General Anaesthetics

Question 1

What are the clinically desirable features of GAs?

Answer 1

• loss of consciousness (low conc)
• suppression of reflex responses (high conc)
• relief of pain (analgesia)
• muscle relaxation
• amnesia

Question 2

What are the types of anaesthetics?

Answer 2

• IV generally contain rings

- Inhalational GAs generally have halogens

Question 3

What isthe Meyer-Overton correlation?

Answer 3

GAs penetrate the lipid bilayer and disrupt AP propagation:

• Evidence for – anaesthetic potency increases as lipid solubility increases
• Evidence against – 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)

Question 4

What are the molecular targets for GAs?

Answer 4

altered synaptic function:
IV agents - Enhance the GABAAR and enhance GABA transmission – subunits targeted:
- b3 – suppression of reflex responses – expressed in spinal cord.
- a5 – amnesia – expressed in hippocampus/amygdala.

Inhalational agents – not as powerful/selective as IV agents (hits more targets but less)
- Halogen inhalational agents: Target the GABAA/Glycine receptors.
> a1 – suppression of reflex responses
> bDecrease firing rate of neuronal NAChR
- Nitrous oxide (non-halogen agents): Block NMDA-type glutamate receptors – compete with co-agonist glycine

Reduced neuronal excitability
Inhalational agents – not as powerful/selective as IV agents (hits more targets but less)
- Halogen inhalational agents: Enhance background leak of K-channels to cause hyperpolarisation of cells
> TREK (background leak) of K+-channels.

Question 5

Which GAs are more selective?

Answer 5

Generally, IV GAs are much more selective and the inhaled GAs are much more non-selective but equally as potent

Question 6

How do GAs induce loss of consciousness?

Answer 6

Depress thalamocortical neurones
- GAs hyperpolarise thalamocortical neurones by activating TREK channels and/or by potentiating GABA Rs

Influence RAF neurones

Question 7

How do GAs suppress reflexes?

Answer 7

dorsal horn GABAAR are at a high density: Depression of reflex pathways in spinal cord

Question 8

How do GAs cause amnesia?

Answer 8

via influences on GABAA a5 subunits:

• Decrease synaptic transmission in the hippocampus and amygdala
• a5 subunits are at a high conc. here as opposed to the rest of the body

Question 9

How do IV agents maintain unconsciousness?

Answer 9

• The time the IV agent is active is dependent on the liver metabolism
• The IV agents are injected directly into the blood where they pass to the brain

Question 10

What is the blood/gas partition coefficient?

Answer 10

how a gas will partition itself between the two phases after an equilibrium has been reached

• Higher BG PC = slower onset of action as a higher uptake of gas into the blood – takes longer for the brain and blood to reach an equilibrium
• • Low BG PC = faster onset of action (drug is more lipophilic and hydrophobic so will not dissolve in blood well).

Question 11

Which type of GA is easier to control?

Answer 11

inhales as diffusion occurs very rapidly

Question 12

What are the different types of GAs used for?

Answer 12

• IV is used for induction

- Inhalation is used for maintenance

Question 13

What are the negative effects of inhalation agents?

Answer 13

coughing and excitatory phenomenon - seizures on table (rare)

Question 14

What are some examples of GAs in the clinical setting?

Answer 14

• Loss of consciousness - Induction – Propofol (IV)
• Suppression of reflex responses - Maintenance – Enflurane (inhalational)
• Relief of pain - Opioids – e.g. IV fentanyl
• Muscle relaxation - NM-blockers – e.g. Suxamethomiun.
• Amnesia - Benzodiazepines – e.g. IV midazolam