Principles of General Anaesthesia Flashcards
what are the 2 key properties of general anaesthesia?
what are some other effects (but these can be done by other drugs too)?
1) loss of conciousness at low concentration
2) suppression of reflex responses at high concentrations
other:
- analgesia
- muscle relaxation
- amnesia
what are the 2 types of GAs that can be used?
1) gaseous/inhalation (contain halogens typically)
2) IV (contain rings)
all their structures are dissimilar
examples of inhalation GAs
- nitrous oxide
- diethyl ether
- halothane
- enflurane
examples of IV GAs
- propofol
- etomidate
what is the Meyer-Overton correlation? what proves this correlation?
GAs penetrate the lipid bilayer and disrupt AP propagation
the more lipid soluble, the more potent the GA (lipid theory)
what is the evidence against the Meyer-Overton correlation?
at relevant concentrations, changes in the bilayer was minute and no changes in lipid bilayer proteins was seen (which would be changed if GAs disrupted AP propagation).
what is the more accepted theory on the mechanism of GA action?
The use molecular targets that either
- change synaptic function
- reduce neuronal excitablity
rather than the Meyer-Overton correlation
what effect do IV agents have on synaptic function?
alter synaptic function:
Enhance the GABAaR action and therefore enhance GABA transmission
bind to beta 3 (reflex suppression) and alpha 5 (amygdala, hippocampus)
what subunits of GABAaR do IV GAs bind to and what effect does this have?
1) beta 3 (expressed in the spinal cord) –> suppression of reflex responses
2) alpha 5 (expressed in the hippocampus/amygdala) –> amnesia
what effect do inhalation/gaseous agents have on synaptic function?
- halogen agents target GABAa/Glycine receptor to increase GABA transmission
- halogen agents decrease the firing rate of neuronal nAChR
- nitrous oxide blocks NMD glutamate receptors (competes with co-agonist glycine)
how do inhalation agents compare to IV agents in their effect on synaptic function
gaseous agents not as powerful/selective as IV agent (binds to more targets but less often)
what subunit of GABAaR do inhalation agents target and what effect does this have?
alpha 1:
halogen agents bind to alpha 1–> suppression of reflex responses
what effect do inhalation agents have on neuronal excitability?
increase TREK activity to cause K+ leakage thereby hyperpolarising the neurone
(they reduce it but not as much as IV agents)
how do halogen agents reduce neuronal excitability?
Enhance background leak of K-channels to cause hyperpolarisation of cells.
TREK (background leak) of K+-channels.
how do IV agents compare in selectivity to inhalation/gaseous agents?
IV agents are more selective
gaseous agents are less selective (more targets)
they equal in potency however
what neuroanatomical sites are targeted to lead to the loss of consciousness?
- 1)thalamocortical neurones –> depressed
- 2)reticular activating neurones –> influenced
GAs will disrupt the communication between the RAF, cortex and thalamus:
Normally the RAS receives sensory input from the frontal cortex in order to remain awake. When the cortical information pathway is disrupted, sensory input is decreased so the brain is induced to sleep
thalamocortical neurones (GABAaR) and RA neurones (TREKs)
how do GAs depress thalamocortical neurones?
GAs hyperpolarise thalamocortical neurones by activating TREK channels and/or by potentiating GABAaRs.
what effect does increasing TREK activity have?
which agents target TREK activation?
increased K+ efflux leads to hyperpolarisation leading to consciousness loss
these do not appear to be affected by IV GAs
inhalation agents make use of it
where is the neuroanatomical site for depression of reflex pathways?
dorsal horn GABAaR in the spinal cord
there is high density of GABAaRs in this area
what is targeted to induce amnesia?
GABA alpha 5 subunits:
to decrease synaptic transmission in the hippocampus and amygdala
(where is there is a high conc of alpha 5 subunits)
targets by IV agents
what receptors are involved in the loss of reflexes?
what specific subunits are targeted to suppress reflexes?
GABAaR and glycine
these being targeted leads to the disconnect between he brain and spinal cord
specific subunits: beta 3 (by IV agents) alpha 1 (by inhalation agents)
what is the journey of IV agents when administered?
what does activity duration depend on?
IV is directly injected into the blood to pass into the brain
the time the IV agent is active is dependent on the liver metabolism
what is the journey of inhalation agents when administered?
air–>lung–> blood—> brain
there is bidirectional movement of the GA
this is very lipid soluble so crosses lung very easily
What does the blood:gas partition coefficient mean?
describe the solubility of inhaled general anaesthetics in blood.
The coefficient is defined as the ratio of the concentration in blood to the concentration in gas that is in contact with that blood, when the partial pressure in both compartments is equal.
what sort of blood:gas partition coefficient is efficacious? what does this tell about the drug?
a low coefficient:
means the GA is still pretty gaseous in the blood i.e. poorly dissolved, so it will be transferred to the brain really well
the GA in the blood is high liphophilic and hydrophobic
what happens to inhalation GA movement when there is a high blood:gas partition coefficient?
what effect does this have on the onset of effects?
this means more of the agent has been dissolved in the blood so less (gas) is available to get into the brain
therefore:
slower onset of action as a higher uptake of gas into the blood
takes longer for the brain and blood to reach an equilibrium.
what are the pros of inhalation agents?
- rapidly eliminated
- rapid control of the depth of anaesthesia as diffusion occurs very rapidly
what are the pros of IV agents?
- fast induction
- less coughing/excitatory phenoma
more selective
which agents are best used in surgery under anaesthesia?
- for induction
- for maintenance
- IV used for induction
- inhalation used for maintenance
what effect does a low BG partition coefficient have on excretion of the GA?
excreted easily by ventilation
what specific GAs should be used for
- induction
- then maintenance
of loss of consciousness and suppression of reflex responses i.e. surgery ?
1) Propofol (IV)
2) Enflurane (inhalational)
what other drugs can be given other than GA for the other desired effects of:
- analgesia
- muscle relaxation
- amnesia
1) Relief of pain–>Opioids
– e.g. IV fentanyl.
2) Muscle relaxation–> NM-blockers
– e.g. Suxamethomiun.
3) Amnesia–>Benzodiazepines – e.g. IV midazolam.
