General anaethetics

Where do general anaesthetics work?

Act on the brain to produce a loss of sensation.

How do general anaesthetics work?

Affect synaptic transmission and neuronal excitability rather than axonal conduction.

Describe the structure of general anaesthetics.

Small, lipid soluble molecules that readily get access to the brain by crossing the BBB.

What does general anaesthesia lead to?

- Loss of memory

- Loss of motor reflexes

- Loss of response to painful stimuli

- Changes in CV and respiratory physiology.

What regions of the brain are affected during anaesthesia?

- Cerebral cortex

- Thalamus

- Hippocampus

- Reticular system

How is the cerebral cortex, thalamus, hippocampus, and reticular system affected by anaesthesia?

- Cortex = Inhibited by anaesthesia.

- Thalamus = Can no longer relay signals.

- Hippocampus = Memory formation cannot occur.

- Reticular system = suppressed ensuring loss of consciousness.

What is the reticular formation, and what areas does it connect?

- A complex network of neurones in the brainstem.

- Extends into the nonspecific thalamic sensory nuclei and connects to the hypothalamus, cerebellum, and cerebral cortex.

What are the key functions of the reticular formation in consciousness and sensory input?

- Arouses the cerebral cortex into wakefulness. Inhibition causes unconsciousness

- Also causes analgesia and loss of memory.

How does the reticular formation relate to anesthesia and memory?

- Inhibition via anaesthetics may cause amnesia due to hippocampal inhibition.

- There is no single anesthesia target site therefore can act on hippocampus and cerebral cortex.

What the stages of anaesthesia?

- Stage 1

- Stage 2

- Stage 3

- Stage 4

Describe stage 1 of anaesthesia.

- Analgesia

- Cortical neurone inhibition

Describe stage 2 anaesthesia.

- Delierum

- Excitation of cortical motor neurones leading to involuntary movements.

Describe stage 3 anaesthesia.

- Surgical anaesthesia.

- Divided into 4 planes.

- There is a decrease in thoracic respiration, muscle tone and laryngeal/pharyngeal reflexes.

Describe stage 4 anaesthesia.

- Can be due to an overdose in anaesthesia in the medulla causing suppression.

- Leads to respiratory and circulatory paralysis.

- No cardiac output.

What are examples of IV general anaesthetics?

- Ketamine

- Thiopental

- Propofol

- Etomidate

What are examples of inhaled anaesthesia?

- Halothane

- Sevoflurane

- Nitrous oxide

- Isoflurane

What determines the initial distribution of anaesthetic agents in the body?

Blood flow. Organs with high perfusion like the brain, heart, lungs, and viscera receive the drug first due to getting 2/3 of the cardiac output.

Why do patients lose consciousness quickly after anaesthesia is administered (IV) e.g., thiopental, propofol?

Due to direct bloodstream administration and high lipid solubility, they rapidly cross the BBB. As the brain receives a large share of cardiac output, they quickly equilibrate with the CNS, causing rapid loss of consciousness.

How does fat tissue affect anaesthetic elimination?

Fat has low perfusion (2% CO), takes hours to absorb the drug, and acts as a long-term reservoir, slowing down full elimination.

Why might obese patients or long surgeries lead to prolonged sedation?

Because more anaesthetic accumulates in fat tissue, leading to a slower clearance after the procedure.

what is the hangover effect of anaesthesia e.g., thiopental?

- The residual drowsiness, confusion, or cognitive slowing that happens after waking up from anaestheisa.

- Even though consciousness returns, the brain/body has not completely cleared the drug.

Why is thiopental slowly eliminated?

That with large or repeated doses, the blood concentration keeps rising because the drug builds up faster than the liver can metabolise it via oxidation. (saturation kinetics = zero order kinetics)

Describe propofol.

- Rapid onset and rapid rate of redistribution.

- Can be used as a continuous infusion.

- No hangover as rapidly metabolised by liver via glucouronidation.

- Has first order kinetics so no saturation kinetics unlike thiopental.

Why is zero-order kinetics slower than first-order?

- Zero-order kinetics (thiopental): Drug is eliminated at a fixed rate because enzymes are used up (saturated)

- This means elimination doesn't speed up, even if drug levels are high

- First-order kinetics (propofol): Drug is cleared faster when concentrations are higher.

What are side effects of propofol and thiopental?

Cause cardiovascular and respiratory depression.

Describe ketamine.

- Increases BP and heart rate and no effect on respiration so acts differently to other anaesthesia.

- Can be used intramuscularly.

- Powerful analgesic.

- Slower onset 1-2 mins

What are side effects of ketamine?

- Can increase intracranial pressure

- Hallucinations.

- Delirium during recovery.