Pancuronium

[SH4:p228-231]

Structure

• Bisquaternary aminosteroid nondepolarising NMBDs

Pharmacodynamics

Effects by systems

CVS

• Pancuronium produces 10-15% increase in HR, MAP, and CO, due to
  * Selective cardiac vagal blockade (atropine-like effect limited to cardiac muscarininc receptors)
  * Activation of sympathetic nervous system
• Increased incidence of cardiac dysrhythmia in patients on digoxin

Others

• Does NOT release histamine

Pharmacokinetics

Distribution

• Variable protein-binding reported (30% - 87%) [PI]

Metabolism

About 10-40% of a single dose undergoes hepatic deacetylation

• Metabolites (after deacetylation) include:
  * 3-desacetylpancuronium
  * 17-desacetylpancuronium
  * 3,17-desacetylpancuronium
• 3-desacetylpancuronium is about 50% as potent as pancuronium at the NMJ
• Other metabolites have minimum effects

Elimination

• 80% excreted unchange in urine
  * 60% [CEACCP 2004 Vol 4(1) "Pharmacology of neuromuscular blocking drugs"]
• 10% excreted unchanged in faeces [PI]

In renal failure, plasma clearance of pancuronium is decreased by 33% to 50%

Action profiles

• Onset of action = 3-5 minutes
• Duration = 60-90 minutes

Pharmaceutics

Presentation

• 2mg/mL in 2 mLs (i.e. 4mg in 2mLs)
• Store at 2-8 degrees

Composition

• Active
  --> Pancuronium
• Inactive
  * Sodium acetate 2mg/mL
  * Sodium chloride 3mg/mL
  * Water
• pH = 3.5 - 4.2

Clinical

Administration

• ED95 = 70mcg/kg [SH4]
• Dose range = 0.05 - 0.15 mg/kg for tracheal intubation [PI]

Special considerations

Acid-base imbalance

• Respiratory acidosis enhance the NMJ blockade effect
• Effect of metabolic acidosis and respiratory/metabolic alkalosis = inconsistent

Liver impairment

Total biliary obstruction and hepatic cirrhosis
--> Increased Vd, decreased clearance, and prolonged elimination halflife of pancuronium
--> Larger initial dose is necessary, but duration of NMJ blockade is prolonged

Elderly

Ageing
--> Decreased renal function
--> Decreased plasma clearance of pancuronium
--> Prolonged elimination half-time and duration or action
* There is no change in pharmacodynamics