Principles of General Anaesthesia Flashcards
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) Relief of pain Muscle relaxation Amnesia
Name 4 inhalational general anaesthetics.
Nitric oxide
Diethyl ether
Halothane
Enflurane
Name 2 IV general anaesthetics.
Propofol
Etomidate
What is the Meyer/Overton correlation?
Anaesthetic potency increases in direct proportion with the oil/water partition coefficient
In other words: anaesthetic potency is directly correlated with lipid solubility
That was the explanation for the Meyer/Overton correlation?
The more lipid soluble the drug, the more it was able to disturb the lipid bilayer
What were the 2 problems with this explanation?
- At therapeutic doses, the changes to the lipid bilayer were minute
- How would this bilayer disturbance impact on membrane proteins?
What are the two actual 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 are targeted by the IV agents that alter synaptic function. What are the desirable effects?
Beta 3 subunit – suppression of reflex responses
Alpha 5 subunit – amnesia
What are the two main receptor targets of inhalational agents that alter synaptic function?
GABA-A receptors
Glycine receptors
Which subunit of the GABA-A receptor do inhalational agents seem to be more selective for? State the desirable anaesthetic effect.
Alpha 1 – 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 acetylcholine receptors with regards to general anaesthesia?
Blocking nAChR leads to reduced nerve conduction
This is important for amnesia and pain relief
Which channels are important in reducing neuronal excitability via the action of inhalational agents? Describe how.
TREK – background leak K+ channels
These lead to hyperpolarisation of neurones and inhalational agents facilitate the opening of these channels
Explain how general anaesthetics cause a loss of consciousness.
- Depress the excitability of thalamocortical neurones
- Influences reticular
activating neurons
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
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?
LOW
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 Opioids b. Muscle relaxation Neuromuscular blockers c. Amnesia Benzodiazepines
