Principles of General Anaesthesia

Question 1

What are the five clinically desirable effects of general anaesthetics? State which two effects are caused by ALL general anaesthetics.

Answer 1

Loss of consciousness (ALL)
Suppression of reflex responses (ALL)
Relief of pain
Muscle relaxation
Amnesia

Question 2

Name 4 inhalational general anaesthetics.

Answer 2

Nitric oxide
Diethyl ether
Halothane
Enflurane

Question 3

Name 2 IV general anaesthetics.

Answer 3

Propofol

Etomidate

Question 4

What is the Meyer/Overton correlation?

Answer 4

Anaesthetic potency increases in direct proportion with the oil/water partition coefficient

In other words: anaesthetic potency is directly correlated with lipid solubility

Question 5

That was the explanation for the Meyer/Overton correlation?

Answer 5

The more lipid soluble the drug, the more it was able to disturb the lipid bilayer

Question 6

What were the 2 problems with this explanation?

Answer 6

1. At therapeutic doses, the changes to the lipid bilayer were minute
2. How would this bilayer disturbance impact on membrane proteins?

Question 7

What are the two actual mechanisms of action of general anaesthetics?

Answer 7

• Reduced neuronal excitability

- Altered synaptic function

Question 8

Describe the difference in the selectivity of IV and inhalational agents.

Answer 8

IV agents are more selective for GABA-A

Inhalational agents are far less selective

Question 9

Which specific subunits of the GABA-A receptor are targeted by the IV agents that alter synaptic function. What are the desirable effects?

Answer 9

Beta 3 subunit – suppression of reflex responses

Alpha 5 subunit – amnesia

Question 10

What are the two main receptor targets of inhalational agents that alter synaptic function?

Answer 10

GABA-A receptors

Glycine receptors

Question 11

Which subunit of the GABA-A receptor do inhalational agents seem to be more selective for? State the desirable anaesthetic effect.

Answer 11

Alpha 1 – suppression of reflex responses

Question 12

Explain how nitrous oxide induces its anaesthetic effect.

Answer 12

Nitrous oxide competes for the glycine-binding site on NMDA receptors (glutamate receptors)
Glycine is an important coagonist of NMDA receptors – it allows the full receptor response to be transduced

Question 13

What is the effect of blocking neuronal nicotinic acetylcholine receptors with regards to general anaesthesia?

Answer 13

Blocking nAChR leads to reduced nerve conduction

This is important for amnesia and pain relief

Question 14

Which channels are important in reducing neuronal excitability via the action of inhalational agents? Describe how.

Answer 14

TREK – background leak K+ channels

These lead to hyperpolarisation of neurones and inhalational agents facilitate the opening of these channels

Question 15

Explain how general anaesthetics cause a loss of consciousness.

Answer 15

• Depress the excitability of thalamocortical neurones
• Influences reticular
  activating neurons

This is mediated by TREK channels and GABA-A
NOTE: the reticular activating system is also involved

Question 16

Explain how general anaesthetics suppress reflex responses.

Answer 16

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

Question 17

Explain how general anaesthetics cause amnesia.

Answer 17

There are a lot of GABA-A receptors in the hippocampus that have the alpha 5 subunit
General anaesthetics stimulate these receptors to decrease synaptic transmission in the hippocampus

Question 18

Explain how blood: gas partition coefficient affects the speed at which the general anaesthetic penetrates the brain.

Answer 18

If you have a GA that dissolves really well in the blood, then there is less GA in the gas phase in blood and hence less GA penetrates the blood-brain barrier and reaches the brain
It is only anaesthetic that remains in the gas phase that diffuses easily into the brain

Question 19

Would a general anaesthetics with a high or low blood: gas partition coefficient be useful for anaesthetics and why?

Answer 19

LOW
This means that less of the GA will dissolve in the blood so more will be left in the gas phase
Hence more of the drug will penetrate the blood-brain barrier and reach the brain

Question 20

What are the benefits of inhalation anaesthetics?

Answer 20

Rapidly eliminated

Good control of the depth of anaesthesia

Question 21

What are the benefits of IV anaesthetics?

Answer 21

Fast induction

Less coughing/excitatory phenomena

Question 22

What types of drugs can be used to achieve:

a. Relief of pain
b. Muscle relaxation
c. Amnesia

Answer 22

a. Relief of pain
Opioids
b. Muscle relaxation
Neuromuscular blockers
c. Amnesia
Benzodiazepines