86例别嘌醇片致不良反应/事件的文献分析

目的：探讨别嘌醇片所致不良反应/事件（ADR/ADE）的临床特征、相关规律及机制,为临床安全合理用药提供参考。方法检索中国生物医学文献数据库、中国期刊全文数据库及中文科技期刊全文数据库1994～2013年关于别嘌醇片所致ADR/ADE的个案报道,并进行统计分析。结果得到符合标准的病例86例,不良反应报告中男性明显多于女性;以中老年患者为主,61～70岁患者构成比最高（27例,31.40%）;不良反应主要集中在用药后1个月内发生（79例,91.86%）;不良反应可累及多个系统-器官,出现很多新的严重的不良反应甚至死亡;不良反应以皮肤系统构成比最高（74例,61.67%）,在皮肤系统损害中主要表现为重症药疹（36例,48.65%）,预后效果较差。结论临床医师、药师应重视并掌握别嘌醇片致不良反应的规律和特点,安全用药,并加强临床监测,以减少不良反应的发生。     

2014~2018年湖北省对乙酰氨基酚不良反应报告回顾性分析

目的:探究对乙酰氨基酚(APAP)所致不良反应(ADR)的特点,为临床安全用药提供参考依据。方法:采用回顾性研究方法,对2014~2018年湖北省药品(医疗器械)不良反应监测中心收集的179份APAP所致ADR报告的上报单位、ADR类型与关联性评价、患者性别年龄、ADR发生时间、ADR累及系统-器官及所涉及的临床症状和转归、药物剂型与联合用药情况等进行统计分析。结果:179份ADR主要来自药品经营企业和医疗机构上报,关联性评价为"可能"的报告比例最高。一般的ADR有156例(87.15%),严重的ADR有13例(7.26%),新的ADR有10例(5.59%),新的严重的ADR有1例(0.56%)。患者男女比例为1.43∶1,年龄主要分布在0~10岁(35.20%);ADR多在用药1~2 d发生(87.15%),累及多个系统-器官,主要为皮肤及附件损害、胃肠系统损害、中枢及外周神经系统损害、全身性系统损害等;导致ADR的APAP剂型以片剂(62.01%)和栓剂(22.35%)为主。174例ADR患者经停药或积极对症处理后治愈或好转。结论:APAP所致ADR主要以皮肤及附件损害和胃肠系统损害为主,长期或者过量使用可产生严重皮肤反应和肝肾功能损害,临床应密切监测患者用药情况,给予相应处理措施,保证患者用药安全。     

59例热毒宁注射液致儿童皮肤系统不良反应报告分析

目的:探讨热毒宁注射液所致儿童皮肤系统药品不良反应(ADR)的临床表现、转归与机制,为临床安全合理用药与针对ADR的药物治疗提供参考。方法:在南京医科大学附属儿童医院不良反应管理平台的ADR已报告板块,以通用名称"热毒宁"对该院2015年1月至2019年8月的数据进行检索,筛选出儿童皮肤系统ADR,并对检索所得的59例热毒宁致皮肤系统ADR的患儿的性别、用药方案、年龄、临床表现和后期处理等进行汇总、分析。结果:所收集的59例热毒宁致皮肤系统ADR中,ADR主要为药疹(86.44%),包括皮疹、斑疹和红斑丘疹,其次为重症多型红斑(8.47%)和荨麻疹(5.08%),停药并用药干预后均缓解。结论:热毒宁致皮肤系统ADR包括药疹、重症多型红斑和荨麻疹,ADR一旦发生应及时停药并给予相应药物治疗,临床在热毒宁用药过程中应注意观察患者临床表现,及时与家属沟通。     

药品不良反应76例分析

目的:分析我院药品不良反应(ADR)发生的相关因素,为促进临床合理用药提供参考.方法:对我院2005年10月～2009年5月的76份ADR报告进行统计分析.结果:76例ADR涉及药物品种33个,抗菌药物引起ADR的比例最高(占36.84%);静脉滴注给药方式导致的ADR比例最多(占74%);ADR临床表现以皮肤及附件损害为主(占56.58%).结论:应高度重视ADR报告和监测工作,提高临床安全用药意识,加强合理用药教育,确保患者用药安全.     

别嘌醇的不良反应文献分析及探讨

目的探讨别嘌醇所致不良反应的发生原因、规律、特点,为临床合理用药提供参考。方法检索中国生物医学文献数据库及中国医院数字图书馆期刊全文库,对1994年1月-2009年8月国内医药学术期刊报道的256例别嘌醇致不良反应病例进行统计、分析。结果中老年男性患者(218例,占85.16%)更易产生不良反应。临床表现为潜伏期长(2d～6个月)、病程长、易反复的特点,且多为迟发反应,潜伏期8～30d156例,占79.90%;别嘌醇引起的不良反应死亡率高,256例中死亡38例,病死率为14.84%。按涉及系统显示,排在前4位的ADR:药疹(226例次,占88.28%)、发热(148例次,占57.81%)、肝脏损害(81例次,占31.64%)、肾脏损害(52例次,占20.31%)。结论临床应重视别嘌醇不良反应的危害性。严格用药指征,对老年患者更应注意其基础疾病,密切观察用药后反应,确保用药安全。     

上海市杨浦区部分医院药品不良反应报告分析

目的:保障上海市杨浦区医疗机构的临床用药安全及促进合理用药。方法:对上海市杨浦区3家二级医疗机构2009年呈报至上海市药品不良反应监测中心的159例药品不良反应(ADR)报告进行统计、分析。结果:159例ADR病例中,涉及药品71种,由抗菌药引起99例(占62.26%),由降压药、抗心绞痛药引起14例(占8.81%),由中药制剂引起10例(占6.29%)。由静脉滴注引起123例(占77.36%)。ADR发生率男性高于女性(1.2∶1);>60岁患者63例(占39.62%),高于其他年龄组。临床表现以皮肤及其附件损害最多,75例(占47.17%)。新的ADR有6例,严重的ADR有5例,死亡1例。结论:临床应重视ADR的监测与报告工作,以促进临床安全、合理用药。     

534例抗菌药不良反应分析

目的:分析抗菌药不良反应(ADR)发生特点,为临床安全用药提供参考。方法:采用回顾性研究方法,统计分析2012年嘉兴市部分医院上报的534例抗菌药ADR病例报告。结果:534例报告共涉及抗菌药12大类51个品种;病例中幼儿的所占比例最大(26.97%);涉及药品以头孢菌素类所占比例最高(48.31%);ADR累及系统(器官)以皮肤及其附件受损(63.42%)为主;β-内酰胺类是引起严重ADR的主要抗菌药。结论:应重视抗菌药合理使用,减少和避免ADR的发生,确保临床用药安全。     

我院137例左氧氟沙星注射液不良反应报告分析

目的:了解左氧氟沙星(LVFX)注射液不良反应(ADR)发生特点,促进临床合理用药。方法:检索、统计我院2006～2009年上报的LVFX注射液ADR137例,并利用Excel电子表格分别对其年龄、性别、用药情况及ADR的临床表现等进行分析。结果:ADR在用药各年龄段人群均可发生,但60岁以上人群发生率最高(32.85%),以皮肤及其附件(62.04%)和胃肠道系统(16.06%)损害为主,大部分为轻、中度ADR。结论:临床应加强LVFX注射液合理应用和ADR监测,保障患者用药安全。     

我院2014~2016年辅助用药药物不良反应分析

目的:分析我院辅助用药发生不良反应(adverse drug reaction,ADR)的特点,为临床合理用药提供参考.方法:对我院2014~2016年上报的药物不良反应报表中288例涉及辅助性用药引起的不良反应进行回顾性研究分析.结果:发现新的严重的ADR共13例(4.5%),ADR多发于50岁以上患者(61.46%),不良反应发生最多的给药途径为静脉滴注(94.44%),累及的系统主要为皮肤及其附件(29.55%)和心血管系统(21.37%),ADR发生率高的辅助用药情况为西医无经中医会诊使用中成药(21.88%)、氨基酸及营养制剂(17.01%)及改善心脑血管循环药物(12.85%).结论:医院需进一步加强ADR监测,医生应重视辅助用药引起的ADR,同时药师要积极参与辅助用药合理用药点评,定期分析反馈,促进临床合理用药.     

舒尼替尼致不良反应文献分析

目的:分析舒尼替尼所致药品不良反应(ADR),为其临床安全用药提供参考。方法:检索2006—2021年6个中英文数据库关于舒尼替尼致不良反应的文献报道,提取相关数据,并进行统计分析。结果:共纳入文献147篇,涉及156例患者,283例次不良事件。不良反应发生在给药31～180 d的比率最高,ADR累及器官/系统以血液及淋巴系统(17.67%)、胃肠系统(15.55%)、皮肤及皮下组织类(10.60%)为主。结论:舒尼替尼所致的不良反应累及全身多个器官/系统,不乏严重致死病例。在临床用药期间应定期监测患者情况,在发生不良反应时及时减少或停止给药,以降低临床用药风险。     

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.