Principles of general anaesthesia Flashcards
What is clinially desirable in general anaesthaesia
Loss of consciousness
Suppression of reflex responses
Relief of pain (analgesia)
Muscle relaxation
Amnesia
What do general anaesthetics all possess and at which concentration
Loss of consciousness at low concn
Suppression of reflex responses at high concn
The other clinically desirable things, some GAs do, some don’t
T/F GAs all have similar structures. If not, how are GAs classified?
F
Classified by inhalational vs iv
Name some gasous/inhalation GAs
Nitrous Oxide
Diethyl Ether
Halothane
Enflurane
Name some intravenous GAs
Propofol
Etomidate
Why was it hard to establish PD of GAs
Because they all have such different structures
What is the meyer overton correlation
Why was it rejected as MAO for GAs
Anaesthetic potency increases
in direct proportion with oil/water
partition coefficient
Disruption of lipid bilayer was thought to cause GA effect
i.e. more lipid soluble, more powerful
PROBLEMS:
1. At relevant anaesthetic concns,
change in bilayer was minute
- So must involve proteins- but ow would this change impact
membrane proteins?
Outline the possible actual MOA of GAs
Either;
Reduced neuronal excitability or
Altered synaptic function
What do IV GA agents target
GABA- A
Promotes hyperpolarisation and enhances inhibitory effect
5 subunit molecle
Structure of GABA-A receptor and how this affects action of GA
5 subunits
If there are lots of b3 i.e. in the brainstem and the spinal cord, this GABA receptor probably responsible for suppression of reflexes
The proteins with lots of a5 e..g hippocampus- responsible for amnesia
How might Halothane and Enflurane have their effects (they are inhalational)
- Still act on GABA/glycine (which are often co-expressed and usually do the same thing) but 50% less selective than IV
May target GABA-A which have a1 subunit (this is important in suppression of reflex response)
- Neuronal nAChR antagonism (only contributes to analgesic, NOT the hypnotic effects)
- TREK (contributes to the lack of conscioussness, these could be involved in normal sleep/wake cycle)
TREK= bakground leak K+ channels
i.e. this is the component involving altered NEURONAL EXCITABILITY as opposed to altered synaptic function
How does NO have GA
No effect on GABA
- Blocks NMDA-type glutamate receptors
Probably compete with co-agonist glycine (note that glycine is usually inhibitory but in some areas of brain they do promote the excitatory effect of glutatmate at NMDA)
Assumed to mediate the anaesthetic induced effects on consciousness and mobility
- Also blocks the nAChR (not just at the nAChR in the brain, like it was for isoflurane, but also in muscle, so it is a NM blocker too)
How do some inhlaaltional GAs affect nAChR
They can reduce the activation of nAChR
What can the inhalatinal GAs do for TREK channels
TREK (background leak) K+ channels
These are involved in transition for sleep to conscioussness
GAs can POTENTIATE the effect of TREK channels
T/F the Inhalational and IV GAs have similar selectivity
Completely separately, what is the effect of glycine
F…..
the inhalational ones act on many more receptors with less selectivity. This might be responsile for the greater number of clinical effects
The IV ones are speciifc to GABA-A and glycine
Glycine is inhibitor !
What is conscioussness usually dependent on
reticular activating system (RAS) emanates from the brainstem and projects upward to the cerebral cortex via the thalamus.
Acetylcholine is released from cholinergic nerve terminals projecting from RAS to the thalamus and cortex. High ACh–> higher conscioussness (i.e. wakefullness)
Which structures are affected by GAs to induce LOC
- Influences retiuclar activating neurons
- Depresses excitability of thalamocortical neuorns
(remember RAS involved brainstem to thamaus= RA neurons, and then from the thalamus to the cortex= thalamocortical neurons)
How does GA affect thalamocortical neurons
Anaesthetics can directly hyperpolarize thalamocortical neurons by activating TREK channels and/or by potentiating GABAAreceptors - information transfer through the thalamus is disrupted.
Although the thalamus might control the state of consciousness, processing in the cortex is responsible for the detailed content of consciousness, and during anaesthetic-induced LOC the cortex is profoundly deactivated.
T/f GAs, such as NO/propofol, only causes consciousness loss
F they are also causing euphoria too. This is because GABA-A receptors are also involved in euphoia
How can you account for GAs causing suppression of reflex responses
Depression of reflex pathways
in the spinal cord
High density of GABA receptors located in the dorsal horn of the spinal cord.
High concentration of b3
How can you account for GAs causing amnesia
Reduced synaptic transmission in hippocampus/amygdala
GABA-A receptor
Why is memory sensitive to GA
Because amnesia occurs at concentrations well below those that cause sedation and analgesia.
Proportion of GABA-A receptors that have a5 is low, but they are distributed at extrasynapse of the hippocampus in relatively high ratio.
What is important with regard to gas getting into the blood from the lungs
What is the effect of the blood gas partition coefficient on speed of induction
If there is low blood:gas partition coefficient:
- large proportion dissolves POORLY into the blood (large proportion remains as a gas)
- in the brain, any gas dissolved in the blood will find it harder to get into the brain. If it’s in gas form in the blood, it gets into the brain quicker
LOW blood gas –> MORE going into the brain
High blood gas –> more gas dissolves ino the blood and much less in gas form in the blood, then there is slower transfer of anaesthetic agent into the brain, so the speed of anaesthesia induction reduces. And more difficult to control
A higher blood gas partition coefficient means a higher uptake of the gas into the blood and therefore a slower induction time. It takes longer until the equilibrium with the brain partial pressure of the gas is reached.
Advantages of low blood: gas partition
I.E., not much dissolved in the blood, most staying as gas in the blood
- Gain access to brain more readily
- Better control because, when you want the patient to come around, you just remove gas from the airway, and then the gas will diffuse from the blood into the lungs, and be removed from the circulation rapidly due to concentratin gradients. Cannot happen if the blood is dissolved
Inhalation anaesthetics advantages
- Rapidly eliminated
- Rapid control of depth of amnesia
IV anaesthetics advantages
- Fast inductions
- Less coughing/excitatory phenomena (i.e they can have seizures on the table)
What is usually given in an operation for GA
induction with: propofol (any IV)
Maintenance with enflurane (any inhalational, so then you can directly control the amount of drug)
What else would be given to allow: relief of pain
Opioid (e.g. i.v. fentanyl)
What drug might be given for muscle relaxation
Neuromuscular blocking drugs (e.g. suxamethonium)
What drug might be given for amnesia
Benzodiazepines (e.g. i.v. midazolam)
What is the solubulity of GA drugs
They sit in your adipose tissue for a long time
So you can get drowsy again
Why can inhalatinal anaesthetics lead to cough
Airway irritation can lead to the cough reflex being initiated
T/F low solubility inhalational GAs will induce anaesthesia more quikcly
T A highly soluble agent will dissolve in the blood very effectively. However, this means that the gas component (partial pressure) will be lower and it is this that determines the speed of brain penetration (not the total amount in the blood). Thus a poorly soluble agent will have a very rapid onset of action.
