治疗糖尿病的新药西他列汀

西他列汀（sitagliptin）是FDA批准上市的第1个二肽基肽酶-Ⅳ（DPP-Ⅳ）抑制剂,用于治疗2型糖尿病。临床研究表明：西他列汀是一个口服有效、市场前景良好的药物,单用或与二甲双胍、吡格列酮合用都有明显的降血糖作用,且服用安全,耐受性好,不良反应少。现对其作用机制与药效学、药动学、临床疗效做一综述。     

维格列汀与阿卡波糖治疗2型糖尿病的疗效比较

<正>阿卡波糖是临床常用的口服降糖药。本研究对维格列汀与阿卡波糖治疗2型糖尿病患者的有效性和耐受性进行了比较,以期为增加相关临床用药经验提供帮助。1对象与方法1.1研究对象以在笔者所在医院就诊的未经口服降糖药(OAD)治疗的符合2型糖尿病临床诊断标准的患者为研究对象,且空腹血糖<15 mmol/L,至少在16周内未服用OAD;研究对象年龄须≥18岁,排除孕期、哺乳期女性患者,排除伴有心肌梗死、不稳定性心绞痛、充血性心力衰竭等急性并     

治疗2型糖尿病的新药维格列汀

2型糖尿病是多基因遗传因素和环境因素共同作用的复杂疾病。维格列汀是一种二肽基肽酶(DPP-Ⅳ)抑制剂,通过增强胰高血糖素样肽(GLP-1)和肠抑胃肽(GIP)的活性而发挥降血糖的作用。作为一种新型的口服降糖药,维格列汀单用或与其他降糖药联合应用控制血糖疗效好、不良反应低、安全且耐受性好。现就其临床药理作用及与其他口服降糖药的联合用药做一综述。     

维格列汀联合胰岛素治疗2型糖尿病1例

患者资料患者女,61岁。因“发现血糖升高10年”入院。10年前随机血糖达17．2mmol／L,偶有多饮、多食、多尿等症状,诊断为“糖尿病”,开始自行服用二甲双胍及参芪降糖颗粒,偶测空腹血糖在9．0mmol／L,餐后血糖13．Ommol／L。     

维格列汀的合成

L-脯氨酰胺经氯乙酰氯酰化得(S)-N-氯乙酰基-2-氨甲酰基吡咯烷(2),2经三氟乙酐脱水得(S)-N-氯乙酰基-2-氰基吡咯烷(3),3与3-氨基-1-金刚烷醇发生亲核取代反应制得2型糖尿病治疗药维格列汀,总收率约70％(以L-脯氨酰胺计).     

维格列汀在管理老年2型糖尿病患者中的作用

老年人2型糖尿病患者是糖尿病防治的重点人群,由于该类人群可能患有多种疾病,机体机能减退,认知能力下降,且合并用药较多,增加了药物相互作用的风险。维格列汀低血糖风险低、耐受性良好,同时能降低老年患者药物相互作用的风险,在治疗方案选择中具有一定优势。     

维格列汀联用其他口服药治疗2型糖尿病1例

1病案报道
　　患者,男,57岁。患者于2000年5月无明显诱因出现多尿,4000-6000ml/d,多饮、多食,主食1.5－2斤/d,体重1周内下降10余斤,多次查餐后血糖大于11.1mmol/L,诊断为“2型糖尿病”,给予二甲双胍片：500mg,3次/d,因腹胀、腹泻明显而停用,后改为消渴丸8粒,3次/d治疗,控制饮食,饭量每日6-7两,每日游泳半小时。血糖控制尚可,无低血糖反应。此后先后服用阿卡波糖50mg3次/d和克糖胶囊（自购中成药,无通用名）2粒3次/d,血糖控制不佳。2009年起先后改用诺和锐30、甘精胰岛素（具体剂量不详）,因皮肤出现明显硬结停用。2013年5月22日,换用优泌乐2512U（早）,8u (晚),格列美脲2mg1次/d,吡格列酮30mg1次/d治疗,未出现硬结,空腹血糖控制在6.0-8.0mmol/L,餐后2h血糖控制在9-12mmol/L。2013年6月19日,患者注射优泌乐25后10min突然出现全身性红色皮疹,胸口麻木、呼吸困难。当时神志清楚,血压80/40mmHg,心率119次/min,休息30min 后自行缓解,立即停用优泌乐25胰岛素方案,并住院治疗。入院查体：T：36.0℃P：89次/min R：18次/min Bp （卧位）：120/80mmHg,立位：110/70mmHg,神清,身高：168cm体重：72kg体重指数：25.5kg/m2神清,甲状腺未触及肿大,无黑棘皮征。心肺腹无异常,左侧足背动脉明显减弱,右侧正常,双侧胫部以下温度觉减退,无水肿。既往无高血压、冠心病,有慢性胃炎病史,有青霉素过敏史。无糖尿病家族史。不饮酒,嗜烟,10余支/d。影像学检查：颈动脉超声：双侧颈总动脉管膜增厚、毛糙并左侧斑块形成。双下肢超声：下肢动脉内膜增厚伴多发硬化斑块形成。实验室检查：入院时查空腹：6.28-8.6mmol/L,三餐2h 后控制在：11.0-13.8mmol/L, HbA1c：6.8%。空腹C肽：3ng/ml(正常值：0.6-3.8ng/ml),60min：10.2ng/ml,2h：8.82ng/ml,初步诊断：2型糖尿病,糖尿病大血管病变。入院后逐步调整降糖方案为格列美脲4mg1次/d,吡格列酮30mg1次/d,阿卡波糖50mg3次/d。患者血糖控制尚可,但于6月24日,7月1日及7月5日发生中餐前出冷汗、心慌等低血糖症状（6月24日中餐前血糖3.8mmol/L,7月1日及7月5中餐前血糖未监测）,于7月6日调整为维格列汀50mg2次/d,格列美脲2mg1次/d,吡格列酮30mg1次/d,阿卡波糖50mg3次/d。并给予阿托伐他汀钙：20mg1/晚,调脂及稳定斑块治疗;银杏叶片2片,3次/d （因该患者既往有慢性糜烂性胃炎,故未给予拜阿司匹林抗血小板聚集治疗）。调整方案后,无低血糖发生。7月15日查血糖：空腹7.0mmol/L,早餐后2h：7.7mmol/L,午餐后2h：8.1mmol/L,晚餐后2h：9.2mmol/L,睡前6.8mmol/L,停用阿卡波糖50mg3次/d,余治疗不变,7月30日查血糖：空腹6.2mmol/L,三餐后2h：7.0-8.2mmol/L,睡前6.7mmol/L,糖化血红蛋白：6.3%,目前定期监测血糖一直控制平稳,无低血糖反应,无酮症酸中毒发生。     

维格列汀在2型糖尿病合并慢性肾脏病患者中的应用

2型糖尿病（type 2 diabetes mellitus,T2DM）合并慢性肾脏病（chronic kidney disease,CKD）患者是一个不容忽视的人群。肾病既是T2DM的主要并发症之一,也是导致终末期肾病的主要原因。降糖治疗是延缓肾病进展的有效手段,但降糖获益可被治疗过程中的不良反应,如低血糖、体重增加等损害,因此选择合适的治疗方案对于此类患者至关重要。本文旨在论述新一代口服降糖药物——二肽基肽酶4（dipeptidyl peptidase 4,DPP-4）抑制剂维格列汀在T2DM合并CKD患者中的应用经验。     

DPP-4抑制剂维格列汀的心血管效应

抗糖尿病药物的心血管安全性及作用备受关注。传统降糖药物,如磺脲类及噻唑烷二酮类均可能出现心血管不良反应。新型口服降糖药物DPP-4抑制剂维格列汀存在对心血管的潜在获益,在糖尿病治疗中的心血管安全性已经得到充分验证。     

抗2型糖尿病新药利拉利汀

利拉利汀是继西他列汀、沙格列汀后的二肽基肽酶-4抑制剂,与饮食和运动结合用于改善2型糖尿病患者的血糖控制能力。现有临床研究表明,利拉利汀是一个口服有效、可能有市场前景的药物。文中对利拉利汀的作用机制、药效学、药代动力学、药物相互作用、临床评价和安全性等进行综述。     

抗糖尿病药物维达列汀

维达列汀是一种口服有效的特异性二肽基肽酶Ⅳ（DPP—Ⅳ）抑制剂，能增强胰高血糖样肽Ⅰ（GLP-1）活性和降低2型糖尿病患者的高血糖症状。研究表明，维达列汀无论是单用还是与其他抗糖尿病药物合用，均能明显降低具有临床意义的糖基化血红蛋白（HbA1c）水平，具有良好的耐受性，且无体重增加和浮肿等不良反应，低血糖和胃肠道等不良反应发生率也较低。现对其药理作用、药动学、临床研究和不良反应等进行综述。     

抗癫痫新药瑞替加滨

瑞替加滨为神经元钾离子通道开放剂,是一种具有全新作用机制的抗癫痫药,临床上用于成人癫痫部分发作的辅助治疗。文中对瑞替加滨的作用机制、药效学、药代动力学、药物相互作用、临床评价和安全性等进行综述。     

治疗心房颤动新药决奈达隆

决奈达隆为新型苯并呋喃衍生物,结构与胺碘酮相似。决奈达隆具有多通道阻滞的电生理特性。Ⅲ期临床试验证实,决奈达隆能有效减少心房颤动(Af)或心房扑动(AF)的复发,减慢Af/AF的心室率,减低心血管发病率及病死率。但在一项纳入重度心力衰竭(HF)及左室功能障碍患者的研究中,决奈达隆使病死率升高。决奈达隆耐受性好,不明显延长QTc间期,无显著肺、甲状腺、肝、眼和神经系统毒性,最常见的不良反应为腹泻、恶心及呕吐。决奈达隆可选择性用于Af/AF的治疗。但在预防Af复发时,决奈达隆疗效逊于胺碘酮,尚需更多有关决奈达隆与胺碘酮疗效的对比研究以确立决奈达隆在治疗中的地位。     

Pregabalin: a new agent for the treatment of neuropathic pain

Pregabalin (Lyrica, Pfizer) is a GABA analog with similar structure and actions to gabapentin. It has antiepileptic, analgesic and anxiolytic activity. Pregabalin is indicated for the management of neuropathic pain associated with diabetic neuropathy and post-herpetic neuralgia. Peak plasma levels occur approximately 1 hour after oral doses and oral bioavailability is about 90%. Based on AUC data, food does not significantly affect the extent of absorption. Pregabalin is not protein-bound and exhibits a plasma half-life of about 6 hours, which is not dose-dependent. Hepatic metabolism is negligible, and most of the oral dose (95%) appears unchanged in the urine. Pregabalin is a safe and well-tolerated new treatment for neuropathic pain. Furthermore, pregabalin has proven efficacy in adjunctive therapy of refractory partial seizures and in the treatment of acute pain, generalized anxiety disorder and social phobia.     

Milatuzumab: a promising new agent for the treatment of lymphoid malignancies

Background: Non-Hodgkin's lymphoma and multiple myeloma are often incurable and respond to a limited set of treatment options. The selective expression of CD74, the invariant chain of the MHC class II molecule, in these malignancies provides an attractive target for antibody-based therapy. Objective: This review evaluates the preclinical data for milatuzumab, a humanized antibody targeting CD74, as a treatment for non-Hodgkin's lymphomas and multiple myeloma. Methods: A review of the literature was carried out using PubMed. Current Phase I protocols using milatuzumab are summarized. Results/conclusion: Milatuzumab is cytotoxic to lymphoma and multiple myeloma cell lines and mouse–human xenografts. The efficacy dramatically increases when milatuzumab is attached to a toxin or a radioactive agent. Phase I trials of milatuzumab are now underway in human subjects with lymphoma and multiple myeloma.     

Metrifonate: a new agent for the treatment of Alzheimer's disease.

The pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of metrifonate, a long-acting cholinesterase inhibitor, are discussed. Attempts to correct the central cholinergic deficits associated with Alzheimer's disease have included administration of cholinergic precursors, cholinergic agonists, and cholinesterase inhibitors. To date, two reversible cholinesterase inhibitors-tacrine and donepezil-have been marketed. Metrifonate, an organophosphate, is converted nonenzymatically to 2,2-dichlorovinyl dimethyl phosphate (DDVP), the active enzyme inhibitor. DDVP produces irreversible inhibition of brain cholinesterase that lasts for several days; enzyme recovery is dependent on synthesis of new enzyme. Several preclinical studies have demonstrated cognition-enhancing effects of metrifonate in animals. Trials in humans have shown improvement on the Alzheimer's Disease Assessment Scale, in Mini-Mental State Examination scores, and in the Clinician's Interview-Based Impression of Change with caregiver input. Clinical improvement noted with metrifonate appears similar to that seen with other cholinesterase inhibitors. Adverse effects noted in clinical trials have been associated primarily with the gastrointestinal tract and have been mild. Metrifonate appears to be a promising agent for the treatment of the symptoms of Alzheimer's disease.     

Tolterodine: a new antimuscarinic agent for the treatment of the overactive bladder

Bladder hyperactivity is a debilitating problem that affects many individuals. A plethora of therapeutic options have been investigated to combat this condition, antimuscarinic therapy being the most widely used. Nevertheless, this medication group has historically been of limited benefit, due to its side-effect profile. Tolterodine is a new muscarinic receptor antagonist that has been shown to be equally effective when compared to oxybutynin. However, the side-effect profile for tolterodine is much better than this commonly used anticholinergic. It has reduced affinity for the salivary glands in animal studies, and, in clinical trials, there has been a reduced incidence of dry mouth with this medication. In Phase III studies, tolterodine has been shown to decrease the number of micturitions per day, decrease the number of incontinence episodes per day and increase the mean volume voided per micturition. The maximal effect of this medication may not be seen for 6 - 8 weeks after initiation of the drug although the exact explanation for this finding has yet to be completely elucidated. The recommended dose is 2 mg b.i.d., which should be adjusted for those with liver failure or those on drugs that inhibit the cytochrome P450 isoenzyme known as CYP3A4. In summary, tolterodine is an effective well-tolerated antimuscarinic which should be considered as a first-line treatment due to its more favourable side-effect profile when than other available medications.     

Dasabuvir: a new direct antiviral agent for the treatment of hepatitis C

Introduction: Treatment of hepatitis C virus (HCV) infection with direct-acting antivirals (DAAs) has revolutionized the care of infected patients. Among these novel compounds are non-nucleoside analogs, which bind viral RNA-dependent RNA polymerase resulting in a conformational change inhibiting RNA synthesis.

Areas covered: Efficacy and tolerability of treatment regimens containing the non-nucleoside analog polymerase inhibitor dasabuvir (ABT-333).

Expert opinion: Dasabuvir-containing regimens achieve high rates of sustained virologic response in HCV genotype 1a and 1b–infected patients when combined with other DAAs, namely paritaprevir (ABT-450), ritonavir and ombitasvir (ABT-267). In the populations studied, dasabuvir seems to be well tolerated and safe. The major limitations of this novel drug are its genotype-restricted activity, the necessity to include ribavirin for HCV genotype 1a and the emergence of resistance if not combined with other DDAs.     

Tolterodine: a new antimuscarinic agent for the treatment of the overactive bladder

Bladder hyperactivity is a debilitating problem that affects many individuals. A plethora of therapeutic options have been investigated to combat this condition, antimuscarinic therapy being the most widely used. Nevertheless, this medication group has historically been of limited benefit, due to its side-effect profile. Tolterodine is a new muscarinic receptor antagonist that has been shown to be equally effective when compared to oxybutynin. However, the side-effect profile for tolterodine is much better than this commonly used anticholinergic. It has reduced affinity for the salivary glands in animal studies, and, in clinical trials, there has been a reduced incidence of dry mouth with this medication. In Phase III studies, tolterodine has been shown to decrease the number of micturitions per day, decrease the number of incontinence episodes per day and increase the mean volume voided per micturition. The maximal effect of this medication may not be seen for 6 - 8 weeks after initiation of the drug although the exact explanation for this finding has yet to be completely elucidated. The recommended dose is 2 mg b.i.d., which should be adjusted for those with liver failure or those on drugs that inhibit the cytochrome P450 isoenzyme known as CYP3A4. In summary, tolterodine is an effective well-tolerated antimuscarinic which should be considered as a first-line treatment due to its more favourable side-effect profile when than other available medications.