Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have studied the effect of i.v. flumazenil 0.01 mg kg-1 on the amnesia and sedation caused by midazolam 2 mg and 5 mg i.v. in volunteers in order to determine the relationship between the actions of the antagonist on these two effects. Midazolam caused dose-dependent central neural depression as assessed by critical flicker fusion frequency, and dose-dependent amnesia for word cards. In subjects given flumazenil 5 min after administration of midazolam, fusion frequency readings and memory were restored to levels comparable to those before midazolam administration. These two effects of flumazenil were similar in time course and extent, suggesting that they share the same mechanism of action. Flumazenil given alone had no effect on memory. The study has demonstrated anterograde amnesia following benzodiazepine administration and antagonism by flumazenil. There was neither retrograde amnesia nor retrograde antagonism of amnesia.
 ...
PMID:Effect of flumazenil on midazolam-induced amnesia. 222 35

Although benzodiazepines have been proven safe and effective for the induction and maintenance of sedation, some instances require the reversal of these events prior to the natural process of metabolism and elimination. Flumazenil, a 1,4-imidazobenzodiazepine, is an antagonist that can reduce or terminate benzodiazepine effects in a dose-dependent manner. The antagonist acts by the competitive inhibition of benzodiazepines at their central nervous system receptor sites. When administered intravenously in incremental doses, flumazenil allows for optimal patient response on an individual basis. Despite its short elimination half-life, small doses of flumazenil are usually effective in producing benzodiazepine reversal. Flumazenil's short duration of activity is due to its rapid hepatic metabolism and elimination. Intravenous antagonist doses of 0.2 mg followed by 0.1 mg/min to a total dose of 1 mg have produced significant results in reversing benzodiazepine sedation. As much as 5 mg of flumazenil have been necessary when treating benzodiazepine or mixed-agent intoxications. In such situations, response rarely exceeds a duration of one hour. If resedation occurs, additional doses or an infusion of the antagonist may provide the desired response. Flumazenil is well tolerated locally as well as systemically. Nausea and vomiting occurring after anesthesia is the most documented adverse effect in both placebo and treatment populations. However, there has been no significant difference in the occurrence of vomiting in placebo compared with flumazenil-treated subjects. Careful observation and slow reversal of central nervous system depression is crucial in the avoidance of benzodiazepine withdrawal in those patients dependent upon these agents. Flumazenil appears to provide a mechanism for the safe and effective reversal of benzodiazepine-induced sedation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Flumazenil: a benzodiazepine antagonist. 224 12

Flumazenil (Lanexat) is the first specific benzodiazepine-antagonist for clinical use. In several controlled investigations, a significant rapidly commencing antagonistic effect on the central effects of benzodiazepines has been demonstrated. Flumazenil possesses only slight side effects which may easily be treated. The immediate indications for employing flumazenil are reversal of the sedation caused by benzodiazepines in outpatients and treatment of cases of poisoning. In addition, flumazenil could be employed to reverse sedation produced by benzodiazepines during general anaesthesia and prolonged sedation in intensive care units. The following should be observed on employing flumazenil: 1. Flumazenil should be administered by slow meticulous titration. 2. The relatively short half-life of flumazenil provides the possibility for partial return of CNS depression. 3. In cases of mixed poisoning, flumazenil may unmask the effects of possible seizure-producing drugs. 4. Care should be employed in using flumazenil in chronic benzodiazepine abusers.
 ...
PMID:[Flumazenil. A specific benzodiazepine antagonist]. 250 84

ICU patients often require sedation. Midazolam (M), a new imidazobenzodiazepine, features rapid onset and rapid elimination time. Flumazenil (Ro 15-1788) is a new benzodiazepine antagonist. We studied the efficacy and safety of M by continuous infusion in 28 ICU patients: 16 post major surgery, and 12 medical patients, aged 20-77 years. M was administered as a loading dose of 0.05-0.15 mg/kg per min followed by continuous infusion of 0.05-0.1 mg/kg per h titrated to maintain patients asleep but arousable. M was administered for up to 14 days in doses of 1-15 mg/h and cumulative doses of up to 1915 mg. No untoward effects were noted except for slight decreases in blood pressure following the loading dose. ACTH challenge tests performed before and 24 h or more following the start of M showed no depression of adrenal responsivity. All patients meeting weaning criteria were weaned off mechanical ventilation while still on M. In 13 patients extubation was performed immediately after M was stopped, and flumazenil (0.38 +/- 0.27 mg, i.v.) given until full awakening. Patients remained awake yet calm. Vital signs remained stable after flumazenil. Midazolam by continuous infusion appears to be a safe and effective mode of sedation in ICU patients. Flumazenil may increase the flexibility and safety of this mode of sedation.
 ...
PMID:Midazolam infusion and the benzodiazepine antagonist flumazenil for sedation of intensive care patients. 284 76

Midazolam, a benzodiazepine with the purportedly shortest half-life of all these compounds, is advocated for the induction of general anesthesia. It is still debatable, however, whether a long-lasting hangover may result in depression of vigilance postoperatively. After midazolam induction (0.18 mg/kg) and enflurane/nitrous oxide/oxygen anesthesia, ten patients received flumazenil (0.8 mg/70 kg) in the postoperative period while another ten received placebo in a double-blind fashion. Continuous recording of EEg activity was performed using the Lifescan monitor, computing the power in the various EEG frequency domains. Additionally, patients were scored with regard to orientation in space and time and their collaboration and comprehension of verbal commands. Compared to placebo, flumazenil induced power in the alpha domain, accompanied by a drop of power in the delta and theta bands. While the increase in alpha activity resolved after 30 min, beta activity increased significantly, an effect that lasted up to the 180th postoperative minute. As with the finding of higher power in the fast-frequency domains, flumazenil patients scored higher with regard to collaboration and comprehension as well as orientation in space and time. 1. When used for induction, midazolam may result in significant depression of vigilance even 120 min after operation. 2. Flumazenil is a specific antagonist with a rapid onset of action. 3. Flumazenil is an antagonist specifically directed to reverse the side-effects of benzodiazepines in a manner similar to naloxone, which is used in opioid overdose.
 ...
PMID:[Postoperative reversal of loss of vigilance following midazolam with the use of the antagonist flumazenil (Ro 15-1788). A comparative study with a placebo and the use of EEG-power spectra]. 313 66

Flumazenil is a specific benzodiazepine antagonist. This study was designed to determine whether it also reverses CNS depression due to acute alcohol intoxication. Intoxication was experimentally induced in 6 healthy volunteers by intravenous infusion of ethanol. Individual constant ethanol plasma concentrations in the range 1.47 +/- 0.04 g.l-1 to 1.71 +/- 0.03 g.l-1 were maintained over 6 h. Two doses of flumazenil (0.1 or 0.2 mg.kg-1) and placebo were administered intravenously in a randomized, double-blind, two-way cross-over fashion. A battery of psychometric tests and subjective ratings of mood and performance were performed at baseline and at regular intervals during the study. Before the administration of flumazenil the characteristic symptoms and signs of ethanol intoxication were present in all subjects. Performance (measured by visual analogue scales), reaction time, digit symbol substitution test, and a tracing test, were markedly impaired by ethanol. After the injection of flumazenil three volunteers reported some subjective improvement in performance. However, in none of the subjects was there a difference between either dose of flumazenil and placebo in terms of an improvement in the objective psychometric variables.
 ...
PMID:Lack of effect of the benzodiazepine antagonist flumazenil (Ro 15-1788) on the performance of healthy subjects during experimentally induced ethanol intoxication. 313 94

This paper reviews the use of prototypic drugs for reversal of the effects produced by anesthetic and sedative agents. Efficacy and toxicity information is presented for naloxone (as used to reverse opioids), physostigmine (as used for reversal of sedatives), and Flumazenil (a new specific benzodiazepine receptor antagonist). Naloxone is very useful and specific for reversing adverse and life-threatening respiratory depression caused by narcotic drugs and should be used in these situations. Physostigmime has been advocated in incremental doses for reversing sedative effects in patients who are obtunded or depressed after having received benzodiazepines, droperidol, scopolamine, opioids, and phenothiazines. Flumazenil has been shown to readily antagonize the sedative, respiratory depressant, anxiolytic, muscle relaxant, anticonvulsant, amnestic, and anesthetic effects of the benzodiazepines; it appears to have tremendous potential for use in anesthesia, conscious sedation, and emergency medicine when available.
 ...
PMID:Reversal agents in sedation and anesthesia: a review. 313 41

Flumazenil is a benzodiazepine receptor antagonist used to reverse sedation and respiratory depression induced by benzodiazepines. Seizures and cardiac arrhythmias have complicated its use in adult patients. Overdose patients who have coingested tricyclic antidepressants have a higher risk of these complications. Little information exists concerning adverse effects of flumazenil in children. We report the occurrence of a generalized tonic-clonic seizure in a pediatric patient following the administration of flumazenil.
 ...
PMID:Seizure after flumazenil administration in a pediatric patient. 765 79

We have studied the effects of midazolam and flumazenil on the carotid sinus baroreflex, by examining mean arterial pressure (MAP) and heart rate (HR) responses to partial or complete bilateral carotid occlusion (BCO) in 12 conscious rabbits after aortic denervation. In eight rabbits, the responses to complete BCO were evaluated before and after cumulative doses of midazolam 0.5 and 1.0 mg kg-1, and after flumazenil 0.3 mg kg-1 following administration of midazolam. Midazolam and flumazenil had no effect on MAP or HR before complete BCO and neither affected the MAP response to complete BCO. Midazolam 0.5 and 1.0 mg kg-1 decreased the HR response to 60% and 58% of control, respectively. Flumazenil restored the midazolam-induced depression of the HR response to the control level. In the other four rabbits, we examined the MAP and HR responses to partial BCO (carotid artery pressure reduced by 5, 10 and 20 mm Hg) before and after midazolam 0.5 mg kg-1 and after flumazenil 0.3 mg kg-1 following administration of midazolam. The response to partial occlusion showed the same tendency as the response to complete BCO. These results indicate that midazolam attenuated the HR response of the carotid sinus baroreflex, flumazenil restored this midazolam-induced depression and neither drug affected the MAP response.
 ...
PMID:Effects of midazolam and flumazenil on carotid sinus baroreflex control of circulation in rabbits. 794 68

To characterize the plasma concentration-effect relationship of flumazenil in the presence of a predefined midazolam level, a double-blind, placebo-controlled, randomized two-way crossover study was conducted in nine healthy male subjects. After reaching a criterion level of midazolam-induced depression of the Digit Symbol Substitution Test (DSST), volunteers received a dose of flumazenil (1.0 mg) or placebo over 1 minute, with the infusion of midazolam continued. Blood samples were collected, simultaneously with the DSST assessment, at predetermined intervals and were assayed for flumazenil and/or midazolam plasma concentrations. Pharmacokinetic-pharmacodynamic modeling techniques were used to estimate the equilibration rate constant (keo) between plasma concentration and effect for flumazenil; a sigmoidal maximum-effect model was used to relate the DSST score to the flumazenil plasma concentration. Flumazenil exhibited a rapid onset (the half-life of equilibration between drug concentration in the blood and drug effect was 3.3 minutes) and short duration of action (the flumazenil plasma concentration causing half-maximal effect was 7.4 ng/ml, which was reached about 1 hour after dosing). The results of this study also show the competitive nature of flumazenil as a midazolam antagonist.
 ...
PMID:The pharmacokinetic-pharmacodynamic (Digit Symbol Substitution Test) relationship of flumazenil in a midazolam steady-state model in healthy volunteers. 795 17


<< Previous 1 2 3 4 5 Next >>