Lecture 11 Flashcards
What are the main neurophysiological changes of anaesthesia?
- unconsciousness - loss of response to painful stimuli (analgesia) - loss of reflexes
General anaesthetics definition
Act in the brain to cause a loss of consciousness
What are general anaesthetics used for?
- operations (induction and maintenance) - experimentally
What are the types of general anaesthetics?
- inhalation - IV infusion
What were the first anaesthetics?
- ether - nitric oxide - chloroform - barbiturates - halothane - isoflurane
What is the structure=-activity relationship amongst general anaesthetics?
There is no strict structure-activity relationship
According to Guedel (1937) how many stages of anaesthesia are there?
Four
Describe Stage 1 of anaesthesia
- awake but drowsy- distorted perception - analgesia at the end - used for obstetrics (gas and air)
Describe Stage 2 of anaesthesia
- most dangerous phase - loss of consciousness - exaggerated reflexes - CSN stimulation= uncontrolled actions - irregular breathing and cardiac dysrhythmia
Describe Stage 3 of anaesthesia
- surgical anaesthesia (desirable state) - regular breathing - cough and vomit reflex depressed - initial pupil constriction before dilation - large skeletal muscles relax - BP drop
Describe Stage 4 of anaesthesia
- depression of medulla oblongata (respiratory centres) - further reduction in breathing, BP, pulse etc
Why are Guedel’s stages difficult to measure?
- depends on muscular movements= cannot detect clinical signs in paralysed patients - use of multiple agents obscures signs
How does the EEG monitor the depth of anaesthesia?
The amplitude of the high frequency components falls with an increase at lower frequencies
What are some factors worth considering when using EEG?
- frequency changes are agent dependent - various pathophysiological events affect EEG e.g. hypotension, hypoxia
What is the Patient State Index?
One method of assessing hypnosis and compares large numbers of EEGs during induction, maintenance and emergence
What is the Cerebral Function Monitor?
Semi-logarithmically signal that represents the overall electrocortical background activity of the brain
What is the Bispectral Index monitor?
Measures muscular and cortical activity using single, small flexible sensor applied to forehead and temporal region
What are the major theories of GA mechanisms of action?
- lipid theory - protein theory - combination of both (lipid/protein interface)
According to the lipid theory, how do GA work?
GA agents dissolve in membrane leading to - changes in bilayer thickness - changes in order parameters e.g. EC50 - changes in curvature elasticity, Changes affect proteins present in membrane
What are the pieces of evidence supporting the lipid theory?
- pressure reversal - no defined chemical structure of GAs - Meyer-Overton correlation
What is the Meyer-Overton correlation for anaesthetics?
As the olive oil:gas partition coefficient increases, the lower the potency of an anaesthetic drug is needed to induce anaesthesia e.g. nitrogen is a poor anaesthetic compared to chloroform
What are the issues of the lipid theory?
- stereoisomers= only one is active - new compounds do not fit MO correlation - increase carbon chain length= cut off effect (increasing solubility does not increase effectiveness) - non-immobilisers (similar structure no effect) - small temperature changes produce similar changes in membrane density and fluidity but do not produce anaesthesia
According to the protein theory, how do GAs work?
GAs bind to specific membrane proteins - GABA-A receptor (inhibitory) - 2 pore K+ channels (control resting potential) - NMDA receptor (excitatory)
What evidence supports the protein theory?
- mutate channels in animal models and either reduce/increase anaesthetic potency - manipulate binding pocket of receptors which GA acts upon