29. Principles of local anaesthesia

Question 1

what are local anaesthetics?

Answer 1

drugs that reversibly block neuronal conduction when applied locally

they are weak bases and they are sodium ion channel blockers

Question 2

outline the generation of a neuronal action potential

Answer 2

1. stimulus
2. VGSCs open
3. sodium rushes into neurone
4. rapid depolarisation
5. sodium channels close within a millisecond
6. VGKCs open
7. potassium leaves neuronal cell
8. repolarisation
9. restoration of the sodium channels to their resting state but potassium channels remain open
10. refractory period
11. both sodium and potassium channels have been restored to their resting state

Question 3

what 3 things do all local anaesthetics have in common?

Answer 3

• aromatic region
• basic amine side chain
• linked by an ester or amide bond (LAs are either esters or amides)

Question 4

give an example of an ester LA and an amide LA

Answer 4

ester LA - cocaine

amide LA - lidocaine

Question 5

what is special about benzocaine?

Answer 5

it is the only LA that doesn’t have the basic amine side chain (it just has an alkyl group on the side)

Question 6

what is the hydrophilic pathway?

Answer 6

a LA can be injected close to sensory, pain-conducting neurones

the unionised form of the LA is soluble and passes through the connective tissue sheath to sensory axons inside the neurone and then through the axon to the inside

once the lipid-soluble form of the LA is inside the axon the equilibrium is established (unionised and ionised versions of the LA)

Question 7

which version of the LA has anaesthetic properties and what does it do?

Answer 7

the ionised form - blocks VGSCs by binding to the inside

Question 8

what does the hydrophilic pathway rely on?

Answer 8

use dependency - for the ionised form of the LA to bind to its target site the channel has to be open

Question 9

what happens if LAs are introduced close to motor neurones?

Answer 9

weakness and relaxation of skeletal muscles

Question 10

what is the hydrophobic pathway?

Answer 10

as the unionised form crosses the axonal membrane, some can drop into the ion channel and convert into the cation ionised form to block the ion channel

this means by the hydrophobic route the LAs can drop into a closed channel as well as an open channel

Question 11

what are the effects of LAs?

Answer 11

• prevent the generation and conduction of APs
• influence channel gating
• selectively block small diameter fibre and non-myelinated fibres (narrow fibres that conduct pain impulses and pain C fibres)

Question 12

why is infected tissue difficult to anaesthetise?

Answer 12

because it tends to be acidic so a larger portion is ionised

Question 13

outline the use of surface anaesthesia

Answer 13

• for mucosal surfaces (mouth, bronchial tree, eyes, nose, throat)
• spray or powder form
• we need high concentrations of the LA to gain an effective anaesthetic action
• HOWEVER high concentrations can lead to systemic toxicity

Question 14

outline the use of infiltration anaesthesia

Answer 14

• LA is directly injected into tissues –> accesses the sensory nerve terminals directly
• injection is given subcutaneously
• applications in minor surgery (stitches)

Question 15

what is given along with infiltration anaesthesia and why?

Answer 15

adrenaline co-injection because adrenaline causes vasoconstriction:

• increasing the duration of action of the LA
• reducing the incidence of systemic side effects (limiting toxicity)

BUT if we are affecting the extremities we do not give adrenaline (–> ischaemic damage)

Question 16

outline the use of intravenous regional anaesthesia

Answer 16

• IV injection is given distal to a pressure cuff - shuts off the blood supply
• this has applications in limb surgery
• systemic toxicity may occur if there is premature cuff release (should be kept on for a min. of 20mins)

Question 17

outline the use of nerve block anaesthesia

Answer 17

• injected close to the nerve trunks
• widely used however there is a relatively slow onset (mins)
• vasoconstrictor co-injection with nerve block anaesthesia

Question 18

outline the use of spinal anaesthesia

Answer 18

• LA is injected into the sub-arachnoid space –> acts on spinal roots
• useful for abdominal, pelvic and lower limb surgery
• injected at L3/L4 - anaesthetic mixes with CSF

Question 19

what side effects may occur due to spinal anaesthesia?

Answer 19

• decreased BP: LA action on small diameter pre-ganglionic sympathetic ANS neurones
• prolonged headache - accesses brain

Question 20

outline the use of epidural anaesthesia

Answer 20

• injected into fatty tissue of epidural space –> action on the spinal roots
• used as spinal anaesthesia but also for painless childbirth

Question 21

what are the advantages and disadvantages of epidural anaesthesia?

Answer 21

ADVANTAGES

• more restricted action
• less effects on BP

DISADVANTAGES

• slower onset
• higher dose required –> more likely to experience systemic side effects

Question 22

what are the pharmacokinetic properties of lidocaine?

Answer 22

• any route of administration
• good absorption
• metabolised via hepatic N-dealkylation
• plasma half life of 2 hours

Question 23

what are the pharmacokinetics of cocaine?

Answer 23

• good absorption
• metabolised in the liver and plasma by non-specific esterases
• plasma half life of 1 hour

Question 24

what are the unwanted effects of cocaine?

Answer 24

• CNS: euphoria and excitation - due to the sympathomimetic action of cocaine
• CVS: increased cardiac output, vasoconstriction and increased BP

(both sympathetic actions)

Question 25

what are the unwanted effects of lidocaine?

Answer 25

• CNS: stimulation, restlessness, confusion and tremor (paradoxical effects because the inhibitory GABAergic neurones in the CNS are more sensitive to LAs)
• CVS: myocardial depression, vasodilation, decreased BP (due to Na channel blockade)