Local anaesthetics

Question 1

Explain the role of voltage-gated sodium channels:

Answer 1

Opens transiently to allow fr depolarisation of the membrane is depolarised

Question 2

What is the difference between inactivation and deactivation of ion channels?

Answer 2

Inactivation: ion flow is blocked by a gating mechanism rather than a closing of the channel

Deactivation is the closing of the ion channel

Question 3

What are the two main methods to achieve local analgesia?

Answer 3

Pharmacological - LA
Non-pharmacological - transcutaneous electrical stimulation, pulsed radiofrequency or nerve ablation

Question 4

What is the effect of LAs?

Answer 4

• Causes reversible local analgesia and a loss in nociception
• by blocking afferent activity in the peripheral and central nervous systems
• produced by stimulation of special nociceptors that only respond to tissue damage caused by intense chemical

Question 5

What are the different techniques of LA?

Answer 5

• Topical
• Infiltration
• Epidural block
• Plexus block
• Spinal anaesthesia (subarachnoid block)

Question 6

Explain why different techniques have different side effects?

Answer 6

Differences in distribution:
- Epidural compartment/topical/infiltration: distribution of LA limited
- CSF: LA has greater distribution

Plexus blocks can also hit the nerve directly, damaging the nerve

Question 7

What are the two types of LA drugs?

Answer 7

Amides and esters

Question 8

What are some examples of amides?

Answer 8

Lidocaine, mepivacaine, bupivacaine

Question 9

What are some examples of esters?

Answer 9

Cocaine, procaine, chloroprocaine and tetracaine

Question 10

What is the mechanism of action of LAs?

Answer 10

They bind to receptors near the intracellular end of sodium channels

This induces a time and voltage-dependent blockage
- The effect is more marked in rapidly firing fibres (bc they are more dependent on sodium channels_

There is a reduction of depolarization and a prolongation of repolarisation

They also have anti-inflammatory effects

Question 11

Does onset of action of LAs depend on absorption and distribution? Why

Answer 11

No, because it is usually injected around the nerves

Question 12

Does absorption and distribution affect offset of action and systemic toxicity of LAs?

Answer 12

No

Question 13

What does systemic absorption depend on?

Answer 13

• Dosage of the drug
• Site of injection (e.g. more vascularized areas more A, less vascularized areas like fat less A)
• Extent of tissue binding (more tissue binding = less absorption)
• Blood flow to the region
• Use of vasoconstrictors (lowers A)
• Drug properties

Question 14

How are ester LAs metabolized?

Answer 14

Rapidly hydrolyzed in the blood by circulating butyrylcholinesteraes to inactive metabolites

Hence they have a short plasma half life

Question 15

How are amide LAs metabolized?

Answer 15

Through CYP 450!

Hence impt to note that there is:
- Reduced metab if liver function affected
- Reduced metab with reduced hepatic blood flow
- Reduced metab if there are other medications competing

Question 16

How are LAs excreted?

Answer 16

By the kidneys

Question 17

What is the significance of LAs being weak bases?

Answer 17

• The charged form is the most active: cannot readily exit closed sodium channels.
• However, uncharged better for crossing the lipid membrane

Best to be in an alkaline environment – drug will be unionized and better able to diffuse into the nerves

Question 18

How can an alkaline environment be achieved when giving LAs?

Answer 18

Can give together with sodium bicarbonate

Question 19

Does topical administration produce analgesia, paralysis or both?

Answer 19

Analgesia only

Question 20

Does a plexus block produce analgesia, paralysis or both?

Answer 20

Both analgesia and paralysis

Question 21

What are the local adverse effects of LAs?

Answer 21

High concentrations in close proximity to the spinal cord or nerve trunks can lead to nerve damage

Injections can cause infection, hematomas, excessive fluid build up or severing of nerves and support tissue, which can then lead to prolonged anaesthesia or paraesthesia

Question 22

What are the adverse CNS effects of LAs?

Answer 22

CNS depression:
- Sleepiness, light headedness
- restlessness
- audio and visual disturbances
- circumoral and tongue numbness, metallic taste
- nystagmus and muscle twitching
- seizures
- coma

Question 23

What are the adverse CVS effects of LAs?

Answer 23

Depresses the CVS:
- Decreased contracility and arteriolar dilation –> hypotension
- Bradycardia
- Arrhythmias

Question 24

What kinds of areas is topical administration of LAs meant to target?

Answer 24

Nasal mucosa, wound margins

Question 25

Name a short acting, medium acting and long acting drug, as well as their class of LA (ester or amide)

Answer 25

Short acting: procaine (ester)
medium acting: lidocaine (amide)
long acting: bupivacaine (amide)

Question 26

How can anaesthetic effect be prolonged?

Answer 26

By increasing the dose

By giving a vasoconstrictor (slows absorption)

Question 27

How can onset of action be accelerated?

Answer 27

By adding sodium bicarbonate into solutions
- LAs are weak bases so would thus be unionized
- This allows for better penetration of the cell

By choosing LAs with faster penetration of the skin