Flumazenil drug withdrawal

Drug withdrawal In individuals who have taken long-term benzodiazepines, flumazenil can provoke acute withdrawal reactions [122, 123 ] and extreme anxiety [124 ]. Duration of exposure to the benzodiazepine does not affect the intensity of withdrawal beyond the first week of exposure [125 ]. 

Although rare, benzodiazepine toxicity may occur from an overdose of the drug. Benzodiazepine toxicity causes sedation, respiratory depression, and coma. Flumazenil (Romazicon) is an antidote (antagonist) for benzodiazepine toxicity and acts to reverse die sedation, respiratory depression, and coma within 6 to 10 minutes after intravenous administration. The dosage is individualized based on the patient s response, widi most patients responding to doses of 0.6 to 1 mg. However, die drug s action is short, and additional doses may be needed. Adverse reactions of flumazenil include agitation, confusion, seizures, and in some cases, symptoms of benzodiazepine withdrawal. Adverse reactions of flumazenil related to the symptoms of benzodiazepine withdrawal are relieved by die administration of die benzodiazepine. 

Flumazenil is a competitive benzodiazepine antagonist with a half-life of approximately 1 hour. It is available only as an intravenous injection. Since its half-life is shorter than the drugs which it is used to antagonise, its beneficial effects are temporary. It is perhaps best used as a means of establishing a diagnosis before instituting appropriate supportive therapy. Flumazenil has been reported as inducing withdrawal symptoms in some habitual benzodiazepine users. 

Flumazenll [floo MAZ eh nill] is a GABA receptor antagonist that can rapidly reverse the effects of benzodiazepines. The drug is available by IV administration only. Onset is rapid but duration is short, with a half-life of about one hour. Frequent administration may be necessary to maintain reversal of a long-acting benzodiazepine. Administration of flumazenil may precipitate withdrawal in dependent patients or may cause seizures if a benzodiazepine is used to control seizure activity. Dizziness, nausea, vomiting, and agitation are the most common side effects. 

Although structurally unrelated to the benzodiazepines, these drugs act on the same macromolecular receptor complex but at different sites from the benzodiazepines their effects can be blocked by flumazenil, the receptor antagonist. Those described below are all effective in insomnia, have low propensity for tolerance, rebound insomnia, withdrawal symptoms and abuse potential but there are few data of their effects in long-term studies. 

One of the problems associated with benzodiazepine anxiolytics is rebound anxiety and/or insomnia, which may occur between dose intervals or after withdrawal of the drug [83, 84], In three experiments performed with squirrel monkeys, (92) (up to 20 mg/kg p.o.) did not cause any apparent physical or behavioural signs of withdrawal after abrupt discontinuation of treatment or even after attempted precipitation of withdrawal by administration of flumazenil. 

B. Specific drugs and antidotes. There are no specific antidotes available. Flumazenil and naloxone are not clinically effective. GHB withdrawal syndrome is managed with benzodiazepine (see p 415) sedation similar to other depressant withdrawal syndromes. Large doses may be needed. Withdrawal refractory to benzodiazepines is not uncommon and may benefit from the addition of barbiturates (p 486) or propofol (p494). 

Nervous system Seizures have been attributed to flumazenil [104, 105, 106, 107, 108, 109, 110, 111 ], including status epilepticus [112, 113 ], which can be fatal. However, it has been suggested that seizures are not a toxic effect of flumazenil, but are in many cases instead due to unmasking of the anticonvulsant effect of the benzodiazepine or to a severe benzodiazepine-withdrawal syndrome furthermore, in some cases they may be due to other drugs taken at the same time, such as tricyclic antidepressants [1143]. Thus, it has been recommended that flumazenil should not be given to patients who have used benzodiazepines for seizure disorders or to patients who have taken other drugs that increase the risk of seizures (e.g. bupropion, ciclosporin, cocaine, cyclic antidepressants, isoniazid, lithium, methylxanthines, monoamine oxidase inhibitors, and propoxyphene). 

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