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
 3.1.3.7.2.2.4. Rocuronium 

Rocuronium

[SH4:p238-p240]

Quick summary

 

 

Usage

 

 

Structure

Structure

  • Monoquaternary aminosteroid nondepolarising NMBD

Pharmacodynamics

Effects by systems

CVS

  • Like other aminosteroid NMBDs,
    --> Rocuronium has no CVS or histamine release effect
  • But unlike other aminosteroid NMBDs,
    --> Rocuronium has a slight vagolytic effect at high doses

Muscle relaxation

  • Laryngeal muscles are more resistant to the effect of rocuronium than adductor pollicis
    * Rapid onset of action at adductor pollicis, like suxamethonium
    * But at laryngeal adductors, action of rocuronium is delayed compared to suxamethonium
  • Laryngeal adductor muscles and diaphragm are more resistant to rocuronium than adductor pollicis
    --> Complete suppression of single-twitch response at the adductor does not confirm laryngeal muscle and diaphragm are paralysed

Pharmacokinetics (PK)

Absorption

IV or IM

Distribution

  • Vd = 203 mL/kg

Metabolism

  • Deacetylation does NOT occur
  • Unlike vecuronium, rocuronium does not have active metabolite

Elimination

  • Rocuronium is mostly excreted unchanged in the bile
    * Up to 50% in 2 hours
  • Renal excreation of rocuronium may be > 30%
  • Clearance = 3.7 mL/kg/min

Action profile

  • Onset of action = within 1 - 2 minutes
  • Duration of action = 20 - 35 minutes
    * With 2 x ED95
    * Action is longer at higher doses
  • Low potency
    --> Large number of rocuronium molecules are administered
    --> Greater number of molecules available to diffuse into the NMJ
    --> More rapid onset of action
  • At doses of 3 or 4 times the ED95
    --> Onset of action resembles suxamethonium
  • Elimination half-time = 73 minutes

Pharmaceutics

Presentation

  • 25 mg in 2.5 mLs
  • 50 mg in 5 mLs
  • 100 mg in 10 mLs

Composition

  • Active = Rocuronium bromide
  • Inactive
    * Sodium acetate
    * NaCl
    * Acetic acid
    * Water
  • pH 3.8 - 4.2

Storage

  • Store at 2 - 8 degrees Celcius
  • Discard after 12 weeks in room temperature

Clinical

Administration

  • ED95 = 0.3 mg/kg
  • Rocuronium 0.45 mg/kg
    --> Acceptable intubation condition after 90 seconds
  • Rocuronium 0.6 mg/kg
    * Acceptable intubation condition after 60 seconds
    * Clinical duration (duration till recovery to 25% control twitch height) = 30 - 40 min
    * Total duration (duration till recovery to 90% control twitch height) = 50 minute
  • Rocuronium 1.0 mg/kg
    * Clinical duration = almost one hour
  • Maintenance dose = 0.15mg/kg
    * Given when twitch height has recovered to 25% of control height, or when there is 2-3 response to train of four stimulation
  • As infusion,
    * 0.3 - 0.6 mg/kg/hour
    * 0.3 - 0.4 mg/kg/hour with inhalational anaesthetics

NB:

  • Doses higher than 1.0 mg/kg do not improve speed of onset, but prolong the route of administration, and the dosage for each different route.

Interaction

Effects of rocuronium is increased in the following conditions

  • Hypokalaemia
  • Hypocalcaemia
  • Hypermagnesaemia
  • Hypoproteinaemia
  • Dehydration
  • Acidosis
  • Hypercapnia
  • Cachexia

Special consideration

Obesity

  • If the dosage is calculated based on real body weight
    --> Duration of action may be prolonged

Renal dysfunction

  • In renal failure, rocuronium may produce a modestly prolonged duration of action

Hepatic dysfunction

  • Liver disease increase Vd
    --> Can prolong duration of action

Elderly

(>70 year old)

  • Similar speed of onset
  • Prolonged duration of action
    * Due to decreased hepatic clearance
  • Pharmacodynamics is unchanged

Hypothermia

  • NMJ effect of rocuronium is increased and duration prolonged

Sugammadex

[Anesthesiology 2006 April Vol 140(4): "Sugammadex: A revolutionary approach to neuromuscular antagonism"]

  • A modified gamma-cyclodextrin
  • Forms very tight 1:1 complexes with aminosteroid-based relaxants
    --> Irreversible chelating agent for rocuronium, pancuronium, and vecuronium
  • Sugammadex does not have equal affinity with all aminosteroids
    * Reversal of pancuronium requires a larger dose
    * Trials cited seem to be based on rocuronium, but the editorial said it works well for vecuronium as well
  • Does not reverse the effect of benzylisoquinolinium NMBDs
  • Seems to have minimal side effects
  • Does not require co-administration of anticholinergic drugs
  • Depends entirely on renal elimination
    --> When rocumonium is bound to sugammadex, hepatic elimination is no longer available

Cyclodextrin

[Wikipedia]

  • Cyclodextrin are cyclic oligosaccharides
  • Alpha-cyclodextrin is a 6 sugar ring molecule
  • Beta-cyclodextrin is a 7 sugar ring molecule
  • Gamma-cyclodextrin is a 8 sugar ring molecule

Trivia

History

 

Others

Brand name = Esmeron