general anaesthetics

Question 1

Describe the protein targets and effects of general anaesthetics in the nervous system

Answer 1

• specific binding points on GABAa receptor
  
  • volatile GAs bind at interface of a and b subunits of GABAa
  • intravenous GAs bind only on B subunit of GABAa
• low conc of volatile GAs activate ‘two pore domain K channels’ → hyperpolarises neurones
• GAs decrease V gated Na ion channels activity and reduce fusion of vesicles to membrane

Question 2

Describe the role of lipids in anaesthetic action

Answer 2

• mayer-overton rule - anaesthetic effect is proportional to molar conc of agent in lipid

limitations
- temperature effect
- saturation effect of binding sites
- loss of activity with homologous series of lipophylic compounds
- increase GABAa receptor affinity for agonists

protein theory
- BINDING SITE FOR GA ON PROTEINS IS ONLY ACCESSABLE FROM WITHIN PLASMA MEMBRANE
- lipid solubility is important

Question 3

Describe the four stages of anaesthesia

Answer 3

1. analgesia
   
   • reduced reflexes e.g NO
2. excitement
   
   • exaggerated reflexes e.g kicking or gagging
3. surgical anaesthesia
   
   • unconscious
   • loss of responses and reflexes
   • short-term amnesia
4. medullary paralysis
   
   • loss of CV reflexes
   • respiratory paralysis
   • death

Question 4

describe the effects of general anaesthetics on the body

Answer 4

unconsciousness

• caused by inhibition of transmission in reticular formation

short term amnesia

• caused by inhibition of transmission in hippocampus

analgesia (pain reduction)

• caused by inhibition of thalamic sensory relay nuclei parts of cortex

inhibition of spinal reflexes

• caused by some volatile anaesthetics

Question 5

Name and describe the properties of common intravenous anaesthetics

Answer 5

• useful for induction of anaesthesia

propofol
- rapid metabolism
- good induction
- short half life

thiopental
- targets GABA a
- pain at site of injection
- high lipid solubility
- can accumulate in body fat = hangover
- low therapeutic index = need lots

ketamine
- sensory loss
- powerful analgesic
- amnesia
- not complete loss of consciousness
- no respiratory depression
- NMDS inhibitor
- involuntary movement
- hallucinations
- irrational behaviour

Question 6

Name and describe the properties of common inhalation anaesthetics

Answer 6

useful for maintenance of anesthesia

• e.g NO, isoflurane, desflurane, sevoflura
• maintaining surfical anaesthesia
• only route of entry and exit is via lungs
• small lipid soluble molecules, easily cross alveolar membrane
• differences arise from solubility of different agents in blood, fat and toxicity

Question 7

Speed of induction is dependent on

Answer 7

• dependent on solubility in blood and fat
  
  • rapid in blood due to low solubility
  • slow in fat but not much goes in
• depth of anaesthesia
  
  • determined by tension of inhalation anaesthetic in brain - blood - alveolar air
• rate
  
  • at which tension of anaesthetic in blood/brain approach tension in inspired air dependent on solubility in blood
    
    • accelerated by increasing initial conc of agent in inspired air