General Anaesthesia

Question 1

What anaesthetics can be inhaled?

Answer 1

-Ether
-Halothane
-Methoxyflurane
-Nitrous oxide

Question 2

What channels/receptors does anaesthetic work through?

Answer 2

-NMDA receptors
-Voltage-gated Na+ channels
-Two-pore domain K+ channels
-GABAa receptors

Question 3

What are the three main sub-types of Nicotinic receptors?

Answer 3

Muscle
Ganglionic
CNS

Question 4

What type of channels are nicotinic receptors?

Answer 4

Ligand-gated ion channels - mediate fast excitatory synaptic transmission

Question 5

What does Nicotine mimic at receptors?

Answer 5

Nicotine mimics the action of ACh, therefore acts as an agonist

Question 6

ACh receptor is selective and only cations can pass through, when opens sodium passes through into the cell causing a depolarisation, what does this cause?

Answer 6

Contraction of skeletal muscle

Question 7

What are examples of non-selective for nAChR?

Answer 7

ACh, Nicotine

Question 7

Inhibition of transmission at the NMJ as well as autonomic ganglia can be achieved by two mechanisms, what are they?

Answer 7

1) Competitive inhibition of the nicotinic receptor = non-depolarising block
2) Depolarising block

Question 7

What drug is selective for the muscle nAChRs?

Answer 7

Suxamethonium

Question 8

Give an example of a nAChR antagonist?

Answer 8

Tubocurarine

Question 8

What does Tubocurarine cause in a human?

Answer 8

Paralysis due to a small depolarisation, no action potential = no contraction occurs!

Question 8

Give an example of a nicotinic agonist?

Answer 8

Nicotine

Question 9

If you increase an agonist ACh what happens to inhibition which is competitive?

Answer 9

Increase of ACh = overcome inhibition

Question 10

What does persistent stimulation of nAChR cause?

Answer 10

Phase 2 block due to desensitisation of nAChRs

Question 11

Why isn’t Tubocurarine not used?

Answer 11

-Hypotension = ganglion block
-Release of histamine

Question 12

What is the duration of action of non-depolarising Pancuronium?

Answer 12

1 hour

Question 13

What is the duration of action of non-depolarising Vencuronium?

Answer 13

Intermediate duration of action

Question 14

What is the duration of action of non-depolarising Atracurium?

Answer 14

Intermediate duration of action

Question 15

What is the duration of action of non-depolarising Mivacurium?

Answer 15

Short duration of action (15 mins)

Question 16

What are depolarising blocking agents which act at the NMJ?

Answer 16

Suxamethonium

Question 17

If cholinesterase inhibitors are present ACh produces a ____________ at the NMJ?

Answer 17

Depolarising block

Question 18

Duration of action of Suxamethomium?

Answer 18

10 minutes as it is hydrolysed by plasma cholinesterase’s

Question 19

When would prolonged paralysis be a worry for a patient given Suxamethomium?

Answer 19

-Neonates
-Patient’s with liver disease
-Patients with genes lacking cholinesterase activity

Question 20

What does general anaesthetic affect?

Answer 20

The synaptic transmission and neuronal excitability

Question 21

What type of molecule is General Anaesthetic?

Answer 21

Small, lipid soluble molecules that readily get access to the brain by crossing the BBB

Question 22

Why can general anaesthetic cause Amnesia?

Answer 22

Hippocampal inhibition

Question 23

What is the reticular formation responsible for?

Answer 23

Wakefulness

Question 24

What is stage 1 of Anaesthesia?

Answer 24

Cortical inhibition. Voluntary eye movements still occur

Question 25

What is stage 2 of Anaesthesia?

Answer 25

Excitation/inhibition of reticular neurones, delirium, involuntary movements. Depression of reticular formation = involuntary movements.

Question 26

What is stage 3 of Anaesthesia?

Answer 26

Surgical anaesthesia. Gradual loss of respiration, reflexes, larynx + Pharynx decrease.

Question 27

What is stage 4 of Anaesthesia?

Answer 27

Overdose: reparatory and circulatory paralysis. No Cardiac Output. = death!

Question 28

Why do IV anaesthetics have a slow elimination from the body compared to inhalation anaesthetics?

Answer 28

-Resides in the lean tissues and fat for longer than the brain, viscera and blood. It builds up in the fat slowly = accumulates over time.

Question 29

What drug distributes into the fat and can cause a 'hangover' feeling?

Answer 29

Thiopental = not used!

Question 30

What type of kinetics does Thiopental display?

Answer 30

Saturation kinetics -Large doses or repeated doses can cause the plateau in the blood concentration to become more and more elevated as more drug accumlates in the body and the metabolism saturates = big disadvantage and why is it not used!

Question 31

As thiopental cannot be used, what drug can?

Answer 31

Propofol

Question 32

Is there a hangover phase with Propofol?

Answer 32

No, it is rapidly metabolised and has a limited cumulative effect

Question 33

What kinetics does Propofol display?

Answer 33

First order kinetics

Question 34

What are the unwanted affects of Propofol and Thiopental?

Answer 34

Cardiovascular and Respiratory depression

Question 35

What drug acts differently to other anaesthetics, as it increases blood pressure and heart rate but doesn't effect respiration?

Answer 35

Ketamine

Question 36

What is the onset of Ketamine?

Answer 36

1-2 mins, slower than other anaesthetics

Question 37

What are the unwanted side effects of Ketamine?

Answer 37

Can increase intracranial pressure, cause hallucinations, delirium during recovery.

Question 38

An ideal general anaesthetic should be readily controllable so that induction and recovery of anaesthesia can be rapid, true or false?

Answer 38

True

Question 39

What inhalation anaesthetics are used in the maintenance of anaesthesia?

Answer 39

Isofuorane, sevofluorane, desfulrane and nitrous oxide

Question 40

What events occur at induction of anaesthesia?

Answer 40

1) Anaesthetic equilibrates with the alveoli 2) Equilibration in the blood this should be RAPID; an ideal inhalation anaesthetic rapidly reaches the required arterial blood concentration and vice versa 3) Blood must become saturated for transfer to the tissues to occur --> SLOW

Question 41

What events occur at induction of anaesthesia SIMPLE?

Answer 41

Inhaled gas --> Alveoli (FAST) --> Blood --> Tissues (SLOW)

Question 42

Why do the kinetic behaviour of inhaled anaesthetics vary?

Answer 42

Solubility

Question 43

What are the two different solubility ratios?

Answer 43

Blood : gas coefficient Oil : gas coefficient (fat solubility)

Question 44

What kinetics determine the pharmacologic effect of the blood : gas coefficient?

Answer 44

Kinetics in arterial blood

Question 45

What is the Oil : gas partition coefficient

Answer 45

Transfer of anaesthetic between the blood and the tissues which affect the kinetics of equilibration

Question 46

What percent of anaesthetic after equilibrium will be in the fat?

Answer 46

95%

Question 47

What drug if used is extremely fat soluble and if a patient has a high fat content will have a slower recovery, with more chance of a hangover feeling?

Answer 47

Halothane

Question 48

What sedative premedication is used in surgery?

Answer 48

Benzodiazepine

Question 49

What IV anaesthetic is used for rapid induction?

Answer 49

Propofol

Question 50

What muscarinic antagonists are used to reduce bronchial and salivary secretions?

Answer 50

Atropine

Question 51

What analgesia is used for pain relief in surgery?

Answer 51

Morphine

Question 52

What physiological factors determine the induction and recovery of inhalation anaesthesia?

Answer 52

1) Alveolar ventilation rate 2) Cardiac output

Question 53

Explain Alveolar ventilation rate?

Answer 53

The greater the minute volume i.e, the amount of air that the patient breaths in 1 min (tidal volume x RR) = faster the equilibration

Question 54

Explain Cardiac output

Answer 54

Reduction of alveolar perfusion reduces alveolar absorption of the anaesthetic so speeds up induction

Question 55

If there is fast ventilation what does this allow for?

Answer 55

Quicker delivery to the alveolus

Question 56

What is minimal alveolar concentration used for?

Answer 56

A measure of potency for individualised GA

Question 57

What is the latest theory of the MOA of aesthetic?

Answer 57

Anaesthetic molecules bind to hydrophobic pockets within specific membrane protein targets

Question 58

How could GABAa be responsible for Anaesthesia?

Answer 58

GABAa receptors increase activity -Bind to hydrophobic pockets within different GABAa receptor subunits = v complex

Question 59

How could Glutamate receptors be responsible for anaesthesia?

Answer 59

Decrease in activity, eg, ketamine blocks NDMA receptors

Question 60

Can Voltage-gated sodium, potassium and calcium channels be responsible for anaesthesia?

Answer 60

Yes

Question 61

What is the effect of mutations at Ser270, Ala291 and Thr294 on GABAa receptors?

Answer 61

Decreased sensitivity to volatile anaesthetics but not to IV anaesthetics. The β subunit is important for the effects of both midazolam and propofol

Question 62

How does the β3(N265M) mutation affect the response to etomidate and neurosteroids?

Answer 62

NO response to neurosteroids, but the receptors still respond to general anesthetics like etomidate

Question 63

What is glutamate?

Answer 63

Major excitatory neurotransmitter in the CNS

Question 64

What drugs at the NMDA receptors?

Answer 64

Nitrous oxide, xenon, isoflurane

Question 65

Where can a mutation reduce alcohol-induced inhibition of glutamate receptors?

Answer 65

Domain 3 and 4

Question 66

Xenon and Isoflurane inhibit NMDA R by competing with what for its regulatory site?

Answer 66

Glycine

Question 67

Why are two pores essential for the role of a voltage-gated sodium and potassium channels?

Answer 67

To regulate resting membrane potentials

Question 68

What do mutations in TM3 result in?

Answer 68

Alters the response to general mutations, therefore we can see where GA's target and can be used to determine MOA.