2009—2010年成都医学院第一附属医院口服抗糖尿病药应用分析

目的:了解我院口服抗糖尿病药的临床应用情况,为临床合理用药提供参考。方法:对我院2009—2010年口服抗糖尿病药的品种、用药频度(DDDs)、用药金额等情况进行统计分析。结果:2010年口服抗糖尿病药的总用药金额较2009年增长41.2%,磺酰脲类DDDs排序居首位,用药总金额和DDDs增长最快的是噻唑烷二酮类。结论:我院口服抗糖尿病药应用中,磺酰脲类药格列齐特、双胍类药二甲双胍均因其疗效好、不良反应较少等居主导地位,我院口服抗糖尿病药的总体应用较为合理。     

2004年7～8月欧洲批准和上市的新产品

GSK／Vertex公司的Telzir(fosamprenavir)获欧盟批准，用于与其他抗HIV感染治疗药联用，治疗成人HIV感染。在与其他抗逆转录病毒药联用时，对新用抗逆转录病毒药和已有用药经验的病人均显示有降低血浆HIV浓度的能力。     

我院2006～2009年抗糖尿病药物用药分析

目的评价我院2006~2009年抗糖尿病药应用状况。方法对2006~2009年抗糖尿病药的用药金额和用药频度(DDDs)进行统计。结果抗糖尿病药用药金额逐年增长。其中,胰岛素用药金额的增长快于口服抗糖尿病药。口服抗糖尿病药以磺酰脲类为主。按照DDDs排序,格列吡嗪是临床最常用的口服抗糖尿病药。结论我院抗糖尿病药物应用基本稳定、合理。     

我院糖尿病患者的用药现状调查分析

目的了解医院糖尿病患者不规范用药情况，提出可行性药学服务措施。方法自行设计调查问卷，对184例糖尿病患者是否用保健品替代口服降糖药物，是否擅自购药、多头开药、重复用药，是否用过江湖游医的“秘方”、“偏方”等情况进行调查。结果75％左右的糖尿病患者都曾有过不规范用药经历，其中60％左右的患者曾在服用保健品的同时停用了其他化学类口服降糖药。结论糖尿病患者对口服降糖药物的种类、作用原理、不良反应及保健品的作用和相关知识缺乏了解，从而导致不规范用药的问题较严重．医药工作者应加强糖尿病患者的健康教育和药学指导服务，使其用药趋于安全、有效、经济、适当。     

普罗帕酮的药物动力学

普罗帕酮是目前抗心律失常药Ic类中应用较多的药物之一。该药的特点是既可静注,也可口服给药;对室上性和室性心律失常均有较好疗效。其不良反应少,安全范围相对较大;是一个值得临床上推广应用的药物。本文介绍该药的药物动力学及其药物相互作用,供临床用药参考。     

2005～2006年我院抗糖尿病药用药分析

目的：评价我院2005-2006年抗糖尿病药应用状况。方法：对2005-2006年抗糖尿病药的用药金额和用药频度（DDDs）进行统计。结果：抗糖尿病药用药金额逐年增长。其中,口服抗糖尿病药用药金额的增长快于胰岛素。口服抗糖尿病药以磺酰脲类、双胍类和α-糖苷酶抑制剂为主。按照DDDs排序,二甲双胍是临床最常用的口服抗糖尿病药。结论：我院连续2年抗糖尿病药应用基本稳定、合理。     

2006～2008年我院门诊口服抗糖尿病药应用分析

目的：了解我院口服抗糖尿病药临床应用情况及用药趋势。方法：对我院2006～2008年门诊口服抗糖尿病药的使用金额、用药频度（DDDs）及日用药金额（DDC）为指标进行分析。结果：我院门诊口服抗糖尿病药的销售金额逐年上升,品种有所增加,口服抗糖尿病药仍占主要地位。结论：该院抗糖尿病药应用基本合理,但仍应注意各类抗糖尿病药的适应证、剂量及联合用药。     

抗糖尿病药致不良反应的文献分析

目的：探讨抗糖尿病药致不良反应发生的情况,为临床合理用药服务。方法：通过中国期刊全文数据库（CNKI）收集1998-2011年发表的抗糖尿病药致不良反应发生的相关文献,对不良反应发生的患者性别与年龄构成、发生时间分布、累及器官或系统、药品种类等进行汇总、分析。同时对糖尿病并发症相关药物的不良反应亦做了归纳与分析。结果：抗糖尿病药引发不良反应的年龄主要集中于51岁以上;发生时间主要集中于1d～2个月;累及器官或系统涉及全身各大系统,其中最常见的为胃肠道反应;严重不良反应主要发生于心血管系统、免疫系统、内分泌系统中,包括室性早搏、低血糖性昏迷、过敏性休克、全身剥脱性皮炎甚至死亡等。结论：糖尿病及其并发症治疗药物产生的不良反应是广泛的,有些甚至是严重的;广大临床医师及药师应对其进行密切的监测,积极推进抗糖尿病药临床合理使用。     

酚妥拉明治疗小儿肺炎心衰致严重反应25例

１２０例小儿肺炎并发心力衰竭应用酚妥拉明治疗后出现严重不良反应２５例。不良反应发生率２０．８％，结果显示该药引起不良反应与年龄，用量及给药速度，首次用药有关。     

降糖药临床不良反应综述

目的综述各种抗糖尿病药物所致临床不良反应的情况,为临床合理用药提供依据。方法对国内外近期公开报道的糖尿病治疗药物的不良反应进行整理、总结、分析。结果在糖尿病治疗过程中,随着药物剂量增加以及其他因素影响会导致很多不良反应,目前已知常见临床不良反应主要有低血糖、消化道症状、变态反应及代谢和营养障碍等。结论抗糖尿病药物的不良反应涉及系统广泛,有的后果严重,应引起临床重视,加强临床合理用药,增强治疗效果,减少患者痛苦。     

罗格列酮安全性再评价:一项基于随机对照研究、队列研究、病例对照研究及病例报告的系统评价

目的：评价与其他抗糖尿病口服药物相比,罗格列酮治疗2型糖尿病患者的安全性。方法：按照检索策略在EMbase、MEDLINE、The Cochrane library等6个数据库中进行电子检索,并人工进行补充检索。按纳入排除标准进行筛选,对纳入文献进行偏倚风险评估,并使用Revman 5.3软件进行统计学Meta分析。结果：共纳入63篇研究,其中随机对照试验17篇。研究结果显示,罗格列酮组的总不良反应发生率与其他口服糖尿病药物相比无显著差异,然而RCT研究结果提示罗格列酮组因不良反应退出的比例高于非TZD类药物组,但低于吡格列酮组。对于心脑血管不良反应发生率,RCT研究和队列研究结果都支持罗格列酮与其他糖尿病药物相比无统计学意义,但病例对照研究结果认为罗格列酮暴露组心脑血管不良反应发生率高于未暴露组。罗格列酮组的低血糖发生率与二甲双胍组无显著差异,且低于磺脲类。RCT研究结果提示罗格列酮组体质量升高的患者比例和水肿发生率高于其他口服降糖药。队列研究结果显示罗格列酮组的骨折发生率高于其他药物,但低于吡格列酮。对于膀胱癌的发病率,队列研究结果显示罗格列酮组发病率低于吡格列酮组以及其他非TZD类糖尿病药物组,而病例对照研究却得到了相反的结果。结论：应用罗格列酮治疗2型糖尿病,总体不良反应发生率不高于其他口服降糖药,且尚无确切证据证明该药致心脑血管事件的风险高于其他抗糖尿病药物,但应对其水肿、体质量增加、骨折的风险加以预防,并警惕其致肿瘤风险。     

Genetic predisposition of life-threatening antiepileptic-induced skin reactions

Background: Thiazolidinediones (TZDs) are widely used antidiabetic drugs with proven efficacy regarding mainly surrogate markers of diabetes management. However, efficacy on surrogate markers may not always translate into benefits in clinical outcomes. Thiazolidinediones are usually well tolerated; however, their use may be associated with several adverse effects. The first TZD, troglitazone, was withdrawn from the market owing to serious hepatotoxicity. However, this does not seem to be the case with newer TZDs. Objective: The aim of the present review is to discuss the safety profile of this drug class. Methods: We searched PubMed up to July 2008 using relevant keywords. Conclusions: Common side effects associated with TZDs include edema, weight gain, macular edema and heart failure. Moreover, they may cause hypoglycemia when combined with other antidiabetic drugs as well as decrease hematocrit and hemoglobin levels. Increased bone fracture risk is another TZD-related side effect. Thiazolidinediones tend to increase serum low density lipoprotein cholesterol levels, with rosiglitazone having a more pronounced effect compared with pioglitazone. Moreover, rosiglitazone increases low density lipoprotein particle concentration in contrast to pioglitazone where a decrease is observed. Rosiglitazone has been associated with an increase in myocardial infarction incidence. On the other hand, pioglitazone may reduce cardiovascular events. Overall, TZDs are valuable drugs for diabetes management but physicians should keep in mind that they are associated with several adverse events, the most prominent of which is heart failure.     

罗格列酮联合二甲双胍治疗2型糖尿病的临床效果观察

目的探讨分析罗格列酮联合二甲双胍治疗2型糖尿病的临床效果。方法选取我院治疗的80例2型糖尿病患者,随机分两组,在饮食和运动等常规糖尿病治疗基础上,对照组予以二甲双胍治疗,观察组再予以罗格列酮治疗,比较两组治疗后的效果情况。结果两组治疗后FPG、2hPG、HbA1c和BMI出现显著性差异;对照组的显效率和总有效率均显著低于观察组;对照组治疗2个月后5例不良反应,观察组仅出现3例,无显著性差异例。结论罗格列酮联合二甲双胍治疗2型糖尿病临床效果显著,不良反应低,具有协同作用。     

吡格列酮与盐酸罗格列酮治疗2型糖尿病疗效比较

目的：比较吡格列酮与罗格列酮治疗2型糖尿病的临床疗效.方法：60例磺酰脲类和双胍类治疗而空腹血糖控制不佳（7.0 mmol·L-1≤空腹血糖（FBG）≤13.0 mmol·L-1）的2型糖尿病患者,随机分入吡格列酮15 mg·d-1组与罗格列酮4mg·d-1组,治疗12周后比较2组疗效.结果：12周后,2组空腹和餐后2 h血糖、胰岛素和糖化血红蛋白均明显下降（P〈0.01）,但2组间差异无统计学意义（P〉0.05）.吡格列酮组总费用合计为189.84元、罗格列酮组为440.16元,2组均无严重不良反应发生.结论：吡格列酮与罗格列酮治疗2型糖尿病疗效相似,但吡格列酮的费用明显低于罗格列酮.     

Effect of ketoconazole on the pharmacokinetics of rosiglitazone in healthy subjects

AIMS: Fungal infection is a significant comorbidity in patients with diabetes mellitus, and ketoconazole, an antifungal agent, causes a number of drug interactions with coadministered drugs. Rosiglitazone is a novel thiazolidinedione antidiabetic drug, mainly metabolized by CYP2C8 and to a lesser extent CYP2C9. We investigated the possible effect of ketoconazole on the pharmacokinetics of rosiglitazone in humans. METHODS: Ten healthy Korean male volunteers were treated twice daily for 5 days with 200 mg ketoconazole or with placebo, using a randomized, open-label, two-way crossover study. On day 5, a single dose of 8 mg rosiglitazone was administered orally, and plasma rosiglitazone concentrations were measured. RESULTS: Ketoconazole increased the mean area under the plasma concentration-time curve for rosiglitazone by 47%[P = 0.0003; 95% confidence interval (CI) 23, 70] and the mean elimination half-life from 3.55 to 5.50 h (P = 0.0003; 95% CI in difference 1.1, 2.4). The peak plasma concentration of rosiglitazone was increased by ketoconazole treatment by 17% (P = 0.03; 95% CI 5, 29). The apparent oral clearance of rosiglitazone decreased by 28% after ketoconazole treatment (P = 0.0005; 95% CI 18, 38). CONCLUSIONS: This study revealed that ketoconazole affected the disposition of rosiglitazone in humans, probably by the inhibition of CYP2C8 and CYP2C9, leading to increasing rosiglitazone concentrations that could increase the efficacy of rosiglitazone or its adverse events.     

Coronary heart disease outcomes in patients receiving antidiabetic agents

BACKGROUND: There is conflicting evidence on the reduction of cardiovascular risk in diabetic patients treated with oral antidiabetic agents. OBJECTIVES: To compare the risk of myocardial infarction (MI) and coronary revascularization (CR) in type 2 diabetic patients treated with rosiglitazone, metformin, or sulfonylurea. METHODS: Using data from a large US insurer, we created propensity-matched cohorts. We identified hospitalizations for MI or CR. We calculated incidence rates and 95% confidence intervals for the outcomes and estimated risks from Cox proportional hazards models. RESULTS: We identified 26,931 initiators of monotherapy, 4,086 initiators of dual-therapy, and 2,346 initiators of combination with insulin therapy. There was no difference between the risk of the composite outcome with rosiglitazone monotherapy compared to metformin monotherapy (HR 1.07, 95% CI: 0.85, 1.34), and similarly with rosiglitazone monotherapy compared to sulfonylurea monotherapy (HR 0.82, 95% CI: 0.67, 1.02). There was no difference in the risk of outcome with rosiglitazone in combination with insulin therapy compared to other oral antidiabetic agents in combination with insulin (HR 0.88, 95% CI: 0.59, 1.32). Overall, there was little difference in the risk of the composite outcome or of the individual outcomes of MI and CR comparing rosiglitazone therapies to non-rosiglitazone therapies (HR for composite outcome 0.93, 95% CI: 0.80, 1.10). CONCLUSIONS: The results from the monotherapy and the dual-therapy comparisons, though not individually significant, are consistent in suggesting that the risk of cardiovascular outcome events in patients using rosiglitazone may lie between the risks associated with sulfonylureas (higher incidence) and metformin (lower incidence).     

Pioglitazone, rosiglitazone, and rosiglitazone + metformin: new drugs. Glitazone + oral antidiabetic combination: inadequately evaluated

(1) When single-agent therapy provides inadequate glycaemic control for patients with type 2 diabetes, most guidelines recommend metformin in combination with a glucose-lowering sulphonylurea as standard treatment, despite the lack of any proven impact on morbidity or mortality. Other options include switching to insulin or abandoning the target of strict glycaemic control. (2) Pioglitazone and rosiglitazone are approved for use in combination with a glucose-lowering sulphonylurea when metformin is poorly tolerated or contraindicated, and in combination with metformin in overweight patients. (3) A fixed-dose combination containing 1 or 2 mg of rosiglitazone plus 500 mg of metformin (hydrochloride) was launched onto the French market in October 2004. (4) The indication for rosiglitazone was extended to include its use as triple-agent therapy in combination with metformin and a glucose-lowering sulphonylurea. (5) No clinical trials assessing effects on mortality or morbidity have evaluated rosiglitazone or pioglitazone in combination with other oral antidiabetic drugs. (6) Several trials have compared the glucose-lowering effects of dual-agent therapy using rosiglitazone or pioglitazone plus a glucose-lowering sulphonylurea or metformin versus dual-agent therapy with metformin and a glucose-lowering sulphonylurea. (7) These clinical trials indicate that in terms of HbA1c level, dual-agent therapy based on rosiglitazone or pioglitazone is about as effective as combination therapy with metformin plus a glucose-lowering sulphonylurea. (8) The main known adverse effect of pioglitazone and rosiglitazone is water-sodium retention, which can provoke oedema and haemodilution anaemia, and can aggravate or reveal heart failure. (9) Pioglitazone has a positive effect on the lipid profile, whereas rosiglitazone increases the LDL-cholesterol level. (10) Dual-agent therapy with pioglitazone and a sulphonylurea causes more weight gain than metformin plus a sulphonylurea. (11) Several trials have assessed triple-agent regimens containing a glitazone. Three placebo-controlled double-blind trials have tested pioglitazone (one trial, nearly 300 patients) or rosiglitazone (two trials, about 1200 patients) for 12 to 26 weeks in patients whose glycaemia was poorly controlled by dual-agent therapy with a sulphonylurea plus metformin. The glycated haemoglobin level fell by 0.3% to 1.1% (in absolute values), depending on the trial and the dosage, but at a cost of the usual adverse effects such as weight gain, anaemia and oedema. Three unblinded trials have compared oral triple-agent regimens containing glitazone versus insulin plus metformin, alone or in combination with a glucose-lowering sulphonylurea; the treatment including glitazone was no more effective in terms of the glycated haemoglobin level, but was associated with an increase in adverse effects and dropouts. (12) Given the limited clinical data available in early 2005, pioglitazone and rosiglitazone have no place in the management of type 2 diabetes.     

蛋氨酸合酶、蛋氨酸合酶还原酶基因多态性与类风湿关节炎患者甲氨蝶呤疗效相关性的研究

目的探讨类风湿关节炎(RA)患者蛋氨酸合酶(MTR)A2756G、蛋氨酸合酶还原酶(MTRR)A66G基因多态性与甲氨蝶呤(MTX)治疗的疗效和不良反应相关性。方法采用实时荧光定量PCR方法检测107例单用MTX的RA患者的MTR A2756G及MTRR A66G基因多态性,并与其治疗疗效和不良反应结合分析。结果MTR A2756G及MTRR A66G的单基因多态性与RA患者服用MTX的疗效及不良反应无相关性(P>0.05)。两基因联合作用分析显示,同时是MTR AG型和MTRR AG/GG型者较同时是MTRAA型和MTRR AA型的RA患者对MTX治疗效果差(OR=0.19,95%可信区间为0.04~0.88),差异有统计学意义(P=0.03),没有发现两者联合作用与其不良反应有相关性(P>0.05)。结论MTR和MTRR基因多态性可能对于RA患者服用MTX的疗效存在预示作用。     

胰岛素增敏剂-文迪雅治疗2型糖尿病的临床观察

目的对胰岛素增敏剂-马来酸罗格列酮（文迪雅）联合其他降糖药物治疗2型糖尿病的临床疗效及安全性进行观察。方法对30例2型糖尿病患者进行为期12周的文迪雅治疗观察。结果文迪雅治疗12周前后相比，患者FBG、PG2h、HbA1c水平均有显著下降。治疗后体重略有增加，TG水平有下降，TC、HDL—C、LDL—C无明显变化。收缩压和舒张压均有降低。结论文迪雅用于原降糖治疗效果不满意的2型糖尿病患者，可显著降低糖化血红蛋白、空腹及餐后血糖，提高胰岛素敏感性，减少胰岛素抵抗，未见肝肾功能损害等严重药物不良反应，是治疗2型糖尿病的有效和安全的新型口服降糖药。     

应用磺脲类药物和二甲双胍治疗2型糖尿病失效后补充第3种降糖药的选择

目的:对应用磺脲类药物和二甲双胍后血糖仍控制不佳的2型糖尿病患者,观察补充第3种药物控制血糖的效果和安全性。方法:119例2型糖尿病患者(年龄(56.1±14.0)岁,糖化血红蛋白A(1HbA1c)(9.1±1.6)%)分为3组,分别随机补充甘精胰岛素、罗格列酮、阿卡波糖,根据血糖调整3种药物用量。补充药物治疗24周前、后,分别测定3组患者的HbA1c、空腹血糖(FPG)、体质量等指标变化。结果:甘精胰岛素组血糖(HbA1c(-1.66±0.24)%,FPG(-3.68±0.28)mmol·L-1)改善比罗格列酮组(HbA1c(-1.15±0.17)%,FPG(-2.85±0.26)mmol·L-1)、阿卡波糖组(HbA1c(-0.75±0.22)%,FPG(-1.85±0.26)mmol·L-1)更明显(P<0.05)。与口服降糖药(罗格列酮或者阿卡波糖)比较,甘精胰岛素组患者外周水肿、胃肠道反应等发生几率更少或更轻微(P<0.05),仅体质量增加比阿卡波糖组明显(P<0.05)。3组患者低血糖发生率和治疗费用差异无统计学意义(P>0.05)。结论:对应用磺脲类药物和二甲双胍后血糖仍控制不佳的2型糖尿病患者,补充甘精胰岛素比补充口服降糖药(罗格列酮或者阿卡波糖)降糖效力更强,且副作用无明显增加。