28. Principles of general anaesthesia

Question 1

what is general anaesthesia?

Answer 1

• loss of consciousness
• suppression of reflex responses
• relief of pain (analgesia)
• muscle relaxation
• amnesia

Question 2

what are the 2 types of general anaesthetics? give examples

Answer 2

gaseous (inhalation) e.g. NO, diethyl ether

intravenous e.g. propofol, etomidate

Question 3

what is the lipid theory for anaesthesia?

Answer 3

a disruption in the lipid bilayer leads to the anaesthetic potency of these drugs

(the more lipid soluble the better the drug)

Question 4

what are the 2 main problems with the lipid theory for anaesthesia?

Answer 4

• at therapeutic doses, changes to the lipid bilayer were minute
• how would the change in the membrane impact on membrane proteins?

Question 5

what is the real mechanism of action of general anaesthetics?

Answer 5

EITHER
- reduced neuronal excitability
OR
- altered synaptic function

Question 6

what do intravenous general anaesthetic agents do?

Answer 6

alter synaptic function, primarily through GABA-A receptors (potentiation)

Question 7

what occurs when given propofol and why?

Answer 7

euphoria

GABA-A is an important receptor in causing euphoria

Question 8

describe the structure of GABA-A receptors and what parts of the structure are targeted by IV agents

Answer 8

GABA-A is a type 1 ionotropic receptor comprised of 5 subunits

IV agents target:

• beta-3 subunit = suppression of reflex responses
• alpha-5 subunit = amnesia

Question 9

what do inhalational general anaesthetics do and what do they target?

Answer 9

alter synaptic function

GABA-A receptors and glycine receptors

Question 10

what does NO do?

Answer 10

blocks the NMDA-type glutamate receptors to induce its anaesthetic effect

it competes at the binding site with glycine (which is an important coagonist of NMDA receptors) on the glutamate receptor

Question 11

what are neuronal nicotinic acetylcholine receptors important in?

Answer 11

important for their analgesic and amnesia effects

increasing the concentration of the inhalational agent leads to a reduction in nerve conduction because the nicotinic ACh receptors are inhibited

the agent enters the brain, binds to and blocks the ACh receptor –> analgesia

Question 12

what is TREK? what do they do?

Answer 12

background leak K+ channels

they stop the neurones from firing in the first place because they tend to hyperpolarise neurones –> reduced neuronal excitability

Question 13

what do inhalational agents do to TREK?

Answer 13

activates TREK so there is enhanced hyperpolarisation

Question 14

what is more selective between IV agents and inhalation agents?

Answer 14

IV agents mainly affect GABA-A and are more selective than inhalation agents

Question 15

why does loss of consciousness occur?

Answer 15

depressing the excitability of thalamocortical neurones –> disconnection of the periphery from brain

anaesthetics also interfere with the reticular activating system which also impacts thalamocortical neurones (greater firing of RAS = greater level of arousal)

Question 16

what is the depression of thalamocortical neurones mediated by?

Answer 16

• background leak K+ channels –> hyperpolarisation

- enhanced GABA function

Question 17

why does suppression of reflex responses occur?

Answer 17

anaesthetic agents that enhance GABA and glycine function in the dorsal horn will decrease the activity in the dorsal pathways

the brain can therefore be disconnected from sensory information coming from the periphery –> suppression of reflex responses

Question 18

why does amnesia occur?

Answer 18

general anaesthetics target GABA receptors in the hippocampus that have the a5 subunit –> decrease in synaptic transmission in the hippocampus (where memory formation occurs)

Question 19

what is the difference between inhalational and IV anaesthetic agents?

Answer 19

METHOD OF EXCRETION

IV agents are injected into the blood and travel to the brain. Excretion rate is difficult to control because of this direct injection.

gaseous agents enter the blood but a large amount is excreted. this gives a better control over the agent.

Question 20

what type of blood:gas partition coefficient is best for anaesthetic agents and why?

Answer 20

low blood:gas partition coefficient

this makes the agent more available to the brain because a large proportion remains in gaseous form and can transfer into the brain effectively. it is also easier to clear from the brain.

Question 21

what is usually the protocol followed for general anaesthetic administration?

Answer 21

induced with IV agent so someone is anaesthetised more (usually propofol)

maintained with gaseous agent so that there is more control and so that the person can be quickly recovered from the anaesthesia (usually enflurane)