General Anaesthetics Flashcards
What is the triad of general Anaesthesia?
Need for unconsciousness
Need for analgesia
Need for muscle relaxation (loss of reflexes)
How do general anaesthetics work?
By depressing CNS activity
What is the general structure of inhalational anaesthetics?
Simple unreactive compounds
short chain molecules
no one chemical class
What is the lipid theory?
lipid solubility / water hydrophobicity is important in creating general anaesthesia as the concentration of the agent to immobilise tadpoles is inversely proportional to its lipid:water partition coefficient.
Explain the subsequent observations of the lipid theory?
Anaesthetic in cell membrane 0.05 mM of any agent of anaesthetic.
Anaesthesia occurs when volume of lipid expanded by 0.4%
High pressure reverses the anaesthesia
How do anaesthetic agents induce anaesthesia?
Agents act by volume expansion of lipid cell membrane and therefore increases fluidity of the cell membrane. This leads to the interference with conduction of nerve impulses.
What is the Protein Theory?
Uses the lipid theory and lipid solubility idea to explain that it is needed to provide access for proteins .
What evidence is there for the protein theory?
Cut-off phenomenon anaesthetic potency –> for homologous series of long chain anaesthetic compounds.
Increased chain length, increases lipid solubility but anaesthetic potency stops beyond an certain length. (size matters)
Stereo selectivity of anaesthetic potency is preserved with protein binding.
Anaesthetics may bind to hydrophobic pockets on proteins.
Why is stereo selectivity important?
Suggests that mirror images (optical isomers) may have one orientation that is more effective than the other if that orientation is the only one that can fit into its target site.
What are the molecular targets for general anaesthetics?
Ion channels (no single target)
GABAa receptors
K channel
What would anaesthetics targeted to GABAa receptors cause?
Increased inhibition
What would anaesthetics targeted to K channels cause?
Leads to activation and therefore decreased membrane excitability
What are some possible other anaesthetic targets?
Excitatory ligand gated channels NMDA receptor (glutamate), 5-HT, nACh Glycine
What are the major effects of anaesthetics on the CNS function?
Decreases neurotransmitter release Decrease post synaptic responsiveness Can depress activity in the entire CNS. Unconsciousness mediated by action at reticular formation in the midbrain Analgesia action at the thalamus.
What are the concentration dependent effects of anaesthetics in their order of lowest conc to highest?
Memory loss
Consciousness
movement
CVRS response
What is the narrow therapeutic window for anaesthetics?
2-3 x clinical dose leads to over dose
What is the 2nd stage of anaesthesia?
Delirium (induction phase):
Excitement, delirium, incoherent speech loss of consciousness, unresponsive to non-painful stimuli,
Dangerous phase:
muscle rigidity, spasmodic movements, cardiac arrhythmias, vomiting, choking
What is the 3rd phase of anaesthesia?
Surgical anaesthesia:
unresponsive to painful stimuli breathing regular abolition of reflexes muscle relaxation synchronised ElectroEncephaloGraph
What is the 4th stage of anaesthesia?
Medullary paralysis (overdose): pupillary dilation respiration/circulation ceases; EEG wanes death
What is the 1st stage of anaesthesia?
I ANALGESIA drowsiness; reflexes intact; still conscious
What makes a good anaesthetic agent?
Should be potent and fast acting
What is MAC?
Measure of anaesthetic potency in man
Minimal Alveolar Concentration:
the concentration of anaesthetic in the alveoli required to produce immobility in 50% of patients when exposed to a noxious stimulus
(variables are patient’s sex, height and weight)
How is MAC expressed?
expressed as % of inspired air (% v/v)
What is MAC inversely proportional to?
Lipid solubility
ie. The more soluble in lipids/oils, the lower the [anaesthetic] in the patients inspired air required to produce anaesthesia
