PS08 [Mar99] [Jul00]
Flumazenil: A. Formulated In propylene glycol in commercial preparation B. Inverse agonist C. Is slowly metabolised making resedation unlikely D. Does not reliably reverse sedation and resp depression (in large agonist dose ?) E. Is a partial agonist at mu opioid receptors
Option D has also been remembered as: D. May significantly reverse evidence of sedation whilst hypoxia or hypercapnia persist D. Reliably reverses the sedating effects of benzodiazepines but marked respiratory depression still can occur
Alternative answers to option D would seem most correct as
- it should still work in the presence of hypoxia and hypercarbia (if these are secondary to respiratory depression caused by decreased respiratory drive) AND
- it is quite reliable in reversing the effects of BZDs and as its duration of action is "30-60 mins" (Stoelting 3rd ed. p 138) compared with much longer durations of actions with longer acting BZDs, so respiratory depression may still occur.
In their absence suggest that B is the next best answer as it has "weak intrinsic agonist activity" Stoeting 3rd ed. p.138.
[Stoelting] 4th p152
Exclusive benxodiazepine antagonist with a high affinity for benzodiazepine receptors where it exerts minimal agonist activity.
It prevents or reverses all the agonist effects of benzodiazepines.
Duration of action - 30 -60 mins.
Mims states: Active. Flumazenil. Inactive. Disodium edetate, acetic acid, sodium chloride, sodium hydroxide in water for injections adjusted to pH 4.0.
Also, flumazenil DOES have some agonist activity...according to other texts It also has some inverse agonist activity to explain precipitating seizures in some people...
In support of preceeding statements, Peck & Williams says that flumazenil acts as:
- Competitive BZ antagonist.
- Some agonist activity.
- Inverse agonist activity.
(See also Goodman & Gillman).
Also, note the drug monograph states "While flumazenil reverses benzodiazepine-induced sedation, it has no proven effectiveness in the treatment of hypoventilation induced by benzodiazepines"
From Goodman & Gilman
- "...effects resembling those of inverse agonists sometimes have been detected at low doses"
- "...slight benzodiazepine-like effects often have been evident at high doses"
I think to then go all out and call it an "inverse agonist" would be less correct than the alternative options for D.