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Flumazenil is a benzodiazepine receptor antagonist that can reverse the effects of benzodiazepines, although its use following benzodiazepine overdose is controversial. Medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. [16]
Many benzodiazepines (including midazolam) have longer half-lives than flumazenil. Therefore, in cases of overdose, repeated doses of flumazenil may be required to prevent recurrent symptoms once the initial dose of flumazenil wears off. [citation needed] It is hepatically metabolised to inactive compounds which are excreted in the urine.
Flumazenil raises concerns with its tendency to induce benzodiazepine withdrawal, and symptoms include seizures and agitation. When a patient overdoses intentionally, benzodiazepines can actually mediate the effects of other lethal drugs in the system, so flumazenil's action to reverse its effects can actually be harmful. [6]
Although benzodiazepines are much safer in overdose than their predecessors, the barbiturates, they can still cause problems in overdose. [19] Taken alone, they rarely cause severe complications in overdose ; [ 161 ] statistics in England showed that benzodiazepines were responsible for 3.8% of all deaths by poisoning from a single drug. [ 21 ]
The antidote for an overdose of diazepam (or any other benzodiazepine) is flumazenil (Anexate). This drug is only used in cases with severe respiratory depression or cardiovascular complications. Because flumazenil is a short-acting drug, and the effects of diazepam can last for days, several doses of flumazenil may be necessary.
Finally, note that the benzodiazepine core is a privileged scaffold, which has been used to derive drugs with diverse activity that is not limited to the GABA A modulatory action of the classical benzodiazepines, [60] such as devazepide and tifluadom, however these have not been included in the list below. 2,3-benzodiazepines such as tofisopam ...
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Severe withdrawal syndromes can occur from these low doses of benzodiazepines even after gradual dose reduction. [73] [74] An estimated 30–45% of chronic low-dose benzodiazepine users are dependent and it has been recommended that benzodiazepines even at low dosage be prescribed for a maximum of 7–14 days to avoid dependence. [75]