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 at low concs(ALL)
• Suppression of reflex responses at high concs (ALL)
• Analgaesia
• Muscle relaxation
• Amnesia

Question 2

Name 4 inhalational general anaesthetics

Answer 2

1. Nitric oxide
2. Diethyl ether
3. Halothane
4. Enflurane

Question 3

Name 2 IV general anaesthetic

Answer 3

1. Propofol
2. Etomidate

Question 4

1) What is the Meyer/Overton correlation?

Answer 4

1)

• For a long time it was believed that anaesthetic potency increases in direct proportion with the oil/gas partition coefficient
• In other words: anaesthetic potency is directly correlated with lipid solubility

Question 5

1) What was the proposed explanation for the Meyer / Overton correlation?
2) What were the problems with this explanation?

Answer 5

1)

• The drugs disturbed the lipid bilayer

2)

• At therapeutic doses, the changes to the lipid bilayer were minute
• How would the change in membrane impact on membrane proteins anyway?
• You get the same effect on the membrane that you get with general anaesthetic as when you increase temperature

Question 6

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

Answer 6

• Reduced neuronal excitability
• Altered synaptic function

Question 7

Describe the difference in the selectivity of IV and inhalational agents

Answer 7

• IV agents are more selective for GABA-A
• Inhalational agents are far less selective

Question 8

Which specific subunits of the GABA-A receptor do IV agents that alter synaptic function target and what are their effects?

Answer 8

• Beta 3 – important in suppression of reflex responses
• Alpha 5 – important in amnesia

Question 9

What are the two main targets of inhalational agents that alter synaptic function - 2 receptors?

Answer 9

• GABA-A receptors (specifically selective alpha-1 containing GABA-A receptors)
• Glycine receptors

Question 10

Which subunit of the GABA-A receptor do inhalational agents seem to be more selective for and what role of general anaesthesia is it important in?

Answer 10

• Alpha 1 – important in suppression of reflex responses

Question 11

Explain how nitrous oxide induces its anaesthetic effect

Answer 11

• 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 12

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

Answer 12

• Blocking nAChR leads to reduced nerve conduction
• This is important for amnesia and relief of pain

Question 13

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

Answer 13

• TREK – background leak K+ channels
• These lead to hyperpolarisation of neurones and inhalational agents facilitate the opening of these channels

Question 14

Inhalational agents are less selective than IV agents. What effect does this have on the dose needed to induce general anaesthesia?

Answer 14

• Generally speaking, a higher dose of inhalational agents is required

Question 15

Explain how general anaesthetics cause a loss of consciousness

Answer 15

• Depressing the excitability of thalamocortical neurones
• Depressing the RAS (reticular activating system)
• The depression of these pathways is mediated by TREK channels and GABA-A

Question 16

Explain how general anaesthetics suppress reflex responses

Answer 16

• Depression of reflex pathways in the dorsal horn of the spinal cord
• This is done by anaesthetics that enhance GABA-A and glycine function

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
• So low : blood gas coefficients mean they enter the brain better

Question 19

Would a general anaesthetic with a high or low blood:gas partition coefficient be preferable in use for anaesthetics? Explain 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:

1) Relief of pain
2) Muscle relaxation
3) Amnesia

Answer 22

1) Relief of pain - Opioids
2) Muscle relaxation - Neuromuscular blockers
3) Amnesia - Benzodiazepines

Question 23

When using GA for a surgical procedure, what might you use to induce the loss of consciousness and then what else might you use to maintain the GA and what other effect must this have and give an example of an agent that might be used for both of these steps?

Answer 23

1. Induction of loss of consciousness: Propofol
2. Maintenance + inhibition of reflexes: Enflurane