12 - Local Anaesthetics

Question 1

Local anaesthetics work by…

Answer 1

Block Na channels on cell memos so they can’t depolarise

Block influx of Na across neuronal membranes

Question 2

You wish to achieve rapid onset of local anaesthesia for insertion of a large catheter - what LA would you choose to infiltrate the skin?

Answer 2

Lignocaine

Question 3

What is the most important factor determining speed of onset for a local anaesthetic drug injected into health subcutaneous tissue?

Answer 3

The drugs pKa

Question 4

Summary of nerve conduction physiology?

Answer 4

• terminal boutons link with dendrites of another cell

- APs are conducted by volt gated Na channels

Question 5

Summary of volt gated Na+ channels

Answer 5

• pore in memba allowing Na movement
• activation and de-activation gate (in resting state act is closed and deact is open)
• the activation gate opens when a threshold depolarisation is reached causing a substantial depolarisation
• after a ms the deactivation gate closes and Na+ can’t enter
• K+ leaves and repolarises the cell

Question 6

Mechanism of action of LAs?

Answer 6

• prevention of voltage dependent increase in Na+
• the non-ionised form of the LA can easily cross the cell memb and enter the cell
• it then becomes re-ionized again and blocks the ion channel from the INSIDE

Question 7

What is the effect of LAs on an AP?

Answer 7

Depolarisation is prevented and the threshold and resting potential are unchanged

Question 8

What is the structure of an LA?

Answer 8

• has a hydrophobic (aromatic) and a hydrophilic end (amine) with an amide or ester link

Question 9

What does whether the LA has an amide or ester link determine?

Answer 9

Determines the site of metabolism and potential to produce allergic reactions.

Esters are more unstable, more rapidly metabolised, shorter acting, more allergenic (aren’t used as commonly)

Question 10

4 examples of ester LAs

Answer 10

• cocaine (numb mucous membranes in the nose - also vasoconstrictor)
• procaine
• benzocaine
• tetracaine

(benzocaine and tetracaine are topicals)

Question 11

4 examples of amide LAs?

Answer 11

• prilocaine
• lignocaine
• bupivacaine
• ropivacaine

Question 12

What determines potency in an LA?

Answer 12

Lengthening alkyl chain increases lipid solubility - the more lipid soluble the LA is the more potent it is (not really a big deal as can just increase dose)

Question 13

Relative potencies of lignocaine, procaine, bupivicaine and prilocaine?

Answer 13

Procaine - 1
Prilocaine - 1.8
Lignocaine - 2
Bupivicaine - 8

Question 14

All LAs are …

Answer 14

Weak bases

Exists as both an ionised form and free base

Question 15

What determines the speed of onset of action for an LA?

Answer 15

Only free base can cross membranes and enter cells - the most free base is present the faster the onset of action.

The amount of free base present at physiological pH depends on the pKa of the drug.

Therefore the drugs pKa determines the speed of onset of action

Question 16

Relative speeds of action of onset?

Answer 16

Slow to fast

Procaine (highest pKa/lowest % free base)
Tetracaine
Bupivicaine 
Ropivacaine 
Prilocaine 
Lignocaine 
Mepivacaine

Question 17

Which LAs have the fastest onset of action?

Answer 17

Those with a pKa closest to physiological pH (lignocaine is 7.9)

Lower pKa > more free base > faster onset of action

Question 18

Why is there a poor quality of block when LA is injected into hypoxic and infected tissue?

Answer 18

Hypoxic, infected tissue becomes acidic and so changes the pH.

Question 19

What determines duration of action in LAs?

Answer 19

Duration of action is proportional to degree of protein binding.

The higher the affinity to protein binding the longer the duration of action.

Question 20

How are amides and esters metabolised?

Answer 20

Amides
- hepatic and so is dependent on liver BF
Esters
- plasma cholinesterase

Question 21

What is the pKa?

Answer 21

The pH at which you have 50% ionised form and 50% free base

Higher pKa than pH > more ionised
Low pKa > more free base

Question 22

What is use dependence?

Answer 22

LAs have a greater affinity for channels that are active (opening often)

Means the ones that are opening and need blocking are being blocked

Question 23

What LA to use for fast relief at post tibial nerve?

Answer 23

Lignocaine

Fast onset of action

Bupivicaine for longer duration

Question 24

Lignocaine summary

Answer 24

• amide
• low potency
• low pKa so fast onset
• low protein binding so short duration of action

Ideal for short surgical procedures like dental or mole removal or IV

Question 25

Bupivicaine summary

Answer 25

• amide
• highly soluble and potent
• high pKa so slower onset of action
• high protein binding - longer duration

Ideal for nerve blocks for analgesia

Question 26

Cocaine?

Answer 26

Ester
Topical to nose
Vasoconstricts

Question 27

Prilocaine?

Answer 27

Amide
Safest agent
Used in IV regional anaesthesia

Question 28

Ropivocaine?

Answer 28

Amide
Slow onset
Long duration of action
Has less cardiac toxicity compared to bupivicaine

Question 29

How can LAs cause toxicity?

Answer 29

1. Allergic reactions - rare with amides
2. Dose dependent CNS toxicity
   > peri-oral paraesthesia
   > tinnitus
   > seizures
3. Dose dependent cardiac toxicity
   > heart block and VF (cardiac arrest)
   > more likely with bupivicaine

Question 30

What is the CC:CNS?

Answer 30

Accidentally get LA into a vein (trying to get a block into the nerve)

More likely to have CNS toxicity (seizure) first

Ratio of dose needed to produce a cardiac arrest compared to a seizure (want big)

Lignocaine = 7
Bupivacaine = 3

Question 31

How are LAs applied topically to the skin?

Answer 31

EMLA - eutectic mixture of LAs

Mixture of lignocaine and prilocaine as an oil preparation that allows most to be free base and so is able to cross the skin (lipid base not aqueous)

Is used for insertion of an IV cannula in kids

Question 32

How are LAs applied topically to mucus membranes?

Answer 32

• Cocaine
  > awake intubation
• Lignocaine spray and viscous preparations
  > instrumentation of the nose, mouth, pharynx, urethra

Question 33

What is soft tissue infiltration?

Answer 33

It is used for minor interventions like mole removal where you would use a fast acting short duration agent

Can also use it for post-op pain relief where you would use a slow acting long duration agent

Question 34

2 types of nerve blocks?

Answer 34

Neuraxial and peripheral nerve blocks

Question 35

How does a peripheral nerve block work?

Answer 35

The LA is infiltrated around a specific nerve usually under US guidance i.e. brachial plexus if operating on the arm

In a mixed nerve the smaller sensory fibres are more susceptible to the LA but the motor fibres can also be affected

Peripheral nerve blocks can also be used during surgery without a general anaesthetic or for post op pain relief

Question 36

How does a neuraxial blockade work?

Answer 36

Spinal anaesthesia

The LA is injected into the intrathecal space below L2 (termination of spinal cord - subarachnoid space/CSF)

Results in a profound distal motor and sensory blockade and so allows for major surgery like a hip/knee replacement, C section to occur in an awake patient

Question 37

What is a an epidural anaesthesia?

Answer 37

A bigger needle is advanced towards the spinal cord until you hit the epidural space (will feel a loss of resistance) and the LA is then infused through the catheter.

It then affects the spinal nerves passing through the epidural space and leave the spinal cord.

CAN be done at every level, while spinal anaesthesia can’t.

Results in a distal sensory and motor blockade
> causes a ‘band’ of numbness

Results in excellent post op labour analgesia if it is inserted at the correct level.

A spinal anaesthesia will wear off in 4-5hours while the catheter can stay there and you can keep infusing LA and have a couple of days of post op analgesia