Lecture 11. General Anaesthetics Flashcards
What are the three main neurophysiological changes caused by anaesthesia?
Unconsciousness
Loss of response to painful stimuli (analgesia)
Loss of reflexes
What are local anaesthetics?
Act locally to block nerve conduction/action potentials by blocking voltage gated Na⁺ channels (eg lignocaine)
What are general anaesthetics?
Act in the brain to cause a loss of consciousness
What are general anaesthetics used for?
Operations (induction and maintenance) and experimentally
What are the two major types of general anaesthetic (GA)?
Inhalation (gases)
IV infusion
What was the first anaesthetic used and why was it not very good?
Alcohol, required huge amounts to have an effect and the patient does not come around very quickly
What were the first “true” anaesthetics and when were they first used used?
Ether, 1846
Nitric oxide (laughing gas), discovered as GA in 1844
Chloroform
When were barbiturates first used?
~1903
When was the archetypal anaesthetic halothane first used?
1960s
When were derivatives of halothane first used (such as isoflurane)?
1970s
What was opium used as?
Analgesic
Why do general anaesthetics have a wide variety of chemical structures?
Because there is no strict structure-activity relationship
What is stage 3 of anaesthesia (surgical anaesthesia)?
Regular breathing
Cough and vomit reflex depressed
Pupils initially constrict but as get deeper into stage pupils dilate
Large skeletal muscles relax
Drop in blood pressure
Corneal reflex disappears
What is stage 1 of anaesthesia?
Still awake but drowsy
Distorted perception
At end of stage: analgesia
Useful stage for obstetrics (gas and air)
What is stage 2 of anaesthesia (excitation)?
Loss of consciousness
Inhibition depressed before motor centres: exaggerated reflexes (vomiting)
Stimulation of CNS: uncontrolled movements, vocalisations
Loss of temperature control: flushing of skin
Irregular breathing and cardiac dysrhythmia
Dangerous phase: move through as quick as possible
What happens when more anaesthetic is given to a patient in stage 3?
Breathing become shallow
Precipitous fall in blood pressure
Feeble pulse
Pupils widely dilated
What happens in stage 4 of anaesthesia (deeper still)?
No ventilation due to depression of medulla oblongata (respiratory centres)
Why are the stages of anaesthesia difficult to measure?
Most of the signs of Guedel’s classification depend upon muscular movements (including respiratory muscles), and thus with paralysed patients’ clinical signs are no longer detectable
Use of multiple agents obscures signs
Stages of anaesthesia measured in this way are often thought of as obsolete
Can the electroencephalogram (EEG) be used to monitor the depth of anaesthesia?
As anaesthesia deepens the amplitude of the high frequency components of EEG falls with an increase at the lower frequencies
What problems may arise from trying to read the depth of anaesthesia with EEG?
The changes are agent dependent
Various events pathophysiological also affect the EEG (e.g. hypotension, hypoxia, hypercapnia)
What is the patent state index?
One EEG method of assessing hypnosis and was developed by comparing large numbers of EEGs during induction, maintenance and emergence
What is cerebral motor function (CFM)?
Signal is filtered, semi-logarithmically compressed, and rectified. Represents the overall electrocortical background activity of the brain
What is the bispectrial index (BIS)
Statistically based, empirically derived complex parameter
What are the three major theories behind the mechanisms of action of GA?
Lipid theory (outdated)
Protein theory
Combination of both (lipid/protein interface)
What is lipid theory?
GA agents dissolve in membrane leading to:
changes in bilayer thickness
changes in order parameters
changes in curvature elasticity
These effects may then effect the proteins present in membrane
What are the 3 pieces of evidence that supported lipid theory?
Pressure reversal
No defined chemical structure of GAs
Meyer-Overton correlation
What were the problems with lipid theory?
Stereo isomers
New compounds do not fit Meyer-Overton correlation
Increase carbon chain length (cut off effect) (too many carbons make compound more lipid soluble but no an anaesthetic)
Non-immobilisers
Small increases in temperature produce similar changes in membrane density and fluidity but do not produce anaesthesia
Similar correlation with partition of GAs into protein
What is protein theory?
General anaesthetics bind to specific membrane proteins
What are the 3 major proteins implicated by protein theory?
GABAA receptor (inhibitory)
2 pore K⁺ channels (control resting potential)
NMDA receptor (excitatory)
What evidence is there for protein theory?
Mutating channels in animal models wither reduces or increases anaesthetic potency
What are 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 sites of the brain should the anaesthetic drug be acting upon?
Sites involved in the sleep-wakefulness cycle
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
No single anaesthetic has these properties so use a combination of agents
What is Minimum Alveolar Concentration (MAC)?
Alveolar partial pressure of an inhaled anaesthetic, which prevents movement in response to a standard noxious stimulus in 50% of patients
What is anaesthetic potency defined by?
Minimum Alveolar Concentration (MAC)
What percentage of inhaled air has to contain methoxyflurane in order to prevent a stimulus in 50% of people?
0.16% (very potent)
What determines the solubility of a drug in the blood?
Blood/gas coefficient
What effect does a greater solubility in the blood have on anaesthesia onest?
Slower rate of anaesthesia onset
What happens when an anaesthetic arrives at lean tissue (eg brain)?
Fast perfusion
Small partition coefficient
Rapid equilibration
What happens when an anaesthetic arrives at fat?
Slow perfusion
Large partition coefficient
Slow equilibration
Why is recovery time longer after a long operation?
Have to wait for all the anaesthetic to exit the fat
What determines the rate of recovery from the anaesthetic?
Rate of reduction of alveolar partial pressure
How are inhaled anaesthetics mainly eliminated from the body?
Ventilation through the lungs
What factors 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 is propofol?
Introvenous anaesthetic
Potentiates GABAA receptor responses
Used as an induction agent
Patient wakes up in 5-10 minutes
What is thiopental?
Introvenus anaesthetic
Barbiturate used to induce anaesthesia
Potentiates GABAA receptors
Highly lipid soluble
Crosses blood brain barrier extremely rapidly and produces unconsciousness in 20-30 seconds
Consciousness returns in 10 to 20 minutes due to the rapid redistribution to other tissues
What is etomidate?
Introvenous anaesthetic
Induction of anaesthesia
Rapid recovery with no hangover effect
What is ketamine?
Rarely used (hallucinations)
Abuse potential and dependence
It is used for paediatric anaesthesia
Useful if repeated administration is required
Novel treatment for depression
What are the most commonly used inhaled anaesthetics?
Halothane, isoflurane, sevoflurane and desflurane
What are all inhalation anaesthetics?
Volatile liquids, produce fast loss of consciousness, smooth induction and recovery, although induction with IV agents often preferred
How do inhalation anaesthetics function?
Produce dose dependent lowering of the mean arterial pressure by their combined action on myocardial function and on peripheral vascular resistance
What is halothane?
Potent
Smooth induction
Non-irritant (seldom induces coughing/breath holding
Moderate muscle relaxation (need muscle relaxants for abdominal surgery)
Not widely used as associated with severe hepatotoxicity
What is isoflurane?
Less potent than halothane
Fall in BP
Depresses respiration
Muscle relaxation and potentiate muscle relaxants
May cause hepatotoxicity but risk much less than halothane
What is nitrous oxide?
Used for maintenance of anaesthesia and for analgesia
Used in 50-66 % with Oxygen
Too low potency for anaesthesia alone used with other agents
Used in obstetrics (gas and air) for pain during labour
What are neuromuscular blocking drugs (muscle relaxants)?
Enable lighter levels of anaesthesia
Relax vocal cords (tracheal tube)
Should have respiration assisted/controlled until drug is inactivated
Atracurium, Cisatracurium, mivacurium etc
Suxamethonium: rapid onset, short duration (2-6 minutes), useful for tracheal intubation
What other medication is given to patients if they’ve had an operation?
Proton pump inhibitor (omeprazole, prevent acid aspiration)
Muscarinic antagonists (to dry secretions)
Sedatives (benzodiazepines)
What other medication is given to patients if they’ve had an operation and are experiencing pain?
Non-opioid analgesics (NSAIDs)
Opioid analgesics
