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

Flumazenil, a benzodiazepine antagonist, reliably reverses midazolam-induced sedation, but its effect on respiratory depression has not been clarified completely. Ten healthy male volunteers received midazolam 0.1 mg.kg-1. Then they received flumazenil 0.5 mg (n = 9) and 1.0 mg (n = 1), intravenously. Rib-cage (RC) and abdominal wall (ABD) movement was measured by mercury-in-silastic strain gauge. Nasal air flow (FLOW), genioglossal electromyogram (EMG) and oxygen saturation (SaO2) were recorded simultaneously. Midazolam caused significant increases of RC movement and respiratory rate, and decreases of ABD movement, FLOW, EMG and SaO2. After administration of flumazenil, although respiratory rate returned to the pre-midazolam values, RC movement decreased on the contrary. ABD movement, FLOW, EMG, SaO2 did not recover to the pre-midazolam values. These data suggest that flumazenil 0.5 mg reverses midazolam-induced sedation completely, but is partially effective for some parameters related to respiratory depression.
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PMID:[Flumazenil antagonism of midazolam-induced respiratory depression]. 801 61

Benzodiazepines, a class of drugs widely used as anxiolytics, can induce a depression of respiration. This study was designed to determine if endogenous benzodiazepine ligands could act in a similar fashion and exert a tonic inhibitory influence on respiration. Administration of a benzodiazepine antagonist should then facilitate respiration. This might be especially visible in hypoxia, the condition characterized by both central respiratory depression and potentially enhanced benzodiazepine expression. We addressed this issue by comparing the effects on the phrenic neurogram of the specific benzodiazepine antagonist flumazenil (200 micrograms i.v. boluses) in the contrasting conditions of hypoxia and hyperoxia in anesthetized, both spontaneously breathing and paralyzed ventilated cats. Contrary to our hypothesis, flumazenil showed a modest but definite inhibitory effect on respiration. Flumazenil also lengthened the duration of the Hering-Breuer inspiratory inhibition. The respiratory depression was neither related to chemical drive nor to the GABA receptor complex, for it was sustained after antagonism of GABA with picrotoxin and bicuculline. We conclude that the endogenous benzodiazepine system is unlikely to play an inhibitory role in the regulation of respiration. The physiologic role of this system remains to be established.
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PMID:Endogenous benzodiazepine system and regulation of respiration in the cat. 809 Oct 23

This investigation studied the effect of two intravenous benzodiazepines and the specific reversal agent, flumazenil, on the sensitivity of upper airway reflexes. In a blinded, randomised, crossover study, we have investigated the effect of a single dose of diazepam ('Diazemuls') (0.2 mg.kg-1) and midazolam (0.07 mg.kg-1), both given intravenously on the sensitivity of upper airway reflexes in eight male volunteers. Reflex sensitivity was assessed by identification of reflex glottic closure in response to a threshold concentration of inhaled ammonia vapour. Both diazepam and midazolam produced significant depression of upper airway reflex sensitivity. This was maximum with both drugs within 10 min of administration, but baseline sensitivity was regained within 60 min. Flumazenil (300 micrograms) administered 10 min after midazolam, resulted in significant reversal of the upper airway reflex sensitivity depression.
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PMID:The effect of intravenously administered diazepam, midazolam and flumazenil on the sensitivity of upper airway reflexes. 812 18

Flumazenil, a specific benzodiazepine antagonist, reverses sedative and respiratory depressant effects of benzodiazepines. We determined whether a large dose of flumazenil, injected alone, induces respiratory depression or alteration of psychomotor performance. After informed consent, eight healthy volunteers participated at three different sessions: 1) flumazenil (0.1 mg/kg) (a dose 7-15 times the clinically recommended dose) injected intravenously over a 5-min period, followed by placebo (NaCl 0.9%); 2) flumazenil at the same dose and injection rate as in Session 1, followed by midazolam (0.1 mg/kg) injected over 5 min; and 3) placebo followed by midazolam at the same dose as above and administered over 5 min. All drug combinations were administered in a randomized and double-blind manner. Tidal volume, respiratory frequency, minute ventilation, and mean inspiratory flow were continuously measured from 15 min before until 120 min after drug injection by noninvasive on-line data acquisition methods. Psychometric performance was evaluated 15 min before the first drug and 15 min after administration of the second drug. During the placebo-midazolam session, tidal volume (-40%), minute ventilation (-25%), and inspiratory flow (-25%) were significantly (P < 0.01) decreased compared both with baseline and with the other two sessions, and psychometric performance was significantly (P < 0.01) altered; in contrast, there was no significant change in any of the measured respiratory or psychometric variables during the flumazenil-placebo or flumazenil-midazolam sessions. We conclude that flumazenil, administered at about 10 times the clinically recommended dose, has no agonist effects on resting ventilation or psychomotor performance in normal subjects.
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PMID:Absence of agonist effects of high-dose flumazenil on ventilation and psychometric performance in human volunteers. 821 37

Flumazenil, a benzodiazepine antagonist, clearly reverses midazolam-induced sedation; reversal of ventilatory depression has not been as well demonstrated. Thirty-two subjects completed this randomized, double-blind, placebo-controlled study investigating the dose-response relationship and duration of flumazenil's effects on ventilatory depression and hypnosis induced by a continuous midazolam infusion. A computer-controlled infusion of midazolam was used to titrate the predicted midazolam plasma concentration to a level at which subjects were unresponsive to verbal commands and then to maintain that concentration. Measurements of ventilation and hypnosis were repeated at predetermined intervals: before midazolam administration, before test drug (flumazenil [1, 3, or 10 mg] or placebo), and 5, 30, 60, 120, and 180 min after test drug administration. Ventilation and tidal volume were measured during an isocapnic hyperoxia clamp at a PETCO2 of 46 mm Hg (VE46 and VT46, respectively). A pseudo-rebreathing technique was used to measure the hypercapnic ventilatory response (HCVR) slope and ventilation intercept at a PETCO2 of 58 mm Hg (VE58). Midazolam reduced VE46, VT46, and VE58, as well as hypnosis scores, in all test drug groups. The reduction in HCVR slope, however, was significant only when all 32 subjects were considered in aggregate. All three doses of flumazenil reversed hypnosis and also reversed the reduction in VE46 and VT46 within 5 min. The reduction in VE58, however, was reversed less consistently. Flumazenil's effect on VE46 and VT46 lasted at least 30 min after 1 mg and at least 60 min after 3 mg, paralleling the effect of these doses on hypnosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of large-dose flumazenil on midazolam-induced ventilatory depression. 825 Mar 14

The ability of flumazenil to reverse benzodiazepine-induced respiratory depression is discussed through a review of the relevant literature. Flumazenil has been shown to be effective in reversing benzodiazepine-induced sedation, but its ability to reverse benzodiazepine-induced respiratory depression is controversial. Part of this controversy stems from the lack of consistent data on the incidence and nature of depressed respiratory function after benzodiazepine administration. In addition, a variety of tests are used to assess respiratory function, but because breathing is both automatic and under voluntary control, the results of some of these tests can be affected by patient effort. In such cases, improvement can result from an increased level of consciousness even though the central respiratory drive remains depressed. Thus, studies using these tests to determine flumazenil's effect on respiratory depression are inconclusive, as they do not accurately measure reversal of the central respiratory depression induced by benzodiazepines. However, studies using methods that do accurately assess central respiratory drive have involved small numbers of subjects and demonstrated a variable incidence of respiratory depression associated with benzodiazepine use. When benzodiazepine-induced respiratory depression was evident, the ability of flumazenil to reverse it was inconsistent and short-lived. Flumazenil may be able to improve breathing through improved consciousness, but its effects on central respiratory depression are inconsistent. Therefore, unless additional information becomes available supporting flumazenil's ability to reverse benzodiazepine-induced respiratory depression, it should not be used for this indication.
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PMID:Effect of flumazenil on benzodiazepine-induced respiratory depression. 835 35

Flumazenil, a specific benzodiazepine antagonist, is useful in reversing the sedation and respiratory depression that often occur when benzodiazepines are administered to patients undergoing anesthesia or when patients have taken an intentional benzodiazepine overdose. Judicious use of flumazenil may provide useful diagnostic information and may obviate the need for mechanical ventilation and other invasive supportive measures. Although some controversy exists regarding the possible precipitation of seizure activity in the setting of mixed tricyclic antidepressant-benzodiazepine overdose, worldwide experience with flumazenil has validated its safety and efficacy.
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PMID:Flumazenil: an antidote for benzodiazepine toxicity. 843 87

In modern anaesthesia various antagonists are used. They provide efficient tools to facilitate better control of pharmacological effects and side effects of drugs routinely used in anaesthesia. Naloxone is a competitive antagonist of opioids without any intrinsic activity. It counteracts respiratory depression, pruritus, sedation and analgesia caused by opioids. It is fast-acting with a duration of action of 45 to 90 min. Several investigators have reported severe side effects of naloxone including hypertension, tachyarrhythmias, left heart failure and cardiac arrest, and hence the use of naloxone must be carefully considered in every single patient. Flumazenil is a competitive antagonist of benzodiazepines. It is a remarkably safe drug and very effective to terminate all benzodiazepine effects in anaesthesia and intensive-care patients. Serious complications caused by flumazenil have been reported in patients receiving benzodiazepines in the treatment of seizure disorders and in patients with mixed intoxications. Neostigmine is one of several antagonists of neuromuscular blocking agents. Its side effects include bradycardia, increased bronchial secretions and increased peristalsis. Indication depends on the results of neuromuscular monitoring. Physostigmine is an unspecific antagonist of the central anticholinergic syndrome, an acute psychosis that may be caused by numerous drugs used in anaesthesia. Generally, antagonists should be carefully titrated. In emergency medicine the use of these antagonists is not recommended; the primary goal is to restore vital functions.
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PMID:[Antagonists in anesthesia]. 854 33

Flumazenil is safe and highly effective at reversing both benzodiazepine-induced sedation and amnesia. Bolus intravenous injection is the most appropriate technique when the goal is to fully reverse conscious sedation. Currently, the proven effective dose of flumazenil is 0.5 mg. For practical purposes, in this clinical setting, true resedation does not occur, and if the appropriate type and dose of agonist have been used, residual sedation is not a clinical problem. Concerns over acute anxiety reactions and precipitation of acute withdrawal syndrome in chronic benzodiazepine users remain theoretical and unsubstantiated by human data. Further clinical studies are required to determine whether the clinical practice of using flumazenil could include this group of patients. Depression of ventilatory responsiveness induced by benzodiazepines can be reversed effectively and promptly by flumazenil. Flumazenil must be immediately available as an emergency drug in any area where benzodiazepines are used. The clinical and economic benefits of elective and routine use of flumazenil have been demonstrated, but yet to gain widespread acceptance.
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PMID:Reversal of conscious sedation by flumazenil: current status and future prospects. 869 23

The addition of a benzodiazepine antagonist to the dental anesthesiologist's armamentarium should provide added safety for conscious sedation using benzodiazepines. A double-blind, placebo-controlled clinical trial of flumazenil, the first available benzodiazepine antagonist, was performed to evaluate its safety and efficacy following conscious sedation induced by diazepam and fentanyl. Flumazenil was found to reverse rapidly much of the central nervous system depression induced by fentanyl and diazepam conscious sedation. Flumazenil appears to be a valuable adjunct for dentists who administer intravenous benzodiazepines for conscious sedation.
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PMID:Flumazenil reversal of conscious sedation induced with intravenous fentanyl and diazepam. 893 56


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