General anaesthetics

Question 1

What is required by an anaesthetic

Answer 1

1. abolition of sensation
2. abolition of pain
3. ‘Triad of General Anaesthesia’
4. unconsciousness
5. analgesia
6. muscle relaxation
7. multiple drugs

Question 2

What are the stages of anaesthesia

Answer 2

1. Stage I - analgesia
   a) conscious, drowsy, antinociception, amnesia
2. stage 2 - excitement
   a) Loss of consciousness but delirium, irregular cardiorespiration, apnea, spasticity, gagging, vomiting
3. Stage 3 - anaesthesia
   a) regular respiration, loss of reflex and muscle tone
4. Stage 4 - medullary paralysis
   a) depression of cardiorespiration, death

Question 3

What are the characteristics of an idea GA

Answer 3

1. stable
2. potent
3. non-toxic
4. controllable
5. rapid on and off
6. adjustable
7. minimal cardio-depressant
8. minimal respiratory depressant
9. non-irritant
10. xenon is ideal - why not use it?- Cost – too expensive

Question 4

What are the types of anaesthetics

Answer 4

1. Inhalation - gasses or vapours

2. Intravenous

Question 5

Describe inhalation method

Answer 5

1. controllable
2. rapid blood-gas exchange
3. usually halogenated ethers or hydrocarbons e.g. halothane, isoflurane
4. stable, potent

Question 6

Describe intravenous method

Answer 6

1. injections
2. very rapid, short acting
3. Induction of anaesthesia

Question 7

What are common anaesthetic procedures

Answer 7

1. to produce rapid unconsciousness with an intravenous injection of a rapid onset, short acting barbiturate (thiopentone).
2. to maintain unconsciousness with one of more inhalation agents (e.g. N2O and Halothane).
3. This can be supplemented with an intravenous analgesic agent (e.g. fentanyl)
4. produce muscle paralysis with a neuromuscular blocking agent such as the nicotinic antagonist tubocurarine.

Question 8

What drug can be used to provide rapid unconsciousness.

Answer 8

1. I.V. with rapid, short acting agent e.g. thiopental

Question 9

What is used to maintain unconsciousness.

Answer 9

1. inhalation agents e.g. N2O and Halothane

Question 10

What is used to supplement analgesia

Answer 10

1. I.V. e.g. fentanyl.

Question 11

What is used to induce paralysis

Answer 11

1. neuromuscular block e.g. suxamethonium.

Question 12

What is used as a pre-op anaesthetic

Answer 12

1. Pre-op (sedation, anxiolysis, amnesia).

2. Midazolam and other benzodiazepines.

Question 13

What are some common inhalation anaesthetics

Answer 13

1. N2O - rapid, low potency, in combination, obstetrics, analgesic- Used for stage 1 but difficult to maintain
2. Volatile halogenated hydrocarbons - Widely used but some side effects especially cardiovascular & nausea

Question 14

Give examples of halogenated hydrocarbons

Answer 14

1. Halothane - vet use, developing countries, hepatotoxic, hangover
2. Enflurane - fast on and off, lower toxicity, epileptogenic
3. Halothane and enflurane are not clinically used because of side effects
4. Halothane used in developing countries as very cheap
5. Isoflurane - non-epileptogenic, cardio and respiratory effects
6. Desflurane - v. fast on and off, cardio effects
7. Sevoflurane – v. fast, potent, maybe hepatotoxic
8. ether (and derivatives), cyclopropane, chloroform- largely obsolete, many side effects, explosive

Question 15

Give examples of common intravenous anaesthetics

Answer 15

1. Thiopental - barbiturate, very fast on (20 s) and off (10-15 min), non-analgesic, respiratory depression, hangover
2. etomidate- rapid metabolism, low cardio-respiratory effects, involuntary muscle jerks
3. Propofol - v. rapid metabolism, induction and maintenance, day surgery, most widely used
4. Ketamine - slow onset, analgesic, dissociative, hallucinogenic, hypertensive and bradycardic, children & veterinary
5. thought children don’t experience hallucinogenic and dissociative affects
6. Midazolam and other benzodiazepines- pre-op

Question 16

How are Local anaesthetics thought to work

Answer 16

1. Voltage-gated sodium channel block.

Question 17

What is the Lipid Theory of anaesthetic action

Answer 17

1. potency proportional to lipid solubility
2. partition coefficient- higher is more lipophilic
3. MAC- minimum alveolar content - What concentration of gas you need in alveoli to induce anesthesia
4. “Narcosis commences when any chemically indifferent substance has attained a certain molar concentration in the lipids of the cell”
5. Idea that membranes are phospholipids
6. Agents that are lipophilic will soak into lipid membrane and make it more fluid and flexible changing the shape of membrane bound proteins causing channels to be blocked
7. But not all lipophilic agents are anaesthetics

Question 18

What is the protein theory of anaesthetic action

Answer 18

1. Franks and Lieb (1987)
2. luciferase inhibition correlates with anaesthetic potency
3. anaesthetics interact with membrane proteins
4. receptors and ligand gated ion channels
5. correlation for potency of inhibiting luciferase and general anaesthesia
6. Probably combination of both theories
7. Anaesthetics affect membrane bound proteins because of lipophilicity

Question 19

How do GAs affect receptors

Answer 19

1. Gas potentiate inhibitory receptors
2. GAs block excitatory receptors
3. GAs affect ion channels - Reduced frequency of action potentials- inhibit sodium channels