27. Principles of general anaesthesia Flashcards
At what level of concentration can all general anaesthesia cause loss of consciousness and reflex suppression?
- Loss of consciousness - low concentration
* Suppression of reflex responses - high concentration
Does general anaesthesia cause pain relief, muscle relaxation and amnesia?
- Some cause pain relief and muscle relaxation
* Most cause amnesia
What is the lipid theory for anaesthesia?
- More lipid soluble anaesthetic - more potent
* A disruption in the lipid bilayer leads to the anaesthetic potency of the drugs
What was the explanation to the lipid theory for anaesthesia, and the 2 problems with this explanation?
The drugs disturbed the lipid bilayer. Problems:
• Minute changes at therapeutic doses
• Membrane proteins are independent of the change in membrane
How was it shown that the lipid theory had a poor explanation?
Rise in temperature had the same effect on the membrane as general anaesthetic
How do IV GAs work?
Potentiation - enhance GABA function
• Target GABAA receptor (selective) - type 1 ionotropic receptor - 5 subunits
• Subunit combination is different in different parts of the brain
• IV agents target beta-3 and alpha-5 subunits of GABAA
• Reduced neuronal activity
• Altered synaptic function
What are the subunits targeted by IV GAs involved in?
- Beta-3 - suppression of reflex responses (synaptic) - spinal cord, medulla
- Alpha-5 - amnesia (extra-synaptic) - hippocampus
Why does IV GA cause euphoria before being knocked out?
GABAA receptor is important in causing euphoria
Is IV or inhalation GA more selective?
IV
How do inhalation GAs generally work?
- Affect GABAA and glycine receptors
- Glycine is an inhibitory neurotransmitter
- Other targets involved make GABA effect 50% less potent
- More selective for alpha-1 containing GABA - important for reflex suppression
- Halogenated GA agents have effects on GABA
How does nitrous oxide work?
- Blocks NMDA-type glutamate receptors
- Less GABA specific and more glutamate specific - almost no effect on GABA
- Glycine is an important co-agonist of NMDA receptors
- N2O competes at binding site for glycine NMDA receptor
- Allows full receptor response to be transduced
- Blocks excitatory effect
What is the significance of neuronal nicotinic ACh receptors in inhalational GA?
- Inhibition of these receptors reduces nerve conduction
- Cholinergic neurones switch off => ANALGESIA
- Also important for amnesia
- No loss of consciousness or reflex suppression
What is TREK and how are they related to inhalational agents?
Background leak K+ channels - activated by GA
• Agents facilitate opening of these channels
• Enhanced hyperpolarisation => reduced neuronal excitability
• Suppression of reflexes
How much inhalation GA is needed compared to IV?
Higher dose
What brain activity is reduced when unconscious?
- Cortical activity
- Excitability of thalamocortical neurones (depression of periphery from brain)
- RAS (reticular activating system)
