3. Old stuff
          3.1. Old pharm stuff (pre 2009)
              3.1.3. Pharmacology
                  3.1.3.7. Neuromuscular blocking drugs
                      3.1.3.7.2. Non-depolarising NMBDs
                          3.1.3.7.2.1. Long-acting nondepolarising NMBDs
 3.1.3.7.2.1.1. Pancuronium 

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