Principles of general anaesthesia Flashcards
What are the clinically desirable effects of general anaesthetics?
Loss of consciousness at low concentrations
Suppression of reflex responses at high concentrations
Relief of pain (analgesia)
Muscle relaxation
Amnesia
What are the two different types of general anaesthetic?
Gaseous/inhalation -Nitrous oxide -Diethyl ether -Halothene -Enflurane Intravenous -Propofol -Etomidate
What is the Meyer/Overton correlation?
Anaesthetic potency increases in direct proportion with oil/water partition coefficient- anaesthetic potency is directly correlated with lipid solubility- these drugs were thought to disturb the lipid bilayer
What were the two main problems with the Meyer/Overton correlation?
At the therapeutic doses, the changes to the lipid bilayer were minute
How would the change in the membrane impact of membrane proteins anyway?
A rise in temp seemed to have the same effect on membrane as general anaesthetic
What is the real mechanism of action of anaesthetics either of?
Reduced neuronal excitability
Altered synaptic function
What sort of GAs are more selectively?
IV- they target the GABA-A receptor
What else is GABA-A an important receptor for?
Euphoria
What type of receptor is GABA-A?
Type 1 inotropic receptor so it is comprised of 5 subunits
How do GABA-A receptors differ throughout the brain?
The subunit combination is different in different parts
What specific subunits do IV agents tend to target?
Beta-3- Suppression of reflex responses (important at synaptic level)
Alpha-5- Amnesia (extra-synaptic)
What are the main targets of inhalation agents?
GABA-A receptors
Glycine receptors
What are inhalation agents more selective for?
Alpha-1 containing GABA- importtant in suppression of reflex responses
How does nitrous oxide induce its anaesthetic effect?
It blocks the NMDA-type glutamate receptors
What is nitrous oxide specificity like?
It is less GABA specific and more glutamate specific
What does nitrous oxide compete for?
It compete for glycine on glutamate receptor
Why is glycine important?
It is an important coagonist of NMDA receptors- allows full receptor response to be transduced
How does increasing the concentration of inhalation lead to reduction in nerve conduction?
An effect on nicotinic acetylcholine receptors
What are nicotinic acetylcholine receptors important for?
Amnesia and relief of pain
What are TREK?
Background leak K+ channels
What do TREK channels lead to?
They tend to hyper polarise neurones -> reduced neuronal excitability
What effect do inhalation agents have on TREK channels?
It facilitates opening of these channels then you will get enhanced hyper polarisation. Important in terms of suppression of reflex responses
How does dosage of effectiveness compare between inhalation agents and IV?
Higher doses of inhalation is needed compared to IV
What causes loss of consciousness?
Decrease in cortical activity- decreased excitability of thalamocortical neurones and influences reticular activating neurones
What is the thalamus?
A relay station for information going between the cortex and rest of the CNS
What does depressing excitability of thalamocortical neurones result in?
Disconnection of the periphery from the brain
What mediates this depression of thalamocortical neurones?
Background leak K+ channels -> hyperpolarisation
Enhanced GABA function
What else affects consciousness?
Reticular activating system
What do thalamocortical neurones respond to?
Sensory information and also impacted by the reticular activating system- greater the firing of RAS, the greater the level of arousal
What causes suppression of reflex responses?
Depression of reflex pathways in the dorsal horn of the spinal cord
How do anaesthetic agents cause suppression of reflex responses?
They enhance GABA and glycine function in the dorsal horn and this will decrease the activity of the dorsal pathways. This is another method by which brain can be disconnected from sensory information coming from the periphery. This suppresses the reflex responses
What tends to be the first effect of general anaesthetics?
Amnesia- occurs at low dose
How do anaesthetics cause amnesia?
There are a lot of GABA receptors in hippocampus that have the alpha 5 subunit. This leads to a decrease in synaptic transmission in the hippocampus
How does IV anaesthetic reach the brain?
Simple- blood
What is used to assess how well an inhaled anaesthetic distributes in the blood?
The blood:gas partition coefficient
What happens if you have an inhaled anaesthetic that dissolves really well in the blood?
The speed at which it penetrates the brain goes down- only anaesthetic agent that remains in gas phase that diffuses easily into the brain
For a good GA, what sort of blood:gas partition coefficient do you want?
Low
Why is IV often used to induce anaesthesia and inhalation used to control the depth?
IV has a fast induction and there is less coughing/excitatory phenomena
Inhalation is rapidly eliminated and there is rapid control of the depth
