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
                          3.1.3.7.2.2. Intermediate-acting nondepolarising NMBDs
 3.1.3.7.2.2.2. Cisatracurium 

Cisatracurium

[SH4:p240-p241]

Quick summary

 

 

Usage

What is the drug used for?

Structure

Structure

  • Benzylisoquinolinium nondepolarising NMBD
  • One of the ten stereoisomers of atracurium
    * About 15% of atracurium

Structure-activity relationship

Cisatracurium vs atracurium

  • Onset of cistracurium is slightly slower than atracurium
  • Cisatracurium cause less histamine release than atracurium

Pharmacodynamics

Side Effects/Toxicity

  • Cisatracurium is devoid of histamine-release effects
    * Unlike atracurium

Pharmacokinetics (PK)

Absorption

IV

Distribution

  • Vd = 121-161 mL/kg

Metabolism

  • Principally by Hofmann elimination at physiological pH and temperature
    * 77%
  • Renal clearance responsible for 16%
    * i.e. excreted unchanged in urine
  • Ester hydrolysis by nonspecific plasma esterase does not seem to be involved in clearance
    * Ester hydrolysis is the main route of clearance of atracurium
  • Metabolites are inactive

Hofmann elimination

  • Forms laudanosine and a monoquaternary acrylate
  • Monoquaternary acrylate can undergo
    * Hofmann elimination (But much slower rate than cisatracurium)
    * Hydrolysis (into monoquaternary alcohol)
  • Laudanosine concentration after cisatracurium is a lot less than after atracurium
    * Possibly due to few molecules of cisatracurium administered

Elimination

  • Metabolites are cleared by liver and kidney
  • 16% of the drugs excreted unchanged in urine
  • Clearance = 4.7 - 5.7 mL/kg/min
  • Elimination half-life = 22 - 29 min

Action profile

  • Onset of action = 3 - 5 minutes
  • Duration of action = 20 - 35 minutes
  • Rate of spontanous recovery is not influenced by prolonged infusion
    * Unlike vecuronium

Pharmaceutics

Presentation

  • 5 mg in 2.5 mLs (2mg/mL)
  • 10 mg in 5 mLs (2mg/mL)
  • 150 mg in 30 mLs (5mg/mL)

Composition

  • Active = Cisatracurium besylate
  • Inactive = Benzenesulfonic acid

Clinical

Administration

  • ED95 = 0.05 mg/kg
    * c.f. Atracurium ED95 = 0.2 mg/kg
  • Recommended intubation dose for adults = 0.15 mg/kg
    --> Intubation condition about 120 seconds after injection
  • Maintenance = 0.03mg/kg
    --> Provides additional 20 minutes of NMJ blockade
  • Infusion
    * Initial rate = 0.18 mg/kg/hour
    * Maintenance infusion = 0.06-0.12 mg/kg/hour
    * Infusion dose should be reduced by up to 40% when administered during isoflurane or enflurane anaesthesia

Special consideration

Elderly

  • Onset of action is delayed approximately by 1 minute
    * Due to slower biophase equilibration

Hepatic and renal dysfunction

  • No clinically important difference in pharmacokinetics of cisatracurium

Paediatrics

  • Shorter clinical effective duration
  • Faster recovery profile

Trivia

History

 

Others

Brand name = Nimbex