Wk7/8 - General anaesthetic

What is anaesthesia?

Greek word meaning "lack of feeling" – loss of sensation

What are the properties of general anaesthetics?

Small, lipid-soluble molecules that cross the BBB; affect synaptic transmission

What are the 4 stages of anaesthesia?

I Analgesia, II Excitation, III Surgical anaesthesia, IV Overdose

What happens in Stage I anaesthesia?

Analgesia, cortical inhibition, loss of memory

What happens in Stage II anaesthesia?

Excitation, delirium, involuntary movements

What happens in Stage III anaesthesia?

Surgical anaesthesia – loss of response to painful stimuli

What happens in Stage IV anaesthesia?

Overdose – respiratory and circulatory paralysis (can cause death)

What are the three intravenous anaesthetics you need to know?

Thiopental, propofol, ketamine

What is the onset and duration of thiopental?

Onset ~20 seconds, duration 5-10 minutes

What is the problem with thiopental?

Saturation kinetics – large or repeated doses cause accumulation and hangover

What makes propofol better than thiopental?

First-order kinetics – no saturation, no hangover, rapid recovery

What is unique about ketamine?

Increases BP and heart rate; no respiratory depression; powerful analgesic; can cause hallucinations

What are the main inhalation anaesthetics?

Isoflurane, sevoflurane, desflurane, nitrous oxide

What is the pathway of inhalation anaesthetics?

Inhaled gas → Alveoli → Blood → Tissues

What determines the kinetic behaviour of inhalation anaesthetics?

Solubility (partition coefficients)

What is the blood:gas coefficient?

How readily drug moves between alveoli and blood – lower = faster induction/recovery

What is the oil:gas coefficient?

Fat solubility – higher = more potent (correlates with MAC)

Which inhalation anaesthetic has the fastest induction/recovery?

Nitrous oxide (blood:gas coefficient = 0.5)

Which inhalation anaesthetic has the slowest induction/recovery?

Ether (blood:gas coefficient = 12)

What is MAC?

Minimal Alveolar Concentration – concentration required to abolish response to surgical incision in 50% of subjects; measure of anaesthetic potency

What did Overton and Meyer discover?

Correlation between MAC and lipid solubility (oil:gas coefficient)

What are the main molecular targets of general anaesthetics?

GABA_A receptors (↑), NMDA receptors (↓), K2P channels (↑), voltage-gated Na⁺/Ca²⁺ channels (↓)

What do most anaesthetics do at GABA_A receptors?

Enhance activity (increase inhibition)

What does ketamine do at NMDA receptors?

Non-competitive antagonist (also blocks channel pore)

What does nitrous oxide do at NMDA receptors?

Blocks the channel pore

What do xenon and isoflurane do at NMDA receptors?

Inhibit NMDA by competing with glycine at its regulatory site

What are K2P channels?

Two-pore domain potassium channels (TREK, TASK, TRESK) – background K⁺ channels that modulate excitability

What do volatile and gaseous anaesthetics do at K2P channels?

Activate them → hyperpolarisation → reduced excitability (IV anaesthetics do NOT affect K2P)

What is balanced anaesthesia?

Combination of drugs: sedative premedication, IV anaesthetic, inhalation anaesthetic, muscarinic antagonist, analgesic

What factors affect induction and recovery of inhalation anaesthesia?

Alveolar ventilation rate (greater = faster) and cardiac output (reduced = faster induction but less brain delivery)