Local Anaesthetic

Question 1

Define a local anaesthetic

Answer 1

A local anaesthetic reversibly blocks nerve conduction when applied to a restricted area of the body without the loss of consciousness.

Question 2

How do local anaesthetics block nerve conduction?

Answer 2

The reflex is pain receptors to sensory neurones (nociception) to the brain. Messages are blocked from the periphery to the brain by interfering with the voltage-gated Na+ channels, therefore ap cannot be conducted.

Question 3

What does nociception stand for?

Answer 3

Sensory nerve cell that responds to damage by sending signals to the spinal cord and brain by a process called nociception.

Question 4

What is the basic structure of a local anaesthetic drug?

Answer 4

Must contain an aromatic ring, an amine group or an ester.

LA are weak bases.

Question 5

What are the functions of cocaine and how can they be used as a local anaesthetic?

Answer 5

Cocaine has two functions: anaesthetic and psychotic effects, therefore the drug can be separated to produce a molecule that process the anaesthetic effects.

Question 6

What linkage is present in procaine/cocaine and how long does the drug last (metabolism rate)?

Answer 6

Ester, short duration.

Question 7

What linkage is present in lidocaine and how long does the drug last (metabolism rate)?

Answer 7

Amide, medium duration

Question 8

What linkage is present in Prilocaine and how long does the drug last (metabolism rate)?

Answer 8

Amide, medium duration

Question 9

What linkage is present in Bupivacain and how long does the drug last (metabolism rate)?

Answer 9

Amide, long duration

Question 10

Anaesthetic drugs contain an aromatic ring. What does this say about the properties of the drug?

Answer 10

It is hydrophobic / lipophilic

Question 11

Local anaesthetics are weak acids, how is the equilibrium affected as the pH changes?

Answer 11

AH + H2O = AH2+ + OH-

An increase in acidity causes the equilibrium to shift to the right therefore increasing the proportion of ionised form.

Question 12

Explain the mechanism of action of how local anaesthetics block voltage gated Na2+ channels and therefore ap.

Answer 12

Outside the cell both ionised and non-ionised form of the local anaesthetic are present in equilibrium. Upon entering the cell the pH is more acidic therefore there the equilibrium shifts to the right and there is an increase in number of ionised form of the drug. Only the ionised form of the drug can block the voltage-gated Na+ channels. An increase in pain means more Na+ channels open causing an increase in blockage.

Question 13

How does inflammation or infection affect the use of the drug?

Answer 13

In inflammation/ infection the pH of the tissue becomes more acidic outside the cell therefore this makes local anaesthetic poor anaesthetic in inflamed or infected environments.

Question 14

There are different sensitivity in nerve fibres explain this.

Answer 14

A(delta) and c nerve fibres have a high sensitivity to pain. Therefore have a high sensitivity to local anaesthetics as more voltage-gated Na+ channels are open there are more to be blocked, therefore easier to block an action potential.
Compared to a motor fibre which has a low sensitivity so is rarely targeted during anaesthetising as it is much harder to block action potentials.

Question 15

Explain the topical administration route of local anaesthetics

Answer 15

Topical is not that effective because it has to penetrate through multiple cell layers from the surface to get to the nerve fibres.

Question 16

Explain the infiltration administration route of local anaesthetics

Answer 16

Works by ring blocking thereby anaesthetising a small area.

Question 17

Explain the nerve block anaesthesia route of local anaesthetics

Answer 17

An injection is administered close to the peripheral nerve, NOT into the nerve as this would cause damage.

Question 18

Explain the epidural anaesthesia administration route of local anaesthetics

Answer 18

An injection into an area of the spine known as the epidural space. Used in child birth.

Question 19

Explain the spinal anaesthesia administration route of local anaesthetics

Answer 19

An injection into the subarachnoid space, through as fine needle around 9 cm in length.

Question 20

What are the unwanted effects of local anaesthetics?

Answer 20

1. Non-specific = hypersensitivity reactions - in LA there are other compounds present (e.g. alkaline solution, pH buffer, antifungal). Some people react.
2. Specific = High does; Injected into vessels; the drug can escape from the area and affect other excitable tissues:
   - CNS causing a tremor, convulsions, respiratory failure
   - Cardiovascular system - cardiac muscle decrease contractility; blood vessels dilate causing a decrease in blood pressure.

Question 21

Why are vasoconstrictors administered with local anaesthetics?

Answer 21

Vasodilation of the vessels causes dilution of the drug and can cause the drug to be washed away and is therefore not kept local. By administering a vasoconstrictor (e.g. adrenaline) it keeps the drug localised away from other areas of the body that would break it down, therefore less drug is needed, increases the duration of the drug and decreases the chance of experiencing adverse effects.

Question 22

What are the properties of a good local anaesthetic?

Answer 22

Reversible,
Blocks nerve conductance in nociceptive neurones,
Effective for time of procedure,
Low toxicity