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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Benzodiazepines such as Valium (diazepam) or Versed (midazolam), as used in dental procedures for intravenous sedation, have been a boon to the profession. Yet in the event of sedation problems, no agent exists that consistently reverses all clinical effects of these drugs. This problem does not exist with narcotics, frequently employed in tandem with benzodiazepines, since an effective reversal agent, Narcan (naloxone hydrochloride), exists. It would be advantageous to effectively reverse benzodiazepines in cases of acute emergency with respiratory depression or paradoxical reactions, and to allow quick, full recovery after short dental procedures. None of the drugs currently available for benzodiazepine reversal, such as physostigmine, give consistent clinical results. The purpose of this paper is to discuss Flumazenil, a new specific benzodiazepine receptor antagonist, and its possible use for dental sedation procedures.
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PMID:Benzodiazepine reversal with flumazenil--a review of the literature. 135 May 1

Flumazenil is effective in reversing sedation resulting from benzodiazepine (BZD) toxicity. Its use for other causes of sedation have not been well described. A 23-y-old male was found unconscious. Upon being aroused, the patient stated he had recently ingested 1 1/2 bottles of vodka/beer and 250 mg of diazepam. Physical examination revealed shallow breathing and respiratory depression. Arterial blood gases were consistent with the clinical diagnosis of respiratory depression (pH 7.34, pCO2 47, pO2 99). However, after receiving 3 mg of flumazenil, the respiratory depression improved so that the patient no longer required intubation. The drug screen returned negative for BZDs and the patient had a blood alcohol level of 332 mg/dl. He later denied BZD use. The patient's clinical course improved throughout the study period, and mechanical ventilation was avoided. This report reflects a possible role for flumazenil in reversing the respiratory depression produced by ethanol ingestion.
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PMID:Reversal of ethanol-induced respiratory depression by flumazenil. 145 8

The influence of diazepam, an agonist, and flumazenil (Ro 15-1788), an antagonist of the benzodiazepine receptor, on repetitive firing of action potentials in cultured spinal neurons and on voltage-dependent Na+ currents in cultured N2A neuroblastoma cells was examined. The effects were compared to those of the antiepileptics phenytoin and carbamazepine and the local anesthetic lidocaine. The whole-cell configuration of the patch-clamp technique was used for potential and current recording. Diazepam (10 microM) or phenytoin (10 microM) reduced the duration of repetitive action potential discharges in 50 or 67% of the spinal neurons, respectively. At a concentration of 100 microM repetitive firing was completely blocked. Flumazenil (100 microM) had no effect. In N2A neuroblastoma cells diazepam, phenytoin, carbamazepine and lidocaine, but not flumazenil, at a concentration of 100 microM reduced the Na+ current to 60-67% of control. At 10 microM no or only a weak depression was seen with any drug. In the presence of diazepam (100 microM) the Na+ channel inactivation curve was shifted in the hyperpolarizing direction by -4.8 +/- 0.5 mV. Phenytoin, carbamazepine and lidocaine (all 100 microM) caused stronger shifts of -17.4 +/- 2.1, -10.6 +/- 0.9 and -17.0 +/- 2.1 mV, respectively. Inhibition of the Na+ current by diazepam increased use-dependently over 9 depolarizing pulses repeated at high frequency (200 Hz), whereas use-dependent effects of the other compounds developed less rapidly. At a low stimulation rate (7 Hz) use-dependent block was pronounced with lidocaine, but weak or absent with diazepam and carbamazepine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Action of diazepam on the voltage-dependent Na+ current. Comparison with the effects of phenytoin, carbamazepine, lidocaine and flumazenil. 165 Nov 46

Ethanol possesses anxiolytic and anticonflict effect in low dose, but exhibits consciousness depression in higher serum level. It also has addictive effects on benzodiazepines (BZD) and its mechanism has been thought to be closely related to GABA-BZD receptor complex. Flumazenil is a well-known potent antagonist in benzodiazepine intoxication. It can restore the patients' consciousness in case of BZD overdose in comatose condition. In the treatment of ethanol intoxication, flumazenil has not been well-accepted as an antidote. We report a case of severe ethanol intoxication (serum level: 512 mg/dl) with deep coma. Flumazenil 0.5 mg restored her consciousness 90 mins after antidote had been administrated. According to the literature, improvement of conscious level was not due to decay of serum ethanol level but flumazenil itself, which has potential benefit to the condition of ethanol intoxication. This effect is delayed as compared with its using in BZD overdose.
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PMID:[Ethanol intoxication treated with flumazenil: a case report]. 166 90

Flumazenil acts as an antidote for pharmacological and toxic effects due to benzodiazepines. Several isolated observations and short uncontrolled series have also suggested a possible effect against the impairment of consciousness induced by pure alcohol intoxication. Patients admitted in the emergency department with coma related to acute alcohol (ALC) or pure benzodiazepine (BZD) intoxication were randomized and treated blindly with either placebo or 1 mg flumazenil. A modified Glasgow score was used to observe the evolution of consciousness. In the 18 ALC patients, 1 mg flumazenil was not more effective than placebo, whereas it appeared to be very active in the BZD group. However, an open administration of higher doses of flumazenil (2-5 mg) in 11 ALC patients, whose condition had not initially improved, was followed by clear improvement of consciousness in five of them. Flumazenil, administered at a dose usually active against BZD sedation, does not improve CNS depression induced by ALC intoxication. Higher doses could be more effective in some patients, but it should also be verified in a placebo-controlled trial.
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PMID:Efficacy of flumazenil in acute alcohol intoxication: double blind placebo-controlled evaluation. 167 45

Flumazenil, a benzodiazepine antagonist, reliably reverses midazolam-induced sedation; however, its effect on respiratory depression has not been established completely. Twelve healthy volunteers received sufficient midazolam (0.13 +/- 0.01 mg.kg-1 mean +/- SE) to render them unresponsive to verbal command; they then received flumazenil 1.0 mg or placebo (flumazenil vehicle) in a randomized, double-blind fashion. Ventilatory drive was measured before and after administration of midazolam, as well as 3, 30, 60, and 120 min after administration of flumazenil or placebo. Seven to 30 days later, the study was repeated, with subjects receiving placebo or flumazenil (whichever they had not received during their first trial). Midazolam caused significant decreases in the slope of the CO2 response (-29 +/- 5%; P less than 0.005); minute ventilation (VE) at end-tidal CO2 tension (PETCO2) = 46 mmHg (-28 +/- 4%; P less than 0.001), and tidal volume at PETCO2 = 46 mmHg (-44 +/- 4%; P less than 0.005). Three minutes after intravenous administration of flumazenil 1.0 mg, VE46 and tidal volume increased to 108 +/- 6% and 105 +/- 6%, respectively, of their premidazolam values; at the same time after administration of placebo, VE46 and tidal volume remained significantly depressed (between groups, P less than 0.005 for each variable). Thirty minutes later, these variables did not differ between groups, probably because the effects of flumazenil and midazolam were diminishing.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Flumazenil antagonism of midazolam-induced ventilatory depression. 185 5

Use of the benzodiazepine antagonist flumazenil may inhibit the effects of benzodiazepines in a competitive manner. The only known partially agonistic effect of flumazenil is a weak anticonvulsive action at high doses. However, reports have claimed that flumazenil reduces the MAC of isoflurane in animal studies. Other reports have found that antagonizing midazolam-induced sedation or anesthesia by flumazenil led to an increase in respiratory depression. The aim of this study was to examine whether flumazenil i.v. increases fentanyl-induced respiratory depression. METHODS. In two separate sessions, ten healthy young volunteers were given either 0.0027 mg/kg fentanyl alone or 0.0027 mg/kg and 1 mg flumazenil i.v. over 4 min each time. The CO2 rebreathing method was used to determine the ventilatory response. RESULTS. Fentanyl alone brought about a significant reduction in CO2 response, characterized by a shift to the right and a decrease in the slope of the rebreathing curve (from 1.95 +/- 0.76 l.min-1.mmHg-1 to 0.86 +/- 0.53 l.min-1.mmHg-1). The infusion of additional flumazenil caused similarly significant respiratory depression (from 2.21 +/- 1.0 l.min-1.mmHg-1 to 0.77 +/- 0.38 l.min-1.mmHg-1). In both groups changes persisted for at least 120 min. No statistically significant differences between the two groups could be detected. CONCLUSION. Flumazenil does not enhance fentanyl-induced respiratory depression. Flumazenil's weak, partially agonistic action is therefore of no clinical importance.
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PMID:[The effect of flumazenil on alfentanyl-induced respiratory depression]. 186 67

Flumazenil, a specific antagonist of benzodiazepines, was administered to adult patients receiving treatment at ICU, and its utility to hasten recovery from sedation was evaluated in 40 patients and its usefulness for differential diagnosis of sedated conditions was also evaluated in 5 patients. The efficacy rate for recovery from sedation induced by benzodiazepines was 85.0%. Moreover, flumazenil was considered to be useful for differentiation of sedated conditions when causes were unknown. Depression of respiration improved in association with improvement of consciousness level. In some patients an elevation in blood pressure was also observed with improved consciousness.
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PMID:[A study on the utility of flumazenil for patients in the ICU]. 197 63

Flumazenil is a recently discovered pharmacologic antagonist of the CNS effects of benzodiazepines. It acts by binding CNS benzodiazepine receptors and competitively blocking benzodiazepine activation of inhibitory GABAergic synapses. Animal studies and some human studies appear to demonstrate that flumazenil has weak intrinsic agonist activity; on the other hand, studies are inconclusive in demonstrating any inverse agonist effects of this agent. Evidence available suggests that flumazenil is well tolerated in human beings over a broad range of doses when given either orally or parenterally and does not produce serious adverse effects. In the setting of isolated benzodiazepine overdose, flumazenil is capable of completely reversing coma within one to two minutes, with this effect lasting between one and five hours. Repeat doses can be given safely to reverse recurrent effects of longer-acting benzodiazepines. Flumazenil is undergoing further evaluation by the Food and Drug Administration; should this drug receive approval, it is likely to be used in emergency departments as well as in a variety of other clinical settings. First, it could be used to effect rapid reversal of benzodiazepine-induced sedation that has been administered to facilitate medical, orthopedic, and surgical procedures, particularly in the event of inadvertent respiratory depression. Second, flumazenil might have a therapeutic role in the management of patients who have taken benzodiazepine overdoses. Although most of these patients can be managed successfully with supportive therapy alone, it is possible that the use of flumazenil may obviate the need for intubation and respiratory support in such patients and eliminate the possible adverse effects of even short-term endotracheal intubation. Finally, flumazenil could have both diagnostic and therapeutic value in patients with acute alterations of mental status of unknown etiology, particularly when possible drug overdose is a consideration. Because flumazenil appears to be specific in its antagonism of benzodiazepine-induced respiratory and CNS depression, it could be used empirically to confirm or exclude a role of benzodiazepines in the generation of mental status changes in the setting of overdose or coma of unknown origin. This in turn might obviate the need for further expensive (eg, computed tomography) and sometimes invasive (eg, lumbar puncture) diagnostic modalities. This might be particularly useful because there is nothing about benzodiazepine-induced coma that clearly distinguishes it from other causes of coma; thus, there are no signs or symptoms that may reasonably allow benzodiazepine overdose to be confirmed or eliminated on clinical grounds. Further studies will continue to define the ultimate use of this new agent.
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PMID:Flumazenil: a new benzodiazepine antagonist. 180 17

Of the numerous benzodiazepines currently available, only a few are used in anaesthetic practice. Midazolam is utilised as a premedicant, sedative, and an induction agent and produces minimal depression of ventilation or of the cardiovascular system. The anticonvulsant activity is similar to that of diazepam. In neuroanaesthesia midazolam may be an acceptable alternative to other intravenous induction agents like barbiturates or etomidate in patients with compromised intracranial compliance. Midazolam produces dose-related reductions in cerebral blood flow and cerebral oxygen consumption. However, midazolam does not necessarily prevent increases in intracranial pressure during induction of anaesthesia. In the electroencephalogram (EEG) midazolam produces a reduction in alpha-activity, an increase in theta-delta-activity and low-voltage beta-activity. Midazolam like other benzodiazepines does not affect early components of auditory and somatosensory evoked responses, whereas late cortical responses may be suppressed. Flumazenil, a specific benzodiazepine antagonist, has been demonstrated to be effective in reversing benzodiazepine-induced sedation. In the EEG midazolam-induced changes vanish almost instantaneously. Flumazenil is also effective in restoring the amplitudes of cortical auditory and somatosensory evoked responses. However, as has been demonstrated in head-injured patients and animal experiments after incomplete cerebral ischaemia, increases in cerebral blood flow and intracranial pressure cannot be excluded after flumazenil administration. When utilising flumazenil for wake-up procedures in midazolam-sedated patients with pathological intracranial compliance, flumazenil has to be titrated very carefully in low doses over prolonged periods.
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PMID:Midazolam and flumazenil in neuroanaesthesia. 210 78


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