General anaesthesia

Question 1

What are the clinically desirable effects of general anaesthetics?

Answer 1

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

Question 2

What is the MOA of IV agents?

Answer 2

Alters synaptic function
1. Act on GABAa receptors to enhance effects
Target beta3 subunit-suppress reflex response
Target a5 subunit-amnesia

Question 3

What is the MOA of Inhalation agents?

Answer 3

Less selective
Alters synaptic function
1. Acts on GABAa and Glycine receptors (inhibitory role).
a1 subunit-suppression of reflex receptors
2. Block NMDA-type glutamate receptors; competes with co-agonist Glycine.
3. Blocks neuronal nAChR

Question 4

What is MOA by which inhalation agents reduce neuronal excitability?

Answer 4

Blocks TREK K+ leak channels
Blocking TREK causes hyperpolarisation of the neurones
=Suppresses reflex response

Question 5

What is the difference in selectivity between inhalation and IV agents?

Answer 5

Inhalational agents have multiple target.

IV agents are more selective.

Question 6

Name some examples of IV agents

Answer 6

Propofol

Etomidate

Question 7

Name some inhalational agents

Answer 7

NO
Diethyl ether
Halothane
Enflurane

Question 8

What is the neuroanatomical correlate for loss of consciousness?

Answer 8

Depress excitability of thalamocortical neurones
->RAS neurone firing rate decreases
Increase GABAa receptor action

Question 9

What is the neuroanatomical correlate for suppression of reflexes?

Answer 9

Depression of reflex pathways in spinal cord, many GABA receptors in dorsal horn.

Question 10

What is the neuroanatomical correlate for amnesia?

Answer 10

Many a5GABAa receptors located in hippocampus, anaesthetics potentiate these.
Decreased synaptic transmission so memories are not formed.

Question 11

What is the implication on induction and maintenance of anaesthesia when using an IV agent?

Answer 11

IV agent is directly administered into blood -> quick access to brain
Metabolism is determined by liver

Question 12

What is the implication on induction and maintenance of anaesthesia when using an inhalational agent?

Answer 12

An agent with low blood: gas partition coefficient, the quicker the onset of action.
Less anaesthetic dissolves in the blood, more available to act in the brain.
Controlled levels of anaesthesia; proportion in the airways is directly proportional to amount in the brain.

Question 13

What is the typical method of giving GAs in a clinical setting?

Answer 13

IV agents for induction of anaesthesia.

Inhalational agents for maintenance.

Question 14

What types of drugs would you give for;
pain relief (analgesia)
muscle relaxation
amnesia

Answer 14

Pain: opioids e.g. fentanyl
Muscle relaxation: neuromuscular blocking drugs e.g. suxamethonium
Amnesia: anxiolytics/benzodiazepines e.g. midazolam