Regulating neuronal excitability

Question 1

Describe the difference between local and general anaesthetics?

Answer 1

Local anaesthetics produce regionalised inhibition of pain/sensory pathways, with no loss of consciousness

General anaesthetics depress cortical processing of pain/sensory signals, and result in loss of consciousness

Question 2

What is the site of action for analgesics?

Answer 2

Peripheral nerves, spinal cord and brain cortex

Question 3

What is the site of action for local anaesthetics?

Answer 3

Peripheral nerves and spinal cord

Question 4

What is the site of action for general anaesthetics?

Answer 4

Brain cortex

Question 5

What the first local anaesthetic?

Answer 5

Cocaine

Question 6

Describe the broad action of local anaesthetics?

Answer 6

Drugs that reversibly block conduction of nerve impulses at the axonal membrane Interfere with influx of Na

Question 7

Are local anaesthetics acidic or basic? Are they strong or weak?

Answer 7

Weak bases

Question 8

How do the various local anaesthetic agents differ?

Answer 8

Differ in onset, duration and toxicity

Question 9

List three classes of local anaesthetics?

Answer 9

Aminoesters Aminoamides Benzocaine

Question 10

What is the difference in duration and metabolism between aminoesters and aminoamides?

Answer 10

Aminoesters are shorter acting and are hydrolysed by esterases Aminoamides are longer acting and undergo hepatic metabolism

Question 11

What sorts of tissue can local anaesthetics affect?

Answer 11

Will affect all nerves and excitable tissue

Question 12

What do local anaesthetics selectively bind to?

Answer 12

Na channels

Question 13

How can systemic distribution of local anaesthetics be limited? Why is this important?

Answer 13

Local application Limits toxicity and makes them safer

Question 14

Describe the difference in sensitivity to local anaesthetics between motor and sensory nerves?

Answer 14

Sensory nerves more sensitive (require less drug for same effect)

Question 15

How can the level of nerve blockade achieved with local anaesthetics be altered?

Answer 15

Alter dose of drug

Question 16

Which part of the Na channel do local anaesthetics interact with?

Answer 16

Transmembrane domain

Question 17

Which part of the Na channel do toxins interact with?

Answer 17

Bind extracellular domain

Question 18

What are the two mechanisms of action of local anaesthetics?

Answer 18

Hydrophobic Hydrophilic

Question 19

What is the difference between the hydrophobic and hydrophilic mechanisms of local anaesthetics, in terms of speed and use dependence?

Answer 19

Hydrophobic: fast, non use dependent Hydrophilic: slow, use dependent

Question 20

What limits the rate of onset/offset of local anaesthetics?

Answer 20

Diffusion across membranes (hydrophobic fast vs hydrophilic slow)

Question 21

How does the size of nerves affect the rate of onset/offset?

Answer 21

Small nerves > smaller membranes > quicker access

Question 22

Are sensory nerves or motor nerves larger?

Answer 22

Motor nerves are larger

Question 23

What is the extracellular gate of the Na channel called?

Answer 23

m-gate

Question 24

What is the intracellular gate of the Na channel called?

Answer 24

h-gate

Question 25

Describe the hydrophobic mechanism for local anaesthetics?

Answer 25

Question 26

Describe the hydrophilic mechanism for local anaesthetics?

Answer 26

Question 27

Why are local anaesthetics that use the hydrophobic mechanism not use-dependent?

Answer 27

Hydrophobic \> can cross membrane \> doesn't matter whether gates are open or closed

Question 28

Why are local anaesthetics that use the hydrophilic mechanism use dependent?

Answer 28

Hydrophilic\> cannot cross membrane \> requires gates to be open

Question 29

What is the effect of local anaesthetics on axon membrane potential?

Answer 29

Stabilises axon membrane No change in resting membrane potential

Question 30

When is the effect of local anaesthetics more pronounced?

Answer 30

In a basic medium

Question 31

Describe the effect of a basic medium on local anaesthetics?

Answer 31

Have a more pronounced effect

Question 32

What determines the toxicity of local anaesthetics?

Answer 32

Proprtional to blood level Dose determines effect

Question 33

Describe some of the toxic cardiovascular effects of local anaesthetics?

Answer 33

Direct myocardial depression Depression of vasomotor centre Hypotension

Question 34

Describe of the toxic CNS effects of local anaestheitcs?

Answer 34

Excitation Tremor Convulsion Respiratory arrest

Question 35

How can we tell if a local anaesthetic is acting in the wrong location?

Answer 35

Begin to see toxic side effects

Question 36

Which side effects of local anaesthetics are not proportional to blood level?

Answer 36

Hypersensitivity reactions

Question 37

Which side effect is particularly common with local anaesthetics?

Answer 37

Hypersensitivity reactions

Question 38

Which forms of local anaesthetics are available over the counter?

Answer 38

Lozenge Gels

Question 39

Which forms of local anaesthetics are for professional use only?

Answer 39

Eye drops Injection

Question 40

Describe the four stages of general anaesthesia?

Answer 40

Stage 1: amnesia, euphoria Stage 2: excitement, delirium, resistance to handling Stage 3: unconsciousness, regular respiration, decreasing eye movement Stage 4: respiratory arrest, cardiac depression and arrest

Question 41

At which stage of general anaesthesia is surgery commenced?

Answer 41

Stage 3

Question 42

How long does it take to progress from Stage 1 to Stage 3 once general anaesthetics are administered?

Answer 42

Seconds

Question 43

What are the main methods of administration for general anaesthetics?

Answer 43

Inhalation Intravenous injection

Question 44

What are some of the respiratory side effects of general anaesthetics?

Answer 44

Impaired ventilation Depression of respiratory centre Obstruction of airways

Question 45

How can retention of secretions due to obstruction of airways be combatted under general anaesthesia?

Answer 45

Administer ant-MuscR

Question 46

List the cardiovascular side effects of general anaesthetics?

Answer 46

Decreased vasomotor centre function Depress contracility Peripheral vasodilation Cardiac arrythmias Inadequate response to fall in BP or CO

Question 47

When can the side effect of inadequate response to fall in BP under general anaesthesia become a problem?

Answer 47

If the patient must be moved upright for surgery

Question 48

What are the theories of mechanism of action of general anaesthetics?

Answer 48

Lipid theory Receptor interaction theory

Question 49

Describe the the lipid theory of general anaesthetics?

Answer 49

Act by dissolving in the fatty fraction of brain cells and removing fatty constituents from them, thus changing activity of brain cells and inducing anaesthesia.

Question 50

Describe the receptor interaction theory of general anaesthetics?

Answer 50

Inhibit excitatory receptors (glutamate, NMDA) Enhance effects on inhibitory receptors (GABA, glycine)