Core pharmacology

Class Group

Antidote

Legacy Cicm Level

Level 3

Indications Uses

1. as an aid to weaning and neurological assessment of ventilated patients who have received benzodiazepine sedation during intensive care
2. as part of the ‘wake-up’ test during scoliosis surgery
3. to reverse oversedation after endoscopy and
4. for diagnosis of, and assessment after, benzodiazepine overdose.

Chemical Pharmaceutics

imidazo-benzodiazepine

Presentation

clear, colourless solution containing 100 micrograms/ml of flumazenil

Main Action

Reversal of the actions of benzodiazepines

Mechanism of action

- competitive reversible antagonist at benzo site on GABA-A receptor
- only intrinsic effect is slight anticonvulsant effect

Onset Peak Duration

Onset: 30-60 sec
Duration: 15-140 min

need repeated doses to prevent relapse

Adverse Effects Toxicity

Minor:
- headache/visual symptoms/↑anxiety/N&V
Major:
- can cause dangerous convulsions if:
> benzo’s being taken for epilepsy
> mixed ODs with CNS stimulants & antidepressants
- seizures & severe withdrawal if taking benzo’s chronically

Absorption

Well absorbed orally (but significant first-pass hepatic metabolism, so not given by this route)

Protein binding

50%

Volume of distribution

0.9 L/kg

Metabolism

Liver
Inert metabolites: carboxylic acid and glucuronide

Excretion

Urine: 95%
Unchanged: 0.1%

Clearance

700-1100 ml/min

Half-life

53 mins

Special Points

improves the quality of emergence from
anaesthesia
reduces post-operative shivering

Route And Dose

IV
Bolus: Titrated in 100mcg increments
Total max adult dose: 1mg/5 mins, 3 mg/1 hr
Infusion: 100-400mcg/hr

question diagnosis if no response to repeated doses