General anaesthesia Flashcards
What are the clinical objectives of anaesthesia?
- Loss of consciousness (at low conc)
- Suppression of reflex responses (at high conc)
- Analgesia (relief of pain)
- Muscle relaxation
- Amnesia
What other drugs are used to facilitate general anaesthesia?
- Opioid (e.g. IV fentanyl) - analgesia
- NM blocking drug (e.g. suxamethonium) for muscle relaxation
- Benzodiazepines - amnesia
What is the Meyer-Overton theory? What was assumed because of it?
- The potency of a G.A. increases in proportion to its oil:water partition coefficient
- Therefore – site of action of G.A.s was the lipid bilayer portion of nerve membranes
What is the problem with the Meyer-Overton theory
- At pharmacologically relevant concentrations, changes to the lipid bilayer are minute
- No-one could understand why is a change in the lipid bilayer would result in a dysfunctional membrane protein
How are the effects of GAs produced?
- Reduced neuronal activity
- Altered synaptic function
How do intravenous anaesthetics work?
E.g. etomidate, propofol
- Potentiate GABA A receptor function (altered synaptic function) – most abundant, fast inhibitory, ligand-gated ion channel in CNS
- B3 subunits present - suppress reflex responses
- a5 subunits - amnesia
How do inhaled anaesthetics work?
- Potentiate GABA A receptor function (and glycine receptors) - NOTE: glycine = inhibitory NT
- Show no subunit selectivity (altered synaptic function)
- a1 subunits present - suppression of reflex responses - Inhibits nAChRs (altered synaptic function) - analgesia
- Facilitate TREK (background leak) potassium channel opening (reduced neuronal excitability) - loss of consciousness
- Reduced NMDA receptor function (altered synaptic function) - nitrous oxide
Are intravenous or inhaled anaesthetics more potent?
Intravenous
What is unconsciousness?
Massive decrease in cortical activity
How do GAs cause loss of consciousness?
Depression of thalamocortical neurones caused by:
- Background leak K+ channels –> hyperpolarisation
- Enhanced GABA function
Results in disconnection of periphery from brain - thalamus acts as relay station for info btwn cortex + rest of CNS
Affect RAS - decreased firing of RAS, decreased level of arousal
How do GAs suppress reflex responses?
- Depression of reflex pathways in the dorsal horn of the spinal cord
- Anaesthetic agents that enhance GABA and glycine function in dorsal horn will decrease activity of dorsal pathways
- Disconnects brain from sensory info from periphery
How do GAs cause amnesia?
- At low dose
- Lots of GABA receptors in hippocampus w/a5 subunit
- Leads to decrease in synaptic transmission in hippocampus (memory formation)
How does route of administration influence the induction/maintenance of anaesthesia?
IV:
- Fast induction
- Difficult to control rate of excretion as injected straight into blood
Inhalation:
- Large amount of inhaled gas is excreted back into lungs
- Gives rapid control of depth of anaesthesia
What is the ideal blood:gas partition coefficient for inhaled anaesthetics?
LOW:
- The majority of the drug that crosses into the blood remains in gaseous form
- Can easily enter brain
- Also much easier to clear from brain if poorly dissolved in blood
If it’s high, majority of drug becomes liquid in blood and struggles to enter brain
How is anaesthesia usually induced?
Intravenous agent - propofol
