Local Anaesthetics

Question 1

What was the first topical, local and spinal anaesthesia?

Answer 1

Cocaine!

Question 2

Draw a nerve conduction to another nerve!

Answer 2

• if you can a threshold depol. then the axon depolarises down to the next nerve
• Depolarisation occurs at each point due to voltage gated ion channels.

Question 3

How doe voltage-gated ion channels work?

Answer 3

They are ‘pores’ through the membrane, that have a resting membrane potential of -90mV.

Once the membrane reaches the threshold depolarisation of -65mV then the activation gate will open and there will be an large/fast influx of Na⁺ down their electrochemical gradient.

As soon as the positive potential is achieved there is an automatic deactivation (deac. gate closes)

Recovering period occurs

Question 4

What does the membrane potential look like during the depolarisation/repolarisation cycle?

Answer 4

Question 5

How do Local Anaesthetics work?

Answer 5

By physciallly blocking voltage-gated sodium channels in excitable cell membranes, therefore blocking action potentions.

It works from within the neuron. It’s a weak base that exists in a solution in its un-ionised form (which is what can cross cell membranes), in the cell it ionises and this is what can block the channel!

Question 6

What is the basic stucture of a local anaesthetic

Answer 6

1. Hydrophobic aromatic group
2. Hydrophilic amine group
3. An amide (modern, longer lasting) or ester (old, vunerable) link

Question 7

What does the ester or amide bond determine for the local anaesthetic?

Answer 7

The link determines the site of metabolism and the potential to produce allergic reactions.

Esters: more rapidly metabolised, shorter acting and more allergenic :(

Question 8

Out of Esters and Amides, what more likely to be topical and whats more likely to be injected?

Answer 8

Esters: topical use eg; cocaine cream (plasma cholinesterases)

Amides: Injected often (metabolised by liver)

Question 9

” All anaesthetics are weak _____.”

What does this mean…

Answer 9

• Therefore if you suspend them in fluid they will exist in two forms; ionised LAH⁺ and unionised free base LA
• Only free base can cross membranes and enter cells, and the amount of free base depends on the pKa of the drug.

“More free base present = faster the onset”

Question 10

What is the pKa of a drug?

Answer 10

When the ionised and un-ionised free base is 50:50.

Low pKa: favours the free base (faster onset as the faster it can get in)

High pKa: favours the ionized form

Question 11

Based on these pKa values, which local anaesthetic will have the fastest speed of onset?

Answer 11

Lignocaine, as it is an aminehas the lowest pKa and therefore the highest % of free base able to enter the cell.

Question 12

Why do you have a poor quality block when a LA is injected intoacidic infected tissue?

Answer 12

Because LAs with pK_a closest to physiological pH have the fastest onset of action

Question 13

How do you make a LA drug more potent?

Answer 13

Lengthing alkyl chain increases lipid solubility

the more lipid soluble = more potent

Question 14

How does protein binding of LA’s relation to their duration of action?

Answer 14

The better the protein binding tendancy of a drug, the longer they last.

Eg; bupivancaine is the longest lasting

Question 15

Explain some properties of Lignocaine

Answer 15

• Amide; standard comparitable agent
• ‘Low’ lipid solubility and low potency
• ‘Low’ pKa, high non-ionised therefore fast onset
• ‘Low’ protein bind and short duration of action

Ideal to cover short surgical procedures eg; mole removal

Question 16

Describe the properties of Bupivacaine

Answer 16

• Amide
• High lipid solubility → more potent then lignocaine
• High protein binding → longer duration of action than lignocaine

Ideal for nerve blocks for analgesia

Question 17

Describe

Cocaine:

Prilocaine:

Ropivacaine:

Answer 17

Cocaine: ester, topical to nose, vasoconst.

Prilocaine: amide, safest, IV use

Ropivacaine: Amide, slow onset, long acting, less cardiac toxicity then bupiv.

Question 18

What type of LA toxicity can you get? WHich is usually due to inadvertent IV administration

Answer 18

Allergic - rare with amides

Dose-dependent CNS toxicity: seizures, usually first, so acts as a red flag

Dose-dependent cardiac toxicity (worse): heart block and ventral fibrillation

Cardiotoxicity of local anesthetics can be compared using the CC/CNS dose ratio that is the ratio of the dose causing cardiac collapse (CC) to the dose causing seizure/convulsions. The lower the number the more cardiotoxic the drug (ex. The CC/CNS for bupivacaine is approximately 3 versus 7 for lidocaine). SO you need to use 3x more bupiv to get a cardiac event then a cerebral. and vice verse for ligno, but 7 (so wider margin of safety)

Question 19

What is the point of using adrenaline with your local anaesthetic?

Answer 19

It vasoconstricts and reduces systemic absorbtion so you can give more of the drug safely and it lasts longer!

Question 20

How does topical to skin administration work?

Answer 20

EMLA: eutectic mixture of LAs

• mix of ligno. and prilo. as an oil that allows most to be a free bease → easily crossing the skin
• For insertion of IV cannulae in children

Question 21

What LA do we use topical to mucus membranes?

Answer 21

• Cocaine
• Ligno. spray and viscous preperations

means you can intubate whilst the patient is awake!

Question 22

Why do we administer LAs via soft tissue infiltration

Answer 22

• For minor interventions eg; mole removal
  fast acting short duration agent eg; lignocaine
• For post op pain relief
  slow acting, long duration agent eg; bupiv.

Question 23

How does a peripheral nerve block work and why would we need one?

Answer 23

• LA is infiltrated around a specific nerve; eg a brachial plexus blcok for surgery on the arm.
• in a mixed nerve, small sensory fibres more susceptible, but motor fibres can be affected
• For surgery without general anaesthesia, or for post-op pain relief

Question 24

How does a spinal nerve block work and why would we need one?

Answer 24

• LA injected into the intrathecal space into CSF, only below L2 where spinal cord terminates
• Profound distal motor and sensory blockade
• Allows major surgery in awake patient as from there down they go numb/weak

Question 25

How does a epidural nerve block work and why would we need one?

Answer 25

• Small catheter inserted into the epidural space and LA infused through the catheter. Affects spinal nerves passing through space
• Distal sensory and motor blockade
• good block op/labour analgesic