Principles of general anaesthesia

Question 1

What are the clinically desirable effects of general anaesthetics?

Answer 1

Loss of consciousness at low concentrations
Suppression of reflex responses at high concentrations
Relief of pain (analgesia)
Muscle relaxation
Amnesia

Question 2

What are the two different types of general anaesthetic?

Answer 2

Gaseous/inhalation
-Nitrous oxide
-Diethyl ether
-Halothene
-Enflurane
Intravenous
-Propofol
-Etomidate

Question 3

What is the Meyer/Overton correlation?

Answer 3

Anaesthetic potency increases in direct proportion with oil/water partition coefficient- anaesthetic potency is directly correlated with lipid solubility- these drugs were thought to disturb the lipid bilayer

Question 4

What were the two main problems with the Meyer/Overton correlation?

Answer 4

At the therapeutic doses, the changes to the lipid bilayer were minute
How would the change in the membrane impact of membrane proteins anyway?
A rise in temp seemed to have the same effect on membrane as general anaesthetic

Question 5

What is the real mechanism of action of anaesthetics either of?

Answer 5

Reduced neuronal excitability

Altered synaptic function

Question 6

What sort of GAs are more selectively?

Answer 6

IV- they target the GABA-A receptor

Question 7

What else is GABA-A an important receptor for?

Answer 7

Euphoria

Question 8

What type of receptor is GABA-A?

Answer 8

Type 1 inotropic receptor so it is comprised of 5 subunits

Question 9

How do GABA-A receptors differ throughout the brain?

Answer 9

The subunit combination is different in different parts

Question 10

What specific subunits do IV agents tend to target?

Answer 10

Beta-3- Suppression of reflex responses (important at synaptic level)
Alpha-5- Amnesia (extra-synaptic)

Question 11

What are the main targets of inhalation agents?

Answer 11

GABA-A receptors

Glycine receptors

Question 12

What are inhalation agents more selective for?

Answer 12

Alpha-1 containing GABA- importtant in suppression of reflex responses

Question 13

How does nitrous oxide induce its anaesthetic effect?

Answer 13

It blocks the NMDA-type glutamate receptors

Question 14

What is nitrous oxide specificity like?

Answer 14

It is less GABA specific and more glutamate specific

Question 15

What does nitrous oxide compete for?

Answer 15

It compete for glycine on glutamate receptor

Question 16

Why is glycine important?

Answer 16

It is an important coagonist of NMDA receptors- allows full receptor response to be transduced

Question 17

How does increasing the concentration of inhalation lead to reduction in nerve conduction?

Answer 17

An effect on nicotinic acetylcholine receptors

Question 18

What are nicotinic acetylcholine receptors important for?

Answer 18

Amnesia and relief of pain

Question 19

What are TREK?

Answer 19

Background leak K+ channels

Question 20

What do TREK channels lead to?

Answer 20

They tend to hyper polarise neurones -> reduced neuronal excitability

Question 21

What effect do inhalation agents have on TREK channels?

Answer 21

It facilitates opening of these channels then you will get enhanced hyper polarisation. Important in terms of suppression of reflex responses

Question 22

How does dosage of effectiveness compare between inhalation agents and IV?

Answer 22

Higher doses of inhalation is needed compared to IV

Question 23

What causes loss of consciousness?

Answer 23

Decrease in cortical activity- decreased excitability of thalamocortical neurones and influences reticular activating neurones

Question 24

What is the thalamus?

Answer 24

A relay station for information going between the cortex and rest of the CNS

Question 25

What does depressing excitability of thalamocortical neurones result in?

Answer 25

Disconnection of the periphery from the brain

Question 26

What mediates this depression of thalamocortical neurones?

Answer 26

Background leak K+ channels -> hyperpolarisation | Enhanced GABA function

Question 27

What else affects consciousness?

Answer 27

Reticular activating system

Question 28

What do thalamocortical neurones respond to?

Answer 28

Sensory information and also impacted by the reticular activating system- greater the firing of RAS, the greater the level of arousal

Question 29

What causes suppression of reflex responses?

Answer 29

Depression of reflex pathways in the dorsal horn of the spinal cord

Question 30

How do anaesthetic agents cause suppression of reflex responses?

Answer 30

They enhance GABA and glycine function in the dorsal horn and this will decrease the activity of the dorsal pathways. This is another method by which brain can be disconnected from sensory information coming from the periphery. This suppresses the reflex responses

Question 31

What tends to be the first effect of general anaesthetics?

Answer 31

Amnesia- occurs at low dose

Question 32

How do anaesthetics cause amnesia?

Answer 32

There are a lot of GABA receptors in hippocampus that have the alpha 5 subunit. This leads to a decrease in synaptic transmission in the hippocampus

Question 33

How does IV anaesthetic reach the brain?

Answer 33

Simple- blood

Question 34

What is used to assess how well an inhaled anaesthetic distributes in the blood?

Answer 34

The blood:gas partition coefficient

Question 35

What happens if you have an inhaled anaesthetic that dissolves really well in the blood?

Answer 35

The speed at which it penetrates the brain goes down- only anaesthetic agent that remains in gas phase that diffuses easily into the brain

Question 36

For a good GA, what sort of blood:gas partition coefficient do you want?

Answer 36

Low

Question 37

Why is IV often used to induce anaesthesia and inhalation used to control the depth?

Answer 37

IV has a fast induction and there is less coughing/excitatory phenomena Inhalation is rapidly eliminated and there is rapid control of the depth