Principles of General Anaesthesia

Question 1

What is general anaesthesia

Answer 1

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

Question 2

What properties/effects do all general anaesthetics have and what concentrations do they occur at

Answer 2

Loss of consciousness at low concentration

Suppression of reflex responses at high concentration

Question 3

What are types of gaseous general anaesthetics

Answer 3

Nitrous oxide
Diethyl ether
Halothane
Enflurane

Question 4

What are the types of of intravenous general anaesthetic

Answer 4

Propofol

Etomidate

Question 5

What is the relationship of general anaesthetic potency with oil/water partition coefficient

Answer 5

Meyer/Overton
Correlation
Anaesthetic potency increases in direct proportion with oil/water partition coefficient

Question 6

What are the effects of general anaesthetics on their molecular targets

Answer 6

Reduced neuronal excitability or altered synaptic function

Question 7

What are the molecular targets of intravenous general anaesthetics and what are the effects of this

Answer 7

GABA-A receptors - activity increased
Beta-3 - suppress reflex response
Alpha-5 - amnesia

Question 8

What are the molecular targets of inhalational general anaesthetics and state their effects

Answer 8

GABA-A/glycine receptors
Alpha1 - suppression of reflex responses

NMDA-type glutamate receptors (NO) blocked
Neuronal nicotinic ACh receptors
TREK (background leak) K+ channels

Question 9

What is the role of glycine receptors

Answer 9

Inhibitory role, particularly in the lower brainstem and spinal cord where they might mediate the action of volatile anaesthetics

Question 10

Describe the effect of intravenous drugs on nicotinic ACh receptors

Answer 10

Intravenous drugs can act on these targets but only at concentrations above that required for anaesthesia.

Question 11

Describe the neuroanatomy involved in the loss of consciousness brought on by general anaesthetics

Answer 11

Depression of excitability of thalamocortical neurons

Influences reticular activating neurons

Question 12

What does consciousness depend on

Answer 12

Consciousness depends on feedback loops between cortex, thalamus and reticular activating system. Sensory information received by the cortex is the primary starting point for consciousness

Question 13

Explain how general anaesthetics causes a loss of consciousness

Answer 13

Direct hyperpolarisation of thalamocortical neurons by activating TREK channels and/or potentiating GABA-A receptors.
Information transfer through the thalamus is disrupted

Question 14

Describe the neuroanatomy involved in the suppression of the reflex responses brought on by general anaesthetics

Answer 14

Depression of reflex pathways in the spinal cord

High density of GABA receptors located in the dorsal horn of the spinal cord

Question 15

Describe the neuroanatomy involved in the amnesia brought on by general anaesthetics

Answer 15

Reduced synaptic transmission in the hippocampus/amygdala

Question 16

What is mechanism of amnesia induction by general anaesthetics

Answer 16

amnesia occurs at concentrations well below those that cause sedation and analgesia.
There are many GABAA alpha-5 subunits at the extrasynapse of the hippocampus in a relatively high ratio. Therefore, it can be assumed that general anesthetics potentiate the tonic currents acting on the α5GABAA receptor in the hippocampus

Question 17

What are the issues with the theory of alteration of the lipid membrane by general anaesthetics

Answer 17

Very little changes in the lipid bilayer at relevant concentrations
There must be an interference of a membrane protein