某院1 435例单唾液酸四己糖神经节苷脂钠应用合理性分析

摘 要 目的：了解某院单唾液酸四己糖神经节苷脂钠（GM1）的使用情况,分析其使用合理性,为临床合理用药提供参考。方法：采用回顾性分析方法,统计某院2018年1~6月住院患者的GM1使用情况,参照说明书及相关指南、共识进行合理性分析。结果：某院GM1平均药物利用指数（DUI）为1.22,使用量最多的为老年病科;1 435例患者中,适应证不合理242例（16.86%）,给药剂量不合理150例（10.45%）,用药疗程不合理206例（14.35%）,溶媒选择不合理52例(3.62%),配伍不合理4例（0.28%）,联合用药不合理16例（1.65%）。结论：GM1的使用存在不合理现象,其中适应证、给药剂量、用药疗程不合理问题较为突出,应提高GM1使用的合理性。     

某院肿瘤患者使用升白细胞药的情况分析

摘 要 目的：了解某院肿瘤患者升白细胞药的使用情况,规范该院肿瘤患者升白细胞药的使用。方法: 采用回顾性分析方法,调查2014年1～12月某院诊断为恶性肿瘤并开具升白细胞药的患者病历579份,收集患者的基本信息、化疗情况、化疗后骨髓抑制情况和升白细胞药使用情况等信息,对升白细胞治疗的药物种类、给药时机、给药剂量、给药频次、使用疗程、联合用药以及溶媒的选择进行分析。结果: 该院升白细胞药物以口服制剂为主;579例病例中合理用药病历414 例,占71.50%,不合理用药病历165份,占28.50%,其中用药剂量和疗程基本符合要求,而不合理病例中主要以品种和给药时机不适宜为主,分别为42.42%和27.88%,其次为重复给药和联合用药不适宜,分别为13.33%和12.73,溶媒选择不适宜发生率较低,为3.64%。结论:该院肿瘤患者升白细胞药的使用有待规范,临床医师需加强升白细胞药应用知识的学习,合理使用该类药物。     

某三甲医院依达拉奉注射液用药合理性调查

摘 要 目的：评价某院依达拉奉注射液临床应用合理性,提升临床合理用药水平。方法: 利用该院病案管理系统,随机提取2016年1～6月应用依达拉奉注射液病历500份,依据药品说明书、相关文献与资料分析其临床应用合理性。结果: 500份病历中神经外科占48%,神经内科37%,重症医学科7%,骨科5%,其他科室占3%。用药不合理病历共计261份（52.2%）;其中超说明书适应证用药108份（21.6%）;给药频次不当180份（36%）;给药疗程不当201份（40.2%）;给药时机不正确37份（7.4%）;溶媒选择错误3份（0.6%）;存在特殊人群使用4份（0.8%）。结论:依达拉奉注射液在该院存在严重的超疗程、超适应症使用等现象,且不能够严格遵照药品说明书规定的给药频次和注意事项合理用药,应引起高度重视。     

管饲给药情况分析

摘 要 目的： 了解我院经饲管给药的药物使用情况,为临床合理用药提供参考。 方法: 调取我院2013年5月～2014年4月管饲给药病例,对药物使用情况、用药合理性等进行统计分析。结果: 一年内共有384例采用了管饲的给药方法,占同期出院病例的1.48%(384/25 946)。经饲管给药的药物以心血管系统药物（21.09%）、消化系统药物（18.16%）及神经系统药物（14.84%）为主;不合理用药有228例（59.38%）,包括选药不当、用法不当与配伍不当等3个方面。 结论: 经饲管给药的特殊性,药师可以更多地在临床用药前实施事前干预,以延续药物治疗的安全有效性。     

某三甲医院普外科2 408例肠外营养处方分析

摘 要 目的：通过对某院普外科肠外营养（PN）处方合理性进行调查分析,为药师处方审核及临床合理用药提供参考。 方法：对某三甲医院普外科2018年1～12月住院患者的PN处方情况进行回顾性统计分析,依据相关指南对全营养混合液处方进行合理性评价。 结果：本次调查的2 408例PN的处方中96.4%的患者具有PN指征;但仍存在微营养素缺失（14.7%）、氨基酸品种选用不当（3.4%）、热氮比不合理（20.3%）、糖脂比不合理（17.9%）、阳离子浓度不合理（2.3%）、胰岛素用量过大（2.8%）等问题。结论：该院普外科PN处方主要存在热氮比、糖脂比不合理和微营养素缺失等问题,临床药师应积极对PN处方进行审核与干预,确保临床安全合理用药。     

某院12 847例患者地佐辛注射液临床使用情况调查

摘 要 目的：调查地佐辛注射液临床使用情况并对其合理性进行评估。方法: 统计分析某院2015年12月～ 2016年11月住院患者中地佐辛注射液的使用情况,从适应证、用法用量、疗程、联合用药等方面进评价其用药合理性。结果: 使用地佐辛的患者共12 847例,年龄0～97岁,平均年龄（49±15.6）岁。11 687例患者是因为手术使用地佐辛注射液,占总比90.97%。使用最多的科室分别是骨科（12.70%）、手外科（10.30%）和肝胆外科（9.39%）。132例患者单次用量超出说明书推荐（1.03%）,主要集中在大型手术科室（心外科）。1 042例患者连续用药超过1周（8.11%）,主要为肿瘤患者。结论: 该院地佐辛注射液临床应用基本合理,但仍存在一些问题,需进一步加强医师培训,提高药物的安全合理应用,降低用药风险。     

帕累托法分析西安地区2 076例药品不良反应

摘 要 目的：了解西安地区药品不良反应（ADR）的发生规律及特点,为临床安全用药提供参考。方法：采用帕累托（Pareto）最优分析法对2013～2015年西安地区医疗机构发生的2 076例ADR报告进行整理,汇总患者年龄、药物品种、给药途径、药物剂型和临床表现等并进行分析。结果：2 076例ADR中,引发ADR的年龄段、药物种类、给药途径、药物剂型及累计的系统/器官及主要临床表现情况的主要因素分别为：0～10岁（16.81%）、51～60岁（16.81%）、61～70岁（13.34%）、71～80岁（12.24%）、21～30岁（11.27%）和41～50岁（10.31%）年龄段;抗感染药物（46.97%）、中药注射剂（14.40%）、中枢神经系统用药（9.34%）和维生素类、营养类药物、酶制剂及调节水、电解质和酸碱平衡药物（8.14%）四大类药物,其中抗感染药物中头孢菌素类的报告例数最多（35.79%）;静脉给药（85.84%）;注射剂（88.05%）;皮肤及其附件损害（41.43%）、消化系统损害（14.92%）、全身性损害（13.49%）和神经系统损害（10.75%）相关的ADR例数较多。结论：根据西安地区ADR发生的规律和特点,应加强临床合理用药管理,有针对性加强重点品种、患者的用药监护与ADR检测,保障患者用药安全。     

某院抗菌药物稀释溶媒使用情况调查分析

摘 要 目的: 调查某院抗菌药物稀释溶媒使用情况,促进临床合理用药。方法: 回顾性抽查某院2012年18 464份使用抗菌药物的住院医嘱,对抗菌药物稀释溶媒的种类和用量进行统计分析。结果:使用的溶媒主要品种为0.9%氯化钠注射液,5%葡萄糖注射液,木糖醇注射液。溶媒品种选择合理率为98.14%,用量使用合理率为75.05%。结论:临床抗菌药物稀释溶媒选择和剂量使用存在不合理的情况,亟待解决。     

某院肿瘤科临床药师干预前后医嘱合理性评价

摘 要 目的：评价某院肿瘤科医嘱的合理性,分析临床药师干预的效果。方法: 选取该院2013年1～6月肿瘤科出院病历180份作为干预前组,2014年1～6月肿瘤科出院病历180份作为干预后组,调查比较干预前后药物选择、用药途径、用法用量等医嘱的合理性。结果: 干预前后不合理率分别为41.11%和8.33%,差异有统计学意义（P＜0.05）。不合理用药主要为适应证不适宜、用法用量不适宜、更换药物不适宜、联合用药不适宜、辅助用药不合理等。结论:通过临床药师的干预,可以显著减少肿瘤科不合理用药现象,提高医院合理用药的水平。     

徐州某医院2005~2016年药品不良反应报告回顾性分析

摘 要 目的：了解徐州某医院药品不良反应（ADR）报告病例的特点,为临床安全用药提供依据和参考。方法：采用回顾性调查方法,对该院2005~2016年上报的ADR病例进行分析,并按年龄、性别、药品种类等进行分类统计。结果：12年间该院共上报ADR病例1 356例,男性679例（50.1%）,平均年龄（36.4±26.1）岁。每年上报的ADR数量从18例到274例不等,以一般不良反应为主（1 169例,86.2%）,给药途径以静脉滴注为主（1 110例,81.9%）,以单一用药引发为主（1 041例,76.8%）;ADR主要累及消化系统（568例次,22.8%）和皮肤及其附件（537例次,21.6%）;ADR由抗微生物药引发最多（1 006例,55.6%）,其次是中成药（175例,10.0%）和抗肿瘤药（125例,7.1%）;抗微生物药主要以喹诺酮类（29.9%）、β-内酰胺类（27.2%）和大环内酯类（22.5%）为主;引发ADR排名前3位的药物分别是阿奇霉素、左氧氟沙星、加替沙星等。结论：该院上报的ADR病例主要由抗微生物药、中成药和抗肿瘤药引起,应加强该类药物的管理,同时积极开展ADR监测,提高医务人员上报ADR的积极性,促进临床用药安全。     

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.

     

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.     

2-(Acetoxyphenyl)-(Z)-styryl sulfides as cyclooxygenase inhibitors

2-(Acetoxyphenyl)-(Z)-styryl sulfides are described as selective cyclooxygenase-2 (COX-2) inhibitors, useful for treating inflammation and COX-2-mediated disorders including neoplasia. 2-(Acetoxyphenyl)-(Z)-styryl sulfide is claimed to be the most potent COX inhibitor in the series with a COX-2 selectivity ratio of 33. This compound is also claimed to be superior to celecoxib (Celebrex^®, Pfizer) in inhibiting cell growth of colorectal carcinoma cells. In this evaluation, the COX inhibitory activity of this compound is compared to that previously disclosed for diarylheterocycles and 2-(acetoxyphenyl)alkyl sulfides. The validity of the DLD-1 cell line in the growth inhibition studies is questioned based on recent literature reports indicating the lack of COX-2 expression in this cell line.     

Sleep-disordered breathing with chronic opioid use

Chronic opioid use for pain relief or as substitution therapy for illicit drug abuse is prevalent in our societies. In the US, retail distribution of methadone and oxycodone has increased by 824 and 660%, respectively, between 1997 and 2003. μ-Opioids depress respiration and deaths related to illicit and non illicit chronic opioid use are not uncommon. Since 2001 there has been an emerging literature that suggests that chronic opioid use is related to central sleep apnoea of both periodic and non-periodic breathing types, and occurs in ～ 30% of these subjects. The clinical significance of these sleep-related abnormalities are unknown. This review addresses the present knowledge of control of ventilation mechanisms during wakefulness and sleep, the effects of opioids on ventilatory control mechanisms, the sleep-disordered breathing found with chronic opioid use and a discussion regarding the future research directions in this area.     

Drug targets for cognitive enhancement in neuropsychiatric disorders

The investigation of novel drug targets for treating cognitive impairments associated with neurological and psychiatric disorders remains a primary focus of study in central nervous system (CNS) research. Many promising new therapies are progressing through preclinical and clinical development, and offer the potential of improved treatment options for neurodegenerative diseases such as Alzheimer's disease (AD) as well as other disorders that have not been particularly well treated to date like the cognitive impairments associated with schizophrenia (CIAS). Among targets under investigation, cholinergic receptors have received much attention with several nicotinic agonists (α7 and α4β2) actively in clinical trials for the treatment of AD, CIAS and attention deficit hyperactivity disorder (ADHD). Both glutamatergic and serotonergic (5-HT) agonists and antagonists have profound effects on neurotransmission and improve cognitive function in preclinical experiments with animals; some of these compounds are now in proof-of-concept studies in humans. Several histamine H3 receptor antagonists are in clinical development not only for cognitive enhancement, but also for the treatment of narcolepsy and cognitive deficits due to sleep deprivation because of their expression in brain sleep centers. Compounds that dampen inhibitory tone (e.g., GABA_A α5 inverse agonists) or elevate excitatory tone (e.g., glycine transporter inhibitors) offer novel approaches for treating diseases such as schizophrenia, AD and Down syndrome. In addition to cell surface receptors, intracellular drug targets such as the phosphodiesterases (PDEs) are known to impact signaling pathways that affect long-term memory formation and working memory. Overall, there is a genuine need to treat cognitive deficits associated with many neuropsychiatric conditions as well as an increasingly aging population.