抗癫痫药物的合理应用

目的:了解我院临床上应用抗癫痫药物的类型,总结合理应用原则,减少其不良反应,指导临床合理用药及更好地发挥药物疗效,提高患者的生活质量。方法:采用荧光偏正免疫方法对我院2002年～2005年主要抗癫痫药物苯巴比妥、丙戊酸和卡马西平481例患者的血药浓度进行监测,大部分患者依从性好、疗效佳,少数患者存在不合理用药。结果与结论:根据我院所监测的结果对使用抗癫痫药给予合理的建议。抗癫痫药治疗指数低,有效剂量个体差异大,血药浓度监测对调整给药剂量有指导意义,同时合理应用抗癫痫药不但能减少不良反应,而且为临床提供了可靠的依据。     

对四种抗癫痫药物进行血药浓度监测的结果分析

目的通过对4种抗癫痫药物646例次血药浓度监测结果分析,为临床提高本类药物的治疗水平作参考。方法运用荧光偏振免疫法测定血药浓度,对我院4种抗癫痫药物血药浓度监测结果进行分析、评价。结果共监测646例次,达到有效治疗浓度者为57.43%;低于有效治疗浓度者为30.80%;高于有效治疗浓度者11.77%。结论抗癫痫药物血药浓度监测对癫痫患者合理用药有重要的指导作用,血药浓度个体差异较大,临床用药时需个体化给药。癫痫患者应重视血药浓度监测,并结合其他因素调整用药方案,以达到安全、有效、合理应用抗癫痫药。     

高原低氧环境影响抗癫痫药物的研究进展

高原低氧环境通过改变机体胃肠排空速率、器官血流量、药物血浆蛋白结合率、药物代谢酶和转运体表达等影响药物的药代谢动力学过程。癫痫是一种需长期用药的脑部疾病,而大多数抗癫痫药物的治疗指数低、有效血药浓度范围窄。临床上常用治疗药物监测(therapeutic drug monitoring,TDM)来寻找抗癫痫药物的最佳个体化用药方法。该文对临床上常用抗癫痫药及其治疗窗进行归纳总结,并分析高原低氧环境对抗癫痫药物药代动力学的影响,为高原抗癫痫药物临床用药提供参考。     

临床药师参与1例抗癫痫药物致神经毒性患者的治疗

目的结合血药浓度监测及药物相互作用分析,为癫痫患者提供合理的治疗方案。方法临床药师参与1例发生神经毒性的癫痫患者药物治疗过程。通过血药浓度监测提示视物晃动、不能行走、视物重影、嗜睡和言语笨拙等症状为苯妥英钠中毒反应,建议暂停苯妥英钠,合理选择治疗方案。结果医师采纳临床药师建议,患者病情明显好转。结论血药浓度监测是提高抗癫痫药物治疗有效性和安全性的必要手段。临床药师参与癫痫药物治疗管理,进行正确的用药指导,保证用药规范性,避免不良反应发生。     

抗癫痫药物在肝肾功能不全患者中使用的研究进展

临床常用抗癫痫药物根据其药动学特点可分为主要经肝代谢、主要经肾排泄和肝肾双通道清除。肝功能不全患者尽量选择主要经肾排泄的抗癫痫药物,如加巴喷丁、普瑞巴林,或评估肝功能不全的程度,适当的减少剂量。肾功能不全的患者尽量选择主要经肝代谢的抗癫痫药物,如丙戊酸钠、卡马西平、拉莫三嗪,或评估患者的肌酐清除率（CLcr）,根据CLcr进行剂量调整。对于透析的患者,结合血药浓度监测透析后补充剂量有助于个体化治疗。肝肾功能不全患者抗癫痫药物的选择、剂量调整应综合考虑患者肝肾功能情况、药物代谢特点、合并疾病、个体耐受性等因素,在抗癫痫药物使用过程中,加强对药物相互作用、药物不良反应等的监护,结合血药浓度监测,以提高临床用药的有效性与安全性。     

181例次抗癫痫药物血药浓度监测结果分析

癫痫是一种由多种原因引起的脑灰质的偶然、特发、过度、快速和局限性放电而导致的神经系统功能紊乱性疾病，是神经系统的多发病。在我国，癫痫的患病率为0．5％-1．0％。治疗癫痫无论是对原发性癫痫，还是对继发性癫痫，都需要服用抗癫痫药控制发作。由于抗癫痫药物的作用机理目前尚未探明，而有的抗癫痫药具有非线性药动学特征，因而使抗癫痫药在患者体内的代谢差异很大，这为医师制定给药方案带来一定困难。同时，抗癫痫药的应用目的不仅要抑制癫痫发作，而且要尽量减少神经方面的不良反应。因此，血药浓度监测成为药物治疗癫痫的重要措施。     

临床药师参与2例重症肺炎癫痫患儿的药学监护

目的:探讨重症肺炎合并癫痫患儿的治疗方案。方法:根据抗癫痫药物的药物代谢动力学特点,结合临床药师参与重症肺炎合并癫痫患儿的实际案例,对药物合理应用进行分析和阐述。结果:重症肺炎合并癫痫患儿的药学监护重点在于抗菌药物的选择及其对抗癫痫药物的影响,通过制定合理的个体化给药方案及用药监护,能达到安全、有效的抗癫痫和抗感染治疗效果。结论:临床药师参与制定个体化给药方案,可避免药物间相互作用发生,提高医疗质量。     

抗菌药物在持续性血液置换治疗中的应用

目的:探讨不同抗菌药物在持续性血液置换治疗(CRRT)中剂量调整方案及药物代谢动力学的差异。方法:收集相关文献资料,归纳CRRT的患者常用抗生素的剂量调整方案,包括β-内酰胺类、头孢菌素类、碳青霉烯类、万古霉素等,总结各药物在CRRT中的药物代谢动力学特点。结果:对于合并感染的危重症患者,需要根据药物的药代动力学参数和CRRT的模式调整给药方案。由于不同药物的代谢通路和分子量大小的不同,药物推荐剂量也不同。结论:大多数抗菌药物在CRRT中均需要调整给药剂量,不合理的剂量方案可能带来治疗失败或发生不良反应。     

181例次抗癫痫药物血药浓度监测结果分析

癫痫是一种由多种原因引起的脑灰质的偶然、特发、过度、快速和局限性放电而导致的神经系统功能紊乱性疾病,是神经系统的多发病。在我国,癫痫的患病率为0·5%~1·0%[1]。治疗癫痫无论是对原发性癫痫,还是对继发性癫痫,都需要服用抗癫痫药控制发作。由于抗癫痫药物的作用机理目前尚未探明,而有的抗癫痫药具有非线性药动学特征[2],因而使抗癫痫药在患者体内的代谢差异很大,这为医师制定给药方案带来一定困难[3]。同时,抗癫痫药的应用目的不仅要抑制癫痫发作,而且要尽量减少神经方面的不良反应。因此,血药浓度监测成为药物治疗癫痫的重要措施。…     

我院2001～2006年抗癫痫药血药浓度监测数据分析

目的:阐述治疗药物监测(TDM)对抗癫痫药合理应用的意义,关注临床科室对TDM的认识程度。方法:建立抗癫痫药Access数据库,对我院2001～2006年抗癫痫药TDM结果进行分析。结果:我院抗癫痫药监测例数逐年上升;由监测结果计算的抗癫痫药有效浓度、高血药浓度、低血药浓度比例显示血药浓度监测极有必要,但患者的个体用药信息缺乏限制了抗癫痫药个体化用药的发展。结论:TDM虽应用日益广泛,但仍需医师、药师共同努力,以最大限度地保证抗癫痫药的个体化应用。     

Efficacy of gut lavage,hemodialysis, and hemoperfusion in the therapy of paraquat or diquat intoxication

Clinical and in vitro investigations were carried out to test the efficacy of gut lavage, hemodialysis, and hemoperfusion in the treatment of poisoning with paraquat or diquat. In a patient suffering from diquat intoxication 130 times more diquat was removed by gut lavage 30 h after ingestion than was removed by complete aspiration of the gastric contents.Determination of in vitro clearances for paraquat and diquat by hemodialysis showed that, at serum concentrations of 1–2 ppm, such as are frequently encountered in poisoning in man, toxicologically relevant quantities of herbicide cannot be removed from the body. At a concentration of 20 ppm, on the other hand, hemodialysis proved to be effective, the clearance being 70 ml/min at a blood flow rate of 100 ml/min. The efficacy of hemoperfusion with coated activated charcoal was on the whole better. Especially at concentrations around 1–2 ppm, the clearance values for hemoperfusion were some 5–7 times higher than those for hemodialysis.In a patient suffering from paraquat poisoning, both hemodialysis as well as hemoperfusion were carried out. The in vitro results could be confirmed: At serum concentrations of paraquat less than 1 ppm no clearance could be obtained by hemodialysis while by hemoperfusion with activated charcoal quite high clearance values were measured and the serum level dropped down to zero.

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Zusammenfassung Klinische Untersuchungen und Laboratoriumsversuche wurden durchgeführt, um die Wirksamkeit von Darmspülung, Hämodialyse und Hämoperfusion bei Paraquat- und Deiquat-Vergiftungen zu prüfen.Bei einem Patienten wurde 30 Std nach Deiquat-Aufnahme durch Darmspülung 130mal mehr Deiquat entfernt als durch vollständige Aspiration des Mageninhaltes. In vitro-Versuche ergaben, daß bei Blutserumkonzentrationen von 1–2 ppm, die bei Vergiftungen oft gemessen werden, durch Hämodialyse keine toxikologisch relevanten Paraquat- oder Deiquat-Mengen entfernt werden können. Dagegen erwies sich die Hämodialyse bei 20 ppm und einer Blutumlaufgeschwindigkeit von 100 ml/min mit einer Clearance von 70 ml/min als wirksam. Die Hämoperfusion mit beschicheter Aktivkohle war in diesen Versuchen aber eindeutig überlegen, denn insbesondere bei Konzentrationen um 1–2 ppm waren die Clearance-Werte 5–7mal höher als bei der Hämodialyse.Die in vitro-Ergebnisse wurden bei einem Patienten mit einer Paraquat-Vergiftung bestätigt: Bei Konzentrationen unter 1 ppm war die Hämodialyse wirkungslos, während durch Hämoperfusion relativ hohe Clearance-Werte erreicht wurden, so daß der Serumspiegel rasch unter die Nachweisgrenze abfiel.

     

In vitro studies on sterically stabilized liposomes (SL) as enzyme carriers in organophosphorus (OP) antagonism

This study describes a new approach for organophosphorous (OP) antidotal treatment by encapsulating an OP hydrolyzing enzyme, OPA anhydrolase (OPAA), within sterically stabilized liposomes. The recombinant OPAA enzyme was derived from Alteromonas strain JD6. It has broad substrate specificity to a wide range of OP compounds: DFP and the nerve agents, soman and sarin. Liposomes encapsulating OPAA (SL)* were made by mechanical dispersion method. Hydrolysis of DFP by (SL)* was measured by following an increase of fluoride ion concentration using a fluoride ion selective electrode. OPAA entrapped in the carrier liposomes rapidly hydrolyze DFP, with the rate of DFP hydrolysis directly proportional to the amount of (SL)* added to the solution. Liposomal carriers containing no enzyme did not hydrolyze DFP. The reaction was linear and the rate of hydrolysis was first order in the substrate. This enzyme carrier system serves as a biodegradable protective environment for the recombinant OP-metabolizing enzyme, OPAA, resulting in prolongation of enzymatic concentration in the body. These studies suggest that the protection of OP intoxication can be strikingly enhanced by adding OPAA encapsulated within (SL)* to pralidoxime and atropine.     

Synthesis,Cytotoxicity and Antileishmanial Activity of Some N-(2-(indol-3-yl)ethyl)-7-chloroquinolin-4-amines

We report herein the condensation of 4,7-dichloroquinoline (1) with tryptamine (2) and D-tryptophan methyl ester (3) . Hydrolysis of the methyl ester adduct (5) yielded the free acid (6) . The compounds were evaluated in vitro for activity against four different species of Leishmania promastigote forms and for cytotoxic activity against Kb and Vero cells. Compound (5) showed good activity against the Leishmania species tested, while all three compounds displayed moderate activity in both Kb and Vero cells.     

Steroidal sapogenin contents in some domestic plants

In order to find out the values of the steroid resources for the future use. the compositions and contents of steroidal sapogenins from 13 domestic plants have been investigated. As a result,Dioscorea nipponica, D. quinqueloba andSmilax china were found to have large amount of diosgenin. And pennogenin inTrillium kamtschaticum andParis verticillata, yuccagenin inAllium fistulosum, hecogenin inAgave americana and neochlorogenin inSolanum nigum were appeared to be major steroidal sapogenins.     

Aquatic Insects and Trace Metals: Bioavailability,Bioaccumulation, and Toxicity

Abstract

The uptake of metals from food and water sources by insects is thought to be additive. For a given metal, the proportions taken up from water and food will depend both on the bioavailable concentration of the metal associated with each source and the mechanism and rate by which the metal enters the insect. Attempts to correlate insect trace metal concentrations with the trophic level of insects should be made with a knowledge of the feeding relationships of the individual taxa concerned. Pathways for the uptake of essential metals, such as copper and zinc, exist at the cellular level, and other nonessential metals, such as cadmium, also appear to enter via these routes. Within cells, trace metals can be bound to proteins or stored in granules. The internal distribution of metals among body tissues is very heterogeneous, and distribution patterns tend to be both metal and taxon specific. Trace metals associated with insects can be both bound on the surface of their chitinous exoskeleton and incorporated into body tissues. The quantities of trace meals accumulated by an individual reflect the net balance between the rate of metal influx from both dissolved and particulate sources and the rate of metal efflux from the organism. The toxicity of metals has been demonstrated at all levels of biological organization: cell, tissue, individual, population, and community. Much of the literature pertaining to the toxic effects of metals on aquatic insects is based on laboratory observations and, as such, it is difficult to extrapolate the data to insects in nature. The few experimental studies in nature suggest that trace metal contaminants can affect both the distribution and the abundance of aquatic insects. Insects have a largely unexploited potential as biomonitors of metal contamination in nature. A better understanding of the physico-chemical and biological mechanisms mediating trace metal bioavailability and exchange will facilitate the development of general predictive models relating trace metal concentrations in insects to those in their environment. Such models will facilitate the use of insects as contaminant biomonitors.     

Alzheimer’s disease – current trends in basic and clinical research. Highlights from the 16th ECNP

Advances in the molecular biological knowledge of neuronal nicotinic acetylcholine receptors (nAChRs) have led to a growing interest by the pharmaceutical industry in the development of novel compounds that selectively modulate nAChR function. The ability of (-)-nicotine, an activator of nAChRs, to enhance attentional aspects of cognition in animals and humans, to exert neuroprotective and anxiolytic-like effects, and presumably to mediate the negative correlation between smoking and Alzheimer's (and Parkinson's) Disease, has focused interest on the potential therapeutic utility of modulators of nAChR function for treatment of some of the deficits associated with these progressive, neurodegenerative conditions. Numerous compounds are known which activate nAChRs and which might serve as lead compounds toward the development of such agents. The pharmacologic diversity of neuronal nAChR subtypes suggests the possibility of developing selective compounds which would have more favourable side-effect profiles than existing agents. This broader class of agents, collectively called cholinergic channel modulators (ChCMs), is anticipated to encompass compounds which would have more favourable side-effect profiles than existing agents, which generally exhibit low selectivity. This selectivity may be achieved by preferentially activating some subtypes of nAChRs (i.e., Cholinergic Channel Activators, ChCAs) or inhibiting the function of other subtypes (Cholinergic Channel Inhibitors, ChCIs). An overview of the biology of nAChRs and the rationale for the use of ChCMs for the treatment of dementia related to neurodegenerative diseases are presented, followed by a discussion of lead compounds and compounds under consideration for clinical evaluation.