Benzodiazepines dependence may produce physical and psychological dependence after chronic (>6 months) use of commonly prescribed low-potency benzodiazepines.
Withdrawal symptoms (irritability, insomnia, tremulousness) appear within 1 to 2 days for short-acting benzodiazepines dependence and within 2 to 5 days for longer-acting drugs.
When administered to patients who have benzodiazepine induced CNS depression of benzodiazepines dependance, flumazenil produces rapid and dependable reversal of unconsciousness, respiratory depression, sedation, amnesia, and psychomotor dysfunction.
Flumazenil can be given before, during, or after the agonist to block or reverse the CNS effects of the agonist.
The usual clinical need is to reverse the effects of agonists given before flumazenil. Flumazenil has successfully reversed the effects of midazolam, diazepam, lorazepam, and flunitrazepam.
The onset is rapid, with peak effect occurring in 1 to 3 minutes, which coincides with the detection of C-flumazenil in human brain.
Tolerance and physical benzodiazepines dependence may occur with prolonged administration of pure agonists, and abrupt discontinuation or administration of an antagonist can result in a withdrawal syndrome.
Tolerance describes the phenomenon that the magnitude of a given drug effect decreases with repeated administration of the same dose or that increasing doses are needed to produce the same effect.Tolerance is not synonymous with dependence.
Physical benzodiazepines dependence is defined as a state of adaptation manifested by a drug class–specific withdrawal syndrome that can be elicited by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, or administration of an antagonist.