General Anaesthetics

Question 1

What is a GA?

Answer 1

an agent used as an adjunct to surgical procedures which renders the patient unconscious or unaware of, and unresponsive, to simulation that would normally lead to pain, stress and/or discomfort

Question 2

What 4 things do GAs produce?

Answer 2

• loss of sensation
• loss of consciousness
• loss of memory (amnesia) for the period under the influence
• loss of most movement (muscle relaxation)

Question 3

What are GAs not?

Answer 3

analgesics or hypnotics

Question 4

Why is alcohol not a good GA?

Answer 4

it does not allow for rapid induction, smooth maintenance and control or a rapid recovery (hangover effects)

Question 5

What are the 4 stages of older versions of anaesthesia?

Answer 5

1. analgesia without amnesia
2. excitement - loss of consciousness, no response to non-painful stimuli but reflex responses to painful stimuli
3. surgical anaesthesia - spontaneous movement ceases and respiration is regular
4. medullary depression/paralysis - respiration and vasomotor control cease and death ensues in minutes

Question 6

Why is stage 2 the danger stage of older versions of anaesthesia?

Answer 6

the subject may move, talk incoherently, hold their breath, choke or vomit

Question 7

How does modern amnesia avoid the stages?

Answer 7

balanced anaesthesia

Question 8

What is balanced anaesthesia?

Answer 8

the use of a combination of agents to take the patient to the desired state as rapidly and smoothly as possible

Question 9

What are the 2 classes of GAs in human pharmacology?

Answer 9

inhalation and intravenous anaesthetics

Question 10

Give examples of common inhalation anaesthetics

Answer 10

• ether
• nitrous oxide
• halothane

Question 11

What is the partition coefficient of inhalation anaesthetics?

Answer 11

the solubility in different media defined as the ratio of the concentration of the agents in two phases at equilibrium

Question 12

What is the main factor of inhalation anaesthetics?

Answer 12

the blood-gas partition coefficient

Question 13

What does the blood-gas partition coefficient determine?

Answer 13

the rate of induction and recovery; the lower the coefficient, the faster the induction and recovery

Question 14

What inhalation anaesthetics have high and low blood-gas partition coefficients and what does this mean?

Answer 14

• nitrous oxide - low i.e. fast acting
• ether - high i.e. slow acting

Question 15

What is the oil-gas partition coefficient?

Answer 15

a measure of fat solubility that correlates with the potency of the anaesthetic

Question 16

What does a high oil-gas partition coefficient indicate?

Answer 16

high potency but slow kinetics and a long recovery (hangover)

Question 17

What inhalation anaesthetics have high and low oil-gas partition coefficients and what does this mean?

Answer 17

• halothane - high i.e. highly potent but can accumulate in fat
• nitrous oxide - low i.e. low potency but rapidly eliminated

Question 18

What is the minimum alveolar concentration (MAC)?

Answer 18

a measure of the concentration of anaesthetic required in the lungs to induce anaesthesia

Question 19

What is the relationship between MAC and potency?

Answer 19

inversely proportional

Question 20

What inhalation anaesthetics have high and low MACs and what does this mean?

Answer 20

• halothane - low i.e. low concentrations required to induce anaesthesia
• nitrous oxide - high i.e. high concentrations required to induce anaesthesia

Question 21

Overall, what does nitrous oxide have?

Answer 21

a fast induction/recovery, a low potency and an excellent analgesic property

Question 22

What are adverse effects of halothanes?

Answer 22

• malignant hyperthermia in genetically susceptible individuals
• hangover due to lipid solubility and accumulation in fat (worse for halothane than other halogenated anaesthetics)
• liver toxicity, especially with repeated use

Question 23

Why is nitrous oxide often used for induction?

Answer 23

due to its speed of action and strong analgesic effect

Question 24

What is the lipid theory (Meyer-Overton correlation)?

Answer 24

the greater the lipid solubility of a compound in olive oil, the greater its anaesthetic potency

Question 25

What do many inhalation anaesthetics do?

Answer 25

• enhance inhibitory GABAA receptor currents
• inhibit excitatory receptors e.g. nitrous oxide interacts with NMDARs and nAChRs

Question 26

How do non-immobilisers (e.g. hexafluorethane) break the Meyer-Overton correlation?

Answer 26

they should be potent anaesthetics according to their oil-gas partition coefficients, but they appear to interact with hydrophobic sites to produce amnesia but not immobility in response to stimuli

Question 27

What are intravenous anaesthetics usually used for?

Answer 27

the induction of GA, followed by an inhalation agent

Question 28

Why are intravenous anaesthetics used?

Answer 28

they have a fast onset of action (20-30s) and are less stressful than a facemask

Question 29

Why are intravenous anaesthetics rarely used for maintenance?

Answer 29

they have a slow elimination compared to inhalation anaesthetics, therefore have a slow recovery and often produce hangover effects

Question 30

What is the primary mechanism of action of intravenous anaesthetics?

Answer 30

enhancement of GABAA currents/activity

Question 31

What are the properties of propofol?

Answer 31

• rapid onset (~30s) due to its rapid transition of the BBB
• rapid rate of distribution
• short action and little hangover effect due to rapid metabolism to its inactive form
• less nausea and vomiting than inhalation anaesthetics

Question 32

What is the exception to intravenous anaesthetics being used for maintenance?

Answer 32

propofol

Question 33

What is the mechanism of action of propofol?

Answer 33

• potentiates GABAA receptor activity
• sodium channel blocker
• possible involvement in endocannabinoid system (regulates cognitive and emotional processes in CNS)

Question 34

What are adverse effects of propofol?

Answer 34

• cardiovascular depressant – can cause hypotension and bradycardia
• occasionally can cause respiratory depression
• pain at site of injection
• propofol infusion syndrome

Question 35

What can cause propofol infusion syndrome?

Answer 35

prolonged administration of high doses (especially in children)

Question 36

Give examples of symptoms of propofol infusion syndrome

Answer 36

• metabolic acidosis
• skeletal muscle necrosis
• hyperkalaemia
• lipaemia
• hepatomegaly
• renal failure
• arrythmia
• cardiovascular collapse