General anaesthetics

Question 1

What are the types of general anaesthetics?

Answer 1

1) Inhalation anaesthitics

2) IV anaesthetics

Question 2

Name some examples

Answer 2

1) halothane, iso/des/seve-flurane, enflurane - often combined with nitrous oxide (N2O)
2) thiopentone, propfol, etomidate

Question 3

What chemical factors increase the potency of an anaesthetic?

Answer 3

unsaturation, halogen-content, ether groups

hydrophilic groups reduce potency

Question 4

What is the ED(50)?

Answer 4

The effective dose in 50% of individuals (50% of individuals have a tolerance less than this dose).

Question 5

Anaesthetic potency

Answer 5

1/ED(50)

Question 6

What is potency proportional to?

Answer 6

oil:water partition coefficient

Question 7

What sort of domains do anaesthetics bind to?

Answer 7

Hydrophobic domains of proteins

Question 8

What receptor types do IV agents (propofil, thiopentone, etomidate) activate?

Answer 8

GABA-a receptors

Question 9

How do they work?

Answer 9

They enhance the effect of GABA at GABA-a Rs

[synaptic and extrasyaptic currents?]

Question 10

What sort of channels do inhalation anaesthetics affect?

Answer 10

Two-pore potassium channels, e.g. TREK-1 and TASK.

These enhance potassium and cause hyperpolarisation, and thus decrease activity.

Question 11

What are NMDA-Rs affected by?

Answer 11

Ketamine, N2O, Xenon (role is unclear)

Question 12

What are the stages of anaesthesia?

Answer 12

1) analgesic (not all anaesthetics under the anaesthetic conc are analgesic)
2) delerium, enthusiasm, some irregular respiration - alcohol!
3) surgical anaesthesia - loss of conscoiousness - eyes roll and are fixed there. Corneal and laryngeal reflexes are lost; pupils dilate and light reflex is lost; shallow abdominal respiration.
4) respiratory paralysis - death (severe brainstem depression)

Question 13

What is MAC?

Answer 13

Minimum alveolar concentraion - essentially an EC50 - conc in air giving a safe level of anaesthsia (gives a lack of pain stimulus) in 50% of individuals

Question 14

Induction of anaesthesia using halothane. What are the pros and cons of this?

Answer 14

MAC = 0.75, lambda (blood/air coefficient)=2.3, so product of these is 1.7

When breathed in, a high concentraion of the drug ends up in the lungs, this then diffuses out into the blood, and the concentration is low once again - rise and fall (not stable) results in a lot of wasted drug.

Question 15

Low blood-solubility anaesthetics vs halothane

Answer 15

blood/gas partition coefficient is lower so variation from safe anaesthetic concentration is minimal.

Less soluble agents have a higher MAC so a higher conc in inspired air - faster at producing desired anaesthesia.

Question 16

What are 2 important properties of general anaesthetics?

Answer 16

A low MAC (high potency)

A low blood solubility (rapid onset and offset)

Question 17

How will obese patients be affected by anaesthetics?

Answer 17

Anaesthetics have a high lipid solubility, so a higher proportion of body fat results in slower recovery from the anaesthetic and therefore a prolonged hangover effect.

Question 18

Any toxic effects?

Answer 18

Some cardiac dysrhythmias. Liver damage from over-use of halothane.
Nausea and vomitting post-surgery (usually to remove metabolites).

Question 19

What are TIVAs?

Answer 19

Total intravenous anaesthetics. e.g. propofol.

Question 20

What IV anaesthetics are used for induction of anaesthesia?

Answer 20

Thiopentone - short acting, <15 mins - not analgesic, causes respiratory depression

Question 21

Give an example of a dissociative anaesthetic.

Answer 21

Ketamine. Incomplete anaesthesia.
Pros - analgesic properties, used in paediatric anaesthesia (children rarely get hallucinations), chance of overdose is low so is administered in combat zones/after trauma
Cons - hallucinations! Used on animals, slow recovery, if abused can cause bladder damage

Question 22

Name 5 examples of other drugs used with anaesthetics.

Answer 22

Local anaesthesia - e.g. lignocaine
Pre-med
Maintenance - inhalation anaesthetics used for this - can control dose well
Induction - e.g. propofol (IV)
Muscle relaxant - reduces level of anaesthesia needed - NMJ blockers