PHARMACOLOGY - Local Anaesthetics

Question 1

What is the mechanism of action for local anaesthetics?

Answer 1

Local anaesthetics prevent the initiation and conduction of action potentials through blocking the voltage-gated sodium channels of nociceptive afferent (sensory) nerve fibres

Question 2

What is pain?

Answer 2

Pain is the unpleasant sensory and emotional experience associated with actual or potential tissue damage

Question 3

Are local anaesthetics weak acids or weak bases?

Answer 3

Local anaesthetics are weak bases

Question 4

How does the ionisation status of a local anaesthetic drug affect its action?

Answer 4

Local anaesthetics must be lipophilic and thus uncharged to pass through the lipid cell membrane (i.e. B) however local anaesthetics have to be charged to bind to the binding sites within the sodium channels (i.e. BH+)

Question 5

What are the two pathways used by local anaesthetics to block sodium channels?

Answer 5

Hydrophobic pathway
Hydrophilic pathway

Question 6

Describe the hydrophobic pathway used by local anaesthetics

Answer 6

The lipophilic, uncharged local anaesthetic molecule (B) passes into the cell membrane and sideways into the sodium channel

Question 7

Describe the hydrophilic pathway used by local anaesthetics

Answer 7

The lipophilic, uncharged local anaesthetic molecule (B) passes through the cell membrane into the intracellular space and into an open sodium channel

Question 8

How can local anaesthetics exhibit use dependence?

Answer 8

The binding of local anaesthetics increases due to increased action potential frequency as this increases how often the sodium channels are open to allow the local anaesthetic to bind to and block these channels

Question 9

Describe how the hydrophillic pathway exhibits use dependence but the hydrophobic pathway does not

Answer 9

The hydrophobic pathway does not exhibit use dependence as the drug moves sideways into the sodium channel which can happen whether or not the sodium channels are open or closed. However, the hydrophilic pathway does exhibit use dependence as this pathway requires the sodium channel to be open in order to enter the sodium channel and carry out an effect

Question 10

Since local anesthetics are weak bases will they be charged or uncharged at physiological pH?

Answer 10

At physiological pH, local anaesthetics are largely uncharged (unionised) (B)

Question 11

How does the degree of ionisation affect the speed of onset of local anaesthetics?

Answer 11

Local anaesthetics must be in their lipophilic, uncharged (unionised) form in order to cross the cell membrane so the more drug available in its unionised form and less in its charged (ionised) form, the faster the speed of onset

Question 12

Why are inflamed tissues resistant to local anaesthetics?

Answer 12

Inflammatory tissue has an acidic environment, which means the equilibrium will shift to the left and more of the local anaesthetic will exist in its charged (ionised) form, reducing the quantity of uncharged (unionised) drug available to cross the cell membrane

Question 13

How does protein binding influence the duration of action of local anaesthetics?

Answer 13

Local anaesthetics have the ability to bind to local structural proteins. The higher degree of protein binding increases the duration of action as their will be a larger resevoir of drug available

Question 14

How does lipid solubility influence the potency of local anaesthetics?

Answer 14

Local anaesthetics must be in their lipophilic, uncharged (unionised) form in order to cross the cell membrane so increased lipid solubility will increase the ability of the drug to cross the cell membrane and carry out its effect

Question 15

Why is bicarbonate sometimes added to local anaesthetics?

Answer 15

Bicarbonate increases the pH causing the equilibrium to shift to the right to increase the quantity of local anaesthetic in its unionised form (uncharged) to increase the quantity of drug that can cross the cell membranes and carry out it’s effect - increasing speed of onset

Question 16

Why is adrenaline sometimes added to local anaesthetics?

Answer 16

Adrenaline acts on α1 adrenoreceptors on vascular smooth muscle which causes a local vasoconstriction which will limit the blood flow to the area which will decrease the volume of blood that can wash the drug away. This will increase the length of time the local anaesthetic can enter surrounding cells, prolonging it’s effect

Question 17

(T/F) Adrenaline can be added to local anesthetics for any administration method

Answer 17

FALSE. Adrenaline can only be added to local anaesthestics that are being administered via local infiltration

Question 18

Describe the chemical structure of local anaesthetics

Answer 18

Local anaesthetics have a lipophillic aromatic group attached to a hydrophilic amine group either by an ester link or amide link

Question 19

What are the two classes of local anaesthetic structure?

Answer 19

Ester-linked local anaesthetics
Amide-linked local anaesthetics

Question 20

How are ester-linked local anaesthetics metabolised?

Answer 20

Ester-linked local anaesthetics are rapidly hydrolysed by non-specific cholinesterases

Question 21

How are amide-linked local anaesthetics metabolised?

Answer 21

Amide-linked local anaesthetics are metabolised by the liver

Question 22

Why do ester-linked local anaesthetics have a shorter half life compared to amide-linked local anaesthetics?

Answer 22

Ester-linked local aneasthetics are rapidly hydrolysed by non-specific cholinesterases leaving them with short half lives, however amide-linked local anaesthetics are metabolised within the liver and thus are required to be washed away by blood to reach the liver and be metabolised, resulting in a longer half life

Question 23

When would you use topical anaesthesia?

Answer 23

To desensitise intact skin or mucous membranes

Question 24

When would you use local infiltration of local anaesthesia?

Answer 24

To desensitise dermal and subcutaneous tissues for minor surgery

Question 25

When would you use cavity instillation of local anaesthetics?

Answer 25

Cavity instillation of local anaesthetics can often be used for diagnostics

Question 26

How should you carry out intravenous regional anaesthesia?

Answer 26

Intravenous administration of the local anaesthetic distal to a tourniquet

Question 27

When would you use a peripheral nerve block?

Answer 27

Peripheral nerve blocks can be used both diagnostically and therapeutically

Question 28

When are harmful side affects to local anaesthetics most likely to occur?

Answer 28

Harmful affects are most likely to occur following an overdose of local anaesthetics or accidental intravenous administration

Question 29

What are the harmful affects that local anaesthetics can have on the central nervous system?

Answer 29

Convulsions
Depression
Coma
Death

Question 30

What are the harmful affects that local anaesthetics can have on the cardiovascular system?

Answer 30

Bradycardia
Hypotension

Question 31

Which structure of local anaesthetics is most likely to cause an allergic reaction?

Answer 31

Ester-linked local anaesthetics