The Uses and Actions of Local Anaesthetics

Question 1

Define local anaesthetic.

Answer 1

A drug that reversibly blocks nerve conduction when applied to a restricted area of the body to enable a procedure to be carried out without loss of consciousness.

Question 2

What is the difference between local and general anaesthetics?

Answer 2

General anaesthetics are used to render a patient unconscious (eg with surgery), whereas local anaesthetics are not.

Question 3

Describe the general chemical structure of local anaesthetics.

Answer 3

1 - An aromatic ring.

2 - An amine group.

3 - A linkage group between them.

Question 4

What are the possible chemical forms of the linkage group in local anaesthetics?

Answer 4

Amide or ester.

Question 5

At which point on the chemical structure are local anaesthetics metabolised?

Why is metabolism of local anaesthetics important?

Answer 5

• At the linkage group.

- Metabolism is important as the effect of local anaesthetic must be reversible.

Question 6

Why do most modern local anesthetics have amide linkages?

Answer 6

• Ester linkages are metabolised faster then amide linkages.

- The metabolites of ester linkages are more toxic than that of amide linkages.

Question 7

Give an example of a local anaesthetic that has an ester linkage.

Answer 7

Procaine.

Question 8

List 3 examples of local anesthetics that have amide linkages.

State their relative durations of effect.

Answer 8

1 - Lidocaine (medium duration).

2 - Prilocaine (medium duration).

3 - Bupivacaine (long duration).

Question 9

What important property does the aromatic ring of a local anaesthetic possess?

Answer 9

Lipid solubility.

Question 10

What important property does the amine group of a local anaesthetic possess?

Answer 10

• The ability to become positively charged (gain a H+).

- Its ionisation state is determined by pH

Question 11

Describe the equilibrium that exists between ionised and unionised local anaesthetics.

How does increasing alkalinity and acidity affect this equilibrium?

Answer 11

Anaesthetic + H2O -> Anaesthetic+ + OH-

• Increasing alkalinity shifts the equilibrium to the side with unionised anaesthetic.
• Increasing acidity shifts the equilibrium to the side with ionised anaesthetic.

Question 12

At physiological pH (~7.4), which form of anaesthetic (ionised or unionised) is greater?

Answer 12

Ionised.

Question 13

Describe the process by which local anaesthetic block nerve conduction at nociceptors.

Answer 13

1 - Unionised and ionised local anaesthetic exists outside the membrane of an axon of a nociceptor.

2 - The unionised local anaesthetic diffuses across the membrane to the inside of the axon.

3 - Some of the unionised local anaesthetic inside the axon dissociates to ionised local anesthetic (the pH inside is the same as the outside so the equilibrium is the same).

4 -The ionised local anaesthetic blocks Na+ channels, preventing nerve conduction.

Question 14

What is use-dependent block?

Answer 14

• Local anaesthetics are said to be use-dependent as the degree of blockage of open channels is proportional to the rate of nerve stimulation (as there will be more open channels).
• Increase pain = increase block.

Question 15

Give an example of a biological factor that can affect the effectiveness of local anaesthetic.

What might bring about a change in this factor to decrease effectiveness of local anaesthetic?

Answer 15

• Tissue pH.

- Inflammation / infection will increase pH.

Question 16

What does the sensitivity of neurones to local anaesthetics depend on?

Answer 16

• Thickness.

- Myelination.

Question 17

Which fibres convey information from nociceptors to the CNS?

Answer 17

1 - A-delta fibres.

2 - C fibres.

Question 18

Why are motor neurones less sensitive to local anaesthetics than A-delta or C fibres?

Answer 18

Because motor neurones are thicker and more heavily myelinated.

Question 19

What is the general principle for the routes of administration of local anaesthetics?

Answer 19

The more proximal the site of administration to the CNS, the greater the area anaesthetised.

Question 20

List and describe the 5 possible routes of anaesthesia.

Answer 20

1 - Topical.

2 - Infiltration (inject into tissue being anaesthetised).

3 - Nerve block (inject more proximal to CNS).

4 - Epidural (inject into epidural space).

5 - Spinal (inject into subarachnoid space).

TINES!

Question 21

List 6 side effects of local anaesthetics.

Answer 21

1 - Allergic reactions.

2 - Tremors.

3 - Convulsions.

4 - Respiratory failure.

5 - Decreased contractility of cardiac muscle.

6 - Vasodilation (so decreased blood pressure).

Question 22

What causes the side effects of local anaesthetics?

Answer 22

The local anaesthetic will affect other excitable tissues (e.g. CNS, cardiovascular system) that operate using voltage gated Na+ channels.

Question 23

Which local anaesthetic is the most cardiotoxic?

Answer 23

Bupivacaine.

Question 24

What other drugs are often administered with local anaesthetics?

Answer 24

Vasoconstrictors (e.g. adrenaline / felypressin).

Question 25

List 4 properties of good local anaesthetics.

Answer 25

1 - Reversible.

2 - Block nerve conduction in nociceptive neurones.

3 - Effective for time of procedure.

4 - Low toxicity.