General anaesthetics (Concepts)

Question 1

What are the main stages of distribution of IV anaesthetic (e.g. thiopentone)?

Answer 1

1. Fast redistribution phase (4-5 minutes): Redistribution throughout tissue
2. Intermediate phase (<10 hours): Non-linear elimination
3. Terminal phase (>10 hours): Linear elimination (true terminal phase)

Question 2

What occurs immediately after thiopentone injection?

Answer 2

Immediately after injection of drug, [drug] is highest in high blood flow tissues (inc. brain). During this period of time, anaesthesia occurs.

Question 3

What occurs in the fast redistribution stage of thiopentone?

Answer 3

Drug diffuses out of high blood flow tissues into low blood flow tissues. Loss of anaesthesia is therefore due to fall in [drug] as a result of redistribution, not elimination.

Question 4

What occurs in the intermediate stage of thiopentone redistribution?

Answer 4

• Drug begins to accumulate in fat, so there is further decrease in concentration of drug around body.
• Rate of redistribution is slower than initially, but still fairly rapid.

Question 5

What occurs in the late stage of thiopentone redistribution?

Answer 5

• Most of the drug has accumulated in fat and there is a fairly uniform distribution of drug across the body.
• Absence of significant redistribution means that elimination only route for drug removal.
• The rate of decrease in [Drug] is very slow but follows 1st order kinetics.

Question 6

What is the most common methody of elimination for IV GAs?

Answer 6

Metabolism

Question 7

What is the relationship between potency of GA and partial pressure of gas needed to induce anaesthesia?

Answer 7

Potency ∝ 1/(Partial pressure)

Question 8

What is the partition coefficient for inhaled GAs?

Answer 8

Partition coefficient = [Drug]_Oil/[Drug]_Gas

Question 9

What is the relationship between partition coefficient of gaseous GA and potency?

Answer 9

Potency ∝ Partiiton coefficient

Question 10

What is the blood:gas partition coefficient (BGPC) for inhaled GAs?

Answer 10

BGPC = C_Blood/C_Alveoli

Question 11

What is the meaning of the BGPC?

Answer 11

The greater the BGPC, the more water solube the drug is

Question 12

What is the relationship between BGPC and rate of induction of anaesthesia?

Answer 12

BGPC ∝ Rate of induction

Question 13

What does large BGPC mean slow rate of induction?

Answer 13

• Ventilation is about 0.3 L in lungs per breath, which is then diluted across ~2.8 L of total lung volume.
• C_alveoli is very low when GA in inhaled.
• It takes a long time for C_alveoli to build up if drug quickly absorbed into blood, and so concentration gradient between alveoli and blood is low, and so drug takes long time to reach effective C_blood.

Question 14

What is the relationship between BGPC and rate of recovery from anaesthesia?

Answer 14

Rate of recovery ∝ 1/BGPC

Question 15

Why does small BGPC result in fast rate of elimination?

Answer 15

• When blood with high [GA] enters the lungs, the majority diffuses into the lungs and is eliminated, so blood leaving the lungs has much [GA] compared to blood entering.
• This means that arterial [GA] reaching brain is kept at fairly low levels, and not enough to induce anaesthesia.
• This is despite large amount of GA still remaining in the body, that then enter systemic circulation to be eliminated in lungs again.

Question 16

Why does large BGPC result in slow rate of recovery from anaesthesia?

Answer 16

• When blood with high [GA] enters the lungs, only small amounts diffuse into the lungs and is eliminated, so blood leaving the lungs has fairly similar [GA] to that entering (i.e. high).
• This means that arterial [GA] reaching brain is kept at fairly high levels that are enough to induce anaesthesia for very long period of time.
• Since the [GA] reaching lungs is dependent on amounts of GA in body; in order for blood levels of GA to fall below that needed to induce anaesthesia, majority of GA needs to be eliminated from body.

Question 17

What is the relationship between the BGPC and a drugs ability to induce anaesthetics “hangover” effect?

Answer 17

Drugs with greater BGPCs have greater ability to induce anaesthetics hangover effect due to slow rate of elimination and build-up of anaesthetics in blood due to diffusion from fat.