Pharm 101: Suxamethonium

Class

Paralytic agent

Pharmacodynamics

• Depolarising neuromuscular blocker that causes rapid neuromuscular blockade at motor endplate nicotinic receptors
• Two phases of action: Phase 1 (depolarising) and Phase 2 (desensitising)
• Phase 1:
  • Binding of drug to nicotinic receptors causes depolarisation of motor endplate
  • Fasciculations (transient contractions of muscle motor units) occur due to spread of impulse to adjacent membranes
  • Depolarised membranes remain depolarised and unresponsive to subsequent impulses, causing flaccid paralysis
• Phase 2:
  • With prolonged exposure, initial end plate depolarisation decreases and membranes become repolarised
  • Membrane is desensitised and cannot easily be depolarised again

Pharmacokinetics

• Rapid onset
• Short duration of action 5-10 minutes
• Rapid hydrolysis by:
  • Pseudocholinesterase in plasma (main pathway)
  • Butyrylcholinesterase in liver
• Because plasma cholinesterase has an enormous capacity to hydrolyse suxamethonium, only a small percentage of the original intravenous dose ever reaches the neuromuscular junction

Clinical uses

• Rapid Sequence Induction (RSI)
  • Dose 0.75-1.50 mg/kg
• Clinical effects
  • Transient muscle fasciculations occur over chest and abdomen within 30 seconds following administration
  • As paralysis develops rapidly (< 90 seconds), the arm, neck and leg muscles are initially relaxed followed by respiratory muscles
  • Duration of blockade ~5-10 minutes

Adverse effects

• Cardiac arrhythmias:
  • Stimulates nicotinic receptors at both sympathetic and parasympathetic ganglia and muscarinic receptors in the heart (e.g. sinus node)
  • Negative inotropic and chronotropic responses
• Hyperkalaemia:
  • Fasciculations following administration of suxamethonium cause release of potassium from muscles
  • Patients with burns, nerve damage or neuromuscular disease, closed head injury and other trauma may develop proliferation of extrajunctional acetylcholine receptors
  • If proliferation is great enough, hyperkalaemia causing cardiac arrest may ensue
• Raised intraocular pressure
• Raised intragastric pressure
  • Increases of 5-40 cm H2O in heavily muscled patients due to fasciculations
• Post-operative myalgia
  • Common in patients who receive large doses
  • Incidence 1-20%
• Prolongation of neuromuscular blockade in patients with plasma cholinesterase deficiency

Further Reading

• Long N. Sugammadex. LITFL