General anaesthetics Flashcards
How on a graph is lipid solubility of a anaesthetic measured
Y - axis - MAC - anaesthetic potency in humans - minimal alveolar concentration required to remove a response in 50% of patients upon incision
X axis - Oil:gas partition coefficient - Predicts the ease of partition into membrane lipids
As MAC goes down the oil:gas coefficient goes up - the lower the MAC value the more potent the anaesthetic , higher solubility
What were the lipid theories used to explain anaesthetic function
- Volume expansion of the plasma membrane - CNS function altered
- Increased lipid fluidity
Anaesthesia results from an alteration of membrane function
What is the current theory of anaesthetic action
Protein theory - Different GAs target different types of proteins found on neurons
They target different ion channels in the neuron membrane
Binding sites for GAs on the ion channels are often varied in their hydrophobic domain
What is the main target for GAs
Potentiation of the GABAa receptor - ligand gated chloride channel
Which interfaces to volatile GAs bind to
Alpha and Beta subunits
What interfaces do intravenous GAs bind to
Only the Beta subunit
What receptor is blocked by ketamine
NMDA (glutamate) receptors
What do low concentrations of volatile GAs activate
two pore domain K channels - Modulate neuronal activity - reduce membrane excitability - analgesia, hypnosis
What are the effects of GAs on neurotransmission at the cellular level
- Enhance tonic inhibition (enhancing GABA), reduce excitation (open K channels) and inhibit excitatory synaptic transmission (depressing transmitter release and ligand gated ion channels)
What are the four stages of anaesthesia
- Analgesia - loss of pain
- Excitement - dangerous stage - exaggerated reflexes, imbalance between inhibitory and excitatory neurotransmission
- Surgical anaesthesia - Unconscious, loss of reflexes, loss of response to pain, short term amnesia
- Medullary paralysis - Loss of cardiovascular reflexes and respiratory paralysis
Which two stages of anaesthesia are wished to be avoided
2 and 4
Give advantages of intravenous anaesthetics
Speed of conduction is very fast (20-30 seconds)
Easy to administer
Give advantages of using the drug propofol
Rapid metabolism - good for the induction of anaesthesia
T0.5 = 2.4mins - rapid recovery and les hangover - can be used as a day case surgery
What are general disadvantages of using intravenous GAs
Pain at the site of injection, complex pharmacokinetics
What are the disadvantages of thiopental
High lipid solubility so rapid induction - BUT - short duration of action due to redistribution and hangover due to accumulation in fat -
Respiratory depression and CV depression 9i4
What is the action of ketamine
Dissociative anaesthesia, sensory loss, analgesia, amnesia, no complete loss of consciousness or respiratory depression, CV excitement
What are inhaled anaesthetics advantages for use
Useful for maintaining anaesthesia
Only route of entry and exit is via the lungs
Small lipid molecules - so cross the alveolar membrane easily
How is the speed of induction and recovery modified
Properties of the anaesthesia - blood:gas coefficient (solubility in blood) Oil:gas coefficient (solubility in fat) Physiological properties Cardiac output Alveolar ventilation rate
How can body tissue be split into compartments and how do they differ
Lean tissue (brain) - havre large blood flow and low partition coefficient for anaesthetics therefore equilibrate rapidly with the blood Fat tissues - have a small perfusion and large partition coefficient - Act as a reservoir of drug during the recovery phase
