3. Pharmacology
          3.3. IV anaesthetic agents
              3.3.6. Benzodiazepine
 3.3.6.3. Flumazenil

Flumazenil

[SH4:p152]

  • Specific and competitive benzodiazepine antagonist
  • High affinity for benzodiazepine receptors
    * Minimal agonist activity
  • Metabolised by hepatic microsomal enzymes to inactive metabolites

Structure

  • 1,4-imidazobenzodiazepine derivative

Pharmacodynamics

Side effect

  • May precipitate acute withdrawal seizures
    * Administration to patients on antiepileptic drugs is not recommended
  • Does NOT cause acute anxiety, increased HR or BP
  • Does NOT alter MAC
  • No agonist effect on resting ventilation or psychomotor function in normal individual

Pharmacokinetics

Metabolism

  • Metabolism of flumazenil is by hepatic microsomal enzymes to inactive metabolites

Action profile

  • Duration of action = 30 to 60 minutes
  • Additional doses may be needed

Pharmaceutics

Presentation

  • 0.5mg / 5 mL

Composition

  • Active = Flumazenil (0.01%)
  • Inactive
    * Disodium edetate
    * Acetid acid
  • pH = 4.0

NB:

  • Aqueous solution, NOT in propylene glycol [PI]

Clinical

Administration

  • Initial IV dose of 0.2mg (8-15 microgram/kg)
    --> Reverse CNS effect within 2 minutes
  • Further doses of 0.1 mg IV can be given every 60 seconds
    * Up to a total of 1 mg IV
    * Usual total dose = 0.3 - 0.6 mg IV
  • Alternatively, continuous infusion at 0.1-0.4 mg/hour

NB:

  • In overdose of unknown drugs, failure to respond to more than 5 mg of flumazenil IV indicates intoxicants other than benzodiazepines

Overdose

  • Even when given at a dose of 100mg IV --> no symptoms of overdose were observed
    * [PI on MIMs]

Trivia

Brand name = anexate



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