyelinated axons (C).

Question 8

Aα, Aγ, C, Aδ, Aβ. Order them according to LA sensitivity.

Answer 8

Aα; +
Aβ; ++ 
Aγ; +++
Aδ; ++++
C;   +++++

Question 9

What are the different sites of LA action?

Answer 9

• Surface anesthesia
• Infiltration (most LAs; injection into tissues to reach nerves)
• IV regional
• Nerve block
• Spinal
• Epidural

Question 10

Give examples of targets for surface anesthesia and example LAs.

Answer 10

Mucus membranes & corneal drops (sprays)
- Lidocaine, tetracaine

Skin (not v effective - cream)
- EMLA (Eutectic Mixture of Local Anaesthetics; lidocaine & prilocaine)

Question 11

Describe LAs in Infiltration.

Answer 11

• Injection into tissues to reach nerves

- Minor surgery (most LAs)

Question 12

What might be added to LAs to complement Infiltration, and when is it not added?

Answer 12

Adrenaline; vasoconstriction (reducing perfusion) preventing diffusion away from site, keeping LA at target.

• Not for fingers/toes due to risk of ischaemia

Question 13

Describe LAs in Nerve block and their applications.

Answer 13

Injection close to nerve trunks reducing sensation peripherally, used in surgery/dentistry.

Question 14

Describe LAs in Spinal and their applications.

Answer 14

Injection into subarachnoid space (containing cerebrospinal fluid; CSF) depressing spinal roots/cord.
- Surgery on: abdomen, pelvis, leg (if general anaesthetic not possible)

Question 15

What might be added to LAs to complement Spinal application and why? Any other precautions and why?

Answer 15

Glucose; increases density, limiting spread of LA.

Can also tilt patient; risk of CVS effects/respiratory depression (VGSCs present) thus limit spread to brain in CSF.

Question 16

Describe LAs in Epidurals and their applications.

Answer 16

Injection into epidural space, blocking spinal roots (not as invasive as Spinal).
- Surgery on: abdomen, pelvis, leg (as for Spinal) and ‘painless childbirth’.