Principles of general aneathesia

Question 1

What is general aneathesia? what would you want it to do?

Answer 1

Creates loss of consiousness, loss of reflex (immobile), loss of pain
Muscle relaxation, amnesia

Most agents dont have all 5 charecteristic-mix and match
the 2 they ALL have is-at low conc loss of conciousness, and at high conc loss of reflexes

all are good euphoriants

Question 2

what are the 2 broad classes of aneathetics?

Answer 2

Gaseous and intravenous
Gaseous-NO, diethyl ether, halothane, enflurane (look nothing similar)

Intravenous-Propofol, etomidate-still dont look similar

They dont look similar but they are all lipid soluble-Meyer/Overton relation-the more lipid soluble it is, the more potent it is
But for a very long time unsure what the target was

Question 3

What is the target for intravenous anaesthetics?

Answer 3

Either change synaptic function or reduce neuronal exctiability –centered around the GABAa receptor (increase activity)
Different GABA receptor composition are targetted differently–apparently GABAaB3 (supression of reflex), GABAaA5-amnesia

minor effects on other ones

Question 4

What are the targets for the inhalation anaesthetics?

Answer 4

Also act on GABA but more complex-and target a lot more-like glycine receptors (mostly in Spinal Chord)–
Much lower effects overall but more promiscuois

Haloginated agents-increase GABA/Glycine
Nitrous Oxide-Blocks NMDA glutamate type rectors
Neuronal nicotinic Ach receptor–inhbited by inhalational actions (especialy the Haloginated)
TREK-background leak K channels-hyper polarise neurons (reduce neuronal excitability) –increased by Haloginated, reduce conciousness
like glycine receptors (mostly in Spinal Chord

Question 5

WHat is the neuroanatomical basis behind loss of conciousness?

Answer 5

Loss of conciousness is bas on inputs from the thalamo-coritcal neurons to the reticular activating neurons
As long as lot of inputs to the RAS-keep awake.
Aneasthetics can “highjack” and reduce those inputs-convince brain its sleep time
Cortical neurons and RAS neurons are very GABAa rich
And especially RAS neurons have lot of TREK channels-depress firing rates there

Question 6

WHat is the neuroanatomical basis behind loss of reflex response?

Answer 6

Glycine and GABA very important in relay of pain/stimuli up the chord to the brain–
try and disconect brain from chord and prevent recieving the stimuli

Question 7

WHat is the neuroanatomical basis behind amnesia?

Answer 7

Linked to hippocampus and amygdala. Have a lot od alpha5 GABAa in these regions-IV aneathetic targets

Question 8

Describe the route of inhaled aneathetics to the brain? WHy is it good?

Answer 8

IV or Inhaled
Inhaled->alveoli –very lipid soluble–> pass easily
If agent has low blood:gas partition coef it remains gaseous in blood–> means it will pass very easily to brain
High blood:gas coef-dissovle in blood–> trapped in blood and cant enter brain

Very good because helps achieve decently fast anethetics–not as fast as IV tho
also low blood:gas means when u remove alveoli gas, the gradient means itll exit the brain very fast -> lot more control over the depth and duration

Question 9

Describe the route of IV aneathetics to the brain? WHy is it good?

Answer 9

IV go through blood straight to the brain-very very fast
But cannot control dosage or its elimination once done -low control
also tend to have deeper effects than inhalant–no coughing like in inhalants

Question 10

So what anetheteics would you use when?

Answer 10

Induce with IV agents
And maintain/extend with inhalants
These always do at least loss of conciousness and loss of reflex

bu

Question 11

How would you combine aneastetics and drugs to reach all the endpoints of aneathesia?

Answer 11

Los of concious and supression of reflex via IV and inhalant
But for pain-opoiods
muscle relaxants
Amnesia-benzodiazepams

need to combine so many drugs at the same time-complex pharmalogical situation