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PHARMACOLOGY OF ANAESTHESIA

Complete NEET PG Notes

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SECTION 1: OVERVIEW & CONCEPTS

Five Desired Effects of General Anaesthesia

1. Unconsciousness (hypnosis)
2. Amnesia
3. Analgesia
4. Inhibition of autonomic reflexes
5. Skeletal muscle relaxation

No single agent produces all five - hence Balanced Anaesthesia uses combinations of inhaled agents + opioids + NMBDs + sedatives.

Guedel's Stages of Anaesthesia (ether era)

MAC (Minimum Alveolar Concentration)

• Alveolar partial pressure at which 50% of unparalyzed patients remain immobile to surgical skin incision
• Measure of potency (lower MAC = more potent); MAC is additive
• Factors decreasing MAC: Old age, hypothermia, pregnancy, hypoxia, hypotension, acute alcohol, opioids, α₂ agonists, lithium
• Factors increasing MAC: Young age, hyperthermia, chronic alcohol, hyperthyroidism, red hair

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SECTION 2: INHALATIONAL ANAESTHETICS

Key Physical Properties

Mechanism of Action

• GABA-A receptor potentiation (main mechanism for volatile agents)
• NMDA receptor inhibition (ketamine, N₂O)
• Potassium channel activation (TREK-1 channels)
• Meyer-Overton hypothesis: Lipid solubility correlates with potency
• Critical volume hypothesis: Membrane expansion disrupts ion channels

CNS Effects

• Immobility mediated via spinal cord; amnesia at 0.2-0.4 MAC
• Cerebral blood flow (CBF):
  • 0.5 MAC → CBF decreases
  • 1.0 MAC → CBF unchanged
  • 1.5 MAC → CBF increases (avoid in raised ICP)

Cardiovascular Effects

Respiratory Effects

• All volatile agents → dose-dependent respiratory depression (↓ tidal volume + ↑ RR)
• Bronchodilators: all volatile agents
• Pungent (avoid for induction in asthma): Isoflurane, Desflurane
• Non-pungent (preferred): Halothane, Sevoflurane, N₂O

Individual Agents - Key Points

• MAC 105% - cannot produce surgical anaesthesia alone
• Diffusion hypoxia on cessation - give 100% O₂ for 5-10 min
• Second gas effect - accelerates co-administered volatile agent uptake
• Expands gas-filled cavities - avoid in pneumothorax, bowel obstruction, middle ear surgery, vitreoretinal surgery
• Inhibits methionine synthase - risk of megaloblastic anemia/SCD with prolonged use
• High greenhouse gas potential

Malignant Hyperthermia (MH)

• Triggers: All halogenated volatile agents + succinylcholine
• Mechanism: RYR1 (ryanodine receptor) gene mutation → uncontrolled Ca²⁺ release from SR
• Features: Hyperthermia, rigidity, ↑↑CO₂, metabolic acidosis, ↑K⁺, myoglobinuria, ↑CK
• Treatment: Stop trigger → Dantrolene 1-3 mg/kg IV (up to 10 mg/kg) + cooling

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SECTION 3: INTRAVENOUS ANAESTHETICS

Comparison Table

Propofol

• 2,6-diisopropylphenol; milky white emulsion (egg/soy - contraindicated in allergy)
• Anti-emetic, antipruritic, euphoric emergence
• TIVA (4-12 mg/kg/h infusion); rapid recovery → day-case surgery
• Propofol Infusion Syndrome (PRIS): >4 mg/kg/h for >48h → metabolic acidosis, rhabdomyolysis, cardiac failure

Ketamine

• NMDA receptor antagonist; dissociative anaesthesia
• Unique: stimulates CVS (↑HR, ↑BP) - used in shock/trauma
• Bronchodilator - RSI drug of choice in severe asthma
• Preserves airway reflexes (relatively); increases secretions (pre-treat with atropine)
• Raises ICP, IOP, intragastric pressure - CONTRAINDICATED in head injury, open eye, ↑ICP
• Emergence delirium/hallucinations - prevent with midazolam/diazepam

Thiopentone

• Alkaline solution (pH 10.8); if injected intra-arterially → vasospasm/gangrene
• Absolute CI: Porphyria (precipitates acute attack)
• Anti-analgesic effect; histamine release; cumulative with repeated doses
• Reduces ICP/CMRO₂ - used in neurosurgery; anticonvulsant

Etomidate

• Safest for CVS; reduces ICP; no histamine release
• Adrenocortical suppression (inhibits 11β-hydroxylase) - avoid in sepsis
• Myoclonus (~30-40%), high PONV, pain on injection

Dexmedetomidine

• Selective α₂ agonist → sedation without respiratory depression
• Analgesic sparing; cooperative sedation; reduces opioid requirements
• Uses: ICU sedation, adjunct to anaesthesia

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SECTION 4: LOCAL ANAESTHETICS

Chemistry & Classification

Mechanism

• Block voltage-gated Na⁺ channels (from inside, after crossing membrane in unionized form)
• Use-dependent/frequency-dependent block (more effective in rapidly firing neurons)
• Infected tissue (acidic pH) → more ionized form → reduced LA efficacy

Order of Block

Individual Agents

Systemic Toxicity (LAST)

1. CNS first: Perioral tingling → tinnitus → convulsions → CNS depression
2. CVS: Arrhythmias → cardiac arrest (bupivacaine most dangerous - slow Na channel dissociation)
3. Treatment: 20% Intralipid 1.5 mL/kg IV bolus + infusion

Vasoconstrictors

• Adrenaline 1:200,000 extends duration; contraindicated in end-artery regions (fingers, toes, nose, ear, penis) and with halothane

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SECTION 5: NEUROMUSCULAR BLOCKING DRUGS (NMBDs)

Classification

Succinylcholine (Suxamethonium)

• Fastest onset (60-90 sec); duration 10-15 min
• Metabolized by plasma pseudocholinesterase (NOT AChE)
• NOT reversed by neostigmine (worsens Phase I block)
• Adverse effects:
  • Fasciculations + post-op myalgia
  • Hyperkalemia (↑0.5-1 mEq/L normal; FATAL in burns/crush/spinal cord injury/prolonged immobility)
  • Malignant hyperthermia trigger
  • Raises ICP, IOP, intragastric pressure
  • Bradycardia (repeat doses, especially children)
  • Scoline apnoea (pseudocholinesterase deficiency)

• Normal pseudocholinesterase: DN = 80 (80% inhibited)
• Atypical pseudocholinesterase (homozygous): DN = 20 → prolonged apnoea (4-8h)
• Heterozygous: DN = 60

Non-Depolarizing NMBDs

• Non-depolarizing: Progressive fade (4 > 3 > 2 > 1)
• Depolarizing: Equal reduction, no fade

Reversal Agents

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SECTION 6: OPIOIDS IN ANAESTHESIA

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SECTION 7: PREMEDICATION

Common Premedicants

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SECTION 8: HIGH-YIELD EXAM TABLE

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