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
What is the criteria for identifying relevant anaesthetic protein targets?
- reversibly alters target function at clinically relevant concentrations (MAC) - protein target expressed in appropriate anatomical location in brain/spinal cord - stereo selective effects in-vivo parallel actions on the target in vitro - target exhibits appropriate sensitivity and insensitivity to model and non-anaesthetic compounds
What are the brain areas associated with the sleep-wakefulness cycle?
- ventrolateral pre-optic nuclei - tuberomamalary nuclei - locus coeruleus - laterodorsal tegmental nuclei - pedunculopontine tegmental nuclei - basal forebrain
What are the properties of an ideal anaesthetic?
- rapid action and recovery - minimal irritant properties - miscible with air/oxygen (no risk of explosion) - analgesic - muscle relaxant
What is the minimum alveolar concentration?
Alveolar partial pressure of an inhaled anaesthetic which prevents movement in response to a standard noxious stimulus in 50% of patients
Do we want a high or a low MAC?
Low MAC- require less anaesthetic in order to induce anaesthesia
What does a greater solubility in blood mean for anaesthetics?
- blood acts as a reservoir - reduced rate of rise of alveolar partial pressure - reduced rate of rise of brain partial pressure - slower rate of anaesthesia onset
What does the blood/gas solubility co-efficient determine?
How a general anaesthetic distributes itself in the blood - low coefficient= rapid onset and offset e.g. nitrous oxide - high coefficient= slower onset and offset e.g. ether
What is the rate of equilibration of inhalation anaesthetics in lean tissues e.g. brain?
- rapid equilibration - fast perfusion - small partition coefficient
What is the rate of equilibration of inhalation anaesthetics in fat?
- slow equilibration - slow perfusion - large partition coefficient
Why is there slower recovery from longer operations?
Longer operations give more time for anaesthetic to equilibrate in fat compared to muscle= long time to remove from body
Does halothane equilibrate more quickly in vessel-rich or vessel-poor tissue?
Vessel-rich
Would a drug with fast induction have a long or short recovery?
Short
What determines the rate of recovery from an anaesthetic?
Rate of reduction of alveolar partial pressure
What are factors that decrease the length of recovery?
- reduction of the inspired concentration - high alveolar ventilation - low blood gas solubility - short duration of anaesthesia (little anaesthetic dissolved in low perfusion tissue_
What are examples of intravenous anaesthetics?
- propofol - thiopental - etomidate - ketamine
Propofol as an intravenous anaesthetic
- potentiates GABA-A receptors - induction agent - mood altering and antiemetic properties - maintenance agent- total intravenous anaesthesia with an opioid - apnoea (respiratory depression) and fall in blood pressure
Thiopental as an intravenous anaesthetic
- potentiates GABA-A receptors- barbiturate that induces anaesthesia - lipid soluble and crosses BBB - slowly metabolised by liver- sedative effects can persist - poor analgesic and muscle relaxant - cardiorespiratory depression
Etomidate as an intravenous anaesthetic
- anaesthesia induction - rapid recovery with no hangover
Ketamine as an intravenous anaesthetic
- hallucinations - abuse potential and dependence - peadiatric anaesthesia - useful for repeated administration - novel treatment for depression
What are examples of inhalation anaesthetics?
- halothane - isoflurane - sevoflurane - desflurane
Effects of inhalation anaesthetics
- fast loss of consciousness, smooth induction and recovery (but IV is preferred) - dose dependent lowering of mean arterial pressure - depress respiration leading to the increase in arterial CO2 level and impairment of O2 exchange - brain metabolic rate decreases even though cerebral blood flow increases - relaxation of skeletal muscles by a central action
Halothane as an inhalation anaesthetic
- potent, smooth induction, non-irritant - moderate muscle relaxation for abdominal surgery - severe hepatotoxicity
Isoflurane as an inhalation anaesthetic
- less potent than halothane - BP fall - depresses respiration - muscle relaxation and potentiate muscle relaxants - less of a risk of hepatotoxicity than halothane
Nitrous oxide as a general anaesthetic
- maintains anaesthesia and analgesia - low potency for anaesthesia alone so used with other agents - obstetrics (gas and air) for labour
Neuromuscular blocking drugs as general anaesthetics
- light levels of anaesthesia - relax tracheal tube for intubation- need assisted respiration
Examples of neuromuscular blocking drugs
- atracurium - cisatracurium - mivacurium - suxamethonium
What are other types of medication used clinically?
- proton pump inhibitors (prevent acid aspiration) - muscarinic antagonists (dry secretions) - sedatives (benzodiazepines) - non-opioid analgesic (NSAIDs) - opioid analgesics
