L9 - General Anaesthetics Flashcards
What is the history of general anaesthetics?
1815 – Horace Wells – Nitrous oxide 1819 – William Morton – Ether - Volatile anaesthetic - Highly flammable 1820s – Warren – first use of Ether as a genera anaesthetic in surgery
What is chloroform used for?
Used to ease pain in labour – widely shown in media
Volatile anaesthetic
Highly flammable
Who discovered chloroform?
1842 - Robert Glover - began testing chloroform effects in dogs
Caused a loss of consciousness and response to painful stimuli
How are general anaesthetics divided into groups?
Depending on their route of administration
What are the two groups of general anaesthetics?
Chemical - Inhalation - Nitrous oxide – laughing gas - Intravenous - Halogenates hydrocarbons – isoflurane - Barbiturates – thiopental - Steroids – alphaxalone Physical - Low pressure - Hypothermia – shown in frogs
What is the lipid solubility of general anaesthetics?
They bind to hydrophobic domains of proteins
They are very lipophilic – enter lipid compartments easily
What is the graph plotted to show the effects of lipid solubility of general anaesthetic potency?
Minimum alveolar concentration plotted against oil:gas partition coefficient
- Amount of drug required to achieve anaesthesia in 50% of patients
Drugs with the highest oil:gas partition coefficient have the lowest minimum alveolar concentration
- Drugs with highest lipid solubility don’t induce anaesthesia as well
What are the two theory’s of the way anaesthetics work?
Membrane expansion
Increasing lipid/membrane fluidity
Both change activity of proteins within lipids impacting neuronal excitability
What factors agree with the lipid theory?
Obey the Meyer-overton rule – relationship between potency and oil:gas coefficient
Pressure effect – reducing atmospheric pressure increases anaesthetic potency
Diverse drug structures – only important factor is that they enter lipid compartment
What factors disagree with the lipid theory?
Temperature effect – lower temperatures reduce fluidity
Binding sites
Loss of activity with homologous series of lipophylic compounds
Increase GABAA receptor affinity for agonists
What is the protein theory?
Must be some specific receptors that the drugs bind to
General anaesthetics regulate activity of?
Neuronal ion channels
What are some example of general anaesthetics that interact with different ion channels?
Many increase action of GABA at GABAA receptors
Volatile ones
- Bind at interface of α and β subunits of GABAA
- Low concentrations activate two pore domain K channels
Intravenous ones bind only β subunit of GABAA
Ketamine and nitrous oxide block NMDA receptors
Where are the amino acids the anaesthetics interact with found?
Buried within the plasma membrane
All general anaethetic interaction with receptors effects?
Neuronal excitability
What is the effect of isoflurane?
Isoflurane depresses nerve terminal action potentials – measured using voltage clamp
The effects of isoflurane on presynaptic ion channels have been analyzed in?
Isolated rat neurohypophysial nerve terminals
Rat calyx of Held
What does isoflurane do in Rat calyx of Held?
Reversibly
- Reduces synaptic vesicle exocytosis
- Reduces action potential amplitude evoked by small current injections
What does isoflurane do in isolated rat neurohypophysial nerve?
Reversibly
- Blocks Na+ currents
- Blocks action potentials evoked by small current injections
What are the effects of low concentrations of general anaesthetics on neurotransmission?
Synaptic transmission in CNS decreased – decrease vesicle fusion
Reticular formation - loss of consciousness
Hippocampus – short term amnesia
Thalamic sensory relay nuclei parts of cortex – analgesia
Some volatile anaesthetics inhibit spinal reflexes
What are the effects of high concentrations of general anaesthetics on neurotransmission?
All brain functions affected - loss of motor control, reflexes, respiration, autonomic regulation
In absence of artificial respiration - death
What are the 4 stages of anaesthesia?
- Analgesia – reduced responsiveness to painful stimuli
- Excitement – exaggerated reflex responses – dangerous phase
- Surgical Anaesthesia
- Unconsciousness
- Loss of response to painful stimulation
- Loss of reflexes
- Short-term amnesia - Medullary Paralysis - loss of cardiovascular reflexes and respiratory paralysis – death
What are the ideal conditions of anaesthesia?
Rapid induction and loss of consciousness
Analgesia
Muscle relaxation (common to give neuromuscular blockers as well)
Rapid recovery
Avoid stages 2 and 4
Why is anaesthesia hard to control in overweight people?
The general anaesthetic is absorbed into fat rather than the CNS
