28. Principles of general anaesthesia Flashcards
what is general anaesthesia?
- loss of consciousness
- suppression of reflex responses
- relief of pain (analgesia)
- muscle relaxation
- amnesia
what are the 2 types of general anaesthetics? give examples
gaseous (inhalation) e.g. NO, diethyl ether
intravenous e.g. propofol, etomidate
what is the lipid theory for anaesthesia?
a disruption in the lipid bilayer leads to the anaesthetic potency of these drugs
(the more lipid soluble the better the drug)
what are the 2 main problems with the lipid theory for anaesthesia?
- at therapeutic doses, changes to the lipid bilayer were minute
- how would the change in the membrane impact on membrane proteins?
what is the real mechanism of action of general anaesthetics?
EITHER
- reduced neuronal excitability
OR
- altered synaptic function
what do intravenous general anaesthetic agents do?
alter synaptic function, primarily through GABA-A receptors (potentiation)
what occurs when given propofol and why?
euphoria
GABA-A is an important receptor in causing euphoria
describe the structure of GABA-A receptors and what parts of the structure are targeted by IV agents
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
what do inhalational general anaesthetics do and what do they target?
alter synaptic function
GABA-A receptors and glycine receptors
what does NO do?
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
what are neuronal nicotinic acetylcholine receptors important in?
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
what is TREK? what do they do?
background leak K+ channels
they stop the neurones from firing in the first place because they tend to hyperpolarise neurones –> reduced neuronal excitability
what do inhalational agents do to TREK?
activates TREK so there is enhanced hyperpolarisation
what is more selective between IV agents and inhalation agents?
IV agents mainly affect GABA-A and are more selective than inhalation agents
why does loss of consciousness occur?
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)
what is the depression of thalamocortical neurones mediated by?
- background leak K+ channels –> hyperpolarisation
- enhanced GABA function
why does suppression of reflex responses occur?
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
why does amnesia occur?
general anaesthetics target GABA receptors in the hippocampus that have the a5 subunit –> decrease in synaptic transmission in the hippocampus (where memory formation occurs)
what is the difference between inhalational and IV anaesthetic agents?
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.
what type of blood:gas partition coefficient is best for anaesthetic agents and why?
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.
what is usually the protocol followed for general anaesthetic administration?
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)
