输液泵持续输注安定治疗破伤风效果观察

2000年1月-2006年9月,我科使用输液泵持续输注安定治疗破伤风20例，在维持安定有效血浓度、对患者的镇静、肌肉松弛作用及降低药物不良反应等方面取得了较满意的临床效果．现报道如下。     

安定在产程中的应用及血药浓度监测

目的 研究安定对产程中产妇的作用，药物透过胎盘屏障及对新生儿的影响。方法 选择产程潜伏期或潜伏期延长的住院产妇３０例，静注安定１０ｍｇ，用荧光偏振免疫分析法（ＦＰＬＡ）测定静注后５ｍｉｎ、２ｈ的母血和胎儿娩出时的母血及脐血的药物浓度，并进行新生儿Ａｐｇａｒ评分。结果 静注后５ｍｉｎ、２ｈ的母血、胎儿娩出时的母血及脐血的安定浓度依次迅速降低且均低于最低有效浓度（４００ｎｇ／ｍｌ）；新生儿１ｍｉｎ和５     

安定代谢物去甲安定血浆浓度的双峰现象

安定代谢物去甲安定血浆浓度的双峰现象马越鸣，程能能，孙瑞元（皖南医学院药理教研室，芜湖２４１００１）中文图书资料分类法分类号Ｒ９７１．３去甲安定是安定在血浆中的主要活性代谢物，其药效强度与安定相当。因此，要准确评价安定在整体情况下的时效过程，必须同时...     

产程中应用安定对新生儿的影响

近年来，随着安定在产程中的广泛应用，虽对产程的进展起到了加速作用，但是对新生儿也产生了一些不利的影响。考虑到它应用的普遍性，有必要对其国产期代谢和安全性作进一步的研究。我们在第M产程早期给产妇静脉注射10mp安定后，测定胎儿娩出时母脐血药物浓度及对新生儿Amp分项评分，以观察安定对新生儿的影响。l资料与方法l．l资料来源筛选IWe年8月一lop年6月在我院足月临产第二产程早期的初产妇56例。孕龄在39周一41周，年龄在23岁一30岁，新生儿体重在3000g－4000g之间。且产妇在近期无用药史及应用安定的禁忌症。把产妇分为安定组和…     

体外循环运用异丙酚麻醉对一氧化氮和内皮素的影响

目的 观察体外循环(CPB)过程中运用异丙酚麻醉对一氧化氮(NO)与内皮素(ET)的影响,进一步探讨异丙酚对缺血再灌注损伤的保护作用.方法 选择CPB下心内直视手术30例,随机分为异丙酚组与咪唑安定组各15例,两组采用相同的麻醉诱导方式.麻醉维持异丙酚组采用异丙酚0.5～4.0 mg/(kg·h),咪唑安定组采用咪唑安定0.03～0.2 mg/(kg·h)并吸入低浓度的氨氟醚或异氟醚.分别测定手术前(T1)、CPB0h(T2)、CPB5min(T3)、CPB停止时(T4)和CPB后1h(T5)等时间点NO和ET在外周血中的浓度,并观察其动态变化.结果 两组的NO浓度均逐渐升高,异丙酚组在CPB前后的各个时间点的NO浓度无显著性差异.咪唑安定组T4和T5与T1,T2,T3各个时间点相比NO浓度显著升高,差异显著性.两组相比,在T4和T5,异丙酚组的NO浓度均明显低于咪唑安定组,定异具有显著性,而CPB停止前各个时间点的NO浓度无明显差异.两组的ET浓度均逐渐下降,异丙酚组在CPB停止前后各个时间点的ET浓度无显著性差异.咪唑安定组CPB停止时与CPB停止前的各个时间点相比ET浓度显著下降,差异具有显著性(P＜0.05),CPB后1h ET浓度与CPB停止时相比显著升高并达到术前水平.两组相比异丙酚组的ET浓度在CPB停止时明显高于咪唑安定组,而在CPB后1h却明显低于咪唑安定组,差异均具有显著性,两组在CPB停止前各个时间点的ET浓度无明显差异.结论 在体外循环过程中采用异丙酚麻醉可以维持NO/ET的动态平衡,对缺血再灌注损伤具有一定的保护作用.     

反相高效液相色谱法测定剖腹产产妇及胎儿血浆中安定浓度

反相高效液相色谱法测定剖腹产产妇及胎儿血浆中安定浓度天津市第一医院药剂科３０００１０王立新，张文柏安定（Ｄｉａｚｅｐａｍ，ＤＺＰ）为苯二氮杂草类，常用于镇静、抗癫痫、麻醉辅助用药。据文献报道［１］，２％利多卡因对剖腹产产妇行硬膜外阻滞加用安定１０ｍｇ...     

安定在产程活跃早期的应用

安定具有镇静、催眠、抗惊厥及较强的肌肉松弛作用。在分娩期选用一定剂量的安定静脉缓慢注射，可减轻产妇焦虑紧张情绪，选择性地作用于子宫颈平滑肌，松弛宫颈口，促进宫颈扩张，加速产程进展。我院近年来在产程中使用安定，取得较好的临床效果，现报道如下。     

Azone对安定的体外透皮促进作用

本文研究了含乙醇及丙二醇的水溶液系统中的Azone 对安定的体外透皮促进作用。发现不同浓度的Azone 溶液均可促进安定的透皮吸收,但以其0.8%的溶液作用最强,且有统计学意义。     

安定在产程中的临床应用

产妇在临产时宫缩引起的阵痛将影响产妇的情绪、休息，使产程延长，增加产妇的痛苦。我们应用安定以促进产程进展，减轻产妇的痛苦，可顺利完成分娩，现报告于下。1．安定在产程过程中的应用：安定为镇静剂，可抑制子宫颈平滑肌的收缩活动，而对子宫肌肉无明显作用；安定可通过抗焦虑及镇静作用改善产妇的恐惧和疲惫状态。我科曾对足月妊娠、单胞头位、年龄在23～45岁的初产妇320人，在她们进入潜伏期且无影响产程进展的合并症及并发症时分2个组，每组160人，一组为安定组，一组为对照组，两组产妇均在潜伏期子宫日扩张2cm时进食蓖麻油餐，…     

SC1001Na对马桑内酯点燃大鼠海马脑片CA1区锥体细胞群体锋电…

作者用离体海马脑片技术，从细胞水平观察及比较了ｓｃ１００１Ｎａ对马桑内酯点燃大鼠海马脑片ＣＡ１区群体锋电位（ＰＳ）的影响。结果表明：不同浓度的ｓｃ１００１Ｎａ和安定对ＰＳ均有抑制作用，其抑制作用在对照组两组比较有显著差异（Ｐ〈０．００１），而在点燃组无显著差异（Ｐ〉０．０５）。提示ｓｃ１００１Ｎａ具有较强的中枢抑制作用。但其作用机制可能与安定不同。     

A case of unusual suicidal poisoning by the organophosphorus insecticide dimethoate

A 20-year-old male who attempted suicide by injecting subcutaneously 10 ml of Sistemin 40 (40% dimethoate) was admitted 16 h later. General weakness, muscular fibrillations and a marked inhibition of red blood cell and serum cholinesterases were the prominent signs of intoxication. The antidotal treatment of intermittent boluses of atropine, oxime HI-6 and diazepam was combined with symptomatic therapy. Cholinesterase activity decreased within the next 3 d. In contrast to the marked general improvement of the patient, the return of cholinesterase activities was very slow. The patient was discharged 24 d after the poisoning with no notable consequences which could be ascribed to the intoxication.     

Cholinesterase activity in blood samples collected from field workers and nonfield workers in California

Blood samples (1221) were obtained from workers through cooperating physicians in farm worker health clinics during the growing and harvest season for lettuce, grapes, peaches, and citrus in January, May, July, and September 1975. The blood samples were analyzed for cholinesterase activity using the dual channel Technicon AutoAnalyzer II system. The dual channel system provided for automatic blanking, the use of different buffers for the enzyme (pH 7.7) and color reactions (pH 8.2), and dialyzers to eliminate the interference of blood components with the color reaction. The cholinesterase activity (micromoles of -SH per minute per milliliter) of the red cell was obtained by difference using the activities of whole blood and plasma and the hematocrit of the blood sample. Acetylthiocholine was used as substrate. The mean plasma (8.3) and red cell (27.9) cholinesterase activities of female field workers were not significantly different from those of nonfield workers or field workers who had not worked in the field during the last 30 days. The mean red cell cholinesterase activity (27.7) of male field workers was significantly lower than the red cell activity (29.6) of nonfield workers in 1975 but not different from field workers who had not worked during the last 30 days (27.5) or nonfield workers in 1976 (27.5). The mean plasma cholinesterase activity of male field workers (9.9) was not significantly different from those of nonfield workers (9.4) in 1975 or 1976, whereas field workers who had not worked in the field during the last 30 days had plasma values (8.9) significantly lower than those working. Red cell values of field workers returning for a repeat test were found to increase slightly between the first test and second, although plasma values remained the same.     

Rates of spontaneous reactivation and aging of acetylcholinesterase in human erythrocytes after inhibition by organophosphorus pesticides

The in vitro rates of spontaneous reactivation and aging in human erythrocyte acetylcholinesterase were studied after inhibition by a dimethoxy (R1R2) and diethoxy substituted (R1R2) organophosphate pesticide (OP) of general structure R1R2P(O)X. These have been compared with data for human plasma cholinesterase previously reported using a similar methodology. A significantly slower rate of aging for erythrocyte acetylcholinesterase was found compared to plasma cholinesterase, whether inhibited by dimethoxy or diethoxy substituted OPs. For diethoxy OPs the rate of spontaneous reactivation of the inhibited plasma enzyme was significantly slower than for the inhibited red cell enzyme. This acetylcholinesterase, and previously published plasma cholinesterase, data suggest that in practise a blood sample taken 30-40 h after significant acute OP exposure will still show inhibition in either plasma or erythrocyte cholinesterase when analysed, but that any inhibited plasma enzyme is more likely to be in the aged form. In contrast a substantial proportion of the erythrocyte acetylcholinesterase is found unaged and therefore sensitive to reactivation by oximes. Samples from an occupational exposure where depressions in plasma or erythrocyte cholinesterase activity from baseline measurements were reactivated ex vivo using the oxime 2-PAM support this hypothesis. These data also confirm that the plasma enzyme is a more sensitive than erythrocyte acetylcholinesterase as an indicator of OP exposure and thus the potential value of ex vivo oxime reactivation of erythrocyte acetylcholinesterase in a blood sample to indicate subclinical OP exposure may be limited. However, this study is too small to draw conclusions on the sensitivity of ex vivo oxime reactivation of acetylcholinesterase as a novel biomarker of excessive OP absorption. Given that there is a better relationship between anticholinergic symptoms and red cell acetylcholinesterase inhibition, and that the slower resynthesis rate of any aged or inhibited red cell enzyme may be interpretatively useful when venepuncture is delayed, it is suggested that red cell acetylcholinesterase activity does have a place in monitoring potential OP exposure.     

HI-6 in man: efficacy of the oxime in poisoning by organophosphorus insecticides.

The efficacy of the oxime HI-6 was studied as a treatment for organophosphorus poisoning. HI-6 was given four times daily as a single intramuscular injection of 500 mg accompanied by atropine and diazepam therapy. Oxime treatment was started on admission and continued for a minimum of 48 h and a maximum of 7 d. HI-6 rapidly reactivated human blood acetylcholinesterase inhibited by dimethoxy organophosphorus compounds, while the dimethoxy-inhibited enzyme was mainly resistant to the treatment by HI-6. Although both HI-6 and pralidoxime chloride reactivated the red blood cell cholinesterase in quinalphos-poisoned subjects, the return of enzyme activities was more rapid following the use of HI-6. The general improvement of poisoned patients, which was sometimes more rapid than the rise of acetylcholinesterase activity, pointed to direct pharmacological effects of HI-6. No undesirable side-effects were noted in patients when HI-6 plasma concentrations were maintained at levels far above the 'therapeutic' concentration for up to 7 d.     

The enzymatic hydrolysis of imidazoleacryloylcholine (murexine) and imidazolepropionylcholine (dihydromurexine) by various cholinesterases

Several choline esters, including the imidazoleacryloyl and imidazolepropionyl compounds, have been hydrolysed by cholinesterases from various sources. The imidazolepropionyl ester was metabolized by cholinesterases obtained from human plasma, ox spleen, ox serum, and guinea-pig liver, but not by rat liver or bovine red cell cholinesterase. It is suggested the imidazolepropionylcholine or a closely related ester might be the natural substrate for “non-specific” cholinesterase.     

Effect of benzodiazepine derivatives: I. Augmentation of T cell-dependent antibody response by diazepam in mouse spleen cells

Oral administration of diazepam at doses of 5-10 mg/kg to restraint-stressed mice resulted in almost complete recovery in the stress-induced suppression of the antibody response to sheep red blood cell (SRBC). Moreover, this compound restored the suppression of antibody response to SRBC in cyclophosphamide-treated mice. Diazepam treatment also enhanced the antibody response against SRBC in normal mice only when the animals were immunized with the reduced amount of antigen. It was demonstrated that antigen specific helper T cell activity was promoted by diazepam administration in mice. Addition of diazepam augmented the in vitro anti-SRBC hemolytic plaque-forming cell (PFC) response in mouse splenocytes without altering kinetics of the response. However, the enhancing effect was observed only when the drug was added to the medium at the culture initiation. On the other hand, antibody response to T cell-independent antigens such as trinitrophenylated (TNP)-Ficoll and TNP-lipopolysaccharide were not enhanced by diazepam. Concanavalin A or LPS-induced 3H-thymidine uptake into splenocytes were not stimulated by diazepam. These results suggest that diazepam promotes the antibody response through stimulating helper T cell functions.     

Poisoning of an urban family due to misapplication of household organophosphate and carbamate pesticides.

A case report of an urban family who experienced excessive exposure to organophosphate and carbamate pesticides is presented. All three family members developed symptoms that were compatible with cholinesterase inhibition: headache, lightheadedness, wheezing, shortness of breath, nausea, and fatigue. Serial measurement of red blood cell and serum cholinesterases soon after exposure and during subsequent months confirmed the diagnosis of pesticide poisoning. This report demonstrates that the misapplication of pesticides commonly used in residences in urban areas can cause acute pesticide poisoning and demonstrates the usefulness of repeated measurements of cholinesterase during the post-exposure period in establishing the correct diagnosis.     

The effect of pralidoxime chloride in the assay of acetylcholinesterase using 5,5'-dithio-bis(2-nitrobenzoic acid) (Ellman's reagent).

Pralidoxime chloride (PAM) hydrolyzes acetylthiocholine, the substrate used in the assay of red cell cholinesterase. The thiocholine that is produced forms a yellow complex when Ellman's reagent is used in the assay. This was tested in blood samples of patients who were treated with PAM after organophosphorus (OP) poisoning and after the observation of an immediate increase in absorption of light at 412 nm.     

Pharmacodynamics and pharmacokinetics of eptastigmine in elderly subjects

Summary Eptastigmine is a new cholinesterase inhibitor, which may be potentially useful for the symptomatic treatment of Alzheimer's disease. A preliminary evaluation of its pharmacodynamic and pharmacokinetic profiles in the elderly has now been made in 6 healthy subjects (63–84 years of age) given 30 mg eptastigmine as a single oral dose. Blood was collected prior to and 1, 2, 3, 4, 6, 8, and 12 h after eptastigmine administration for measurement of cholinesterase inhibition in plasma and red blood cells and the plasma drug concentrations.The maximum plasma cholinesterase inhibition was 17%, which was reached 2.7 h after treatment. In red cells the maximum inhibition of the enzyme was 29% after 3.8 h. The estimated half-time of cholinesterase recovery was 12.4 h in plasma and 13.6 h in red blood cells. The peak plasma concentration of eptastigmine of 0.86 ng·ml^–1 was reached after 1.4 h. Following absorption the drug was rapidly distributed into tissues (t_1/2 = 0.44 h) and then eliminated with a half-life of 12.1 h. The drug was well tolerated in all but one subject, who showed bradycardia with hypertension and nausea for about 2 h after the dose.The results indicate that oral administration of eptastigmine to elderly subjects produces long lasting inhibition of cholinesterase activity in plasma and in red blood cells.     

Red blood cell and total blood acetylcholinesterase and plasma pseudocholinesterase in humans: observed variances

Although acetylcholinesterase is the target molecule of organophosphate poisoning, it is not always assayed in clinical evaluations which include only the determination of plasma or serum cholinesterase. In this paper we present observations on workers exposed to, or poisoned by, ethylparathion. Acetylcholinesterase decreased earlier and more intensely than cholinesterase, with the suggestion of an initial increase of acetylcholinesterase activity in newly exposed, workers. A simplified standard Ellman assay of total acetylcholinesterase activity of hemolyzed total blood correlated with that of washed erythrocyte acetylcholinesterase. All results were standardized to both red blood cell and hemoglobin concentration. Normal values in a group of unexposed subjects were acetylcholinesterase: 1225 +/- 181 nU x 10/RBC and 39.30 +/- 5.05 U/g Hb for men, 1321 +/- 234 nU x 10/RBC and 42.57 +/- 6.85 U/g Hb for women. Differences between total and erythrocyte acetylcholinesterase were not statistically significant. Plasma cholinesterase appeared to be decreased in pregnancy and increased in anesthesia, liver and kidney disease and neuropathologic conditions attributed to metal poisoning while total acetylcholinesterase was unaffected. The determination of both cholinesterase and acetylcholinesterase assists the evaluation of individuals exposed to or poisoned by organophosphate, the differentiation of other conditions affecting cholinesterase and the recognition of genetically atypical cholinesterase.