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

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

What was the explanation for the Meyer/Overton correlation?

Answer 5

The drugs disturbed the lipid bilayer

Question 6

What were the problems with this Meyer/Overton correlation?

Answer 6

At therapeutic doses, the changes to the lipid bilayer were minute

How would the change in membrane impact on membrane proteins anyway?

Question 7

What are the two real 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 do IV agents that alter synaptic function target and what are their effects?

Answer 9

Beta 3 – important in suppression of reflex responses

Alpha 5 – important in amnesia

Question 10

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

Answer 10

potentiate GABA-A receptors

potentiate Glycine receptors

block NMDA-type glutamete receptors

Blocking neuronal nicotinic ACh receptors

Question 11

Which subunit of the GABA-A receptor do inhalational agents seem to be more selective for?

Answer 11

Alpha 1 – important in 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 acetylcholinereceptors with regards to general anaesthesia?

Answer 13

Blocking nAChR leads to reduced nerve conduction

This is important for amnesia and relief of pain

Question 14

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

Answer 14

TREK – background leak K+ channels

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

Question 15

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

Answer 15

Generally speaking, a higher dose of inhalational agents is required

Question 16

Explain how general anaesthetics cause a loss of consciousness.

Answer 16

Conciousness is thought to be due to signals sent from the reticular activating system in the

Loss of consciousness is caused by depressing the excitability of thalamocortical neurones

This is mediated by TREK channels and GABA-A

Question 17

Explain how general anaesthetics suppress reflex responses.

Answer 17

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 18

Explain how general anaesthetics cause amnesia.

Answer 18

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 19

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

Answer 19

A low coefficient means most of the drug doesn’t dissolve in the blood

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 20

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

Answer 20

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 21

What are the benefits of inhalation anaesthetics?

Answer 21

Rapidly eliminated - remove anesthetic from lungs and the drug will follow its concentration gradient out of the brain to lungs where you can expel it

Good control of the depth of anaesthesia

Question 22

What are the benefits of IV anaesthetics?

Answer 22

Fast induction

Less coughing/excitatory phenomena such as seizures

Question 23

What types of drugs can be used to achieve:

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

Answer 23

a. Relief of pain
Opioids

b. Muscle relaxation
Neuromuscular blockers

c. Amnesia
Benzodiazepines

Question 24

Where are beta 3 and alpha 5 GABA subunits located?

Answer 24

Beta 3 - spinal cord

Alpha 5 - hippocampus

Question 25

Are IV or inhilational general anesthetics more powerful?

Answer 25

IV

Inhilational agents less than 50% as effective on GABAa receptor