PHARM: Local Anaesthetic

Question 1

how do local anaesthetics work and how are they selective?

Answer 1

• binds to intracellular part of voltage-gated Na+ channel > prevent AP so pain signal doesn’t reach the brain
• block pain > temp > touch, recovery is in reverse
• preferentially inhibit C fibres b/c unmyelinated so easier to get thru

Question 2

how does pH affect local anaesthetics?

Answer 2

• most are weak bases (ionised and NOT lipid soluble)
• become unionised (lipid soluble) in basic environents e.g. intestines
• therefore can move across plasma membrane to complete function

Question 3

chemical structure of a local anaesthetic

Answer 3

• lipophilic part (benzene ring)
• intermediate bond: ester or amide linkage (determines class)
• hydrophilic group (tertiary amine)

Question 4

example of ester local anaesthetic
- metabolism
- duration of action
- what is it used for

Answer 4

• amethocaine (tetracaine)
• broken down by esterases in tissue + plasma - made more water-soluble for renal excretion
• short lasting
• used topically b/c we don’t want systemic side effects

Question 5

example of amide local anaesthetic
- metabolism
- duration of action
- hypersensitivity risk?

Answer 5

• lignocaine (lidocaine - used for allergy)
• metabolised by liver, made more water-soluble for renal excretion
• longer duration of action
• lower risk of hypersensitivity (allergic) reaction

Question 6

why do more inflamed areas require more local anaesthetic to block the pain?

Answer 6

• increased inflammation = more acidic
• LAs are weak bases so need more to neutralise this

Question 7

use-dependence

Answer 7

• b/c LA acts on the intracellular portion of the channel, they preferentially target open or recently activated channels (non-resting)
• therefore: higher frequency of AP firing = more proportion of open channels = more LA block

Question 8

infiltration anaesthetic

Answer 8

• multiple small injections of anaesthetic
• reduce pressure insult from a large bolus (dose)
• allows more targeted delivery of anesthetic
• e.g. suturing, biopsies, dental procedures

Question 9

nerve block

Answer 9

• injected more deeply and closer to a nerve trunk/plexus
• numbs all sensation distal to that area
• used for larger surgeries e.g. fractures, replacements

Question 10

epidural/spinal anaesthesia

Answer 10

• used for childbirth or major surgeries
• safer and more effective than oral or IV opioids
• contraindicated if there is increased intracranial pressure or other neurological conditions

Question 11

regional intravenous anaesthetic (bier block)

Answer 11

• area is exsanguinated (double cuff applied to prevent blood flow) and then LA injected into the veins (VERY important to prevent systemic effects)
• useful for brief surgical procedures or manipulations of the upper limb

Question 12

why are vasoconstrictors e.g. epinephrine commonly co-administered w/ LA?

Answer 12

• to prevent overflow of the LA and hence systemic toxicity (altho this is rare)
• also prolongs duration of action by confining LA to the site and reducing the dose required

Question 13

systemic effects of LA (in order, getting worse)

Answer 13

• drowsiness
• paraesthesia in mouth and tongue
• tinnitus, auditory hallucination
• muscle spasm
• seizure
• coma
• respiratory arrest
• cardiac arrest

Question 14

3 examples of local anaesthetic drugs and what they’re used for

Answer 14

• lidocaine/lignocaine - allergy
• bupivacaine - cardiotoxicity, allergy
• amethocaine/tetracaine - skin redness, cornea damage, allergy