General anaesthetics

What is general anaesthesia?

a reversible, drug-induced state characterised by:

• Loss of consciousness

• Amnesia

• Analgesia

• Muscle relaxation (immobility)

What general anaesthesia useful for

Allowing surgery to be performed without pain, awareness, or movement, while maintaining physiological stability.

What are the four core components of general anaesthesia?

• Hypnosis – loss of consciousness

• Amnesia – loss of memory formation

• Analgesia – abolition of pain perception

• Muscle relaxation – suppression of reflex movement

Why is general anaesthesia described as “balanced”?

Because it uses a combination of drugs, each targeting different physiological systems, to:

• Reduce the dose of any single agent

• Minimise toxicity and adverse effects

• Achieve optimal hypnosis, analgesia, and immobility.

Why are multiple physiological systems targeted during general anaesthesia?

Because no single pathway controls consciousness, pain, memory, and movement — each requires separate neural suppression.

What was the lipid theory of general anaesthetic action?

The theory that anaesthetics act by dissolving into neuronal lipid membranes, altering membrane fluidity and disrupting neuronal function

Why is the lipid theory now considered insufficient?

• It does not explain drug specificity,

• Anaesthetic effects occur at clinically low concentrations,

• Specific protein targets (ion channels and receptors) have been identified.

At a cellular level, what do general anaesthetics primarily inhibit?

Synaptic transmission, they reduce communication between neurons, rather than preventing action potential propagation.

Which excitatory receptors are inhibited by general anaesthetics?

• Glutamate receptors

• Ionotropic acetylcholine receptors

This reduces excitatory neurotransmission in the CNS.

Which inhibitory receptors are activated by general anaesthetics?

• GABA a​ receptors,

• Glycine receptors,

• K2P channels.

These cause neuronal hyperpolarisation and CNS depression.

What is the net CNS effect of general anaesthetics?

• ↓ Neuronal excitation

• ↑ Neuronal inhibition

• → leading to global CNS depression.

Which brain region is responsible for loss of consciousness during anaesthesia?

The midbrain reticular activating system, which normally maintains wakefulness

How is analgesia achieved at a higher CNS level

suppression of thalamic sensory relay nuclei, preventing sensory information reaching the cortex.

Which brain region is linked to amnesia during anaesthesia?

The hippocampus, particularly affected by benzodiazepines and some GABAergic agents.

How do general anaesthetics contribute to muscle relaxation centrally?

By acting at the spinal cord, reducing reflex arcs and motor neuron excitability

What cardiovascular effects are commonly produced by general anaesthetics?

• ↓ Cardiac contractility,

• ↓ Cardiac output,

• ↓ Blood pressure,
  leading to circulatory depression.

Why do general anaesthetics often require ventilatory support?

Because they cause profound respiratory depression, reducing:

• Respiratory rate,

• Tidal volume,

• CO₂ responsiveness.

How do general anaesthetics cause muscle relaxation peripherally?

By acting at the neuromuscular junction, either:

• Blocking nicotinic ACh receptors, or

• Causing sustained depolarisation.

What is Minimum Alveolar Concentration (MAC)?

The alveolar concentration of an inhaled anaesthetic that prevents movement in 50% of patients in response to a painful stimulus.

How does MAC relate to anaesthetic potency?

• Lower MAC = higher potency

• Higher MAC = lower potency

Why is MAC a useful clinical measure?

It allows comparison of volatile anaesthetics and helps guide dosing during maintenance of anaesthesia

What are the five major components/stages of general anaesthesia?

• Premedication

• Induction

• Maintenance

• Pain relief

• Muscle relaxation

What is premedication?

Premedication is a combined drug treatment, typically administered 1–3 hours before anaesthesia

What are the purposes of premedication?

• Reduce anxiety

• Reduce pain

• Promote amnesia

• Reduce postoperative nausea and vomiting

Which drug classes can be used for premedication?

• Benzodiazepines — e.g. diazepam

• Muscarinic acetylcholine receptor antagonists (mAChR antagonists) — e.g. atropine

• Opioid receptor agonists — e.g. morphine

• Antiemetics — e.g. metoclopramide

How does diazepam work as a premedication drug?

Diazepam is a benzodiazepine that enhances inhibitory GABAᴀ receptor activity, producing sedative effects

Why is atropine used as premedication

Atropine is an mAChR antagonist that:

• Reduces secretions

• Helps prevent vagal reflexes.

Why can morphine be used as premedication?

Morphine is an opioid receptor agonist that provides:

• Analgesia

• Sedation

Why can metoclopramide be used during premedication?

Metoclopramide is an antiemetic used to limit nausea and vomiting.

Why might premedication not always be used?

• Some patients prefer not to receive premedication

• the potential benefits may be outweighed by the risks associated with the drugs.

What is the purpose of induction?

Induction produces loss of consciousness and amnesia, initiating the anaesthetic state

Which drugs are commonly used for IV induction?

• Propofol

• Sodium thiopental

What is the mechanism of action of propofol and thiopental?

By activating GABAᴀ receptors, thereby increasing inhibitory neurotransmission

What properties make IV induction agents suitable for rapid induction?

• Small

• Highly lipophilic

• Able to rapidly reach the brain

How quickly can IV induction agents produce loss of consciousness?

20 seconds

Why does the effect of an IV induction agent terminate relatively quickly?

Initially, the drug's action is terminated primarily through distribution into large compartments, including muscle. This decreases the concentration reaching the brain

Why is propofol favoured as an induction agent?

its rapid metabolism and lack of a hangover effect

What is ketamine's mechanism of action?

Ketamine acts as an antagonist at NMDA glutamate receptors, thereby reducing excitatory glutamatergic neurotransmission

What psychological adverse effects can ketamine produce?

• Dysphoria

• Hallucinations

These effects are less pronounced in children, so ketamine is typically used in paediatric medicine

What is the purpose of the maintenance stage?

Maintenance maintains:

• Loss of consciousness

• Amnesia

It is primarily achieved using volatile inhaled anaesthetic agents

Give examples of inhaled maintenance anaesthetics.

• Isoflurane

• Nitrous oxide

• Halothane

Why are inhaled anaesthetics useful for maintenance?

• Relatively fast onset and offset

• Easily controllable depth of anaesthesia

• Rapid elimination

• Fewer side effects

Why are opioids used during general anaesthesia?

IV opioids are used to provide analgesia e.g., morphine and fentanyl

What additional effects can opioids have during anaesthesia?

• Sedation

• Cardiorespiratory depression

What adverse effects of opioids can be relevant during anaesthesia?

• Nausea and vomiting

• Bronchospasm

• Anaphylaxis

What are the two major types of neuromuscular blockers?

• Competitive/non-depolarising blockers — competitive antagonists at nAChRs.

• Depolarising blockers — agonists that cause a sustained depolarising block of the muscle endplate.

How do competitive nAChR blockers work?

They act as competitive antagonists at nicotinic acetylcholine receptors at the NMJ. They prevent acetylcholine from activating the receptor and therefore prevent normal depolarisation and muscle contraction

Give examples of competitive/non-depolarising neuromuscular blockers.

• Atracurium

• Pancuronium

Why are competitive nAChR blockers useful in obstetrics?

do not cross the placenta

How do depolarising neuromuscular blockers produce paralysis?

They are agonists at nAChRs and continually stimulate the NMJ.

• persistent depolarisation of the muscle endplate.

• The muscle initially contracts, but cannot subsequently repolarise and relax

• causing loss of excitability and paralysis

What is the main example of a depolarising neuromuscular blocker

Suxamethonium