L22 - local anaesthetics

Question 1

what are sensory nerves called that transmit pain signals - what exactly do they detect

Answer 1

nociceptors

tissue damage

Question 2

how do local anaesthetics work (generally)

Answer 2

prevent pain by stopping the initiation or propagation of action potentials before they reach the brain

Question 3

how do Local anaesthetics stop pain transmission

Answer 3

block voltage dependant Na channels in sensory nerves (these channels are found in many tissues)

Question 4

describe the structure of a local anaesthetic molecule

Answer 4

aromatic head linked to a basic side chain by either an ester or amide bond

Question 5

give an example of a local anaesthetic that has a
amide bond
ester bond

Answer 5

amide - lignocaine

ester - amethocaine

Question 6

how are local anaesthetics broken down

Answer 6

1. those with an ester bond can be broken down by esterase enzymes found in tissues
2. those with an aide bond have to be broken down in the liver

Question 7

are ester or amide local anaesthetics longer acting?

Answer 7

amide, because they have to travel to the liver to be broken down, ester ones are broken down in the tissues by esterases

Question 8

what is the pKa of Local anaesthetics, and what are they chemically?

Answer 8

8.0

weak bases

Question 9

what happens to the Local anaesthetic at physiological pH (7.4)

Answer 9

1. because the pH is more acidic than the pKa, it means there are more H+ ions
2. due to the equilibrium ( LA are weak bases) the H+ ions shift the equilibrium to the right forming the conj acid
3. both the weak base and conj acid are present at physiological pH

Question 10

write the equilibrium equation for Local Anaesthetics

Answer 10

R - NR2 + H+ —-> RN+R2H

base conj acid (accepted H+)

Question 11

describe the sodium channel and how this affects the action of Local anaesthetic molecules

Answer 11

1. the drug binding site is deep in the pore
2. the extracellular opening of the channel is too small for the drug molecule to fit through,
3. the intracellular opening of the pore is big enough for the drug molecule but is guarded by activation & inactivation gates (charge gated)
4. LA molecules can gain access to binding site by two pathways : HPhilic and Hphobic

Question 12

explain the Hydrophobic pathway for Local Anaesthetics

Answer 12

1. the uncharged basic form dissolves into the lipid bilayer (the acidic form cant do this)
2. dissolves from inside the membrane into the channel and into the biding site
3. becomes charged when in the binding site

Question 13

explain the Hydrophilic pathway for Local Anaesthetics

Answer 13

1. uncharged molecule diffused across membrane into cell
2. new equilibrium is set up in the cell
3. the charged form can enter the channel from the inside if the voltage dependant gates are open

Question 14

define use dependence (in terms of HPhilic pathway)

Answer 14

the more often you open the gates of the channel (by AP’s) the more readily the drug can gain access
so, nerves that fire AP at high frequency are more susceptible to block

Question 15

what factors can decrease effectiveness of LA’s

Answer 15

1. anything that increases ionisation ( charged form cant cross lipid bilayer)
   eg:
   drop in pH
   (inflammation can cause a drop in pH)

Question 16

what can increase effectiveness of LA’s

Answer 16

1. small diameter nerve fibres

Question 17

explain surface anaesthesia

Answer 17

1. drug applied to body surfaces eg skin (includes all orifices eg nose

Question 18

limitations of surface anaesthesia

Answer 18

1. not very effective when applied to skin as skin is protective barrier
2. have to be careful if applying to large area / damaged skin that too much doesnt enter blood

Question 19

examples of when surface anaesthesia is used

Answer 19

minor eye surgery

catheterisation (urinary tract)

Question 20

explain infiltration anaesthesia

Answer 20

LA injected into localised area

Question 21

examples of when infiltration anaesthesia is used

Answer 21

dentistry

wound stitching

Question 22

explain nerve block anaesthesia

Answer 22

LA injected into a nerve trunk eg brachial plexus in neck to nub entire arm
requires less drug than infiltration but affects wider area
accurate injection important

Question 23

when is nerve block anaesthesia used

Answer 23

minor surgery

Question 24

explain spinal and epidural anaesthesia

Answer 24

spinal - injected into spinal cord
epidural - injected around spinal cord

all nerves entering below injection site are blocked

Question 25

when is spinal/epidural anaesthesia used

Answer 25

major surgery

childbirth

Question 26

explain intravenous regional anaesthesia

Answer 26

LA injected intravenously into limb which is isolated from circulation by pressure cuff

Question 27

when is intravenous regional anaesthesia used

Answer 27

limb surgery eg resetting broken bones

Question 28

what needs to be considered during intravenous regional anaesthesia

Answer 28

1. must keep procedure short (<90 mins) to avoid ischaemic damage to limb
2. must release cuff slowly to prevent high conc of LA getting into systemic circulation at once

Question 29

what are the side effects if LA enters systemic circulation?

Answer 29

1. confusion, restlessness, tremor, convulsions, respiratory depression
2. vasodilation —> drop in Blood Pressure
3. myocardial depression (cant produce AP)

Question 30

what can prolong the effect of Local Anaesthetics

Answer 30

1. effect decreases as the LA seeps away from injection site and slowly enters circulation
2. this can be slowed by vasoconstrictors eg adrenaline