Pharmacology 28 - General Anaesthesia Flashcards
List the clinically desirable traits of general anaesthesia
- Loss of consciousness
- Suppression of reflex responses (immobile)
Also…
- Relief of pain (analgesia)
- Muscle relaxation
- Amnesia
List the shared properties of general anaesthetic agents
- Loss of consciousness (low concentration - first thing that happens)
- Suppression of reflex responses (high concentration)
List the two classes of general anaesthetics
Gaseous/inhalation agents
- Nitrous oxide
- Diethyl ether
- Halothane
- Enflurane
Intravenous agents
- Propofol
- Etomidate
Describe the meyer/overton correlation
- Anaesthetic potency increases in direct proportion with oil/water partition coefficient
- More lipid soluble an anaesthetic became, the more potent it became
- Anaesthetics disrupt lipid membranes
(this is wrong)
List the problems of the meyer/overton correlation
- At relevant anaesthetic concentrations,
change in bilayer was minute - This would not alter the protein channel actions
Describe MOA of IV general anaesthetics
Change synaptic function
- Alter GABAa receptors (increase the activity)
- B3 subunit of GABAa activity suppression of reflex responses
- a5 subunit of GABAa activity linked to amnesia
Describe MOA of inhalational general anaesthetics
Altered synaptic function
- Stimulate GABAa in the brain/ glycine receptors in the spinal cord (not as effective action on GABAa as IV anaesthetics)
- Suppress reflex responses via a1 subunits, particularly in the glycine receptor
- Nitrous oxides block NMDA-type glutamate receptors
- Analgesic effects via suppression of neuronal nicotinic ACh receptors
Reduced neuronal excitability
- TREK (background leak) K+ channels stimulated, causing increased duration of hyperpolarisation via slowly leaking potassium. This is strongly linked to conscioussness
How do general anaesthetics cause loss of consciousness?
- Depress excitability of thalamocortical neurons
- Influence reticular activating neurons (reduced flow of information to the RAS results in sleep)
- Both of these neurones are GABAa receptor rich (inhibiting neuronal activity)
- TREK channels are heavily expressed in the RAS system (therefore, potentiation causes hyperpolarisation)
How do general anaesthetics suppress reflex responses?
- Depression of reflex pathways in the spinal cord
- Via GABAa and glycine receptors, which are in high density of the dorsal horn of the spinal cord (important in relay of painful stimuli to the brain)
How do general anaesthetics cause amnesia?
- Decreased synaptic transmission in the hippocampus/ amygdala
- a5 GABAa receptors in this region stimulated
Compare inhalation and intravenous anaesthetic
- Inhalation anaesthetics are rapidly eliminated once there is a low concentration into the lungs, and therefore can be used to rapidly control the depth of anaesthesia
- IV anaesthetics have fast induction, and cause less coughing and excitatory phenomena. Once injected, can only be excreted by the liver
- Both are combined for fast onset and fast removal
Which general anaesthetics are used for loss of consciousness and suppression of reflex responses?
- Induced using propofol (IV agent)
- Maintained using enflurane (inhalational agent - ensures quick recovery)
Which drugs are used for relief of pain, muscle relaxation and amnesia?
- Opioids for pain relief (iv. fentanyl)
- Neuromuscular blocking drugs for muscle relaxation (suxamethonium)
- Benzodiazepines for amnesia (iv midazolam)
Compare low blood:gas partition coefficient to high
- Molecules with low coefficient does not dissolve well into the blood, remains in the gaseous state. This allows very efficient transfer into the brain. Quickly excreted when concentration gradient is towards the lungs.
- High coefficient easily dissolves into blood, however it is more difficult to transfer into the brain. However, the transfer back into the lungs is also slower.
- Low blood gas partition coefficient is beneficial as it ensures the anaesthetic is quickly cleared from the body, and it is also fast acting.
