General Anaesthesia Flashcards
What anaesthetics can be inhaled?
-Ether
-Halothane
-Methoxyflurane
-Nitrous oxide
What channels/receptors does anaesthetic work through?
-NMDA receptors
-Voltage-gated Na+ channels
-Two-pore domain K+ channels
-GABAa receptors
What are the three main sub-types of Nicotinic receptors?
Muscle
Ganglionic
CNS
What type of channels are nicotinic receptors?
Ligand-gated ion channels - mediate fast excitatory synaptic transmission
What does Nicotine mimic at receptors?
Nicotine mimics the action of ACh, therefore acts as an agonist
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?
Contraction of skeletal muscle
What are examples of non-selective for nAChR?
ACh, Nicotine
Inhibition of transmission at the NMJ as well as autonomic ganglia can be achieved by two mechanisms, what are they?
1) Competitive inhibition of the nicotinic receptor = non-depolarising block
2) Depolarising block
What drug is selective for the muscle nAChRs?
Suxamethonium
Give an example of a nAChR antagonist?
Tubocurarine
What does Tubocurarine cause in a human?
Paralysis due to a small depolarisation, no action potential = no contraction occurs!
Give an example of a nicotinic agonist?
Nicotine
If you increase an agonist ACh what happens to inhibition which is competitive?
Increase of ACh = overcome inhibition
What does persistent stimulation of nAChR cause?
Phase 2 block due to desensitisation of nAChRs
Why isn’t Tubocurarine not used?
-Hypotension = ganglion block
-Release of histamine
What is the duration of action of non-depolarising Pancuronium?
1 hour
What is the duration of action of non-depolarising Vencuronium?
Intermediate duration of action
What is the duration of action of non-depolarising Atracurium?
Intermediate duration of action
What is the duration of action of non-depolarising Mivacurium?
Short duration of action (15 mins)
What are depolarising blocking agents which act at the NMJ?
Suxamethonium
If cholinesterase inhibitors are present ACh produces a ____________ at the NMJ?
Depolarising block
Duration of action of Suxamethomium?
10 minutes as it is hydrolysed by plasma cholinesterase’s
When would prolonged paralysis be a worry for a patient given Suxamethomium?
-Neonates
-Patient’s with liver disease
-Patients with genes lacking cholinesterase activity
What does general anaesthetic affect?
The synaptic transmission and neuronal excitability
What type of molecule is General Anaesthetic?
Small, lipid soluble molecules that readily get access to the brain by crossing the BBB
Why can general anaesthetic cause Amnesia?
Hippocampal inhibition
What is the reticular formation responsible for?
Wakefulness
What is stage 1 of Anaesthesia?
Cortical inhibition. Voluntary eye movements still occur
What is stage 2 of Anaesthesia?
Excitation/inhibition of reticular neurones, delirium, involuntary movements.
Depression of reticular formation = involuntary movements.
What is stage 3 of Anaesthesia?
Surgical anaesthesia. Gradual loss of respiration, reflexes, larynx + Pharynx decrease.
What is stage 4 of Anaesthesia?
Overdose: reparatory and circulatory paralysis. No Cardiac Output. = death!
Why do IV anaesthetics have a slow elimination from the body compared to inhalation anaesthetics?
-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.
What drug distributes into the fat and can cause a ‘hangover’ feeling?
Thiopental = not used!
What type of kinetics does Thiopental display?
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!
As thiopental cannot be used, what drug can?
Propofol
Is there a hangover phase with Propofol?
No, it is rapidly metabolised and has a limited cumulative effect
What kinetics does Propofol display?
First order kinetics
What are the unwanted affects of Propofol and Thiopental?
Cardiovascular and Respiratory depression
What drug acts differently to other anaesthetics, as it increases blood pressure and heart rate but doesn’t effect respiration?
Ketamine
What is the onset of Ketamine?
1-2 mins, slower than other anaesthetics
What are the unwanted side effects of Ketamine?
Can increase intracranial pressure, cause hallucinations, delirium during recovery.
An ideal general anaesthetic should be readily controllable so that induction and recovery of anaesthesia can be rapid, true or false?
True
What inhalation anaesthetics are used in the maintenance of anaesthesia?
Isofuorane, sevofluorane, desfulrane and nitrous oxide
What events occur at induction of anaesthesia?
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
What events occur at induction of anaesthesia SIMPLE?
Inhaled gas –> Alveoli (FAST) –> Blood –> Tissues (SLOW)
Why do the kinetic behaviour of inhaled anaesthetics vary?
Solubility
What are the two different solubility ratios?
Blood : gas coefficient
Oil : gas coefficient (fat solubility)
What kinetics determine the pharmacologic effect of the blood : gas coefficient?
Kinetics in arterial blood
What is the Oil : gas partition coefficient
Transfer of anaesthetic between the blood and the tissues which affect the kinetics of equilibration
What percent of anaesthetic after equilibrium will be in the fat?
95%
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?
Halothane
What sedative premedication is used in surgery?
Benzodiazepine
What IV anaesthetic is used for rapid induction?
Propofol
What muscarinic antagonists are used to reduce bronchial and salivary secretions?
Atropine
What analgesia is used for pain relief in surgery?
Morphine
What physiological factors determine the induction and recovery of inhalation anaesthesia?
1) Alveolar ventilation rate
2) Cardiac output
Explain Alveolar ventilation rate?
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
Explain Cardiac output
Reduction of alveolar perfusion reduces alveolar absorption of the anaesthetic so speeds up induction
If there is fast ventilation what does this allow for?
Quicker delivery to the alveolus
What is minimal alveolar concentration used for?
A measure of potency for individualised GA
What is the latest theory of the MOA of aesthetic?
Anaesthetic molecules bind to hydrophobic pockets within specific membrane protein targets
How could GABAa be responsible for Anaesthesia?
GABAa receptors increase activity
-Bind to hydrophobic pockets within different GABAa receptor subunits = v complex
How could Glutamate receptors be responsible for anaesthesia?
Decrease in activity, eg, ketamine blocks NDMA receptors
Can Voltage-gated sodium, potassium and calcium channels be responsible for anaesthesia?
Yes
What is the effect of mutations at Ser270, Ala291 and Thr294 on GABAa receptors?
Decreased sensitivity to volatile anaesthetics but not to IV anaesthetics.
The β subunit is important for the effects of both midazolam and propofol
How does the β3(N265M) mutation affect the response to etomidate and neurosteroids?
NO response to neurosteroids, but the receptors still respond to general anesthetics like etomidate
What is glutamate?
Major excitatory neurotransmitter in the CNS
What drugs at the NMDA receptors?
Nitrous oxide, xenon, isoflurane
Where can a mutation reduce alcohol-induced inhibition of glutamate receptors?
Domain 3 and 4
Xenon and Isoflurane inhibit NMDA R by competing with what for its regulatory site?
Glycine
Why are two pores essential for the role of a voltage-gated sodium and potassium channels?
To regulate resting membrane potentials
What do mutations in TM3 result in?
Alters the response to general mutations, therefore we can see where GA’s target and can be used to determine MOA.
