General Anaesthetics Flashcards
When were general anaesthetics first discovered?
In the mid 1800s, NO was observed to have anaesthetic effects.
Ether was also discovered- reduced pain and sometimes cause unconsciousness.
Chloroform was also discovered and given to women in labour.
What did all the early anaesthetics have in common?
They were all small molecules, and in the case of ether and chloroform, they were both volatile and highly flammable.
What are the two broad classes of GAs?
Inhalation e.g. NO
Intravenous e.g. halogenated hydrocarbons such as isoflurane
In what physical ways can you dampen the pain response?
Low pressure or hypothermia.
They are non analgesic, they just lose the ability to respond to the pain.
What is the relationship between drugs and their oil:gas partition coefficient?
The potency of the drug is positively correlated with this i.e. the more soluble the drug in the membrane, the more potent the drug is.
What is the minimal alveolar concentration.
The MAC is the lowest concentration of drug needed to induce anaesthesia in 50% of the patients.
Drugs which have a very low MAC (more potent) have the highest levels of lipid solubility.
What is the lipid theory?
Molecules exert their action by entering the membrane- this expanded the membrane and thus altered the properties of the neurons, allowing them to enter a state of anaesthesia.
Another idea- it increased lipid fluidity- this would affect the fluidity of the membrane and thus how proteins acted in it- there would therefore be some effect on neuronal excitability.
How was the lipid theory backed up?
It obeyed the Meyer Overton rule (oil:gas coefficient).
If you decrease pressure- increase membrane fluidity and thus excitability. Low pressure does reduce pain perception.
All of the drugs tested up until this point were diverse in their structures so the only thing that should have mattered was their ability to fit into the membrane.
How was the lipid theory counteracted?
Temperature- if you decrease the temperature, should see a decrease in fluidity of the membrane and thus no anaesthetic effect- this was not true..
Binding site- with certain drugs there is saturation, so this indicates that that there is a specific receptor.
Just creating a drug which enters the lipid membrane was not sufficient to induce anaesthesia.
What is the protein theory?
Drugs are interacting with specific proteins in the lipid membrane- this was altering their function and thus neuronal function.
How do GAs work?
The regulate the activity of ion channels, This was discovered through mutating receptors and observing the effects of the GAs.
What is the relationship between GABA and GAs.
Many GAs increase the activity of GABAa receptors. They bind to the alpha and beta subunits of the receptors.
Binding site for the drug is in the lipid membrane which explains why lipid solubility is important.
What is the relationship between TwoPoreDomain K channels and GAs?
Low concentrations of GAs activate these channels- hyperpolarise the membrane and make it harder to fire an AP.
What effect do ketamine and NO have?
Block NMDA receptors
What effect does isofulrane have?
Decrease Na current across the membrane. The size of APs is thus reduced.
What impact do GAs have on vesicles?
Inhibit fusion with the membrane and thus less NT is released- less likely to fire APs.
What affect do GAs have on neurotransmission?
Synaptic transmission in the CNS is decreased (not the PNS)- decreases vesicle fusion.
In the reticular formation this causes loss of consciousness.
In the hippocampus- amnesia.
In the thalamic nuclei- analgesic effect.
In spinal cord this can have an effect on spinal reflexes.
What are the dangers of high concentrations of GAs?
All brain functions are affected- loss of motor control, reflexes, respiration, autonomic regulation e.g heart rate etc- can lead to death.
What are the four stages of anaesthesia?
- Analgesic- reduced responses to painful stimuli
- Excitement- this is stage that you want to avoid. There can be exaggerated responses in the reflexes/muscles which makes it dangerous to carry out surgery.
- Surgical- loss of consciousness, loss of response to painful stimuli, short term amnesia and loss of motor and autonomic reflexes.
- Medullary paralysis- death
Why is performing surgery on obese patients dangerous?
Drugs are lipid soluble so they will go to areas of high lipid content, meaning that in obese patients, the drugs are entering the fat instead of the CNS
What is the ideal path of controlling anaesthesia?
Rapid induction Avoid stages 2 and 4 Analgesia Muscle relaxation (common to co-administer neuromuscular blockers Rapid recovery
What are the advantages of using intravenous GAs?
Easy to administer
Rapid induction-easily crosses the BBB
Most have fast metabolism
What are the disadvantages of using Intravenous GAs?
Pain at the site of injection
Complex pharmacokinetics
Can have side effects such as respiratory and cardiovascular depression in the periphery
What are the properties of ketamine?
Powerful analgesic Sensory loss and amnesia Can cause frightening hallucinations CV excitement, involuntary movements Increased intercranial pressure Irrational behaviour
What the advantages of using inhaled GAs?
Useful for the maintainence of surgical anaesthesia- if there is an issue, you can alter the conc of drug being administered/rate of ventilation- you are not having to rely on metabolism to alter drug conc
Only route of entry is the lungs
Very rapidly change administered concentration
What do the speed of induction of and recovery from GAs depend on?
Solubility of the drug in fat and blood
What is malignant hyperthermia and what is it caused by
Triggered by halogenated GAs.
Rapid rise in temp, tachycardia, hypertension, increased muscle contraction.
Due to mutations inthe ryanodine Ca channels in the sarcoplasmic reticulum of muscles.
Massive release of Ca from the stores which leads to rapid increase in muscle contraction and metabolism
