Flumazenil , and

Flumazenil Flumazenil and nalmefene can induce seizures in animals. Remain aware of the potential risk of seizures from agents in these classes. 

Seizures The use of flumazenil has been associated with the occurrence of seizures. These are most frequent in patients who have been on benzodiazepines for long-term sedation or in overdose cases where patients are showing signs of serious cyclic antidepressant overdose. Individualize the dosage of flumazenil and be prepared to manage seizures. 

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

File SE, Zharkovsky A, Hitchcott PK. Effects of nitrendepine, chlordiazepoxide, flumazenil and baclofen on the increased anxiety resulting from alcohol withdrawal. Prog Neuropsychopharmacol Biol Psychiatry 1992 16 87-93. 

Several benzodiazepine antagonists, such as flumazenil, and inverse agonists (compounds with opposite physiological effects to benzodiazepines), such as ethy 1-[3-carboline-3-carboxy 1 ate, competitively inhibit the binding of benzodiazepines. 

The effects of flumazenil and midazolam on adrenocorti-cotrophic hormone and cortisol responses to a corticotro-phin-releasing hormone challenge have been assessed in eight healthy men (412). Flumazenil significantly reduced adrenocorticotrophic responses compared with... 

Whitwam JG. Flumazenil and midazolam in anaesthesia. Acta Anaesthesiol Scand SuppI 1995 108 15-22. 

Antagonism occurs when the action of one drug opposes the action of another. The two drugs simply have opposite pharmacodynamic effects, e.g. histamine and adrenaline on the bronchi exhibit physiological or functional antagonism or they compete reversibly for the same drug receptor, e.g. flumazenil and benzodiazepines exhibit competitive antagonism. 

GABA)-benzodiazepine receptors by flumazenil and (c) inhibition of false neurotransmitters by optimizing amino acid balance. ... 

Zolpidem and a newer agent, zaleplon, are nonbenzodiazepines used in sleep disorders. They activate BZt receptors (reversed by flumazenil) and are more selective hypnotics because they are not effective in chronic anxiety, for seizure disorders, or for muscle relaxation. Possibly less tolerance and lower abuse liability and dependence than BZs. 

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). 

Combination studies The combination of intranasal midazolam 0.53 mg/kg and intranasal sufentanil 1 microgram/kg resulted in over-sedation in a 3-year-old girl, which responded to a combination of flumazenil and naloxone [ISO ]. 

Heard C, Creighton P, Lerman J. Intranasal flumazenil and naloxone to reverse over-sedation in a child undergoing dental restorations. Paediatr Anaesth 2009 19 795-9. 

Flumazenil has been used as a non-specific treatment in patients with hepatic encephalopathy [88, 89. However, it was effective in only some subjects in a double-blind, placebo-con-trolled, crossover study in 527patients with cirrhosis and hepatic encephalopathy grade III and IVa, of whom 265 received flumazenil and 262 received placebo [90 ]. There was improvement of the neurological score in 18% of the patients with grade III encephalopathy and in 15% of those with grade IVa compared with 3.8% and 2.7% respectively of those who received placebo electroencephalography improved in 28% and 22% compared with... 

In a single-dose, crossover, double-blind, placebo-controlled study of flumazenil and placebo in 16 subjects with Parkinson s disease, scores on the Unified Parkinson s Disease Rating Scale tended to improve, but the effect was not significant the most common adverse events were light-headedness or dizziness [92 ]. 

Butler TC, Rosen RM, Wallace AL, Amsden GW. Flumazenil and dialysis for gabapentin-induced coma. Ann Pharmacother 2003 37(1) 74-6. 

Spivey WH. Flumazenil and seizures analysis of 43 cases. Clin Ther 1992 14(2) 292-305. 

---