General anaesthetics

Question 1

What are the clinically desirable effects of general anaesthesia?

Answer 1

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

Question 2

What do pharmacological general anaesthetics all do?

Answer 2

Loss of consciousness: at low concentration.

Suppression of reflex responses: at high concentration.

Question 3

How can general anaesthetics be administered?

Answer 3

Gaseous/inhalational

Intravenous

Question 4

Give examples of gaseous/inhalational general anaesthetics.

Answer 4

Nitrous oxide
Diethyl ether
Halothane
Enflurane

Question 5

Give examples of intravenous general anaesthetics.

Answer 5

Propofol

Etomidate

Question 6

How do general anaesthetics cause loss of consciousness?

Answer 6

Depress excitability of thalamocortical neurons.

Influence reticular activating neurons.

Question 7

How do general anaesthetics cause suppression of reflex responses?

Answer 7

Depression of reflex pathways in the spinal cord.

Target GABA and glycine.

Question 8

How do general anaesthetics cause amnesia?

Answer 8

Decreased synaptic transmission in hippocampus/amygdala- GABA-A receptors containing alpha-5 subunit within hippocampus.

Question 9

Which are more selective: intravenous general anaesthetic agents or inhalational general anaesthetic agents?

Answer 9

Intravenous agents are more selective.

Question 10

What are the molecular targets of intravenous general anaesthetic agents?

Answer 10

Alter synaptic function primarily via GABA-A receptors.

Beta-3 subunit- suppression of reflex responses.

Alpha-5 subunit- amnesia.

Question 11

What are the molecular targets of inhalational general anaesthetic agents?

Answer 11

Altered synaptic function via GABA-A/glycine receptors.

Alpha-1 subunit- suppression of reflex responses.

Nitrous oxide alters synaptic function as it blocks NMDA-type glutamate receptors- probably compete with coagonist glycine.

Altered synaptic function via neuronal nicotinic ACh receptors for analgesic effects.

Reduced neuronal excitability via TREK (background leak) K+ channels- for consciousness.

Question 12

What are the differences in distribution and excretion of intravenous vs. inhalational general anaesthetic agents?

Answer 12

Intravenous administration:

• drug directly enters blood, goes to brain and has anaesthetic effect
• rate of excretion difficult to control (via liver, kidneys etc.)

Inhalational administration:

• drug goes into lungs, enters bloodstream but large amount excreted back into lungs- better control
• remove drug from lungs, concentration gradient shifts quickly so that drug is excreted by airways, better control

Question 13

What is the significance of the blood:gas partition coefficient in relation to general anaesthetics?

Answer 13

Fill lungs with anaesthetic agent, it diffuses into blood- how well does it dissolve?

Low blood:gas partition coefficient = large proportion remains in gaseous form in blood and transfers into brain effectively, more available.

Inhalation anaesthetics: rapidly eliminated, rapid control of the depth of anaesthesia.

Intravenous anaesthetics: fast induction, less coughing/excitatory phenomena.

Induction: propofol
Maintenance: enflurane