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What are the five clinically desirable effects of general anaesthetics? State which two effects are caused by ALL general anaesthetics.

Loss of consciousness (ALL)
Suppression of reflex responses (ALL) - at higher concentrations
Relief of pain
Muscle relaxation


Name 4 inhalational general anaesthetics.

Nitric oxide
Diethyl ether


Name 2 IV general anaesthetics.



What is the Meyer/Overton correlation?

For a long time it was believed that anaesthetic potency increases in direct proportion with the oil/gas partition coefficient
In other words: anaesthetic potency is directly correlated with lipid solubility


What was the explanation for the Meyer/Overton correlation?

The drugs disturbed the lipid bilayer


What were the problems with this explanation?

At therapeutic doses, the changes to the lipid bilayer were minute
How would the change in membrane impact on membrane proteins anyway?


What are the two real mechanisms of action of general anaesthetics?

Reduced neuronal excitability
Altered synaptic function


Describe the difference in the selectivity of IV and inhalational agents.

IV agents are more selective for GABA-A
Inhalational agents are far less selective


Which specific subunits of the GABA-A receptor do IV agents that alter synaptic function target and what are their effects?

Beta 3 – important in suppression of reflex responses
Alpha 5 – important in amnesia


What are the two main targets of inhalational agents that alter synaptic function?

GABA-A receptors- much less effective tho compared to IV ones
Glycine receptors


Which subunit of the GABA-A receptor do inhalational agents seem to be more selective for?

Alpha 1 – important in suppression of reflex responses


Explain how nitrous oxide induces its anaesthetic effect.

Nitrous oxide competes for the glycine-binding site on NMDA receptors (glutamate receptors)
Glycine is an important coagonist of NMDA receptors – it allows the full receptor response to be transduced


What is the effect of blocking neuronal nicotinic acetylcholinereceptors with regards to general anaesthesia?

Blocking nAChR leads to reduced nerve conduction
This is important for amnesia and relief of pain


Which channels are important in reducing neuronal excitability via the action of inhalational agents?

TREK – background leak K+ channels
These lead to hyperpolarisation of neurones and inhalational agents facilitate the opening of these channels


Inhalational agents are less selective than IV agents. What effect does this have on the dose needed to induce general anaesthesia?

Generally speaking, a higher dose of inhalational agents is required


Explain how general anaesthetics cause a loss of consciousness.

Loss of consciousness is caused by depressing the excitability of thalamocortical neurones
This is mediated by TREK channels and GABA-A
NOTE: the reticular activating system is also involved


Explain how general anaesthetics suppress reflex responses.

Depression of reflex pathways in the dorsal horn of the spinal cord
This is done by anaesthetics that enhance GABA-A and glycine function


Explain how general anaesthetics cause amnesia.

There are a lot of GABA-A receptors in the hippocampus that have the alpha 5 subunit
General anaesthetics stimulate these receptors to decrease synaptic transmission in the hippocampus


Explain how blood: gas partition coefficient affects the speed at which the general anaesthetic penetrates the brain.

If you have a GA that dissolves really well in the blood, then there is less GA in the gas phase in blood and hence less GA penetrates the blood-brain barrier and reaches the brain
It is only anaesthetic that remains in the gas phase that diffuses easily into the brain


Would a general anaesthetics with a high or low blood: gas partition coefficient be useful for anaesthetics and why?

This means that less of the GA will dissolve in the blood so more will be left in the gas phase
Hence more of the drug will penetrate the blood-brain barrier and reach the brain


What are the benefits of inhalation anaesthetics?

Rapidly eliminated
Good control of the depth of anaesthesia


What are the benefits of IV anaesthetics?

Fast induction
Less coughing/excitatory phenomena


What types of drugs can be used to achieve:
a. Relief of pain
b. Muscle relaxation
c. Amnesia

a. Relief of pain
b. Muscle relaxation
Neuromuscular blockers
c. Amnesia


Ion channels affected in thalamocortical neurones by general anaesthetics



What is blood:gas coefficient

Amount of a substance that dissolves in the blood- having a high blood:gas coefficient means more will dissolves in the solvent


Normal clinical procedure of delivering a GA

Induced with IV propofol as rapidly initiates loss of conciousness then maintained with an inhalatory enflurane as can be rapidly withdrawn and easy to control depth. Other 3 aspects can be controlled by supplementary drugs