Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012833 (dizziness)
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Flumazenil, a benzodiazepine antagonist, reverses the residual central nervous system effects of benzodiazepines. In this US double-blind, multicenter study, the efficacy of flumazenil was compared with that of placebo in antagonizing the effects of midazolam, a benzodiazepine used to induce intravenous conscious sedation. The mean dose of flumazenil was 0.7 mg, administered intravenously. At 5 minutes posttreatment, 82% of 131 flumazenil-treated patients, compared with 15% of 65 placebo-treated patients, demonstrated complete reversal of sedation. In 85% of patients who responded to flumazenil, this reversal of sedation was maintained throughout the 180-minute observation period. Psychomotor performance returned to prestudy levels 5 minutes posttreatment in 87% of the flumazenil-treated patients, compared with 28% of the placebo-treated patients. At the doses administered, flumazenil was less effective in reversing midazolam-induced amnesia, with only 60% of patients demonstrating partial recovery of memory. It was, nevertheless, more effective than placebo. Flumazenil was well tolerated. Dizziness (10%) and nausea (9%) were the most frequently reported adverse effects. Results of this study demonstrate that flumazenil antagonizes the central nervous system effects of midazolam after intravenous conscious sedation.
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PMID:Reversal of central nervous system effects by flumazenil after intravenous conscious sedation with midazolam: report of a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group I. 128 95

Flumazenil is a competitive benzodiazepine antagonist that rapidly reverses the residual effects of benzodiazepines following intravenous conscious sedation. In a double-blind, multicenter study, postoperative patients who had been sedated with intravenous diazepam were randomly allocated to receive intravenous doses of flumazenil (0.4 mg to 1 mg) or placebo. Levels of sedation and psychomotor impairment were evaluated prestudy, at baseline, and at 6 intervals from 5 to 180 minutes posttreatment. A global evaluation of effectiveness was made at the 5-minute assessment, and memory was assessed at the 180-minute assessment. Flumazenil (mean dose: 0.73 mg [7.3 ml]) was significantly more effective than placebo (mean dose: 8.9 ml) in reversing sedation, psychomotor impairment, and amnesia within 5 minutes after the start of administration. At the 5-minute posttreatment assessment, 84% of 102 flumazenil-treated patients (compared with 42% of 52 placebo-treated patients) experienced complete reversal of sedation. Ninety-two percent of 93 flumazenil-treated patients (compared with 41% of 46 placebo-treated patients) had normal psychomotor function. Reversal of amnesia at the 5-minute assessment was achieved in 75% of 101 flumazenil-treated patients and in 20% of 51 placebo-treated patients. Statistically significant differences between flumazenil and placebo were also observed at the 15-minute assessment. Thereafter there were no significant differences between the two treatment groups. Most (70%) flumazenil-treated patients exhibited no recurrence of sedation during the 180-minute assessment period. The most frequent adverse reaction in the flumazenil group was dizziness (6%). There were no serious adverse experiences related to the test drug. Flumazenil provided prompt, controlled reversal of residual effects, especially sedation, in the majority (84%) of patients recovering from intravenous conscious sedation induced by diazepam. For most (70%) of these flumazenil-treated patients, the reversal was maintained throughout the 180-minute assessment.
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PMID:Reversal of central benzodiazepine effects by flumazenil after conscious sedation produced by intravenous diazepam. The Flumazenil in Intravenous Conscious Sedation with Diazepam Multicenter Study Group I. 128 97

The efficacy and safety of flumazenil in antagonizing the central effects of the benzodiazepine midazolam was demonstrated in patients in whom conscious sedation was induced with midazolam plus an opioid (fentanyl, meperidine, or morphine). In a double-blind, multicenter study, 240 patients were administered flumazenil postoperatively at an average intravenous dose of 0.7 mg (7 ml) and 114 patients were administered an average dose of 9 ml placebo. Complete reversal of sedation was observed in 80% of flumazenil-treated patients and 30% of placebo-treated patients 5 minutes posttreatment. In 87% of patients who responded to flumazenil, the level of alertness was maintained throughout the 180-minute observation period. Midazolam-impaired psychomotor performance returned to normal 5 minutes posttreatment in 80% of the flumazenil-treated patients and 28% of the placebo-treated patients. Flumazenil was less effective in reversing midazolam-induced amnesia, with only 70% of flumazenil-treated patients (and 15% of placebo-treated patients) able to recall the picture shown them at the 5-minute assessment, and fewer patients able to recall pictures shown at later times. Flumazenil was well tolerated, although adverse effects were reported slightly more often than in the placebo group. The most frequent adverse events in both groups were dizziness and nausea. Vital signs were not affected.
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PMID:Reversal of central benzodiazepine effects by intravenous flumazenil after conscious sedation with midazolam and opioids: a multicenter clinical study. The Flumazenil in Intravenous Conscious Sedation with Midazolam Multicenter Study Group II. 128 96

A double-blind clinical trial was conducted to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist, in 146 hospitalized patients, who had had general anesthesia induced by midazolam and a long-acting opioid. Ninety-eight patients received flumazenil and 48 received placebo. Administered postoperatively at a mean intravenous dose of 0.84 mg (range: 0.2 mg to 1 mg), flumazenil reversed benzodiazepine-induced sedation to a greater extent than did placebo. At 5 minutes posttreatment, 61 (76%) of 80 flumazenil-treated patients and 7 (18%) of 40 placebo-treated patients had attained a score of 4 or 5 on the Observer's Assessment of Alertness/Sedation Scale, indicating that they were drowsy or fully awake and alert. This level of arousal was maintained for the full 180-minute posttreatment assessment period in 79% of flumazenil-treated patients. Between-group differences in mean change from baseline in level of alertness were statistically significant (P < 0.01) until 60 minutes posttreatment, when the spontaneous recovery of placebo-treated patients resulted in declining intergroup differences. The global efficacy rating (based on the physician's general impression of the effectiveness of the reversal of sedation 5 minutes after test drug administration) was good or excellent in 64 (80%) of the 80 flumazenil-treated patients and 5 (13%) of the 40 placebo-treated patients evaluated. Flumazenil, compared with placebo, was not associated with an increased frequency of operative-site pain, and no serious adverse effects of this benzodiazepine antagonist were reported. The most frequent adverse experiences in both treatment groups were nausea, shivering, and operative-site pain. Vomiting, dizziness, and injection-site reactions were also reported in > or = 5% of patients treated with flumazenil.
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PMID:Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia and use of a long-acting opioid in hospitalized patients: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Hospitalized Patients Study Group II. 128

Flumazenil was studied in a double-blind multicenter trial to confirm its efficacy and safety in antagonizing the central effects of benzodiazepines after general anesthesia (midazolam, short-acting narcotic, nitrous oxide) with muscle relaxants and selected potent volatile anesthetics as needed. One hundred seventy-two outpatients were randomly assigned to receive either flumazenil or placebo titrated to the point of reversal of sedation or a maximum dose of 1 mg of flumazenil or 10 ml of placebo. The test drug was given intravenously (0.2 mg flumazenil or 2 ml placebo) at 1-minute intervals. Tests of alertness, psychomotor function, and memory were conducted prestudy and at baseline before the administration of flumazenil and at 5-, 15-, 30-, 60-, 120-, and 180-minute intervals after administration. The changes from prestudy or baseline scores were analyzed to compare differences between treatment groups. Seventy-five percent of the 105 flumazenil-treated patients and 14% of the 55 placebo-treated patients who met the qualifications for efficacy evaluations obtained a criterion level of response as measured by the Observer's Assessment of Alertness/Sedation Scale. Most (76%) patients who were alert at 5 minutes maintained their level of wakefulness throughout the 180-minute observation period. All 172 patients were included in evaluations of safety. Fifty percent of 113 flumazenil-treated patients and 31% of 59 placebo-treated patients reported one or more adverse experiences. The most frequently reported were nausea, vomiting, and dizziness. Only 6 adverse effects in the flumazenil group and 1 in the placebo group were considered severe; the remainder were mild or moderate. None were considered serious or potentially serious. Postoperative administration of flumazenil (mean dose, 0.85 mg) safely provided a prompt, controlled reversal of the sedative and psychomotor effects of midazolam in most patients.
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PMID:Reversal of the central effects of midazolam by intravenous flumazenil after general anesthesia in outpatients premedicated with an opioid and a muscle relaxant: report of a multicenter double-blind clinical study. The Flumazenil in General Anesthesia in Outpatients Study Group II. 128 1

The degree of sedation and amnesia, subjective assessment of awakening and side effects after intravenous injection of 3-4 mg midazolam and 1 mg flumazenil or placebo were studied directly after colonoscopy, and on the first and the eight day. A total of 91 patients were studied; 45 patients were given flumazenil and 46 patients a placebo. Five minutes after injection of the test drugs all 45 patients given flumazenil but only 38 patients given the placebo were alert (p = 0.006). All three response criteria (for sedation, amnesia and subjective assessment of awakening) were fulfilled by 84.4% of the patients given flumazenil and 45.7% of the patients given the placebo (p = 0.0002). Thirty minutes after injection of the test drugs dizziness, nausea, and fatigue were found in 3 patients given flumazenil and in 10 patients given placebo. One day after colonoscopy 9 of 45 patients (20%) given midazolam and flumazenil complained of fatigue and 9 of 46 patients (19.5%) given midazolam and placebo. Eight days (+/- 1 day) later two patients in each group complained of headache, nausea and fatigue. No patient developed phlebitis at the injection site. Flumazenil seems to be a safe and efficient drug for reversing the sedative effect of midazolam, premedication after colonoscopy. However, resedation due to the effects of midazolam may occur. Flumazenil thus permits administration of a higher dose of midazolam without prolongation of the surveillance time. Improved exploitation of time, space and nursing resources is thus possible without jeopardizing patient safety, although caution is necessary since patients may not be fit to resume all normal activities.
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PMID:A randomised controlled trial to evaluate the effects of flumazenil after midazolam premedication in outpatients undergoing colonoscopy. 177 38

Flumazenil (Anexate) reverses promptly the hypnotic effects of all known benzodiazepines. From the point of view of traffic medicine the question is of interest whether side effects after application of flumazenil can be seen and must be taken in account. Our investigations were concerned in answering this question. 20 mg flumazenil or placebo was administered in a randomized doubleblind crossover fashion. The following psychometric tests were employed: Befindlichkeitsskalen von Zersen (Bf-S), State-Trait-Inventory (STAI), Hamilton Anxiety Scale (HAMA) und visual analogue scales (VAS). In addition, subjective condition was inquired. Pharmacokinetics were investigated by a radio-receptor-assay. Flumazenil leads to an increase of negative sensations in respect to an invers agonizing effect. Lack of concentration and dizziness were reported by the probationer.
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PMID:[Flumazenil (Anexate): an antagonist of benzodiazepines. Its pharmacopsychologic significance and role in traffic medicine]. 197 67

The effects of i.v. administered flumazenil (3.0 mg) were studied in healthy male subjects who received pretreatment with p.o. placebo or lorazepam. The duration of placebo or lorazepam (3.0 mg single p.o. daily dose) pretreatment before a flumazenil or placebo injection was 1, 3, 7 or 14 days in four sequential groups of subjects. Initial administration of lorazepam produced a classic sedative profile of effects on various psychomotor/behavioral performance, observer-rated and subject-rated measures. Tolerance to repeated daily administration of lorazepam was suggested by a progressive diminution of performance disrupting effects. In subjects pretreated with placebo, flumazenil increased subject-ratings of dizziness over preinjection ratings. Flumazenil produced an immediate reversal of lorazepam effects in subjects who were not tolerant to lorazepam (1- and 3-day pretreatment groups). Flumazenil did not precipitate withdrawal symptoms in subjects who received a single administration of lorazepam. Precipitated withdrawal symptoms were evident after 3 and 7 days of lorazepam pretreatment, and there was a tendency toward precipitated withdrawal symptoms (that included one panic attack) after 14 days of lorazepam pretreatment. Precipitated withdrawal was characterized by an elevation in subject-rated symptoms including dizziness, tenseness, tachycardia, perceptual disturbance and sweating. Symptoms were maximal immediately after injection, usually mild in severity and usually resolved within 1 hr. There was no evidence of precipitated withdrawal on psychomotor/behavioral performance or observer ratings. The present study provides the strongest human experimental evidence to date that flumazenil can precipitate withdrawal symptoms after a history of repeated benzodiazepine exposure.
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PMID:Intravenous flumazenil following acute and repeated exposure to lorazepam in healthy volunteers: antagonism and precipitated withdrawal. 851 1

We studied the frequency of use of flumazenil by emergency departments in our region and compared it to recommendations made by specialists in poison information at our poison control center. For a 5-mo period, we prospectively collected cases involving benzodiazepines or zolpidem. Data was documented only from calls from emergency departments. Emergency department personnel were asked the following: If given, the dose and frequency, contraindications, and adverse reactions. Each case was followed to completion. Flumazenil was not given in 55 cases. Of the remaining 14 cases in which it was given, 10 of the cases received flumazenil prior to poison control center consultation. We noted 1 case of dizziness. Ten cases given flumazenil had contraindications (eg ethanol abuse or possible seizurogenic coingestants). Despite possible contraindications, flumazenil was given 10/14 times (71%) prior to calling the poison control center. These results point to potential overuse of this antidote where contraindications or cautions are suspected in the overdosed patients. Our study suggests that when flumazenil use is contemplated by an emergency department physician, a poison control center consult may have a contrary recommendation.
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PMID:Emergency department use of flumazenil prior to poison center consultation. 925 Nov 78