Local Anaesthetic

Question 1

How do local anaesthetics stop nerve conduction?

Answer 1

Blocking of voltage-gated Na+ channels

Question 2

Nerve axons differ in their susceptibility to block by LA, list the order of block of different nerve fibres

Answer 2

1. A delta
2. C
3. A beta
4. A alpha

Question 3

Describe the mechanism by which sodium channels are blocked by LA and how this affects the nerve

Answer 3

1. LA binds to a site in the sodium channel
2. LA blocks the channel and prevents Na influx
3. This blocks action potential generation and propagation
4. Block persists so long as a sufficient number of Na+ channels are blocked

Question 4

What other areas can LA effect and what problems can this cause?

Answer 4

1. LA block Na+ channels in other excitable tissue (e.g. heart muscle)
   - LA can cause bradycardia and hypotension

Question 5

What are the 3 organic components are present in LA?

Answer 5

1. Aromatic region (hydrophobic)
2. Ester or almond bond
3. Basic amine side chain (hydrophilic)

Question 6

How are LA presented and why is this useful?

Answer 6

Presented as hydrochloride (B.HCL)

- renders the amine base more water soluble

Question 7

When can LA cross the cell membrane?

Answer 7

Only in un-ionised form

Question 8

When are LA active?

Answer 8

When they are ionised

Question 9

Why are LA much less effective on acidic tissues?

Answer 9

Dissociation of B.H+ will not act quickly due to the high number of H+ ions around the tissue. This makes it much more difficult for the LA to pass through the cell membrane

Question 10

Why are smaller diameter axons more susceptible to LA block?

Answer 10

Because the number of sodium channels in smaller axons is less, therefore less LA is needed to block all sodium channels

Question 11

Why are myelinated axons susceptible to LA?

Answer 11

Sodium channels (and potassium channels) are concentrated into the nodes of Ranvier

Question 12

What is ‘safety factor’ in relation to LA?

Answer 12

To block AP in myelinated nerve fibres, the LA needs to act on several nodes of Ranvier along the axon - so more LA is used than in unmyelinated nerve fibres

Question 13

Describe the composition of LA preparation

Answer 13

1. LA base present as hydrochloride to increase solubility in aqueous solution
2. 2-4% solutions for dental injections
3. Reducing agent (sodium metabisulphide)
4. Preservatives and fungicide
5. Vasoconstrictor (+-)

Question 14

What esters have been/are used as LA?

Answer 14

1. Cocaine
2. Procaine
3. Benzocaine (used now)

Question 15

What amides are used as LA?

Answer 15

1. Lignocaine(lidocaine)
2. Prilocaine
3. Árticaine
4. Mepivacaine
5. Bupivacaine
6. Ropivacaine

Question 16

Why are vasoconstrictors important to include in LA preparations?

Answer 16

1. Most LA are vaso dilators
   - increased blood flow will increase ‘wash out’ of LA
   - therefore a vasoconstrictor will increase duration of action

Question 17

What vasoconstrictors are often used in LA?

Answer 17

Adrenaline

Felypressin (synthetic vasopressin)

Question 18

Describe the adrenoreceptors that vasoconstrictors interact with

Answer 18

1. Vasoconstrictors act on receptors on vascular smooth muscle
   • adrenoreceptors:
   - alpha receptors: vasoconstriction
   - Beta 2 receptors: vasodilation
   - Beta 1 receptors:
   . In cardiac muscle have positive chronotropic and inotropic effect (increase heart rate and force)

Question 19

How effective is adrenaline as a vasoconstrictor?

How does it effect blood pressure?

Answer 19

1. Adrenaline is equally effective on alpha and beta receptors
2. Given locally, it has a vasoconstrictor effect (action on Alpha receptors)
3. Systemically, it lowers Total Peripheral resistance (B > a)
4. Adrenaline increases cardiac output
   - but overall has little to no effect on mean arterial blood pressure

Question 20

How effective is noradrenaline as a vasoconstrictor?

How does it effect blood pressure?

Answer 20

1. Noradrenaline is more effective on alpha than beta receptors
   - given locally, it has a vasoconstrictor effect (alpha receptors)

2.

• systemically, it increases TPR (a>B)
• increases cardiac output
• therefore raises mean arterial BP
• this can result in a fall of BP

Question 21

How are LAs inactivated?

Answer 21

1. ‘Washout’ from tissues by blood supply
2. Countered by presence of vasoconstrictor agent
3. Ester types broken down by tissue esterases
   - action quite brief
4. Amide types broken down by liver amidases
   - longer duration of action

Question 22

List different modes of administration for local anaesthetics

Answer 22

1. Surface application (‘topical’)
2. Injection
3. Local infiltration
4. Regional nerve block
5. Nerve root block (‘spinal’, ‘epidural’)
6. IV

Question 23

List LA preparations for dental injections using lignocaine and prilocaine

Answer 23

1. Lignocaine
   - 2% lignocaine HCL
   - 2% lignocaine HCL + 1:80,000 adrenaline
2. Prilocaine
   - 4% prilocaine HCL
   - 3% prilocaine HCL + felypressin (0.03U/ml)

Question 24

How are percentage solutions calculated?

Answer 24

X% solution = Xmass/volume

Question 25

What is the maximum dose of lignocaine?

Answer 25

4mg per kg of body weight

Question 26

What is the maximum dose of adrenaline?

Answer 26

500micrograms