General anaesthetics

Question 1

How on a graph is lipid solubility of a anaesthetic measured

Answer 1

Y - axis - MAC - anaesthetic potency in humans - minimal alveolar concentration required to remove a response in 50% of patients upon incision
X axis - Oil:gas partition coefficient - Predicts the ease of partition into membrane lipids
As MAC goes down the oil:gas coefficient goes up - the lower the MAC value the more potent the anaesthetic , higher solubility

Question 2

What were the lipid theories used to explain anaesthetic function

Answer 2

1. Volume expansion of the plasma membrane - CNS function altered
2. Increased lipid fluidity
   Anaesthesia results from an alteration of membrane function

Question 3

What is the current theory of anaesthetic action

Answer 3

Protein theory - Different GAs target different types of proteins found on neurons
They target different ion channels in the neuron membrane
Binding sites for GAs on the ion channels are often varied in their hydrophobic domain

Question 4

What is the main target for GAs

Answer 4

Potentiation of the GABAa receptor - ligand gated chloride channel

Question 5

Which interfaces to volatile GAs bind to

Answer 5

Alpha and Beta subunits

Question 6

What interfaces do intravenous GAs bind to

Answer 6

Only the Beta subunit

Question 7

What receptor is blocked by ketamine

Answer 7

NMDA (glutamate) receptors

Question 8

What do low concentrations of volatile GAs activate

Answer 8

two pore domain K channels - Modulate neuronal activity - reduce membrane excitability - analgesia, hypnosis

Question 9

What are the effects of GAs on neurotransmission at the cellular level

Answer 9

1. Enhance tonic inhibition (enhancing GABA), reduce excitation (open K channels) and inhibit excitatory synaptic transmission (depressing transmitter release and ligand gated ion channels)

Question 10

What are the four stages of anaesthesia

Answer 10

1. Analgesia - loss of pain
2. Excitement - dangerous stage - exaggerated reflexes, imbalance between inhibitory and excitatory neurotransmission
3. Surgical anaesthesia - Unconscious, loss of reflexes, loss of response to pain, short term amnesia
4. Medullary paralysis - Loss of cardiovascular reflexes and respiratory paralysis

Question 11

Which two stages of anaesthesia are wished to be avoided

Answer 11

2 and 4

Question 12

Give advantages of intravenous anaesthetics

Answer 12

Speed of conduction is very fast (20-30 seconds)

Easy to administer

Question 13

Give advantages of using the drug propofol

Answer 13

Rapid metabolism - good for the induction of anaesthesia

T0.5 = 2.4mins - rapid recovery and les hangover - can be used as a day case surgery

Question 14

What are general disadvantages of using intravenous GAs

Answer 14

Pain at the site of injection, complex pharmacokinetics

Question 15

What are the disadvantages of thiopental

Answer 15

High lipid solubility so rapid induction - BUT - short duration of action due to redistribution and hangover due to accumulation in fat -
Respiratory depression and CV depression 9i4

Question 16

What is the action of ketamine

Answer 16

Dissociative anaesthesia, sensory loss, analgesia, amnesia, no complete loss of consciousness or respiratory depression, CV excitement

Question 17

What are inhaled anaesthetics advantages for use

Answer 17

Useful for maintaining anaesthesia
Only route of entry and exit is via the lungs
Small lipid molecules - so cross the alveolar membrane easily

Question 18

How is the speed of induction and recovery modified

Answer 18

Properties of the anaesthesia - blood:gas coefficient (solubility in blood)
Oil:gas coefficient (solubility in fat)
Physiological properties
Cardiac output
Alveolar ventilation rate

Question 19

How can body tissue be split into compartments and how do they differ

Answer 19

Lean tissue (brain) - havre large blood flow and low partition coefficient for anaesthetics therefore equilibrate rapidly with the blood
Fat tissues - have a small perfusion and large partition coefficient - Act as a reservoir of drug during the recovery phase