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