analgesia and anaesthesia

Question 1

5 clinically desirable features of general anaesthesia

Answer 1

loss of consciousness, suppression of reflex responses, analgesia, muscle relaxation, amnesia

Question 2

2 shared properties of all general anaesthetics

Answer 2

loss of consciousness at low concentration, suppression of reflex responses at high concentration

Question 3

2 classes of general anaesthetics

Answer 3

gaseous/inhalation, intravenous

Question 4

4 types of gaseous/inhalation general anaesthetics (do same thing but structurally all very different)

Answer 4

nitrous oxide, diethyl ether, halothane, enflurane

Question 5

2 types of intravenous general anaesthetics (do same thing but structurally all very different)

Answer 5

propofol, etomidate

Question 6

lipid theory of mechanism of action of general anaesthetics

Answer 6

Meyer/Overton correlation, so affect brain (oil/water partition coefficient, so as it becomes more lipid soluble, it becomes more potent)

Question 7

2 problems with lipid theory of mechanism of action of general anaesthetic

Answer 7

at relevant anaesthetic concentrations, change in lipid bilayer was minimal; wouldn’t change impact of membrane proteins

Question 8

2 molecular targets of general anaesthetics

Answer 8

reduce neuronal excitability, alter synaptic function

Question 9

intravenous general anaesthetic molecular target, and effect

Answer 9

GABA-A receptor, increasing effect (inhibitory neurotransmitter causing hyperpolarisation)

Question 10

intravenous general anaesthetic: what are B3 subunits linked to

Answer 10

suppression of reflex responses

Question 11

intravenous general anaesthetic: what are a5 subunits linked to

Answer 11

amnesia

Question 12

inhalational general anaesthetic molecular targets

Answer 12

GABA-A receptors (50% less effective than i.v. general anaesthetic), glycine receptors (more heavily expressed in spinal cord)

Question 13

inhalational general anaesthetic: what are a1 subunits linked to

Answer 13

suppression of reflex responses

Question 14

inhalational general anaesthetic: effect of nitrous oxide

Answer 14

blocks excitatory NMSA-type glutamate receptors, probably by competing with co-agonist glycine

Question 15

inhalational general anaesthetic: major effect of halogenic anaesthetics and how this is achieved

Answer 15

analgesic, by suppressing neuronal nicotinic ACh receptors

Question 16

inhalational general anaesthetic: describe halogenic effect of TREK (background leak) K+ channels on consciousness

Answer 16

directly affect nerve depolarisation, opening TREK and increasing K+ efflux, so hyperpolarisation duration is longer, affecting consciousness

Question 17

describe features of general anaesthetic mechanisms of action (molecular targets), including differences between i.v. and inhalational agents

Answer 17

all target a variety of receptors; i.v. agents significantly affect only GABA-A and glycine receptors; inhalational agents bind to more targets; all show significant or little potentiation/inhibition of GABA-A, glycine, nACh (muscle) and nACh (neuro) receptors

Question 18

how is loss of consciousness caused

Answer 18

affects reticular activating system (if this receives sensory input from cortex -> thalamus, causes consciousness): general anaesthetics depress excitability of thalamocortical neurones (stimulate GABA-A receptors), influencing reticular activating neurones (stimulate GABA-A receptors and heavily expressTREK channels), and causing loss of consciousness

Question 19

how is suppression of reflex responses caused

Answer 19

depression of reflex pathways in spinal cord (stimulate GABA-A receptors, preventing painful stimuli information being sent to brain via spinothalamic tract)

Question 20

how is amnesia caused

Answer 20

decreased synaptic transmission in hippocampus and amygdala (stimulate GABA-A receptors, particularly a5 subunits)

Question 21

describe transfer of general anaesthetic to brain (inhaled gas vs i.v.)

Answer 21

inhaled gas (air) to blood (water) to brain (lipid); for i.v., just blood (water) to brain (lipid)

Question 22

what does bood:gas partition coefficient describe

Answer 22

describes how gas will partition itself between 2 phases after equilibrium reached

Question 23

effect of higher blood:gas partition coefficient on transfer to brain and excretion

Answer 23

dissolves well in blood, so remains in blood and very inefficient transfer into brain; excreted very inefficiently via lungs

Question 24

effect of lower blood:gas partition coefficient on transfer to brain and excretion

Answer 24

ideal: doesn’t dissolve well in blood (remains in gaseous state in blood), allowing for very efficient transfer into brain; excreted very quickly as well via lungs

Question 25

inhaled vs intravenous anaesthetics, specifically elimination, induction; clinical outcome

Answer 25

inhaled: rapidly eliminated and rapid control of depth of anaesthesia; i.v.: fast induction, less coughing/excitatory phenomena (less airway irritation); therefore combine both

Question 26

what anaesthetic induces loss of consciousness and suppression of reflex responses

Answer 26

propofol (i.v.)

Question 27

what anaesthetic maintains loss of consciousness and suppression of reflex responses

Answer 27

enflurane (inhalational)

Question 28

what other drugs are used to relieve pain (analgesia)

Answer 28

opioid (e.g. i.v. fentanyl)

Question 29

what other drugs are used to cause muscle relaxation

Answer 29

neuromuscular blocking drugs (e.g. suxamethonium)

Question 30

what other drugs are used to induce amnesia

Answer 30

benzodiazepines e.g. i.v. midazolam