13. NEUROMUSCULAR BLOCKERS

Introduction

Neuromuscular blockers are drugs that relax skeletal muscles by blocking transmission at the neuromuscular junction (NMJ). They are commonly used during surgical procedures, endotracheal intubation and in conditions where controlled muscle relaxation is required. These drugs help surgeons operate easily and safely by reducing the dose of general anaesthesia required.

Neuromuscular Junction: Basic Idea

The NMJ is the junction between a nerve ending and a skeletal muscle fibre. The neurotransmitter released here is acetylcholine (ACh), which activates nicotinic receptors on muscles, causing muscle contraction. Neuromuscular blockers interfere with this process and produce muscle relaxation.

Classification of Neuromuscular Blockers

  • Non-depolarising blockers (competitive blockers)
  • Depolarising blockers (persistent depolarisers)

1. Non-Depolarising Blockers

These drugs compete with ACh for nicotinic receptors at NMJ but do not activate them. As a result, sodium channels do not open and muscle contraction does not occur. They are also called competitive blockers.

Examples

  • d-Tubocurarine (prototype)
  • Atracurium, Cisatracurium
  • Vecuronium, Rocuronium, Pancuronium
  • Mivacurium, Pipecuronium

Mechanism of Action

They bind to nicotinic receptors and prevent ACh from activating them. No depolarisation occurs and the muscle remains relaxed. The block can be reversed by anticholinesterase drugs such as neostigmine or pyridostigmine which increase ACh levels.

Pharmacokinetics (Simple Points)

  • Not absorbed orally; given IV.
  • Do not cross the blood–brain barrier → no CNS effects.
  • Do not cross placenta → safe in caesarean section.
  • Duration depends on elimination route (kidney → long, liver → intermediate, plasma cholinesterase → short).

Pharmacological Effects

  • Muscle weakness → flaccid paralysis.
  • Small muscles (eye, face, fingers) block first.
  • Large muscles block next.
  • Diaphragm is last to be paralysed and first to recover.

Adverse Effects

  • Hypotension (especially d-TC, atracurium) due to histamine release.
  • Bronchospasm (d-TC).
  • Pancuronium can cause tachycardia.
  • Prolonged paralysis in renal/hepatic disease for steroid-based blockers.

Drug Interactions (Synergists)

  • Aminoglycosides (gentamicin), polymyxin, tetracyclines enhance the block.
  • Inhalational anaesthetics (halothane) increase the blockade.
  • Local anaesthetics, quinidine and propranolol may enhance the effect.
  • Myasthenia gravis increases sensitivity to non-depolarising blockers.

2. Depolarising Blocker

Succinylcholine (SCh) is the only depolarising neuromuscular blocker used clinically.

Mechanism of Action

SCh acts like ACh but is broken down slowly by plasma pseudocholinesterase. It keeps the nicotinic receptors continuously depolarised, leading to:

  • Initial muscle fasciculations (twitching)
  • Followed by flaccid paralysis

This initial block is called Phase I block. With prolonged infusion, a Phase II block may occur which resembles the action of non-depolarising blockers.

Pharmacokinetics

  • Given IV; onset within 1 minute.
  • Very short duration (5–10 minutes).
  • Broken down by plasma pseudocholinesterase.
  • Prolonged action occurs in patients with atypical pseudocholinesterase (low dibucaine number).

Adverse Effects

  • Hyperkalaemia: dangerous in burn patients, spinal injury, renal failure.
  • Malignant hyperthermia: genetic; treated with dantrolene.
  • Prolonged apnoea in pseudocholinesterase deficiency.
  • Muscle soreness, increased intra-ocular pressure.
  • Bradycardia followed by tachycardia.

Drug Interactions

  • Neostigmine worsens Phase I block.
  • Calcium channel blockers enhance the block.
  • Hypothermia prolongs its action.

Therapeutic Uses of Neuromuscular Blockers

  • During general anaesthesia: to provide skeletal muscle relaxation.
  • Endotracheal intubation: SCh is preferred for rapid sequence intubation.
  • Electroconvulsive therapy (ECT): SCh prevents fractures during convulsions.
  • Orthopaedic procedures: helps in manipulation of fractures.
  • Ventilator control: useful in patients with severe respiratory distress.
  • Severe spastic conditions: used when benzodiazepines alone are not enough.

Reversal of Neuromuscular Blockade

Only non-depolarising blockers can be reversed. Reversal is done using:

  • Neostigmine + Atropine/Glycopyrrolate (to block muscarinic effects)
  • Pyridostigmine (alternative agent)

Detailed Notes:

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