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 (analgesia)
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

Anesthetic potency directly correlated with lipid solubility (oil/water partition coefficient)

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 the Meyer/Overton explanation?

Answer 6

At therapeutic doses, changes to the lipid bilayer were minute
How would the change impact on membrane proteins?

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 two main targets of inhalational agents that alter synaptic function?

Answer 10

GABA-A receptors (mainly in brain)
Glycine receptors (mainly in spinal cord)
(increase inhibitory activity of both)

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

NO competes for + blocks 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

Important for analgesic effect

Question 14

Which channels are important in reducing neuronal excitability via the action of inhalational agents? What effect is associated with this?

Answer 14

TREK (background leaky K+ channels)
Opening TREK leads to hyperpolarisation of neurones + reduced excitability
Loss of consciousness

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, a higher dose of inhalational agents is required

Question 16

Explain how general anaesthetics cause a loss of consciousness.

Answer 16

Loss of consciousness is caused by depressing the excitability of thalamocortical neurones + reticular activating system neurones
Mediated by TREK channels + GABA-A receptors
Tricks brain that there is lack of sensory stimulus

Question 17

Explain how general anaesthetics suppress reflex responses.

Answer 17

Depression of reflex pathways in the dorsal horn of the spinal cord
By anaesthetics that enhance GABA-A + glycine function

Question 18

Explain how general anaesthetics cause amnesia.

Answer 18

Many GABA-A receptors in the hippocampus with alpha 5 subunit
GA’s 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

If GA dissolves readily in blood, there is less GA in the gas phase in blood + hence less penetrates the BBB to reach the brain
Only anaesthetic in the gas phase 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
Less GA dissolves in the blood so more is left in the gas phase
Hence more of the drug will penetrate the BBB + reach the brain

Question 21

What are the benefits of inhalation anaesthetics?

Answer 21

Rapidly eliminated

Good control of the depth of anaesthesia

Question 22

What are the benefits of IV anaesthetics?

Answer 22

Fast induction

Less coughing/ excitatory phenomena

Question 23

What types of drugs can be used alongside general anaesthetics to achieve:

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

Answer 23

Relief of pain: Opioids
Muscle relaxation: Neuromuscular blockers
Amnesia: Benzodiazepines

Question 24

How are general anaesthetics often administered in a clinical setting?

Answer 24

Induce LOC + suppression of reflexes with Propofol (IV)

Maintain effects with Enflurane (Inh.)