Intermediate-acting nondepolarising NMBDs

[SH4:p231-241]

Long-acting vs intermediate-acting

Compared to long-acting nondepolarising NMBDs, intermediate-acting NMBDs:

• More efficient clearance
• More expensive
• Similar onset rate of maximum neuromuscular blockade
  * Except for rocuronium
• Approximately 1/3 the duration of action of long-acting nondepolarising NMBDs
• 30-50% more rapid rate of recovery
• Minimal to absent cumulative effects
• Minimal to absent cardiovascular effects

The priming principle

For other intermediate-acting non-deploarising NMBDs, onset of action is accelerated by:

• Inital small subparalysing dose (approximately 10% of the ED95)
• Followed by the larger dose (2 to 3 times the ED95) in approximately 4 minutes

Mechanism of the priming principle

1. Initial binding of spare receptors results in no observable clinical effects
2. Subsequent deepening of the blockade

Reversal

NMJ blockade by intermediate-acting nondepolarising NMBDs are reliably antagonised by anticholinesterase within 20 minutes

Rapacuronium

[CEACCP 2004 Vol 4(1) "Pharmacology of neuromuscular blocking drugs"]

• Withdrawn in USA in March 2001
  * Due to high incidence and severity of bronchospasm
• Less potent
  --> Given in large doses
  --> Rapid onset of action
• Short duration of action
• Rapidly cleared by hepatic uptake and deacetylation
  * 3-desacetylrapacuronium has more potent NMJ blockade than the parent drugs
• Causes histamine release
  --> Bronchospasm