SGLT2抑制剂Canagliflozin——Ⅱ型糖尿病治疗的新药

钠依赖的葡萄糖转运蛋白2(sodium-dependent glucose transporters 2,SGLT2)是一种低亲和力、高容量的转运体,主要分布在肾脏近曲小管S1部位,负责肾脏中约90%葡萄糖的重吸收。因此,抑制SGLT2,阻止近曲小管对葡萄糖的重吸收,通过增加尿糖的排出来降低血糖已经成为糖尿病治疗的一种新的策略。文章简述了目前处于临床阶段的SGLT2抑制剂,重点阐述了第1个被FDA批准的SGLT2抑制剂——Canagliflozin,包括它的合成、药动学、药效学、临床研究及不良反应等。     

2型糖尿病治疗新药坎格列净的研究进展

坎格列净是一种钠-葡萄糖共转运蛋白2抑制药,抑制葡萄糖的肾重吸收,增加葡萄糖的尿排泄.美国FDA于2013年3月批准其上市,用于治疗2型糖尿病.坎格列净可有效降低2型糖尿病患者的血糖水平,还可降低患者体质量和收缩压,且低血糖风险较小.不良反应是增加泌尿生殖道感染.本文就其作用机制、药动学、临床疗效及安全性等作一综述.     

社区2型糖尿病患者用药调查

目的：了解社区2型糖尿病患者降糖药物购买以及使用情况。方法：对社区131例确诊为2型糖尿病的患者进行上门表格式调查,记录患者一般资料、用药品种、药物来源、血糖水平等。结果：131例患者中,79例（A组）按医嘱进行正规药物治疗,血糖控制良好;52例（B组）在进行一段正规治疗后,中断正规治疗而自己购买非正规药物进行治疗,血糖控制差。A组患者对糖尿病的认知度高于B组,平均学历高于B组。患者自购药物均为非药准字号“食品”。B组有17例患者在非正规治疗后血糖控制差而恢复胰岛素治疗。结论：患者对糖尿病的认知程度与其治疗用药密切相关,加强并普及社区糖尿病患者的健康教育势在必行。     

肠促胰素类药物治疗糖尿病的潜在风险

目的:总结分析肠促胰素类药物治疗糖尿病的潜在风险。方法:收集近来国内外相关报道并进行分析。结果和结论:肠促胰岛素类药物的血糖控制及减轻体重疗效不劣于其他降糖药物,且低血糖发生率低,故其问世以来得到广泛应用。但相关流行病学调查、动物实验及临床研究均提示应用该类药物存在胰腺病变及促进肿瘤发生的潜在风险,其药物安全性备受关注,为正确评价药物安全性需进一步完善高质量的临床研究。     

Accelerating Drug Development Using Biomarkers: A Case Study with Sitagliptin, A Novel DPP4 Inhibitor for Type 2 Diabetes

The leveraged use of biomarkers presents an opportunity in understanding target engagement and disease impact while accelerating drug development. For effective integration in drug development, it is essential for biomarkers to aid in the elucidation of mechanisms of action and disease progression. The recent years have witnessed significant progress in biomarker selection, validation, and qualification, while enabling surrogate and clinical endpoint qualification and application. Biomarkers play a central role in target validation for novel mechanisms. They also play a central role in the learning/confirming paradigm, particularly when utilized in concert with pharmacokinetic/pharmacodynamic modeling. Clearly, these attributes make biomarker integration attractive for scientific and regulatory applications to new drug development. In this review, applications of proximal, or target engagement, and distal, or disease-related, biomarkers are highlighted using the example of the recent development of sitagliptin for type 2 diabetes, wherein elucidation of target engagement and disease-related biomarkers significantly accelerated sitagliptin drug development. Importantly, use of biomarkers as tools facilitated design of clinical efficacy trials while streamlining dose focus and optimization, the net impact of which reduced overall cycle time to filing as compared to the industry average.     

2型糖尿病门诊口服降糖药用药分析

目的 对2型糖尿病人的门诊口服降糖药用药做初步的分析,以便了解此类药物用药的合理性.方法 采用DDD分析法,分析门诊2004～2006年3年中口服降糖药用药频度、用药费用,随机抽取临床诊断为糖尿病的处方300张做联合用药分析.结果 磺酰脲类使用量大,胰岛素促泌剂和胰岛素增敏剂逐年增加,联合用药普遍,用药基本合理.结论 疗效确切和不良反应小的药物得到广泛应用,联合用药安全有效.     

1例2型糖尿病伴慢性肾脏病降糖方案的优化

临床药师参与1例2型糖尿病伴慢性肾脏病（CKD3期）降糖方案的优化,对患者全程进行药学监护,在保证其血糖控制达标的同时,也将药物对肾脏的影响降至最低,体现临床药师的自身价值。     

高剂量卡格列净对2型糖尿病安全性的Meta分析

目的 系统评价高剂量卡格列净对2型糖尿病患者的安全性.方法 检索PubMed、Medline、Cochrane Library、Embase、中国知网、万方数据、维普网、中国生物医学文献数据库,检索时间为建库至2019年9月23日,收集卡格列净低剂量(100 mg/d)及高剂量(300 mg/d)用于治疗2型糖尿病的随...     

The Apoptosome: Emerging Insights and New Potential Targets for Drug Design

Apoptosis plays a crucial role in tissue homeostasis, development and many diseases. The relevance of Apaf1, the molecular core of apoptosome, has been underlined in mitochondria-dependent apoptosis, which according to a growing body of evidence, is involved in various pathologies where the equilibrium of life-and-death is dysregulated, such as heart attack, stroke, liver failure, cancer and autoimmune diseases. Consequently, great interest has emerged in devising therapeutic strategies for regulating the key molecules involved in the life-and-death decision. Here we review recent progress in apoptosis-based pharmacological therapies and, in particular, we point out a possible role of the apoptosome as an emerging and promising pharmacological target. Marcello D’Amelio and Elisa Tino equally contributed to this work.     

药学干预对于接受多药治疗的2型糖尿病住院患者的影响

目的探讨药学干预对于接受多药治疗的2型糖尿病患者的影响。方法将我院2009年2月至2010年2月之间收录的80例2型糖尿病住院患者随机的分为两组,对照组的患者给予常规的药物指导,而观察组的患者给予药学干预,观察两组的患者用药依从性和药物使用的不良事件发生率以及患者满意度等情况。结果观察组的患者用药依从性和满意度明显的高于对照组的情况(P<0.05);观察组的药物使用的不良事件发生率与对照组的比较无明显的差异(P>0.05),统计学无意义。结论临床中对于接受多药物治疗的2型糖尿病患者给予药学干预措施能够有效的提高患者的用药依从性和满意度,并降低药物不良事件发生率,值得临床中应用。     

G—四链体DNA：抗肿瘤药物的潜在靶点

除了常见的双链DNA,某些富含G碱基的DNA序列通过四个鸟嘌呤环的互联作用可折叠成四链螺旋结构,这样的DNA二级结构被称为G－四链体。本文综述了G－四链体可能在生物学么及作为抗肿瘤药物潜在靶点能与其相互作用的化合物的研究与开发。     

Patent Evaluation: A New Method for the Prevention and Treatment of Type I Diabetes

Summary

Novelty: Novel phenols and benzamides, and pharmaceutical compositions thereof, are disclosed. They have potential use for the prevention and treatment of Type I diabetes.

Biology: Two assays describing the activity of the compounds using non-obese diabetic (NOD) mice are described. In vitro, pancreatic islet cells from the female BALB/c mice were tested in a disease recurrence model. The survival times, compared with control, of mice administered with the test compound are reported in tabular form. In an inhibition of cyclophosphamide-induced diabetes assay, male NOD mice (Taconic Farm) were given a 250 mg/kg dose of cyclophosphamide ip. Mice given 4-[(dimethyl amino)-methyl]-2,6-bis(1,1-dimethyl-ethyl)phenol took 15.7 days to become diabetic (control, 12 days).

Chemistry: Fifty-seven compounds are disclosed; syntheses are not given. Eight examples of formulations containing the active compunds are detailed. Several methods of administration including capsules, tablets, aerosols and suppositories are detailed. A wide dose range of 0.1-50mg/kg/day (adult human) is reported. Two compounds are specifically claimed including 4-[(dimethylamino)-methyl]-2,6-bis(1,1-dimethyl-ethyl) phenol.

Structure:      

急性心力衰竭治疗的新药重组人松弛素

目的:最近重组人松弛素的临床试验为急性心力衰竭(AHF)的治疗提供了新的希望,笔者主要对重组人松弛素的作用机制、药理学特性、临床特征及治疗AHF的作用做一综述。方法:使用Pubmed/Medline database对文献进行查找,收集到21篇相关文献。结果 :研究表明重组人松弛素显著改善AHF患者的症状,缩短住院时间,降低病死率。目前的资料表明这些临床益处与重组人松弛素的多效性有关,包括改善全身、心脏和肾脏血流动力学,通过抗炎、抗细胞死亡、抗纤维化、抗心肌肥厚及促进血管新生保护细胞和器官免受损伤。结论 :重组人松弛素是一种有前景的治疗AHF药物。正在进行中的研究旨在验证先前的试验结果、安全性和血流动力学效应,探讨这些效应的分子机制。     

药学监护对2型糖尿病患者出院后用药的影响

目的:评价规范化药学监护对于2型糖尿病患者出院后用药依从性等指标的影响。方法:设计一项随机、对照、前瞻性试验,试验组患者接受临床药师提供的全程化药学服务,对照组患者接受传统医疗服务。在患者出院1个月后随访调查,考察患者出院后的用药依从性、药品不良事件(ADE)发生率、复诊(或再入院)率和满意度等各项指标,评价患者住院期间所接受的药学服务对其出院后用药的影响。结果:与对照组比较,试验组患者对于胰岛素、促泌剂、双胍类、α-糖苷酶抑制剂的数量依从性及时间依从性,均显示有统计学差异(P<0.05),而对噻唑烷二酮类药的依从性无统计学差异(P>0.05);2组患者总的ADE发生率比较无统计学差异(P<0.05),但可预防的和严重ADE的发生率比较2组均有统计学差异(分别为P<0.05和P<0.01);复诊(或再入院)率无统计学差异(P>0.05);满意度有极显著的统计学差异(P<0.01)。结论:为2型糖尿病住院患者提供规范化的药学监护,可改善患者出院后对于多数药品的用药依从性,提高患者的满意度,降低可预防的和严重ADE的发生率,而对于患者复诊(或再入院)率无显著影响。     

TRPV1 Channel: A Potential Drug Target for Treating Epilepsy

Epilepsy has 2-3% incidence worldwide. However, present antiepileptic drugs provide only partial control of seizures. Calcium ion accumulation in hippocampal neurons has long been known as a major contributor to the etiology of epilepsy. TRPV1 is a calcium-permeable channel and mediator of epilepsy in the hippocampus. TRPV1 is expressed in epileptic brain areas such as CA1 area and dentate gyrus of the hippocampus. Here the author reviews the patent literature on novel molecules targeting TRPV1 that are currently being investigated in the laboratory and are candidates for future clinical evaluation in the management of epilepsy. A limited number of recent reports have implicated TRPV1 in the induction or treatment of epilepsy suggesting that this may be new area for potential drugs targeting this debilitating disease. Thus activation of TRPV1 by oxidative stress, resiniferatoxin, cannabinoid receptor (CB1) activators (i.e. anandamide) or capsaicin induced epileptic effects, and these effects could be reduced by appropriate inhibitors, including capsazepine (CPZ), 5''-iodoresiniferatoxin (IRTX), resolvins, and CB1 antagonists. It has been also reported that CPZ and IRTX reduced spontaneous excitatory synaptic transmission through modulation of glutaminergic systems and desensitization of TRPV1 channels in the hippocampus of rats. Immunocytochemical studies indicated that TRPV1 channel expression increased in the hippocampus of mice and patients with temporal lobe epilepsyTaken together, findings in the current literature support a role for calcium ion accumulation through TRPV1 channels in the etiology of epileptic seizures, indicating that inhibition of TRPV1 in the hippocampus may possibly be a novel target for prevention of epileptic seizures.     

艾塞那肽治疗2型糖尿病的临床观察

目的:观察艾塞那肽的临床疗效和不良反应。方法:将79例接受口服降糖药后不能有效控制血糖的2型糖尿病(T2DM)患者随机分为艾塞那肽组(39例)与胰岛素组(40例),治疗24周后观察2组的疗效及不良反应。结果:艾塞那肽组治疗后与治疗前比较空腹血糖(FPG)、餐后2h血糖(P2hPG)、糖化血红蛋白(HbA1c)、体重差异有统计学意义(P<0.05);与胰岛素组比较,艾塞那肽组FPG、体重和胃肠道不良反应发生率差异有统计学意义(P<0.05)。结论:艾塞那肽能降低T2DM患者的FPG、P2hPG、HbA1c和体重;与胰岛素比较,减轻体重效果明显,但胃肠道反应较常见。     

艾塞那肽治疗2型糖尿病的系统评价

目的:系统评价艾塞那肽治疗2型糖尿病的疗效及安全性。方法:计算机检索Cochrane图书馆、PubMed、Embase、CBM、VIP、CNKI数据库,对纳入的随机对照试验(RCT)进行质量评价,并用RevMan5.0软件进行Meta分析。结果:共纳入5个RCT,Meta分析结果显示:艾塞那肽与胰岛素在改善2型糖尿病患者糖化血红蛋白水平方面差异无统计学意义[MD=0.07,95%CI(-0.02,0.17),P=0.13];在降低空腹血糖方面艾塞那肽组疗效不及胰岛素组[MD=1.21,95%CI(1.15,1.27),P<0.00001];治疗过程中发生低血糖方面的概率2组相当[OR=0.69,95%CI(0.47,1.03),P=0.07]。结论:本系统评价结果初步显示,艾塞那肽可以用于治疗口服降糖药无法有效控制血糖的2型糖尿病患者。远期结果有待进一步研究探讨。