General Anaesthetics

Question 1

List 2 routes by which general anesthetics can be administered.

When are these routes used?

Answer 1

1 - Inhalation (inhalation anaesthetics - used when administering a single drug).

2 - Intravenous (balanced anaesthetics - used when administering a combination of different drugs for optimal clinical effect with lowest risk).

Question 2

List 3 early general anaesthetics.

Answer 2

1 - Diethyl ether.

2 - Chloroform.

3 - Nitrous oxide.

Question 3

Define anaesthesia.

Define analgesia.

Answer 3

• Anaesthesia is the loss of sensation.

- Analgesia is the loss of pain.

Question 4

What is the triad of general anaesthesia?

Answer 4

• 3 requirements for anaesthesia:

1 - Unconsciousness.

2 - Analgesia.

3 - Muscle relaxation (loss of reflexes).

Question 5

Which component of the nervous system is targeted by general anaesthetics?

Answer 5

General anaesthetics target the CNS only.

Question 6

List 3 chemical properties of general anaesthetics.

Answer 6

1 - Simple, short-chain molecules.

2 - Unreactive.

3 - Belong to no single chemical class.

Question 7

What is the lipid theory for the mechanism of general anaesthesia?

Answer 7

• The lipid theory states that the concentration of agent required to produce general anaesthesia is inversely proportional to the agent’s lipid:water partition coefficient.
• This coefficient is a measure of the lipid solubility of the agent - the higher the coefficient the more lipid soluble.
• I.e. a more lipid soluble general anaesthetic requires a lower concentration to produce general anaesthesia (because it is able to infiltrate the cell membrane more easily).
• This is because the agents act by volume expansion of the lipid membrane, or by increasing the fluidity of the membrane, which interferes with conduction of nerve impulses.

Question 8

List 3 observations that support the lipid theory for the mechanism of general anaesthesia.

Answer 8

1 - The concentration of a general anaesthetic in a cell membrane must be 0.05mM to produce anaesthesia for any agent.

2 - Anaesthesia occurs when the volume of a lipid (i.e. those found in the cell membrane) expands by 0.4%.

3 - High pressure reverses the anaesthesia.

Question 9

What is the protein theory for the mechanism of general anaesthesia?

Answer 9

• The protein theory states that the concentration of agent required to produce general anaesthesia is inversely proportional to the agent’s protein affinity.
• Lipid solubility is still required (as seen in the lipid theory), however it is only required for access to membrane proteins.

Question 10

List 2 observations that support the lipid theory for the mechanism of general anaesthesia.

Answer 10

1 - Protein binding of general anaesthetics exhibits the cut-off phenomenon for long chain compounds. This means that there is a cut-off in chain length where agents abruptly lose their ability to produce general anaesthesia, perhaps due to a loss in protein-binding ability.

2 - The stereoselectivity of general anaesthetics is preserved with protein binding.

Question 11

What type of membrane proteins are targeted by general anaesthetics?

List 6 examples of these proteins.

Answer 11

• Ion channels. Particularly:

Inhibitory targets:

1 - GABAa receptor.

2 - K+ channels.

Excitatory targets:

3 - Glutamate receptors, specifically NMDA.

4 - Serotonin receptors.

5 - Nicotinic receptors.

6 - Glycine receptors.

*NB the result of general anaesthetics binding to their targets is always depression of the CNS, regardless of whether the target is excitatory or inhibitory.

Question 12

List 4 functions that are lost with increasing concentrations of general anaesthetics.

List from low concentration to high concentration of general anesthetic.

Answer 12

1 - Memory is impaired first.

2 - Consciousness.

3 - Movement.

4 - Cardiovascular response at high concentrations (bad).

Question 13

List and describe the stages of general anaesthesia.

Answer 13

1 - Analgesia.

• Drowsiness.
• Intact reflexes.
• Still conscious.

2 - Induction phase.

• Delirium.
• Spasmodic movements.
• Incoherent speech.
• Eventual loss of consciousness
• Unresponsive to non-painful stimuli.

3 - Surgical anaesthesia.

• Unresponsive to painful stimuli.
• Loss of reflexes.
• Muscle relaxation.
• Synchronised electroencephalograph.

4 - Medullary paralysis (overdose).

• Pupillary dilation.
• Respiration ceases.
• Circulation ceases.
• electroencephalograph wanes.

Question 14

Why is the induction phase of general anaesthesia a particularly dangerous stage?

Answer 14

Due to the risk of:

1 - Cardiac arrhythmias.

2 - Vomiting.

3 - Choking.

Question 15

List 2 desirable properties of a general anaesthetic drug.

Answer 15

1 - Potent (so not much needs to be administered to achieve general anaesthesia).

2 - Fast acting and fast recovery (to quickly pass the dangerous induction phase).

Question 16

What is MAC?

What is MAC used for?

Answer 16

• Minimal alveolar concentration.
• It is the concentration of a general anaesthetic in the alveoli (expressed as a % of inspired air) required to produce immobility in 50% of patients when exposed to a noxious stimulus.
• MAC is used as a measure of anaesthetic potency.

Question 17

How is the MAC of a general anaesthetic used clinically?

Answer 17

2-3x the MAC of a general anaesthetic is given to patients in clinical practice (to be sure that general anaesthesia is produced).

Question 18

What determines the MAC of a general anaesthetic?

Answer 18

MAC is inversely proportional to lipid solubility.
- I.e. more lipid soluble substances can produce general anaesthesia at a lower concentration - see lipid and protein theory cards.

Question 19

List 7 factors that increase the speed at which a general anaesthetic induces general anaesthesia, and the speed at which general anaesthesia is reversed.

Answer 19

1 - Low blood:gas partition coefficient.*1

2 - High tissue:blood partition coefficient.

3 - High concentration of anaesthetic inhaled.

4 - High rate and depth of breathing.

5 - High rate of pulmonary blood flow.

6 - Low partial pressure of the drug in venous blood (speed of drug movement into the blood decreases over time as the drug saturates the blood).

7 - Low solubility in blood.*2

8 - Tissue blood flow.

• 1 This is because the drug does not bind strongly to the blood, so it will move more quickly from the blood into the brain tissue.
• 2 This is because the blood will have a lower capacity for a drug that is less soluble in blood, and the blood must be saturated before any will move to the brain, which is easier to achieve if the blood has a low capacity for the drug.

Question 20

What is the tissue:blood coefficient of all general anaesthetics in lean tissue (such as the brain)?

Answer 20

The tissue:blood coefficient of all general anaesthetics in lean tissue is 1.

Question 21

Why might the speed of induction of general anaesthesia be lower in a fat (thicc) patient?

Answer 21

• Because general anaesthetics are highly soluble in lipids, so adipose tissue has a high capacity for general anaesthetics.
• This decreases the rate at which the general anaesthetic absorbs into the brain.
• This is also true for reversal of general anaesthesia.

Question 22

How are general anaesthetics eliminated from the body?

Answer 22

• General anaesthetics are eliminated via the lungs.

- Metabolism is not important for most general anaesthetics. This reduces toxicity).

Question 23

List 5 general anaesthetics.

For each, list a few advantages and disadvantages.

Answer 23

1 - Halothane (potent, fairly fast but possible liver toxicity).

2 - Enflurane (less liver toxicity but possible seizures).

3 - Isoflurane (rapidly action, effectively relaxes muscles but smells bad).

4 - Sevoflurane (pleasant odour, rapid recovery but possible renal damage).

5 - Nitrous oxide (very rapid, used for strong analgesic properties but low potency and only used in general anaesthetics when combined with other agents).

Question 24

List 2 advantages of balanced anaesthetics.

Answer 24

1 - Rapid onset.

2 - Short acting (therefore useful for short procedures).

Question 25

What is the mechanism of action of intravenous anaesthetics?

Give 2 examples of intravenous anaesthetics.

Answer 25

• Mechanism of action is the same as inhaled general anaesthetic but through interaction with more specific ligand-gated receptors:

1 - Steroid anaesthetics such as barbiturates and benzodiazepines potentiate GABAa receptor action.

2 - Ketamine is an NMDA receptor antagonist.

Question 26

What is different about the anaesthesia induced by ketamine compared to other general anaesthetics?

Answer 26

• Although ketamine causes sensory loss, analgesia, paralysis, and a surgical level of anaesthesia, it doesn’t cause loss of consciousness.
• This is known as dissociative anaesthesia.

Question 27

List 5 drug classes that act as adjuncts to general anaesthetics.

What effects are brought about by these drugs?

Answer 27

1 - Benzodiazepines (sedation, anxiolysis, amnesia, muscle relaxation).

2 - Opioids (pain relief).

3 - Antimuscarinics (to facilitate intubation and ventilation).

4 - Neuromuscular blockers (to induce muscle relaxation).

5 - Antiemetics (to decrease perioperative nausea).

Question 28

List 2 benzodiazepines used as premedication for general anaesthesia and to induce muscle relaxation for surgery.

Answer 28

1 - Lorazepam.

2 - MIdazolam.

Question 29

List 3 opioids used as premedication for general anaesthesia.

Answer 29

1 - Morphine.

2 - Fentanyl.

3 - Pethidine.

Question 30

List 3 antimuscarinics used as premedication for general anaesthesia.

Answer 30

1 - Atropine.

2 - Hyoscine.

3 - Glycopyrronium.

Question 31

List 4 neuromuscular blockers used to induce muscle relaxation for surgery.

Answer 31

1 - Tubocurarine.

2 - Pancuronium.

3 - Gallamine.

4 - Suxamethonium.

Question 32

Give an example of an antiemetic used to decrease perioperative nausea.

Answer 32

Metoclopramide.

Question 33

Why are muscle relaxants given as adjuncts to general anaesthetics in balanced anaesthesia?

Answer 33

To relax abdominal muscles, tracheal muscles and the diaphragm, allowing for a lower dose of general anaesthesia to be given.