Pharm 101: Vecuronium

Class

Paralytic agent

Pharmacodynamics

• Non-depolarising steroid neuromuscular blocking agent
• At low doses, acts predominately as a competitive inhibitor of Acetylcholine (ACH) at nicotinic receptors
• At higher doses, enters pore of ion channel causing more intense neuromuscular blockade
• Also blocks pre-junctional Na channels which interferes with ACH mobilisation at nerve endings

Pharmacokinetics

• IV use
• Undergoes rapid initial distribution phase followed by slower elimination phase
• Highly ionised therefore small volume of distribution 0.1L/kg
• Onset of action: within 1 minute
• Maximal effect at 3-5 minutes
• Intermediate-acting: duration of action 20-35 minutes
• Rapidly distributed to extracellular space
• Metabolism: liver
• Elimination: liver (75-90%) and kidney

Clinical uses

• Rapid Sequence Induction (RSI)
  • Dose 0.1mg/kg
• Clinical effects:
  • Initially motor weakness followed by skeletal muscles becoming flaccid and unexcitable to electrical stimulation
  • Larger muscles (e.g. abdominal, trunk, diaphragm) are more resistant to neuromuscular blockade and recover more rapidly than smaller muscles (e.g. facial, foot, hand)
  • Diaphragm is the last muscle to be paralysed

Sugammadex

• Sugammadex is a modified cyclodextrin antidote used for rapid reversal of rocuronium and vecuronium
• Binds tightly to rocuronium in a 1:1 ratio, and this complex is excreted unchanged in the urine
• This decreases free plasma concentration and establishes a concentration gradient for rocuronium to diffuse away from the neuromuscular junction back into circulation for further binding to free sugammadex
• Dosing varies for desired reversal effects:
  • 2mg/kg: reversal of shallow neuromuscular blockade
  • 4mg/kg: reversal of deeper blockade
  • 16mg/kg: immediate reversal following administration of single dose 1.2mg/kg rocuronium
• Adverse effects:
  • Anaphylaxis in 0.3% of patients receiving 16mg/kg dosage
  • Hypersensitivity reactions are common
  • Bradycardia (may progress rapidly to cardiac arrest)
  • Coagulopathy: 25% elevation of APTT and PT/INR values lasting up to one hour

Precautions/contraindications

• Enhanced neuromuscular blockade:
  • Myasthenia gravis
  • Aminoglycosides
• Reduced neuromuscular blockade:
  • Corticosteroids
  • Phenytoin
• Reduced clearance:
  • Hepatic failure
  • Advancing age

References

• The Royal Children’s Hospital Melbourne. Parkville, Victoria, Australia. July 2017. Medication guidelines: Vecuronium
• Katzung BG. Basic & Clinical Pharmacology. 14th ed. United States of America: McGraw-Hill Education; 2018. 476-484 p.