general anaesthesia

Question 1

what are the clinically desirable effects of general anaesthesia?

Answer 1

• loss of consciousness at LOW conc

- suppression of reflexes at HIGH conc

Question 2

what are the types of general anasethesia?

Answer 2

• separated into IV and inhalational types
• IV generally contains rings e.g. Propofol, Etomidate
• gaseous/inhalation types generally have halogens e.g. nitrous oxide, halothane, enflurane

Question 3

what is the main difference between inhalation and intravenous?

Answer 3

• inhalation not as powerful/selective as IV agents

- hits more targets but less

Question 4

what is the main idea for MoA of general anaesthesia?

Answer 4

molecular targets:

• altered synaptic function
• reduced neuronal excitability

Question 5

how do IV agents alter synaptic function?

Answer 5

• enhance GABAaR and enhance GABA
  subunits
  subunits targeted:
• beta 3: suppression of reflex responses (expressed in spinal cord)
• alpha 5: amnesia, expressed in hippocampus/amygdala

Question 6

what are the 2 types of inhalational agents?

Answer 6

• halogen inhalational agents

- nitrous oxide (non-halogen agents)

Question 7

how do halogen inhalational agents alter synaptic function?

Answer 7

• target GABAa/glycine receptors –> alpha 1 (suppression of reflex responses)
• dec. firing rate of neuronal NAChR

Question 8

how do non-halogen inhalational agents work?

Answer 8

block NMDA-type glutamate receptors

compete with co-agonist glycine

Question 9

describe how reduced neuronal excitability is achieved by inhalational agents

Answer 9

• enhance background leak of K channels

- cause hyperpolarisation of cells

Question 10

how do GAs cause loss of consciousness?

Answer 10

• depress thalamocortical neurones
• GAs hyperolarise thalamocortical neurones by activating TREK channels and by potentiating GABA Rs
• influence reticular activating neurones
• GAs will disrupt communication b/ RAF, cortex, thalamus

Question 11

How do GAs achieve suppression of reflex responses?

Answer 11

• dorsal horn: GABAaR are at a high density

- depression of reflex pathways in spinal cord

Question 12

how do GAs cause amnesia?

Answer 12

• via influences on GABAa alpha 5 subunits
• dec. synaptic transmission in hippocampus and amygdala
• alpha 5 subunits are at high conc. here opposed to rest of body

Question 13

describe the pharmacokinetics of IV agents

Answer 13

• time the IV agent is active is dependent on liver metabolism
• IV agents are injected directly into blood where they pass to brain

Question 14

describe the pharmacokinetics of inhalation agents

Answer 14

• inhaled agents pass from air to blood and to brain

- have an extra membrane to diffuse through

Question 15

what is the blood/gas partition coefficient?

Answer 15

how a gas will partition itself b/ 2 phases after an equilibrium has been reached

Question 16

what does a 1.36 blood gas partition coefficient mean?

Answer 16

if the gas is in eqm, the concentration in the blood will be x1.36 higher than in the conc. in alveoli

Question 17

what does a higher BG PC mean?

Answer 17

slower onset of action as a higher uptake of gas into blood

takes longer for brain and blood to reach an eqm

Question 18

what does a lower BG PC mean?

Answer 18

• faster onset of action
• drug is more lipophilic and hydrophobic so will not dissolve in blood well
• inhaled GAs are much easier to control as diffusion occurs very rapidly

Question 19

which form of GA is used for induction/ maintenance?

Answer 19

• IV used for induction

- inhalation is used for maintenance

Question 20

what are the positives of IV?

Answer 20

• fast induction

- less coughing/ excitatory phenomena

Question 21

in a clinical setting, what drug is used for loss of consciousness and suppression of reflex responses?

Answer 21

• loss of consciousness - induction = Propofol (IV)

- suppression of reflex responses - maintenance = Enflurance (inhalational)

Question 22

in surgery, what drugs are used for pain relief, muscle relaxation and amnesia?

Answer 22

• pain relief: opiods (IV fentanyl)
• muscle relaxation: NM-blockers (suxamethonium)
• benzodiazepines (IV midazolam)