Benzodiazepine overdoses

Although flumazenil binds with high affinity to the benzodiazepine site of GABAa receptors, it has practically no action when given alone. However, flumazenil competitively blocks the action of benzodiazepine site agonists. Flumazenil can be used to terminate the action of benzodiazepines, e.g., after a benzodiazepine overdose. It may also serve as a diagnostic tool in this regard. 

Pharmacodynamic tolerance to the psychomotor effects of benzodiazepines has been demonstrated after single or multiple doses (File 1985 Greenblatt and Shader 1978 Rosenberg and Chiu 1985). Pharmacodynamic tolerance to the anxiolytic effect (over a 6-month period) has not been demonstrated (Rickels et al. 1983), and clinical experience supports the view that many patients with anxiety disorders require long-term therapy with benzodiazepines or alternative antianxiety agents. An important clinical consequence of tolerance to sedative effects is observed in benzodiazepine overdoses, when patients may initially be... 

The only medication that blocks GABA activity is flumazenil (Mazicon). Flumaze-nil is used only in the emergency room or in an inpatient hospital setting to treat benzodiazepine overdose. It quickly and reliably reverses the toxic effects when a patient has accidentally or purposefully taken an overdose. Restricted to emergency situations, flumazenil is never used on a routine basis. 

Suspected benzodiazepine overdose The recommended initial dose is 0.2 mg (2 mL) administered IV over 30 seconds. If the desired level of consciousness is not obtained after waiting 30 seconds, a further dose of 0.3 mg (3 mL) can be administered over another 30 seconds. Further doses of 0.5 mg (5 mL) can be administered over 30 seconds at 1-minute intervals up to a cumulative dose of 3 mg. Most patients with benzodiazepine overdose will respond to a cumulative dose of 1 to 3 mg, and doses beyond 3 mg do not reliably produce additional effects. 

Most cases of pure benzodiazepine overdose recover within 24 8 hours with simple supportive treatment. Gastrointestinal decontamination is probably not warranted, since it is unlikely to affect the outcome. 

Singh PK. Flumazenil and suspected benzodiazepine overdose. J Accid Emerg Med 2000 17(3) 214. 

Combined use of any of the drugs in this category increases the risk of death. While a single drug may not depress respiration markedly, a combination of drugs can do so. The antidote for benzodiazepine overdose is an intravenous injection of Romazi-con (flumazenil). 

Compared to barbiturates, benzodiazepines are relatively safe medications that produce little tolerance and suppression of REM sleep, and benzodiazepine overdoses are much less common. However, benzodiazepines are not without unwanted side effects. As mentioned above, longer-acting benzodiazepines can produce residual drowsiness, grogginess, and weakness the next day (benzodiazepines are also muscle relaxants). Benzodiazepines can produce rebound insomnia, in which the person experiences significant insomnia after he or she stops taking the medication. This is particularly true with benzodiazepines that have short half-lives. To avoid this, the patient should never stop cold turkey rather, the dosage should be slowly tapered off over several days to a week. 

Flumazenil reverses the sedative actions of benzodiazepines. However, its duration of action is short and its antagonism of respiratory depression unpredictable. Therefore, the use of flumazenil in benzodiazepine overdose must be accompanied by adequate monitoring and support of respiratory function. 

In a retrospective analysis of 352 consecutive cases of fatal overdose, temazepam accounted for 65% of all deaths from benzodiazepine overdose (11). Acute rhab-domyolysis, usually associated with intravascular injection, has been seen after an oral overdose of temazepam (SEDA-17, 45). 

Patients treated for benzodiazepine overdose may experience CNS excitation... 

Benzodiazepine overdose 0.2 mg over 30 seconds can administer 0.3 mg over next 30 seconds can administer 0.5 mg over 30 seconds after 1 minute maximum 5 mg... 

Safety and efficacy for reversal of benzodiazepine overdose, general anesthesia induction or resuscitation of a ne A/born have not been established, but anecdotal data suggest similar safety and efficacy as for conscious sedation... 

Flumazenil (Romazicon) is a benzodiazepine antagonist that can reverse the CNS depressant effects of these agents. It should be used with caution in acute intentional benzodiazepine overdoses. Because acute benzodiazepine overdoses generally result in only mild toxicity, it has limited clinical utility in this setting. Flumazenil s use in the acute benzodiazepine intoxicated patient may lead to an unnecessarily long observation period after fumazenil s infusion. This observation is necessary to be certain that reoccurrence of benzodiazepine toxic effects do not occur... 

Trade names Anexate Lanexat Romazicon (Roche) Indications Benzodiazepine overdose Category Benzodiazepine antagonist Half-life terminal 41-79 minutes... 

Benzodiazepines may be identified and quantified in serum, generally by HPLC, but such quantitative information is not warranted in cases of benzodiazepine overdose because serum levels are not predictive of severity of intoxication. However, a urine or serum immunoassay screening test for benzodiazepines is valuable to aid in the evaluation of patients with an unlmown cause of CNS depression. 

Weinbroum AA, Haishon R, Sorkine P. A risk-benefit assessment of flumazenil in the management of benzodiazepine overdose. Drug Saf 1997 17 181-196. 

Flumazenil is an antidote that antagonizes actions of benzodiazepines on the CNS by blocking receptors. It is used for complete or partial reversal of sedative effects of benzodiazepines where general anesthesia is induced or maintained with benzodiazepines, where sedation is produced with benzodiazepines for diagnostic or therapeutic procedures, and for the management of benzodiazepine overdose. 

The primary indications for the use of flumazenil are the management of suspected benzodiazepine overdose and... 

Is flumazenil useful in reversing the respiratory depression caused by benzodiazepine overdose ... 

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