Local Anaesthetics

Question 1

Define Local Anaesthetic.

Answer 1

Drugs that reversibly block neuronal conduction when applied locally

Question 2

What is the rapid depolarisation stage of the action potential caused by?

Answer 2

Opening of voltage-gated sodium channels

Influx of Na+

Question 3

What are the three components that make up all local anaesthetics?

Answer 3

Aromatic region
Basic amine side-chain
Amide or ester link

Question 4

What are the two types of local anaesthetics? Give an example of each.

Answer 4

Ester = COCAINE 
Amide = LIDOCAINE

Question 5

Name a local anaesthetic that doesn’t fit the structure of all other local anaesthetics.

Answer 5

Benzocaine: has an alkyl group rather than an amine side chain
Thus it’s relatively weak but highly lipid soluble (good for surface anaesthesia)

Question 6

What are the two pathways of local anaesthesia? State which one is more important.

Answer 6

HYDROPHILIC – most important

Hydrophobic

Question 7

Describe the hydrophilic pathway.

Answer 7

Unionised LA from the blood crosses the axon membrane + gets into the axon
Within the axon it forms the cation form of the LA
Cation then binds to the inside of the VGSCs (when open) + block Na+ entry
Blocks AP conduction

Question 8

What feature of local anaesthetics helps make it more selective for nociceptive neurones? Can they block motor neurones?

Answer 8

Use-dependency

Can block MN’s but less intensely (fire less + are myelinated)

Question 9

Describe the hydrophobic pathway. What is advantageous about this pathway?

Answer 9

Very lipophilic LAs move into the cell membrane (in unionised form) + drop straight into the sodium channel
Then transition to cation form in the sodium channel
+ will block Na+ influx
VGSCs don’t need to be open for LA to bind

Question 10

What effect do local anaesthetics have on resting membrane potential?

Answer 10

No effect on resting membrane potential

Question 11

Explain the effect of local anaesthetics on channel gating.

Answer 11

Suggestion: LA’s bind more strongly to the VGSCs in their inactive state
Once bound it holds it in the inactive stage for longer thus increasing the refractory period + reducing the frequency of APs

Question 12

Describe the selectivity of local anaesthetics.

Answer 12

Preference for small diameter axons (e.g. nociception neurones)
Tend to block non-myelinated axons

Question 13

Describe the pKa of all local anaesthetics. What does this mean for local anaesthetics acting at our physiological pH?

Answer 13

8-9
All local anaesthetics are WEAK BASES
Only small % will be unionised + can pass into neurones

Question 14

Explain why it is difficult to anaesthetise infected tissue.

Answer 14

Infected tissue is ACIDIC

So less anaesthetic will be unionised

Question 15

What are the 6 methods of administration of local anaesthetics?

Answer 15

Surface anaesthesia 
Infiltration anaesthesia 
Intravenous regional anaesthesia  
Nerve block anaesthesia 
Spinal anaesthesia  
Epidural anaesthesia

Question 16

What are the consequences of using high doses in local anaesthesia?

Answer 16

Can cause systemic toxicity- go to heart then brain

Question 17

What is infiltration anaesthesia?

Answer 17

Injection of anaesthetic directly into tissue near the sensory nerve terminals
Used for minor surgery

Question 18

What is often coadministered with infiltration anaesthesia and what are the benefits of this? When is this avoided?

Answer 18

Adrenaline: causes vasoconstriction + increases the duration of action of LA meaning a lower dose can be used
Also slows bleeding at site of injection + reduces the amount of LA going into the systemic circulation
Avoided in LA of extremities as risk of ischaemic damage

Question 19

What is intravenous regional anaesthesia and how can this cause systemic toxicity?

Answer 19

LA administered intravenously, distal to pressure cuff (which restricts blood flow)
Used in limb surgery
Removing pressure cuff too early can lead to a bolus of anaesthetic entering the systemic circulation

Question 20

What is nerve block anaesthesia? Describe the dosage and onset.

Answer 20

Inject anaesthetic close to the nerve trunks

Low doses + slow onset

Question 21

What is coadministered with nerve block anaesthesia?

Answer 21

A vasoconstrictor e.g. adrenaline

Question 22

What is another name given to spinal anaesthesia?

Answer 22

Intrathecal

Question 23

Where is the anaesthetic inserted in spinal anaesthesia?

Answer 23

Into the subarchnoid space (into the CSF)

Question 24

Which parts of the body can be anaesthetised effectively with spinal and epidural anaesthesia?

Answer 24

Abdomen, pelvis, lower limbs

Question 25

How does spinal anaesthesia affect blood pressure and why does it have this effect?

Answer 25

Can cause drop in BP due to effects on preganglionic sympathetic nerves (have small diameter) Leads to reduced sympathetic output + hence a drop in BP Can cause prolonged headaches

Question 26

What trick can anaesthetists do to get better control over the location of the spinal anaesthesia?

Answer 26

Add glucose to the anaesthetic mixture | Increases specific gravity of the LA meaning the patient can be tilted to move the bolus of anaesthetic to target site

Question 27

Describe the difference in metabolism of lidocaine and cocaine.

Answer 27

Lidocaine: hepatic – N-dealkylation Cocaine: hepatic + plasma by non-specific cholinesterases

Question 28

Describe the difference in half-life between lidocaine and cocaine.

Answer 28

Lidocaine: 2 hours Cocaine: 1 hour

Question 29

What are 4 CNS side-effects of lidocaine? Explain why it has these effects.

Answer 29

``` CNS stimulation Restlessness Confusion Tremor Paradoxical- GABA system (inhibitory effect on CNS) is very sensitive to LA's so effected 1st ```

Question 30

What are 3 CVS side-effects of lidocaine? Why do they arise?

Answer 30

Myocardial depression Vasodilation Decrease in BP Due to sodium channel blockade

Question 31

What are the CNS side-effects of cocaine? Why do they arise?

Answer 31

Euphoria + excitation | Due to blockade of monoamine transporters

Question 32

What are the 3 CVS side effects of cocaine? Explain why it has these effects.

Answer 32

Increased CO Vasoconstriction Increased BP Due to increased sympathetic drive caused by blockade of monoamine transporters

Question 33

Where does surface anaesthesia act? How is it often administered?

Answer 33

Mucosal surfaces e.g. mouth | Spray or powder

Question 34

Where is the anaesthetic inserted in epidural anaesthesia?

Answer 34

Fatty tissue of epidural space | needle doesn't pierce dura

Question 35

What are the uses of epidurals?

Answer 35

Abdominal, pelvic + lower limb surgery | Painless childbirth

Question 36

What is the disadvantage of using epidural anaesthesia?

Answer 36

Slower onset so higher doses are required | Thus more likely to cause systemic toxicity

Question 37

What are the advantages of epidurals over spinal anaesthetics?

Answer 37

Epidurals have more restricted action as doesn't diffuse into CSF + less likely to effect BP

Question 38

Describe the absorption across mucous membranes and plasma protein binding of lidocaine and cocaine

Answer 38

Both have good absorption | Both highly PPB

Question 39

Name a local anaesthetic with a longer duration of action (~6 hours)

Answer 39

Bupivicaine