Premedication for elective Caesarean section

Four coded, but otherwise unidentified, premedicants were prescribed in randomised order for 219 patients who were to undergo elective Caesarean section. Seventy-six (35%) of these patients affirmed at the pre-operative visit that they were not anxious. Diazepam 5 mg and lorazepam 1 mg appeared to be superior to the placebo and to 10-6 ml of 90% alcohol in inducing calmness and/or drowsiness, although the differences were not statistically significant. The incidence of awareness or unpleasant dreams was considerably higher in the placebo and alcohol series (6.2% and 7.5%) than in the diazepam and lorazepam series (nil and 2.1%). There was no remarkable difference in the condition of the immediate newly-born related to the premedicant received by the mother, any small differences being much less impressive than that related to the duration of the U-D interval. No notable differences were observed in the long term conditions between the infants in the placebo, alcohol and diazepam series but the incidence of "reluctance to feed". If relief from preoperative anxiety-and possibly a reduction in the likelihood of awareness-without undue effect upon the infant is considered desirable, diazepam 5 mg is the preferred choice from the four drugs investigated.     

Therapeutic choices in convulsive status epilepticus

Introduction: Convulsive status epilepticus (SE) is one of the most frequent and severe neurological emergencies in both adults and children. A timely administration of appropriate antiepileptic drugs (AEDs) can stop seizures early and markedly improve outcome.

Areas covered: The main treatment strategies for SE are reviewed with an emphasis on initial treatments. The established first-line treatment consists of benzodiazepines, most frequently intravenous lorazepam. Benzodiazepines that do not require intravenous administration like intranasal midazolam or intramuscular midazolam are becoming more popular because of easier administration in the field. Other benzodiazepines may also be effective. After treatment with benzodiazepines, treatment with fosphenytoin and phenobarbital is usually recommended. Other intravenously available AEDs, such as valproate and levetiracetam, may be as effective and safe as fosphenytoin and phenobarbital, have a faster infusion time and better pharmacokinetic profile. The rationale behind the need for an early treatment of SE is discussed. The real-time delays of AED administration in clinical practice are described.

Expert opinion: There is limited evidence to support what the best initial benzodiazepine or the best non-benzodiazepine AED is. Recent and developing multicenter trials are evaluating the best treatment options and will likely modify the recommended treatment choices in SE in the near future. Additionally, more research is needed to understand how different treatment options modify prognosis in SE. Timely implementation of care protocols to minimize treatment delays is crucial.     

劳拉西泮片在健康人体的药代动力学和生物等效性

目的研究劳拉西泮片(镇静药)在中国健康人体的药代动力学和生物等效性。方法健康志愿者20名,随机双交叉单剂量口服试验和参比制剂劳拉西泮片3mg;于服药后48h内,抽取静脉血;用高效液相色谱法测定血浆中劳拉西泮浓度;用3P97药代动力学程序计算相对生物利用度并评价2种制剂生物等效性。结果劳拉西泮的药代动力学参数Cmax分别为(35.77±6.84),(36.95±4.60)μg·L-1;tmax分别为(2.38±0.56),(2.23±0.48)h;t1/2(Ke)分别为(13.72±2.07),(13.83±2.49)h;AUC(0-48)分别为(542.19±84.33),(527.53±63.52)ng·h·mL-1;AUC(0-inf)分别为(605.22±93.52),(599.37±71.56)ng·h·mL-1。试验制剂与参比制剂的相对生物利用度F=(103.5±15.9)%。结论2种制剂具有生物等效性。     

Transfer of Lorazepam and its Conjugate Across the Human Placenta

Abstract: The concentrations of lorazepam and its conjugate were determined in maternal venous serum, in umbilical vein and artery serum, and in amniotic fluid after a single 2 mg intramuscular and 2.5 mg oral maternal administration. During normal delivery (2 mg intramuscular injection) and caesarean section (2.5 mg orally) both the unconjugated and conjugated forms of lorazepam were found in the umbilical circulation and amniotic fluid. The serum protein unbound fraction was 14.0±4.8 (S.D.) % in maternal circulation and 20.8 ±3.1% in umbilical circulation. Generally, lorazepam was a useful anxiolytic agent during normal delivery and as a sedative on the night before caesarean section.     

Plasma lorazepam levels

Plasma lorazepam levels were studied following single doses of 2 mg and 4 mg in patients and volunteers. There was a slightly more rapid uptake of drug following deep intramuscular injection than when taken by mouth. Plasma levels declined rapidly following intravenous injection (t1/2 of approximately 2-3 hours). Two hours after giving the drug the plasma levels were similar irrespective of the route of administration. The second phase decline was very slow and one third of the peak concentration was still in the blood at 24 hours.     

劳拉西泮与碳酸锂治疗躁狂症的比较

目的：评估劳拉西泮对躁狂症的疗效。方法：用劳拉西泮治疗男性躁狂症１９例（年龄２８±ｓ１０ａ，病程２．０±１．３ｍｏ），剂量６～１８ｍｇ／ｄ，疗程３ｗｋ，并与碳酸锂治疗男性躁狂症２０例（年龄２８±１１ａ，病程２．０±１．３ｍｏ）对照，剂量１．５～２．５ｇ／ｄ，疗程３ｗｋ。结果：劳拉西泮组，总有效率８９％，碳酸锂组，总有效率９５％（Ｐ＞０．０５），但劳拉西泮起效时间较碳酸锂为早，不良反应以嗜唾、头晕为主。结论：劳拉西泮可作为控制躁狂症急性发作的有效药物。     

In Vitro Binding of Lorazepam and Lorazepam Glucuronide to Cholestyramine,Colestipol, and Activated Charcoal

Pharmaceutical Research -     

Triazolam premedication

A randomised, double blind study, of 58 female patients undergoing laparoscopic investigation was carried out to compare triazolam 0.25 mg, lorazepam 2 mg, or placebo as oral premedication. Each patient was assessed by only one of the authors both pre- and postoperatively with regard to anxiolysis, sedation and rapidity of recovery. Triazolam and lorazepam were each associated with a significant reduction in anxiety compared to the initial assessment, whereas placebo had no anxiolytic effect. Sixty minutes after premedication, patients who had received triazolam were significantly more sleepy than patients given placebo or lorazepam. Two hours after the operation, the patients who had had triazolam or lorazepam were significantly more sleepy than those who received placebo. However, at 6 hours postoperatively there was no difference between triazolam and placebo, whilst those who had been given lorazepam were still significantly more sleepy than those given placebo. Triazolam appears to offer advantages over either lorazepam or placebo in patients who require rapid recovery, sedation and reduction in pre-operative anxiety.     

Study of effects of clobazam and lorazepam on memory and cognitive functions in healthy subjects

This was a double-blind, placebo-controlled crossover study in 15 healthy female volunteers. It consisted of five sessions, separated by 1 week wash-out between sessions. The purpose of the trial was to study the potential amnesic and sedative activity of clobazam and lorazepam, and the potential antagonism between these effects under the joint influence of a high noise level and intense intermittent light stimulation (ILS), aimed at increasing the level of alertness. The study drugs were administered as a single daily oral dose. The amnesic and sedative effects were evaluated by objective measurements (digit span, Buschke selective reminding test, critical flicker fusion, reaction time, tapping, mental arithmetic test) and subjective measurements (visual analogue scale and adverse effect questionnaire) before each administration, then 1 h, 2 h, 2·5 h, 3 h, 4 h and 7 h post-dosing. An analysis of variance according to a balanced Latin square design was performed. Clobazam, at a dosage of 10 mg, was devoided of sedative and amnesic effects; at a dosage of 30 mg it induced only moderate memory disturbances. In contrast, lorazepam, administered at doses of 1 and 3 mg, produced marked and dose-dependent disturbances of memory, alertness and cognitive functions. The use of visual and sound stimuli, designed to increase the level of alertness, did not counteract the sedative effects induced by lorazepam.     

A multicentre double-blind comparative trial of fluvoxamine versus lorazepam in mixed anxiety and depression treated in general practice

Fluvoxamine, a selective serotonin reuptake inhibitor, was compared with lorazepam in a multicentre double-blind, parallel group study in 112 general practice patients with mixed anxiety and depression. For inclusion, patients were required to have minimum baseline scores of 21 on the Montgomery-Asberg Depression Rating Scale (MADRS) and 11 on the Clinical Anxiety Scale (CAS). Treatment was for 6 weeks. There were no significant differences between treatments at any point except in an elderly subgroup in whom anxiety improved more rapidly with lorazepam. There were significant improvements in MADRS, CAS and global ratings compared with baseline at all subsequent assessments. Improvement continued during the whole treatment period. Lorazepam produced more sedation, whilst fluvoxamine produced significantly more nausea and vomiting; this was usually early in onset and, if tolerated, resolved during the course of the study. As it is now widely recognized that benzodiazepines should only be given in short courses of 2-4 weeks, the continued improvement up to 6 weeks has implications regarding choice of treatment.