General anaesthetics Flashcards
What substances were used as early general anaesthetics? (3)
- Nitrous oxide
- Ether
- Chloroform
What are the 2 main categories of general anaesthetics?
- Chemical
- Physical
What are the 2 forms of chemical general anaesthetics?
- Inhalational
- Intravenous
Why are volatile liquid general anaesthetics no longer used? (3)
- Ether and chloroform
- Highly flammable/explosive
- Hard to control dose
What are physical general anaesthetics? (2)
- Low atmospheric pressure
- Hypothermia
What kind of general anaesthetic is nitrous oxide?
Inhalational (chemical)
What are examples of intravenous general anaesthetics? (2)
- Barbiturates e.g. thiopental
- Steroids e.g. alphaxalone
What is the lipid theory of general anaesthetics? (3)
- Direct correlation between lipid solubility of drug and its effectiveness as anaesthesia
- Theory that drugs insert into lipids of plasma membrane and increase its fluidity
- More lipid soluble = less of the drug needed to cause unresponsiveness
What is the Meyer-Overton rule? (2)
- The anaesthetic effect of a drug is proportional to the molar concentration of the drug in the lipid membranes
- Anaesthesia results from membrane disruption
What are the issues with the lipid theory? (3)
- Doesn’t explain the anaesthetic effect of temperature (lipids lose fluidity when cold)
- Doesn’t explain saturation effect (indicates limited number of receptors)
- Doesn’t explain evidence that anaesthetics alter GABAa receptor affinity for agonists
Which proteins are targets for general anaesthetics? (3)
- GABAa receptors
- Two Pore Domain K+ channels
- NMDA receptors
How are GABAa receptors involved in anaesthesia?
Increase inhibitory neurotransmission in the CNS
How do volatile general anaesthetics interact with GABAa receptors?
Bind to the interface between the alpha and beta subunits of GABAa
How do intravenous general anaesthetics interact with GABAa receptors?
Bind to the beta subunit of GABAa
How do volatile general anaesthetics interact with Two Pore Domain K+ channels? (3)
- Activate the channels
- Membrane potential is more hyperpolarised (more negative)
- Harder for neurons to fire action potentials
What are NMDA receptors?
Ionotropic glutamate receptors
Which protein does ketamine and nitrous oxide act on?
Blocks NMDA receptors
Which general anaesthetics target GABAa receptors? (2)
- Volatile
- Intravenous
Which general anaesthetics activate Two Pore Domain K+ channels?
Volatile
Which general anaesthetics block NMDA receptors? (2)
- Nitrous oxide
- Ketamine
Where are protein binding sites for general anaesthetics located?
Plasma membrane
What do general anaesthetics regulate? (2)
- Ion channels
- Synaptic transmission
How do general anaesthetics interfere with synaptic transmission? (2)
- Inhibit action potentials in neurons
- Interfere with exocytosis of neurotransmitter vesicles
What does inhibition of the reticular formation cause?
Unconsciousness
What does inhibition of the hippocampus cause?
Short term amnesia
What does inhibition of the thalamic sensory relay nuclei of the cortex cause?
Analgesia
What are the 4 stages of anaesthesia?
Stage 1 - Analgesia
Stage 2 - Excitement
Stage 3 - Surgical anaesthesia
Stage 4 - Medullary paralysis
What stage of anaesthesia does nitrous oxide achieve?
Stage 1 - analgesia
What happens during the excitement stage of anaesthesia?
Exaggerated reflexes (kick/gag)
What happens during the surgical stage of anaesthesia? (4)
- Unconscious
- Unresponsive to painful stimuli
- Loss of reflexes
- Short term amnesia
What happens during the medullary paralysis stage of anaesthesia? (2)
- Loss of cardiovascular reflexes and respiratory paralysis
- Death
Which stages of anaesthesia need to be avoided?
Stages 2 and 4
What drugs are examples of intravenous anaesthetics? (3)
- Propofol
- Thiopental (barbiturate)
- Etomidate
What are the advantages of propofol? (2)
- Highly lipid soluble so rapid induction
- Fast recovery time due to rapid metabolism
What are the disadvantages of thiopental? (4)
- Painful at site of injection
- Complex pharmacokinetics
- Hangover due to accumulation in body fat
- Not much of an increase required to move from stage 3 to stage 4 = dangerous so not widely used anymore
Which type of general anaesthetic is best for induction of anaesthesia?
Intravenous
Why are intravenous anaesthetics ideal for induction of anaesthesia? (2)
- Easy to administer
- Rapid induction because enter the brain easily
Which intravenous anaesthetic doesn’t cause cardiovascular depression?
Etomidate
What are the disadvantages of intravenous anaesthetics? (2)
- Respiratory depression
- Cardiovascular depression
What kind of anaesthetic is ketamine?
Dissociative anaesthetic
What useful anaesthetic effects does ketamine cause? (3)
- Sensory loss
- Powerful analgesia
- Amnesia
Why is ketamine unsuitable as an anaesthetic for long surgeries?
No complete loss of consciousness
What is an advantage of ketamine?
No respiratory depression
What are the side effects of ketamine? (3)
- Hallucinations
- Involuntary movements
- Increased intracranial pressure
When is ketamine used as an anaesthetic? (2)
- Paediatrics
- Veterinary
Which type of general anaesthetic is best for maintenance of anaesthesia?
Inhalational
What drugs are examples of inhalational anaesthetics? (4)
- Nitrous oxide
- Isoflurane
- Desflurane
- Sevoflurane
Why are inhalational anaesthetics ideal for maintenance of anaesthesia? (2)
- Very easy to control their concentrations in the CNS by controlling conc of inhaled air and ventilation rate
- Concentration is not altered by metabolism unlike intravenous
What does the stage of anaesthesia depend on?
Concentration of the general anaesthetic in the brain
When is the use of inhalational anaesthetics problematic?
When patients have diseased/damaged lungs
Why do inhalational anaesthetics need to be lipid soluble?
Can easily cross alveolar membrane
How does blood and lipid solubility of inhalational anaesthetics affect speed of induction and recovery? (3)
- Inhalational anaesthetics have low solubility in blood but high solubility in lipid
- Alveolar concentration equilibrates quickly with the blood, readily delivered to tissues due to high lipid solubility
- Can accumulate in fat but usually doesn’t because of poor perfusion
How is the concentration of inhalational anaesthetics in the CNS controlled? (2)
- To increase = increase conc. in inspired air and increase ventilation rate
- To decrease = decrease conc. in inspired air and increase ventilation rate
What problem can halogenated general anaesthetics cause?
- Can trigger malignant hyperthermia
- Rise in body temp, increase in heart rate, increased muscle contractions, hypertension
- Halogenated GAs activate ryanodine receptors causing increased Ca2+ in skeletal muscle, rapid production of heat
What is malignant hyperthermia?
Inherited mutation in ryanodine receptors on sarcoplasmic reticulum of skeletal muscle
What drug is used to treat malignant hyperthermia? (2)
- Intravenous dantrolene
- Ryanodine receptor inhibitor
Why aren’t intravenous anaesthetics used for maintenance of anaesthesia?
Reversal relies on the patient’s metabolism which is more difficult to control than ventilation rate
