氟西泮中毒引起心肌严重损害1例

<正> 氟西泮(flurazpam或Dalmadorm)是一种新型的作用较强的催眠药物,可治疗各型不眠症,现将我院遇到1例服氟西泮过量引起心肌严重损害的病例,报告如下。 患者女,45yr,因服氟西泮后神志不清伴阵发性抽搐半天,于1987年8月30日入院。入院前半个月左右,患者因神经衰弱求治于我市精神病院,投予瑞士进口的催眠新药氟西泮口服,30mg,qd共服10d。入院前1d,上午因生气,1次吞服该药7     

单盐酸氟西泮胶囊

本品含单盐酸氟西泮按氟西泮(C₂₁H₂₃ClFN₃O)计,应为标示量的90.0-110.0%。     

大鼠对氟西泮抗痫耐受和依赖时海马中一氧化氮合酶的变化

目的通过测定大鼠对氟西泮抗痫耐受性和依赖性时海马中一氧化氮合酶(NOS)蛋白表达及活性的变化,探讨一氧化氮(NO)在此过程中可能的作用。方法建立大鼠对氟西泮抗痫耐受性和依赖性的模型。运用免疫印迹及免疫组化法检测海马中NOS蛋白表达,以及比色法检测NOS活性的变化。结果大鼠对氟西泮抗痫耐受组的海马中NOS蛋白表达明显高于对照组;而对氟西泮抗痫依赖组则与对照组差别无统计学意义。两组NOS活性均显著高于各自的对照组。结论NO可能是介导氟西泮抗痫耐受性和依赖性的因素之一。     

氟西汀联用碳酸锂治疗抑郁症

目的:评价氟西汀联用碳酸锂治疗抑郁症的疗效及安全性。方法:100例符合中国精神疾病诊断分类第3版(CCMD-3)抑郁发作标准的抑郁症病人分为2组,每组各50例,分别给予氟西汀联用碳酸锂治疗(研究组)和单用氟西汀治疗(对照组),疗程均为8 wk。根据汉密尔顿抑郁量表(HAMD)减分率评定疗效,用副反应量表(TESS)评定用药的安全性,在治疗前和治疗后的wk 1,2,4,6,8末分别对2组进行检查评定。对病人随访1 a转躁狂情况。结果:研究组总有效率为94％,对照组总有效率为77％2组间,疗效比较差异有非常显著意义(P＜0．01),不良反应的发生率差异无显著意义(P＞0．05),研究组的转躁率2％低于对照组15％。结论:氟西汀联用碳酸锂治疗抑郁症可增强疗效,起效快,安全性好,转躁率低。     

用HPLC法同时测定比格犬血浆中地西泮、去甲西泮和氟马西尼的浓度

目的:建立测定比格犬血浆中地西泮、去甲西泮和氟马西尼浓度的HPLC法.方法:采用Kromasil 100-5 C18色谱柱(250 mm×4.6 mm,5μm);以氯硝西泮为内标,甲醇(A)-水(B)-四氢呋喃(C)为流动相(55∶40∶5),流速1.0 ml/min,检测波长254 nm;柱温25 C.结果:地西泮、去甲西泮和氟马西尼在浓度范围为0.025～1.000 μg/ml时线性良好(r=0.999 9,0.999 0,0.998 9),日内和日间RSD均＜6％(n=5),回收率接近100％.结论:本方法准确、快速、简便,可用于比格犬血浆中地西泮、去甲西泮和氟马西尼浓度的同时测定.     

用Ro 15-4513逆转氟西泮耐受性并观察GABAA受体亚单位表达的影响

目的：探讨苯二氮卓类抗惊厥耐受性和用Ro 15-4513逆转耐受性的受体分子机制。方法：一组大鼠腹腔注射氟西泮2周，产生有氟西泮耐受性而无依赖性的听源性惊厥大鼠模型，另一组大鼠于用药第8d，每天加用腹腔注射一次Ro15-4513，观察对耐受性的影响，用竞争性定量RT－PCR测定大鼠脑皮质运动区和海马区的GABAA受体α1，α3、α5、γ2L和γ25亚单位mRNA的含量。结果：氟西泮耐受组大鼠皮质运动区的α1亚单位下降24％，α3下降17％，α5上升33％，γ2L下降35％，γ25下降45％，海马区的α下降33％，γ2L下降35％，γ2S下降45％，海马区的α1下降33％，γ2L降35％,γ2s下降27％，与对照组比较均有显著性差异，合用Ro 15-4513组大鼠皮质运动区GABAA受体α1，α3，α5，γ2L和α2S亚单位mRNA含量与对照组相比均无显著性差异；海马区α1，α5、γ2L和γ2s亚单位mRNA含量与对照组相比也同样都无显著性改变。结论：听源性惊厥大鼠的氟西泮耐受机制与中枢GABAA受体α1，α3，α5，γ2L和γ2S亚单位mRNA皮质运动区含量的适应性改变有关。Ro15-4513通过影响皮质运动区和海马区部分α及γ2亚单位的表达而产生逆转听源性惊厥大鼠对氟西泮耐受性的效应。     

西酞普兰与氟西汀治疗中国抑郁症患者疗效和安全性的meta分析

目的 比较西酞普兰与氟西汀在中国抑郁症患者中的疗效和安全性.方法 计算机检索CBM、CNKI、万方数据库,采用RevMan 5.0软件进行meta分析.结果 西酞普兰与氟西汀抗抑郁治疗6周后,以汉密尔顿抑郁量表(HAMD)评定疗效,总有效率的meta分析结果表明,有效率比值比OR值为1.29,其95％的可信区间为0.98～1.69,两者不存在显著性差异.疗程为1、2周时,西酞普兰治疗组的HAMD评分比氟西汀治疗组低,具有统计学差异,即西酞普兰起效速度优于氟西汀;疗程为4、6周时,西酞普兰治疗组的HAMD评分与氟西汀治疗组差异无统计学意义,即两者疗效无统计学差异性.以西酞普兰与氟西汀抗抑郁治疗失败的相对危险度RR比较其不良反应的危险度,结果显示便秘、失眠这2个不良反应的合并RR值分别为0.4 (95％CI 0.24,0.64)和0.54 (95％CI0.34,0.86),表明西酞普兰便秘和失眠不良反应的发生率均低于氟西汀,具有统计学差异.结论 西酞普兰与氟西汀长期治疗效果相当,但西酞普兰起效快于氟西汀,且西酞普兰便秘和失眠不良反应的发生率均低于氟西汀.     

度洛西汀与氟西汀治疗广泛性焦虑障碍对照研究

目的:探讨度洛西汀与氟西汀治疗广泛性焦虑障碍(GAD)的疗效及安全性.方法:选取GAD患者100例采用随机数字表法分为两组,各50例.观察组采用度洛西汀治疗,对照组采用氟西汀治疗,6周后比较两组疗效及安全性.结果:观察组总有效率88.00％,对照组总有效率70.00％,差异有统计学意义(P<0.05).两组药物副反应差异无统计学意义(P>0.05).结论:度洛西汀治疗GAD的临床疗效明显优于氟西汀,且不增加药物副作用的发生风险,值得临床推广.     

逍遥丸联合氟西汀治疗产后抑郁症的临床疗效及安全性评价

目的 观察逍遥丸联合氟西汀治疗产后抑郁症的临床疗效和不良反应.方法 120例产后抑郁症患者,随机分为观察组和对照组,每组60例,观察组口服逍遥丸和氟西汀治疗,对照组单用氟西汀治疗,运用爱丁堡产后抑郁量表(EPDS)和汉密尔顿抑郁量表(HAMD)评价临床疗效,运用抗抑郁药副反应量表(SERS)评价药物不良反应 结果 观察组和对照组的有效率分别93.33％和80.00％;两组治疗前、后抑郁症状的各项指标有显著改变(P＜0.05),与对照组比较,观察组患者的改善更加显著(P＜0.05);观察组和对照组的不良反应发生率分别为40.00％和71.67％,且观察组的不良反应指标多数显著低于对照组 结论 逍遥丸联合氟西汀对产后抑郁症有显著疗效,能明显改善患者的各种抑郁症状.     

氟西汀治疗溃疡性结肠炎的疗效观察

目的:观察氟西汀对溃疡性结肠炎(UC)的疗效。方法:采用Zung抑郁自评量表进行测评,评分结果换算成抑郁严重度指数。从108例活动期UC患者中筛选出抑郁指数>0.5者62例,随机分为氟西汀治疗组35例,对照组27例,比较2组疗效。结果:治疗组与对照组的治愈率分别为65.7%、44.4%(P<0.05),总有效率分别为88.6%、63.0%(P<0.01)。治疗后第4周,腹痛,腹胀、纳差,腹泻及大便性状改变缓解率,治疗组与对照组分别为76.9%、83.9%、85.7%和38.1%、50.0%、55.6%(P<0.05),第8周治疗组与对照组上述症状缓解率分别为92.3%、90.3%、93.5%和42.9%、58.3%、59.3%(P<0.01)。2组不良反应比较无差异。结论:对伴有抑郁的UC患者加用氟西汀可提高疗效。     

A clinical and psychometric evaluation of flurazepam.

1 The efficacy of flurazepam (15 mg or 30 mg) as a hypnotic, and the residual effects of each dose were compared with placebo in a double-blind cross-over trial involving thirty patients in a general practice setting. Patients received each medication for one week. Daily self-ratings of onset, duration and quality of sleep, together with reports of any untoward effects were made. At the end of each period of medication psychomotor tests (reaction time, pursuit rotor, tapping speed) were administered at 09.00 hours. 2 Both doses of flurazepam were significantly more effective than placebo in inducing sleep, improving the quality of sleep and extending its duration. 3 'Hangover' effects were marked following 30 mg, but not after flurazepam (15 mg). Flurazepam (30 mg, but not 15 mg) significantly impaired performance on the pursuit rotor test and tapping speed. Flurazepam thus appears to be an effective hypnotic drug with the optimum dose for use in general practice being 15 mg at night.     

Hypnotic efficacy of estazolam compared with flurazepam in outpatients with insomnia

Estazolam is a new benzodiazepine hypnotic agent with an intermediate half-life of 12 to 15 hours. The authors designed an investigation to compare its hypnotic efficacy to that of flurazepam, generally considered the reference standard. The hypnotic efficacy of estazolam at two doses (1 mg and 2 mg) was compared with that of flurazepam (30 mg) in a double-blind, placebo-controlled, multicenter, 7-night study that involved 223 outpatients with insomnia. On subjective assessments of the patients, no differences were noted between estazolam 2 mg and flurazepam 30 mg on any of six sleep parameters. Patients who were receiving estazolam 1 mg rated their sleep significantly better than did patients who were receiving placebo on all parameters except sleep latency. Global evaluation of the physicians indicated significant improvement in quality of sleep, sleep depth, sleep duration, and nocturnal awakenings in all three active treatment groups; estazolam 2 mg and flurazepam also decreased sleep latency significantly. The percentage of patients who reported any adverse experience was 68% for flurazepam, 58% for estazolam 2 mg, and 54% for estazolam 1 mg; the incidence of adverse events in the placebo group was 43%. In conclusion, estazolam 2 mg was found to be as effective a hypnotic as flurazepam 30 mg. Estazolam 1 mg is also effective in the treatment of outpatients with insomnia, but to a lesser degree.     

Residual and acute effects of flurazepam and triazolam in normal subjects

Residual and acute effects of flurazepam and triazolam were studied in two double-blind, crossover, placebo controlled, single-dose experiments. Psychological and physiological effects were determined 10 h after night administration (flurazepam 30 mg and triazolam 0.5 mg), and for 6 h after morning ingestion (flurazepam 15 mg and triazolam 0.25 mg). Both drugs produced similar "hangover" effects, impairing motor performance and increasing sleepiness on the following morning. After morning administration pronounced sedative effects were found with triazolam, while flurazepam effects were mild and hard to distinguish from placebo. The clinical relevance of these findings is discussed, suggesting that these drugs may be conceived as belonging to two different types of hypnotic agents.     

The thymoleptic action of two salts of flurazepam ('Dalmane').

A double-blind comparison was made of two dose levels (15 and 30 mg.) of the monohydrochloride and dihydrochloride salts of flurazepam ('Dalmane') in 40 hospitalised patients requiring a night-time hypnotic. Each patient in the four drug/dose groups was his own control and took a placebo for 3 nights followed by the active compound for a further 3 nights. On waking each morning a mood state questionnaire was completed. The results indicate that flurazepam is not only an effective hypnotic, but that it has an apparent anxiolytic effect the following morning. Patients report feeling less anxious and more cheerful following drug administration and this result was most noticeable with the 15 mg. monohydrochloride dose.     

Comparative study of zopiclone,a novel hypnotic,and three benzodiazepines

Summary The hypnotic effect and tolerance of zopiclone 7.5 mg, nitrazepam 5 mg, flurazepam 30 mg, flunitrazepam 2 mg and placebo were compared in a one-night double blind study in 414 hospitalised patients who were to undergo an operation on the following day. Zopiclone was slightly superior to nitrazepam but was inferior both to flurazepam and flunitrazepam. All the active drugs differed clearly from placebo. The results from a subset of patients, excluding those who felt anxious either before treatment on the evening prior to the operation or on the following morning, were analysed separately. All the active products differed significantly from placebo; zopiclone was slightly less effective than the three benzodiazepines. All the benzodiazepines decreased the precentage of patients feeling anxious about the operation by about 25%, zopiclone by about 10% and placebo did not change it at all.     

Effects of estazolam and flurazepam on cardiopulmonary function in patients with chronic obstructive pulmonary disease.

Benzodiazepine drugs have been shown to suppress respiratory function in patients with chronic obstructive pulmonary disease (COPD). We designed a placebo-controlled crossover study to compare the effects of a new benzodiazepine, estazolam ('ProSom'), with those of flurazepam ('Dalmane') on cardiopulmonary function in COPD patients. 29 patients completed all treatment phases (estazolam 2 mg, flurazepam 30 mg or placebo). Respiratory and cardiovascular function were assessed in awake patients on days 1 and 5 (acute and cumulative effects). Eight patients were also assessed during sleep in each period. The effects of estazolam and flurazepam on ventilatory response to CO2 and mouth occlusion pressure were no different from those of placebo. However, acute administration of flurazepam lowered tidal volume and increased inspiratory flow. Although no clinical signs of respiratory depression were observed with any long term treatment, flurazepam decreased oxygen saturation and inspiratory time and increased respiratory frequency. Neither drug altered breathing control during sleep. Our results indicate that estazolam 2 mg is equally as safe a hypnotic agent as flurazepam for patients with mild COPD.     

Estazolam and flurazepam: a multicenter, placebo-controlled comparative study in outpatients with insomnia

A multicenter, double-blind placebo-controlled clinical trial was designed to compare the safety and efficacy of estazolam compared with flurazepam as hypnotics. Outpatients complaining of insomnia were randomized to receive either estazolam 2 mg, flurazepam 30 mg or placebo for 7 consecutive nights. The analysis of efficacy was based on the patients' daily assessments of sleep and the investigators' global evaluations. Adverse events which were considered by the investigator to be attributable to, or of unknown relationship to the test medication were analyzed. The patient subjective questionnaire indicated that estazolam and flurazepam significantly improved all parameters (P less than .05) as compared to placebo. A marked or moderate improvement in sleep was reported by 81% (58/72), 78% (63/81) and 36% (27/76) of estazolam, flurazepam, and placebo recipients, respectively. There were no significant differences in hypnotic effect between estazolam and flurazepam. All efficacy parameters of the investigators' global evaluation improved significantly more (P less than .05) for patients receiving estazolam or flurazepam (except quality of sleep) than for those receiving placebo. The percentage of patients reporting any adverse experience was greatest for flurazepam (72%), followed by estazolam (59%), and placebo (43%). Somnolence and hypokinesia were the most commonly reported adverse events. An analysis of the global evaluation of side effects showed that flurazepam had a significantly worse side effect profile than estazolam (P less than .05) or placebo (P = .001). Estazolam and flurazepam effectively, and comparably, relieved insomnia when administered for 7 nights in adult patients complaining of insomnia. Estazolam demonstrated a more favorable side effect profile than flurazepam.     

A double-blind, placebo-controlled investigation of the residual psychomotor and cognitive effects of zolpidem-MR in healthy elderly volunteers

AIM: To assess residual psychomotor and cognitive effects of a modified-release formulation of zolpidem (zolpidem-MR), developed to provide sustained hypnotic efficacy during the whole night, compared with placebo and flurazepam. METHODS: Twenty-four healthy elderly volunteers received four study treatments (zolpidem-MR 6.25 mg and 12.5 mg, placebo and flurazepam 30 mg) using a randomized, cross-over, double-blind design. Residual psychomotor and cognitive effects were assessed with a psychometric test battery. Quality of sleep and residual effects were evaluated subjectively with the Leeds Sleep Evaluation Questionnaire. RESULTS: Psychometric performance was significantly impaired with flurazepam but not with zolpidem-MR at either dose. Ease of falling asleep and sleep quality were significantly improved with both doses of zolpidem-MR and with flurazepam. Neither active drug modified perception of well-being on awakening. CONCLUSION: In elderly subjects, zolpidem-MR showed no residual functional impairment in psychometric or cognitive tests sensitive to flurazepam.     

Classification and bioavailability studies with WE 941 by quantitative pharmaco-EEG and clinical analyses

Psychoactivity, pharmacodynamic properties and drug tolerance of 2-bromo-4-(2-chlorophenyl)-9-methyl-6H-thieno[3,2-f]1,2-(4-triazolo)[4,3-a][1,4]diazepine (WE 941), a new triazolodiazepine, were studied in 10 normal subjects utilizing quantitative pharmaco-EEG and clinical evaluation methods. In the double-blind, placebo-controlled trial, the subjects received randomized at weekly intervals oral single doses of 0.1 mg, 0.3 mg and 0.5 mg WE 941, placebo, and 30 mg flurazepam as reference substance. Measurements were obtained before and at the 2nd, 4th, 6th h post drug. EEG power spectral density analysis demonstrated no changes after placebo, while WE 941 and flurazepam induced statistically significant alterations characterized by an increase in beta-activity, a decrease in alpha-activity and increase in average frequency ("anxiolytic pharmaco-EEG profile"). In addition, 0.3 mg and 0.5 mg WE 941 and 30 mg flurazepam produced a significant augmentation of delta-activity indicating hypnotic qualities. Considering spontaneous and placebo-induced alterations, evaluation of the time- and dose-effect relationship indicated that all active substances exerted a tranquilizing effect throughout 8 h, while the hypnotic properties of 0.1 mg WE 941 were minimal (up to the 4th h), those of 0.3 mg WE 941 were moderate (up to 6 h) and those of 0.5 mg WE 941 were marked (up to 8 h). The dosage equipotent to 30 mg flurazepam is 0.3 mg WE 941. Heart rate and blood pressure exhibited no relevant changes, while side effects including fatigue, drowsiness and dizziness were mostly observed after the highest dosage of WE 941.     

Comparative hypnotic effects of flurazepam, triazolam, and placebo: a long-term simultaneous nighttime and daytime study

We studied sleep and daytime function in insomniac patients who took either flurazepam, 30 mg, triazolam, 0.5 mg, or placebo 30 minutes before bedtime. Subjects were 21 patients with either a primary or a secondary diagnosis of chronic psychophysiological insomnia or insomnia associated with personality disorder. Seven subjects were randomly assigned to each condition. The study used a three group by 9 week, double-blind design with three nocturnal sleep recordings each week. During week 1, subjects took no capsules; week 2, subjects took placebo; weeks 3 to 7, flurazepam, triazolam, or placebo; weeks 8 and 9, placebo. Daytime tests for alertness and performance were administered during weeks 1, 3, 5, 7, and 8. Flurazepam showed hypnotic efficacy for weeks 3 to 5. Triazolam showed hypnotic activity for weeks 3 to 7. Although not significant overall, discontinuation of flurazepam produced rebound insomnia in six of seven subjects sometime during the two withdrawal weeks. The relationship between plasma concentration of desalkylflurazepam, the principal active metabolite of flurazepam, and sleep disturbance suggested that the onset of the rebound insomnia depended on the rate of drug washout. Discontinuation of triazolam produced a significant rebound insomnia on the first and second nights of drug withdrawal. Placebo subjects showed improved sleep throughout weeks 2 to 9 of the study. Daytime testing revealed significantly decreased daytime alertness and decreased performance for flurazepam subjects during weeks 3 to 7, although these effects reverted toward baseline despite continued drug administration.