Pharm 29 - Principles of general anaesthesia

Question 1

What are the clinically desirable effects of general anaesthesia

Answer 1

All general anaesthetics do:

1. Loss of consciousness at low conc
2. Suppression of reflex responses at high conc

(may also do - pain relief, muscle relaxation, amnesia)

Question 2

What are the gaseous general anaesthetic agents?

Answer 2

Nitrous oxide
Diethyl ether
Halothane
Enflurane

Question 3

What are the IV general anaesthetic agents

Answer 3

Propofol

Etomidate

Question 4

General anaesthetics either work by reducing neuronal excitability or by altering synaptic function. How do IV agents work

Answer 4

Potentiate GABAa receptors (inhibitory, consist of 5 subunits that can vary)

GABAa receptors may have Beta-3 subunits (suppression of reflex responses) and alpha-5 subunits (amnesia)

Question 5

How do inhalation general anaesthetic agents work

Answer 5

1. They act on GABAa (less powerfully than IV agents) and glycine (important in spinal cord) receptors.

They affect the alpha-1 subunit of GABAa receptors - suppression of reflex responses

2. Nitrous oxide works by blocking NMDA-type glutamate receptors (compete with coagonist glycine)

Question 6

How can inhalational agents cause analgesia?

Answer 6

By inhibiting neuronal NAChR

Question 7

How can inhalation agents cause loss of consciousness

Answer 7

They activate TREK (background leak) K channels - causing hyper polarisation

Question 8

IV agents almost exclusively work through potentiating GABAa. What about inhalation agents

Answer 8

Inhalational agents far less selective - anaesthetic effects mediated via multiple targets in brain

Question 9

How can general anaesthetics cause loss of consciousness

Answer 9

Information goes from RAS –> Thalamus —> Cortex

1. GAs depress excitability of thalamocortical neurones (e.g. via GABAa and TREKs)
2. Influences Reticular activating neurones (RAS)

Question 10

How can general anaesthetics cause suppression of reflex response

Answer 10

Depression of reflex pathways in spinal cord (GABAa, glycine)

Question 11

How can general anaesthetics cause amnesia (fastest effect)

Answer 11

Gabaa Receptors (with alpha-5 subunit) located in hippocampus

Decreases synaptic transmission in hippocampus/amygdala

Question 12

As an anaesthetist, you want a low blood:gas partition. Why

Answer 12

If you have a higher blood:gas partition, more drug dissolves into blood, and when drug is dissolved in liquid form, poorer diffusion into brain.

However, if drug dissolves poorly (i.e. has a low blood:gas partition), more drug is in gaseous form in blood –> enters brain quicker.

Drug with low blood:gas partition will diffuse faster back out of brain –> blood –> back out into airways than drug with high blood:gas partition

Question 13

Which allows greater control of anaesthesia, inhalational or IV

Answer 13

Inhalational - some drug excreted by lung so better control

Question 14

How is anaesthesia used in clinical practice

Answer 14

Induce anaesthesia with IV - e.g. propofol

Then maintain anaesthesia with inhalation because more control e.g. enflurane

These 2 induce loss of consciousness and suppress reflex responses

Other features of anaesthesia (e.g. analgesia (opioid - fentanyl), muscle relaxation - NM blocker - suxamethonium), amnesia - benzodiazepines - midazolam) achieved by using other drugs

Question 15

Compare and contrast inhalational vs IV anaesthetic

Answer 15

Inhalational = rapidly eliminated, rapid control of depth of anaesthesia

IV = fast induction, less coughing/excitatory pneumonia

Question 16

Anaesthetics are really lipid soluble. What is a consequence of this

Answer 16

Sometimes anaesthetic stored in adipose - and slowly leaks back out - so some patients start to feel drowsy again 24 hrs after