L10- General Anaesthetics

Introduction to General Anaesthetics

Focus of lecture: General anaesthetics, components, stages, pharmacological agents, mechanisms, advantages, and disadvantages.

Key Components of Anaesthesia

Analgesia: Pain relief, reduces patient anxiety.
Loss of Consciousness with Amnesia: Used to facilitate controlled interventions.
Muscle Relaxation: Eases access to surgical sites and reduces anaesthetic requirements.
These components create a controlled, reversible state of CNS depression.

Four Stages of General Anaesthesia

Stage One: Analgesia
- Begins with anesthetic administration until loss of consciousness.
- Decrease in pain awareness, potential amnesia, vivid dreams, auditory and visual hallucinations.
- Speech becomes indistinct; hearing is the last sense to diminish.

Stage Two: Disinhibition
- Characterized by excitement and delirium; reflexes may be enhanced.
- Amnesia occurs; irregular respiration, potential retching or incontinence.
- Varies greatly among individuals based on anesthesia type and premedication.

Stage Three: Surgical Anaesthesia
- Patient is fully unconscious, pain reflexes are abolished.
- Respiration and blood pressure remain stable; divided into four planes of increasing depth.
- Most surgeries conducted in plane two or upper plane three; plane four signifies risk of critical complications.

Stage Four: Medullary Depression
- Severs respiratory and cardiovascular depression; mechanical support often needed.
- Risk of overdose, respiratory arrest, vasomotor collapse; may require artificial respiration.

Typical Surgical Approach to General Anaesthesia

Induction: Typically via an intravenous agent (rapid unconsciousness).
Maintenance: Administer inhalational agents to maintain unconsciousness.
Additional agents: Analgesics, neuromuscular blockers, and pre-anesthetic agents may be used:
- Benzodiazepines: For anxiety relief. Mechanism: Enhance GABA-A receptor affinity for GABA, leading to increased chloride ion conductance, hyperpolarization, and inhibition of neuronal firing.
- Antihistamines: For allergic reactions. Mechanism: Block histamine (H1) receptors, preventing histamine-induced activation of neurons, thus reducing alertness and anxiety.
- Antiemetics: For nausea and vomiting. Mechanism: Example: Ondansetron blocks serotonin (5-HT3) receptors in the vomiting center and the chemoreceptor trigger zone (CTZ).
- Opioids: For analgesia. Mechanism: Activate mu-opioid receptors in the CNS, reducing neurotransmitter release and diminishing pain signals.
- Atropine: To prevent bradycardia. Mechanism: Blocks muscarinic acetylcholine receptors, inhibiting parasympathetic activity, leading to increased heart rate.

Classes of General Anaesthetics

Inhalation Anaesthetics:
- Gases: Nitrous oxide. Mechanism: NMDA receptor antagonist, reducing excitatory neurotransmission.
- Volatile Liquids: Isoflurane, sevoflurane, halothane, desflurane, enflurane. Mechanism: Potentiate GABA-A receptors, enhancing inhibitory neurotransmission and causing CNS depression.
- Properties include:
  - Blood Gas Partition Coefficient: Affect solubility, induction speed, and recovery time (smaller coefficients = faster induction). (\lambda_{blood/gas})
  - Oil Gas Partition Coefficient: Indicates potency; higher lipid solubility equates to greater potency but slower recovery. (\lambda_{oil/gas})
  - Minimum Alveolar Concentration (MAC): Measures potency; 1.3 MAC provides 98% chance of surgical anesthesia; affected by age and temperature.

Intravenous Anaesthetics:
- Includes propofol, thiopental, etomidate, ketamine, and midazolam.
- Propofol: Induction agent, rapid recovery, not accumulative; risks respiratory and cardiac depression; propofol infusion syndrome is a severe adverse effect. It acts primarily through potentiating GABA A receptors, enhancing inhibitory neurotransmission in the CNS.
- Thiopental: Short-acting barbiturate; quick onset but hangover effect; cardiovascular and respiratory depression risks. It enhances GABAergic neurotransmission by increasing the duration of chloride ion channel opening, leading to neuronal hyperpolarization.
- Ketamine: NMDA antagonist; causes dissociative anesthesia without respiratory depression; side effects include postoperative nausea, vomiting, and hallucinations. It selectively blocks the NMDA receptor, reducing glutamate-induced excitation in the CNS.
- Etomidate: Hypnotic agent with rapid onset/maintenance; less cardiovascular risk; potential for adrenocortical suppression. It modulates GABA A receptor activity, increasing its affinity for GABA, thus enhancing inhibitory neurotransmission.
- Midazolam: Benzodiazepine; provides sedation without major respiratory depression; effective amnesia; reversible with flumazenil. It binds to the benzodiazepine site on the GABA A receptor, enhancing GABA's inhibitory effects by increasing the frequency of chloride channel opening.

Advantages and Disadvantages of IV Anaesthetics

Advantages:
- Rapidly induce unconsciousness, easy administration; less fire hazard; reducible inhalation dosage.

Disadvantages:
- Minimal muscle relaxation (except ketamine); elimination via hepatic and renal excretion; can cause various allergic and cardiovascular responses.

Mechanism of Action

General anaesthetics function primarily by potentiating the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA) at the GABA A receptor. This leads to increased chloride ion influx, resulting in neuronal hyperpolarization and a decreased neuronal excitability. Additionally, some general anaesthetics inhibit the N-methyl-D-aspartate (NMDA) receptor, which blocks excitatory neurotransmission mediated by glutamate. This dual action contributes to the overall effects of general anaesthesia, including analgesia, loss of consciousness, and muscle relaxation.

Conclusion

General anaesthetics achieve goals of analgesia, amnesia, and muscle relaxation through specific mechanisms focusing on GABA A receptor potentiation and NMDA receptor inhibition.
They are classified into inhalation and intravenous types, each with distinct properties and clinical applications.