苯二氮(卓)类药物使用现状分析

苯二氮量类药物(benzodiazepines BZD)具有良好的镇静催眠抗焦虑作用,广泛应用于多种生理心理疾病的治疗,特别是焦虑和失眠.由于起效快、安全性好,从第一种BZD氯氮(卓)(chlordiazepoxide)于1960年上市以来,就迅速成为主要的抗焦虑药物[1-2].但由于存在滥用风险,长期使用可产生依赖性,骤停还会引起原有症状的复发、反跳,甚至恶化,即“真正的戒断症状群(the true abstinence symptoms)”[2-4],因此一般认为,较少滥用风险和毒副作用的抗抑郁剂和新型镇静催眠剂,如佐匹克隆(zopiclone)应当作为抗焦虑镇静催眠治疗的一线药物[3-5],并且在有些国家,这些药物的使用比例已经超过了BZD.     

精神科住院患者使用苯二氮革类药分析

苯二氮革类药物（BZD）除抗焦虑作用外，常作为镇静催眠药物使用。在精神科病房使用也较广泛。其中不合理使用是导致BZD滥用的一个重要原因，为了了解在使用中存在的问题，现对我院在院住院患者使用BZD的情况进行调查。     

苯二氮类药物使用现状分析

苯二氮类药物（benzodiazepines BZD）具有良好的镇静催眠抗焦虑作用,广泛应用于多种生理心理疾病的治疗,特别是焦虑和失眠。     

精神病院门诊患者苯二氮(艹卓)类药物的用药评价

目的:了解精神病院门诊患者BZD类药物的使用状况,评价临床用药的合理性。方法:回顾性调查我院2002年6月―12月门诊处方,对其中使用BZD类药物的处方用药数据进行分析。结果:使用BZD类药物的处方约占17.8%。其中BZD单、联或加用其它镇静、催眠、抗焦虑药占37.36%;BZD+抗精神病药11.63%,BZD +抗抑郁药49.66%,BZD+抗“精”+“抑”药1.342%。结论:DUI值提示,氯硝安定、氟安定有一定滥用倾向;高比例联合用药,较长的服药周期必须引起临床高度重视。     

精神病院门诊患者苯二氮卓类药物的用药评价

目的：了解精神病院门诊患者BZD类药物的使用状况，评价临床用药的合理性。方法：回顾性调查我院2002年6月-12月门诊处方，对其中使用BZD类药物的处方用药数据进行分析。结果：使用BZD类药物的处方约占17．8％。其中BZD单、联或加用其它镇静、催眠、抗焦虑药占37．36％；BZD 抗精神病药11．63％，BZD 抗抑郁药49．66％，BZD 抗“精” “抑”药1．342％。结论：DUI值提示，氯硝安定、氟安定有一定滥用倾向；高比例联合用药，较长的服药周期必须引起临床高度重视。     

2003年～2005年我院镇静催眠药应用分析

目的：了解我院镇静催眠药物应用情况及发展趋势。方法：对2003年-2005年我院镇静催眠用药金额，用药频度及日均费用等数据进行统计、分析。结果：3年中镇静催眠药用药金额用药频度大幅增长，而苯巴比妥类药物用量逐步下降，苯二氮草类药物（BZD）呈上升趋势。新型的镇静催眠药非BZD有上升趋势，其中唑吡坦，扎兰普仑增长最明显。     

精神疾病患者应用苯二氮卓类药物状况分析

目的了解精神疾病患者应用苯二氮卓（BZD）类药物状况,为临床能更好应用这类药物提供参考依据。方法对本院门诊及住院精神疾病患者进行问卷调查,调查患者的一般情况、使用BZD种类、剂量、用药时间、用药原因、不良反应等。结果门诊及住院精神疾病患者中服用BZD类药物者占41．3％;BZD类药物主要用于镇静催眠、焦虑症、癫痫、控制戒断症状等的治疗;连续服药1月以上易发生药物戒断反应。结论目前临床上治疗精神疾病时应用BZD类药物较为普遍,滥用情况较为严重。应采取相应干预措施,加强处方管理,合理用药,杜绝BZD类药物滥用,减少药物依赖性的发生。     

49例女性住院患者应用苯二氮革类药物调查分析

目的：了解女性住院患者苯二氮革类药物（BZD）的使用情况。方法：采用自编的住院精神病患者调查表,对在院49例女性住院患者BZD使用情况进行调查,并与同期的130例男性住院患者进行对照。结果：我院精神病住院患者使用BZD为179人,占44．97％;两组在疾病类型上比较,无显著性差异（P〉0．05）;在用药原因方面,女性患者以改善睡眠为多,男性患者以抗焦虑为多,有显著性差异（P〈0．05）。男女两组住院患者BZD使用频率依次为阿普唑仑、氯硝西泮、艾司唑仑、劳拉西泮、地西泮等,无显著性差异（P〉0．05）。结论：住院精神病患者BZD的用药剂量及用药原因是合理的,但不宜长期使用。     

49例女性住院患者应用苯二氮(艹卓)类药物调查分析

目的:了解女性住院患者苯二氮(艹卓)类药物(BZD)的使用情况.方法:采用自编的住院精神病患者调查表,对在院49例女性住院患者BZD使用情况进行调查,并与同期的130例男性住院患者进行对照.结果:我院精神病住院患者使用BZD为179人,占44.97％;两组在疾病类型上比较,无显著性差异(P＞0.05);在用药原因方面,女性患者以改善睡眠为多,男性患者以抗焦虑为多,有显著性差异(P＜0.05).男女两组住院患者BZD使用频率依次为阿普唑仑、氯硝西泮、艾司唑仑、劳拉西泮、地西泮等,无显著性差异(P＞0.05).结论:住院精神病患者BZD的用药剂量及用药原因是合理的,但不宜长期使用.     

苯安定的天然配体——chrysjn的抗惊厥作用

结构与苯安定(BZD)不同的化合物,在神经组织中总能与BZD)受体结合,二黄酮类3＇,8＇-双-4＇,5,7-三羟基黄酮(biflavonoid a-mentoflavonc)就是其中之一,作者曾对具镇静药用价值的11种无花植物及3种有花植物进行筛选,发现其中含有BZD受体及其它受休的配体,作者对西番莲Passiflora coeruleaL.进行了深入研究,从中分离纯化出5,7-二羟黄酮(chrysin),并在离体动物实验中证实chrysin对中枢BZD受体有较高的亲和力,而外周BZD受体的亲和力其小;在体动物实验     

Benzodiazepine use among opiate-dependent subjects in buprenorphine maintenance treatment: correlates of use, abuse and dependence

BACKGROUND: Previous studies from North America, Europe and Australia have reported high levels of benzodiazepine use among opiate-dependent patients in opiate maintenance treatment. However, to date, there are no available data on patterns of abuse and dependence on benzodiazepines according to DSM criteria among these patients. AIMS: To describe the independent correlates of use, abuse and dependence on benzodiazepines among buprenorphine patients selected from standard treatment settings. METHODS: Cross-sectional study in France between June 2001 and June 2004. Buprenorphine patients treated for over 3 months were recruited via physicians prescribing buprenorphine. Patients answered a self-administered questionnaire, the DSM-IV criteria for benzodiazepine abuse and dependence, the Beck Anxiety and Depression Inventories (BAI, BDI) and the Nottingham Health Profile (NHP). Main outcome was modalities of benzodiazepine use: no use vs. simple use vs. problematic use (abuse or dependence according to DSM-IV). RESULTS: 170 patients were recruited. 54% did not use benzodiazepines during the previous month, 15% were simple users and 31% were problematic users. Benzodiazepine use (all modalities) was associated with poly-use of psychotropics. Simple users of benzodiazepines were not statistically different from non-users for the other factors explored. Problematic users of benzodiazepines had higher depression and anxiety levels, correlated with quality of life impairment and precariousness. They used higher dosages of benzodiazepines than simple users. CONCLUSIONS: Characteristics of simple benzodiazepine users were distinct from problematic users but not from non-users in this sample of buprenorphine patients. This should be taken into account in the clinical management of benzodiazepine use among buprenorphine patients.     

Alprazolam (Xanax, the Upjohn Company)

Alprazolam is a triazolobenzodiazepine, a derivative of the benzodiazepines. Comparison studies of alprazolam and diazepam or chlordiazepoxide in patients suffering from clinical anxiety secondary to anxiety neurosis or chronic alcohol withdrawal suggest an equal efficacy of those agents. Studies examining the use of alprazolam for the treatment of "primary depression" suggest that it is as effective as imipramine in the treatment of exogenous (reactive) depression. Although alprazolam may be effective in patients with exogenous depression, no extrapolation can be made to the treatment of endogenous depression. Mechanisms of action have not been fully elucidated, but probably are similar to those of other benzodiazepines. Peak blood levels are reached in 0.7-1.6 hours and the elimination half-life after steady state is approximately 19 hours. Daily dosages established from clinical studies ranged from 1 to 6 mg. Clinically, alprazolam appears to be ten times more potent than diazepam. Drowsiness, headaches, lightheadedness, dry mouth, and depression appear to be the most common side effects of the drug. It is concluded that alprazolam offers no striking therapeutic advantage over currently marketed benzodiazepines.     

Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation

The effect of equimolar cumulative concentrations of 11 different benzodiazepines on the indirectly evoked twitch contraction was investigated in the rat in-vitro phrenic nerve-hemidiaphragm preparation. Depending on the pattern of the concentration-response curves two groups of benzodiazepines can be distinguished: (i) a first group with a biphasic action, e.g. potentiation of twitch tension in low concentrations and depression of twitch tension in high concentrations, and (ii) a second group with primary depression of twitch tension with increasing concentrations. All of the tested compounds ultimately caused a 100% depression of twitch tension at concentrations ranging from 0.175 to 0.35 mmol litre-1. Although this peripheral effect of benzodiazepines on neuromuscular function is not the main site of action of these compounds, there are enough arguments to state that it is not a simple toxic effect. There is some evidence from this study that the peripheral component of the benzodiazepine effect on muscle relaxation may involve a multi- rather than one single receptor system.     

The Pharmacology and Toxicology of the ‘Holy Trinity’

Combining opioids with benzodiazepines and skeletal muscle relaxants (‘The Holy Trinity’) has been reported to potentiate the ‘high’. Through unique interactions with colocalized μ‐opioid and GABA_A receptors, the combined use of these agents induces a synergistic increase in dopamine in the nucleus accumbens (NAc) and depression of respiration. The inhibition of GABA release mediated by μ₁‐opioid receptor activation results in a subsequent increase in dopamine in the NAc. Benzodiazepines activate the GABA_AR to suppress respiration in the medullary respiratory centres. The skeletal muscle relaxant, carisoprodol, appears to bind to a unique binding domain within the GABA_AR to further enhance the respiratory depressant effects of the benzodiazepines. Therefore, the opioids, the benzodiazepines and carisoprodol alone or in combination are capable of inducing respiratory depression. Current guidelines for opioid prescribing recommend against the concomitant use of benzodiazepines but do not recognize the potential risk associated with the addition of skeletal muscle relaxants.     

Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment

Benzodiazepines are among the most frequently prescribed drugs worldwide. This popularity is based not only on their efficacy but also on their remarkable safety. Pure benzodiazepine overdoses usually induce a mild to moderate central nervous system depression; deep coma requiring assisted ventilation is rare, and should prompt a search for other toxic substances. The severity of the CNS depression is influenced by the dose, the age of the patient and his or her clinical status prior to the ingestion, and the coingestion of other CNS depressants. In severe overdoses, benzodiazepines can occasionally induce cardiovascular and pulmonary toxicity, but deaths resulting from pure benzodiazepine overdoses are rare. Quantitative determinations of benzodiazepines are not useful in the clinical management of intoxicated patients since there is no correlation between serum concentrations and pharmacological and toxicological effects. Benzodiazepine overdoses occurring during pregnancy rarely induce serious morbidity in mothers or fetuses, although large doses administered near delivery can induce respiratory depression in neonates. The teratogenic potential of benzodiazepines remains controversial, but is probably small if it exists at all. There is clear evidence that the prolonged use of even therapeutic doses of benzodiazepines will lead to dependence. The risk of developing significant withdrawal symptoms is related to dosage and duration of treatment. Prevention of gastrointestinal absorption should be initiated in all intentional benzodiazepine overdoses. Forced diuresis and dialysis techniques are not indicated since they will not significantly accelerate the elimination of these agents. Intravenous administration of flumazenil, a pure benzodiazepine antagonist, effectively reverses benzodiazepine-induced CNS depression.     

对1例苯二氮■类依赖的老年抑郁症的药学监护

1例对苯二氮类(BZD)依赖的老年抑郁症患者因复发抑郁住院,临床药师参与此患者治疗方案、疗效评估、不良反应鉴定及用药宣教等药学监护,最终大幅度减少苯二氮类的用药剂量,提高其用药安全性、依从性和有效性.     

The emergence of new psychoactive substance (NPS) benzodiazepines: A review

The market for new psychoactive substances has increased markedly in recent years and there is now a steady stream of compounds appearing every year. Benzodiazepines consist of only a fraction of the total number of these compounds but their use and misuse has rapidly increased. Some of these benzodiazepines have only been patented, some of them have not been previously synthesised, and the majority have never undergone clinical trials or tests. Despite their structural and chemical similarity, large differences exist between the benzodiazepines in their pharmacokinetic parameters and metabolic pathways and so they are not easily comparable. As benzodiazepines have been clinically used since the 1960s, many analytical methods exist to quantify them in a variety of biological matrices and it is expected that these methods would also be suitable for the detection of benzodiazepines that are novel psychoactive substances. Illicitly obtained benzodiazepines have been found to contain a wide range of compounds such as opiates which presents a problem since the use of them in conjunction with each other can lead to respiratory depression and death. This review collates the available information on these benzodiazepines and provides a starting point for the further investigation of their pharmacokinetics which is clearly required.     

湖州三院苯二氮(艹卓)类药物的用药分析

目的:了解苯二氮类BDZ药物在精神科疾病中的应用情况,保证患者用药合理、安全、有效、经济。方法:应用回顾性调查的方法,对湖州三院2001年9～10月份BDZ类3412张处方进行分析。结果:发现在精神科失眠、焦虑、抑郁患者较为多见,用药频率较高。结论:BDZ药物是目前国内外具有发展前途的常用药物,注意BDZ药物的依赖性,应交替使用不同品种,以保证患者用药安全,减少药物不良反应。     

A meta-analytic review of the efficacy of drug treatment in generalized anxiety disorder

A meta-analytic review of the efficacy of pharmacological treatment in generalized anxiety disorder was conducted. The main substance classes were compared: benzodiazepines and azapirones. The impact of methodological variables was investigated such as sample size and use of a placebo run-in. After a comprehensive literature search to May 2002 (via databases, hand search, secondary sources, internet, contact of researchers, and pharmaceutical companies), the results of 48 studies were integrated. Weighted Hedges g was computed and a random-effects analysis was done. Effect sizes were computed for anxiety, depression, and clinical significance. Sensitivity analyses were conducted. Pharmacotherapy was superior to placebo in all symptom categories. Azapirones and benzodiazepines were equally effective. Compliance (as measured by dropout rate) was higher for benzodiazepines. Only sample size was significantly associated with effect size. Pharmacotherapy, especially benzodiazepines and azapirones, is effective in the short-term treatment of patients with generalized anxiety disorder. There was no superiority of 1 drug class in reducing symptomatology.