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Skin Reactions Associated to Phenytoin Administration: Multifactorial Cause 与苯妥英相关的皮肤反应:多因素原因
Pub Date : 2014-10-29 DOI: 10.4172/2167-065X.1000125
M. Vázquez, P. Fagiolino, Silvana Alvariza, M. Ibarra, Cecilia Maldonado, R. González, A. Laborde, M. Uría, A. Carozzi, C. Azambuja
Purpose: Cutaneous reactions can be associated with phenytoin administration. Such reactions can be explained by the formation of reactive species (arene oxide and quinones) capable of interacting covalently with cell macromolecules during phenytoin metabolism. Enzymes involved in reactive species detoxification are polimorphically expressed in humans. A genetic abnormality leading to a defective microsomal epoxidase hydrolase (main detoxification enzyme) activity could be one of the causes leading to this kind of adverse effect, but not the only one. The purpose of this study was to give a deeper insight into the main causes leading to skin reactions. Methods: Cutaneous reactions experienced by some healthy volunteers enrolled in a pharmacokinetic study of phenytoin were analyzed in depth. The activity of the microsomal epoxidase enzyme was determined. Results: Six out of twelve healthy volunteers receiving phenytoin in multiple doses exhibited rash. More female subjects or volunteers with a rapid input of the drug and/or a faster phenytoin metabolism or defective microsomal epoxidase hydrolase activity experienced these cutaneous reactions. Conclusions: Arene oxide metabolite seems to be the responsible entity for cutaneous reactions. The genesis of this adverse effect after phenytoin administration is multifactorial revealing that other risks factors (not only the genetic one) such as being a woman in the fertile life period or under contraceptive therapy, or a rapid drug input and /or a faster phenytoin metabolism could lead to a higher formation rate of the arene oxide.
目的:皮肤反应可能与苯妥英给药有关。这种反应可以解释为在苯妥英代谢过程中能够与细胞大分子共价相互作用的活性物质(氧化芳烃和醌)的形成。参与活性物种解毒的酶在人类中是多态表达的。遗传异常导致微粒体环氧酶水解酶(主要解毒酶)活性缺陷可能是导致这种不良反应的原因之一,但不是唯一的原因。这项研究的目的是为了更深入地了解导致皮肤反应的主要原因。方法:对一些参加苯妥英药代动力学研究的健康志愿者的皮肤反应进行深入分析。测定微粒体环氧化酶活性。结果:12名接受多剂量苯妥英的健康志愿者中有6人出现皮疹。更多的女性受试者或志愿者快速输入药物和/或更快的苯托英代谢或有缺陷的微粒体环氧化酶水解酶活性经历这些皮肤反应。结论:氧化芳烃代谢物可能是皮肤反应的主要原因。苯妥英给药后这种不良反应的成因是多因素的,揭示了其他风险因素(不仅仅是遗传因素),如处于生育期或正在接受避孕治疗的女性,或快速的药物输入和/或更快的苯妥英代谢可能导致芳烃氧化物的形成率更高。
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引用次数: 5
Evolution of Drug Utilization in Nursing Homes in Belgium 比利时养老院药物使用的演变
Pub Date : 2014-10-07 DOI: 10.4172/2167-065X.1000124
J. D. Wolf, T. Dilles, R. V. Stichele, M. Elseviers
In 2005, the PHEBE study highlighted the problem of polypharmacy and the emerging use of psychotropic medication in nursing home residents (PHEBE 1). In 2011, new collected data were compared (PHEBE 2). The total mean number of prescriptions in PHEBE 1 was 8.4, containing a mean of 7.6 for chronic medication only. For PHEBE 2 this was 8.6 for total and 8.1 for chronic medication. In both investigations (2005-2011, resp.) the main categories were ‘Nervous system’ (88.3-89.2%), followed by ‘Cardiovascular system’ (78.0-84.8%) and ‘Alimentary tract and metabolism’ (81.1-83.2%). This study found that polypharmacy remains a major problem in residential care. The use of chronic medication further increased with a high consumption of psychotropic medication, beta-blockers and laxatives.
2005年,PHEBE研究强调了养老院居民的多重用药问题和精神药物的新使用(PHEBE 1)。2011年,比较了新收集的数据(PHEBE 2)。PHEBE 1的处方总数平均为8.4张,其中仅慢性药物的处方总数平均为7.6张。对于PHEBE 2,总评分为8.6,慢性用药评分为8.1。在这两项调查(2005-2011年)中,主要类别是“神经系统”(88.3-89.2%),其次是“心血管系统”(78.0-84.8%)和“消化道和代谢”(81.1-83.2%)。本研究发现,多药仍然是一个主要问题,在住宿护理。随着精神药物、受体阻滞剂和泻药的大量使用,慢性药物的使用进一步增加。
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引用次数: 7
Tolerabilities of Artemisinin-Based Combination Drugs among Patients with Uncomplicated Malaria in a Tertiary Institution Benin City, Nigeria 尼日利亚贝宁市某高等教育机构无并发症疟疾患者青蒿素类联合药物耐受性研究
Pub Date : 2014-10-01 DOI: 10.4172/2167-065X.1000123
S. Aghahowa, H. Obianwu, A. Isah
Background: The policy governing the treatment of malaria in Nigeria was changed in 2005 instituting the Artemisinin-Based Combination Therapies [ACTs] as first-line Drugs instead of Chloroquine due to rapidly developing resistance of Plasmodium falciparum. Methodology: The tolerability to [ACTs] was assessed in patients using a structured questionnaire and Visual analogue scale. These instruments were distributed systematically among the patients that presented with uncomplicated malaria after obtaining consent from the University of Benin Teaching Hospital, Benin City, Nigeria. Results: Among the five hundred and twenty patients that participated in the tolerability assessment of four different types of ACTs, male and female ratio was 1.3:1, Mean age 32.06 ± 2.3 years [Mean ± SD]. Artemether-Lumefantrine was the most frequently utilized and most tolerable. Two hundred and five [52.69%] respondents reported with forty-one different types of adverse effects of nine major systemic classes. Body weakness was the most frequent adverse effects reported in 112[54.63%] respondents. Adverse effects were significantly dependent on the type of ACTs used p<0.05; these were found to be most common with Artesunate-Mefloquine. Eleven patients were hospitalized due to very severe Body weakness and Dizziness. These severities were found common with Artesunate-Amodiaquine and Artesunate- Mefloqunie respectively. Despite the adverse effects, four hundred and seventy-six respondents (91.53%) were willing to repeat ACTs another time they have malaria. There were significant differences in symptomatic response on Days 0, 1, 2, 3, 7, 14 and 28 (p<0.05). 93% respondents felt extremely sick on Day 0, 68% had persistent fever on the third day of treatment and 71% had improved response after day 7. Conclusion: Anecdotal reports showed that ACTs have a modest tolerability, they are therefore recommended for patients that have uncomplicated malaria.
背景:由于恶性疟原虫快速发展的耐药性,尼日利亚于2005年改变了疟疾治疗政策,将以青蒿素为基础的联合疗法(ACTs)作为一线药物取代氯喹。方法:采用结构化问卷和视觉模拟量表评估患者对[ACTs]的耐受性。在获得尼日利亚贝宁市贝宁大学教学医院的同意后,系统地向无并发症疟疾患者分发了这些仪器。结果:参与4种不同类型ACTs耐受性评估的520例患者中,男女比例为1.3:1,平均年龄32.06±2.3岁[Mean±SD]。Artemether-Lumefantrine是最常用和最耐受性的药物。225名(52.69%)受访者报告了9个主要系统类别的41种不同类型的不良反应。112例(54.63%)受访者报告的不良反应中,身体虚弱是最常见的。不良反应显著依赖于使用的ACTs类型p<0.05;这些症状在甲氟喹-青蒿琥酯中最为常见。11名患者因严重的身体虚弱和头晕而住院。这些严重程度分别在青蒿琥酯-阿莫地喹和青蒿琥酯-甲氟喹中发现。尽管有不良反应,476名应答者(91.53%)在再次患疟疾时愿意重复以青蒿素为基础的联合治疗。第0天、第1天、第2天、第3天、第7天、第14天、第28天的症状反应差异有统计学意义(p<0.05)。93%的受访者在第0天感到极度不适,68%的人在治疗的第三天持续发烧,71%的人在第7天后反应有所改善。结论:坊间报告显示,以青蒿素为基础的联合治疗具有一定的耐受性,因此推荐用于无并发症的疟疾患者。
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引用次数: 8
The Pharmacology of Acute Respiratory Distress Syndrome 急性呼吸窘迫综合征的药理学研究
Pub Date : 2014-09-23 DOI: 10.4172/2167-065X.1000120
A. Chamberlain, B. Varisco
Acute Respiratory Distress Syndrome (ARDS) is a common respiratory complication of critical severe illness or injury. Despite steady improvement in outcomes over the last three decades, ARDS remains a common cause of morbidity and mortality in pediatric and adult intensive care units. Due to its extensive burden, ARDS has been the focus of numerous multi-center clinical trials which have attempted to translate animal, ex vivo, and small single center studies into wider practice. Since the results of several of these large studies have been recently published, we sought to review the pharmacology of ARDS, summarize the major non-pharmacologic interventions shown to improve outcome, and update the reader on evolving therapies which may enter clinical practice in the coming decade.
急性呼吸窘迫综合征(Acute Respiratory Distress Syndrome, ARDS)是危重疾病或损伤后常见的呼吸系统并发症。尽管在过去的三十年里,ARDS的预后稳步改善,但它仍然是儿童和成人重症监护病房发病率和死亡率的常见原因。由于其广泛的负担,ARDS已成为许多多中心临床试验的重点,这些试验试图将动物,离体和小型单中心研究转化为更广泛的实践。由于最近发表了几项大型研究的结果,我们试图回顾ARDS的药理学,总结显示改善结果的主要非药物干预措施,并更新读者在未来十年可能进入临床实践的不断发展的治疗方法。
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引用次数: 0
Assessment of Drug Related Problems Among Hypertensive Patients on Follow up in Adama Hospital Medical College, East Ethiopia 东埃塞俄比亚阿达玛医院医学院随访高血压患者药物相关问题评价
Pub Date : 2014-09-23 DOI: 10.4172/2167-065X.1000122
M. Hussein, J. Lenjisa, M. Woldu, Gobeze Temesgen Tegegne, G. Umeta, Hunduma Dins, B. K. Gelaw
Hypertension is an important worldwide public-health challenge because of its high frequency and risk factor for cerebrovascular, cardiovascular and kidney disease. Drug therapy problems are a significant challenge to health care providers. It severely compromises the effectiveness of treatment making this a critical issue in population health both from the perspective of quality of life and of health economics. Therefore, the objective of this study is to determine the pattern and magnitude of drug therapy problems in the study hospital and to find out risk factors for these problems. The study was questionnaire-based Cross sectional design which was conducted from April to May 2014 at Adama Hospital Medical College. A convenient sampling method was used and a total of 192 hypertensive patients were included in the study. Data were analyzed using SPSS software program. In this study 155 (80.7%) patients have at least one drug therapy problem and a total of 452 drug therapy problems were identified in them. The most common drug therapy problem identified in this study was drug interaction (n=259, 58.7%), followed by non-adherence and adverse drug interaction constituting 19.5% and 18.6% respectively. Under dose accounts only 0.9% of all drug therapy identified. Marital status, number of drugs and number of co morbidities significantly affect drug therapy problems. The study showed that 80.7% of the patients in the study have drug therapy problems. Number of complications and number of drugs significantly affect drug therapy problems. Therefore, patients with multiple diagnosis and patients using multiple drugs should be closely monitored for drug therapy problem, to avoid clinically significant harmful consequences.
高血压是一项重要的全球公共卫生挑战,因为它是脑血管、心血管和肾脏疾病的高频率和危险因素。药物治疗问题是卫生保健提供者面临的一个重大挑战。它严重损害了治疗的有效性,从生活质量和卫生经济学的角度来看,这是人口健康中的一个关键问题。因此,本研究的目的是确定研究医院药物治疗问题的模式和程度,并找出这些问题的危险因素。本研究采用问卷横断面设计,于2014年4 - 5月在安道玛医院医学院进行。采用方便的抽样方法,共纳入192例高血压患者。数据采用SPSS软件进行分析。本研究中155例(80.7%)患者至少存在一种药物治疗问题,共鉴定出452种药物治疗问题。本研究中发现的最常见的药物治疗问题是药物相互作用(n=259, 58.7%),其次是不依从和药物不良相互作用,分别占19.5%和18.6%。剂量不足仅占已确定的所有药物治疗的0.9%。婚姻状况、药物数量和合并症数量显著影响药物治疗问题。研究显示,80.7%的患者存在药物治疗问题。并发症的数量和药物的数量显著影响药物治疗问题。因此,应密切监测多重诊断患者和使用多种药物的患者的药物治疗问题,以免出现临床显著的有害后果。
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引用次数: 32
Synthetic Biodegradable Polymers Used in Controlled Drug Delivery System: An Overview 合成可生物降解聚合物在受控药物输送系统中的应用综述
Pub Date : 2014-09-22 DOI: 10.4172/2167-065X.1000121
Amit Jagannath Gavasane, H. Pawar
Polymers are becoming increasingly important in the field of drug delivery. The pharmaceutical applications of polymers range from their use as binders in tablets to viscosity and flow controlling agents in liquids, suspensions and emulsions. Use of polymer is now extended to controlled release and targeting drug delivery system. Polymers are obtained from natural source as well as synthesized chemically. Polymers are classified as biodegradable and nonbiodegradable. Biodegradable polymers have been widely used in biomedical applications because of their known biocompatibility and biodegradability. The present review gives an overview of the different biodegradable polymers that are currently being used in the development of controlled drug delivery system.
聚合物在给药领域中发挥着越来越重要的作用。聚合物的制药应用范围从片剂的粘合剂到液体、悬浮液和乳液中的粘度和流量控制剂。聚合物的使用现已扩展到控释和靶向给药系统。聚合物可以从天然来源获得,也可以通过化学方法合成。聚合物分为可生物降解和不可生物降解。生物可降解聚合物由于具有生物相容性和生物可降解性而广泛应用于生物医学领域。本文综述了目前在受控给药系统开发中应用的不同的可生物降解聚合物。
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引用次数: 56
Neuroblastoma in the Adult: Which Therapy is Effective? 成人神经母细胞瘤:哪种治疗有效?
Pub Date : 2014-08-08 DOI: 10.4172/2167-065X.1000119
F. Karaca, ÇiÄdem Usul AfÅar, Meral GünaldÄ, Berksoy Åahin
The examination of a twenty-eight-year-old male patient with lower back pain revealed a mass that extended through the spinal canal at the L1-L2 level and exhibited left paravertebral extension which was indistinguishable from the psoas muscle. Neuroblastoma was diagnosed after performing a biopsy. The disease progressed in that same year and in the following years, even after performing surgery, radiotherapy, chemotherapy, and bone marrow transplantation. The course of the disease was resistant to different high-dose chemotherapies and radiotherapy. The patient died four years after diagnosis. Neuroblastoma, a tumor which more frequently appears in children, is seen as an advanced or metastatic disease in adults. Currently there is no standard treatment for neuroblastoma in adults. The treatment protocols applied in children are insufficient for adults. Generally neuroblastoma is characterized as a localized disease, but in adults it is more aggressive.
检查一名28岁男性腰痛患者,发现肿块延伸至L1-L2水平的椎管,并表现出与腰肌难以区分的左侧椎旁延伸。神经母细胞瘤是在活检后确诊的。在同一年和接下来的几年里,即使在接受手术、放疗、化疗和骨髓移植后,病情仍在恶化。病程对不同的大剂量化疗和放疗具有耐药性。该患者在确诊后4年死亡。神经母细胞瘤是一种常见于儿童的肿瘤,在成人中被视为一种晚期或转移性疾病。目前成人神经母细胞瘤没有标准的治疗方法。适用于儿童的治疗方案不适用于成人。一般来说,神经母细胞瘤的特点是局部疾病,但在成人中,它更具侵袭性。
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引用次数: 0
A Comparative Study of Olmesartan and Valsartan on Insulin Sensitivity in Hypertensive Patients with Diabetes Mellitus or Impaired Glucose Tolerance (OVIS Study) 奥美沙坦与缬沙坦对高血压合并糖尿病或糖耐量受损患者胰岛素敏感性的比较研究(OVIS研究)
Pub Date : 2014-07-25 DOI: 10.4172/2167-065X.1000118
S. Biro, T. Saikawa, Takatoshi Otonari, Y. Sawayama, M. Ageta, H. Obata, S. Kono, J. Sasaki
Activation of renin angiotensin system is implicated in insulin resistance. In mega trials, it has been suggested that angiotensin receptor blockers may be beneficial on insulin sensitivity in hypertensive patients. We conducted a multicenter, open-label, parallel-group trial to compare the effects of olmesartan and valsartan on insulin sensitivity and adiponectin levels in 206 hypertensive patients with diabetes mellitus or impaired glucose tolerance. Patients were randomly assigned to either olmesartan 20 mg/day or valsartan 80 mg/day treatment for 24 weeks. Blood pressure, fasting glucose, fasting insulin, glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), and serum adiponectin levels were measured. The efficacy was evaluated in 197 patients (olmesartan, n=98; valsartan, n=99). At baseline, all parameters except for systolic blood pressure (SBP) and serum triglyceride did not differ between the 2 groups. HbA1c decreased slightly after a 24-week treatment with valsartan, but not olmesartan, while the decrease did not significantly differ in the two groups. There was no difference in the change from the baseline between olmesartan and valsartan groups concerning fasting glucose, fasting insulin, HOMA-IR, and adiponectin levels after 24-week treatment. The decrease in SBP tended to be greater in the olmesartan group than in the valsartan group even with adjustment for the baseline difference. In conclusion, there was no significant difference in insulin sensitivity or adiponectin levels between the olmesartan and valsartan groups. In the standard dose, olmesartan significantly decreased SBP as compared with valsartan.
肾素血管紧张素系统的激活与胰岛素抵抗有关。在大型试验中,血管紧张素受体阻滞剂可能对高血压患者的胰岛素敏感性有益。我们进行了一项多中心、开放标签、平行组试验,比较奥美沙坦和缬沙坦对206例合并糖尿病或糖耐量受损的高血压患者胰岛素敏感性和脂联素水平的影响。患者被随机分配到奥美沙坦20mg /天或缬沙坦80mg /天治疗24周。测量血压、空腹血糖、空腹胰岛素、糖化血红蛋白(HbA1c)、胰岛素抵抗稳态模型评估(HOMA-IR)和血清脂联素水平。对197例患者(奥美沙坦,n=98;缬沙坦,n = 99)。在基线时,除收缩压(SBP)和血清甘油三酯外,两组之间的所有参数均无差异。缬沙坦治疗24周后,HbA1c略有下降,但奥美沙坦没有,而两组的下降没有显著差异。治疗24周后,奥美沙坦组和缬沙坦组的空腹血糖、空腹胰岛素、HOMA-IR和脂联素水平从基线变化没有差异。即使调整了基线差异,奥美沙坦组的收缩压下降幅度也大于缬沙坦组。总之,奥美沙坦组和缬沙坦组在胰岛素敏感性和脂联素水平上没有显著差异。在标准剂量下,与缬沙坦相比,奥美沙坦显著降低收缩压。
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引用次数: 1
Therapeutic Targets for Diabetes Mellitus: An Update 糖尿病的治疗靶点:最新进展
Pub Date : 2014-05-15 DOI: 10.4172/2167-065X.1000117
Nivedita Tiwari, A. Thakur, Vinay Kumar, A. Dey, Vikas Kumar
Diabetes mellitus is a common form of metabolic disorder where level of blood glucose in the bloodstream raises high, because of deficiency of insulin and development of insulin resistance in diabetic individuals. It is categorize under modern age life style disorder, commonly affected by middle-aged people and the children in adolescents in most developed countries. Diabetic patients develop serious complication with the development of disease, such as obesity, risk of stroke and heart failure. The worldwide prevalence of diabetes is likely to increase from 382 million people in 2013 to 592 million by 2035. Globally antidiabetic drugs formulate the second-largest market by sales in the pharmaceuticals industry after cancer. Various novel targets have identified and recently various therapeutic leads successfully completed their different phases of clinical trials such as GLP-1 agonist, DPP-IV inhibitors, SGLT2 inhibitors, and are going to be the next generation therapy for management of diabetes. Presently the information was collects from PubMed, Science Direct, SciFinder and Google Scholar. In this review, we spotlighted on some common therapeutic targets involved in type 2 diabetes, offering a new concept for developing new drug candidates to produce newer generation antidiabetic drugs against type 2 diabetes.
糖尿病是一种常见的代谢紊乱,由于糖尿病患者缺乏胰岛素和胰岛素抵抗,血液中的血糖水平升高。它被归类为现代生活方式障碍,常见于大多数发达国家的中年人和青少年儿童。糖尿病患者随着疾病的发展会出现严重的并发症,如肥胖、中风和心力衰竭的风险。到2035年,全球糖尿病患病率可能从2013年的3.82亿人增加到5.92亿人。全球范围内,降糖药是仅次于癌症的第二大医药市场。各种新的靶点已经确定,最近各种治疗先导成功完成了不同阶段的临床试验,如GLP-1激动剂,DPP-IV抑制剂,SGLT2抑制剂,并将成为糖尿病管理的下一代治疗方法。目前收集的信息来自PubMed, Science Direct, SciFinder和Google Scholar。本文综述了2型糖尿病的一些常见治疗靶点,为开发新的候选药物以生产新一代抗2型糖尿病药物提供新的思路。
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引用次数: 44
Macromolecular Design of Platinum Drug Conjugates 铂类药物偶联物的大分子设计
Pub Date : 2014-05-02 DOI: 10.4172/2167-065X.S2-006
N. Koseva
Cisplatin and its analogues display common drawbacks such as unfavorable toxicological profile, short blood circulation time and non-specific bio-distribution. Besides that, in biological fluids cisplatin is inactivated by nitrogenand sulphur-containing biomolecules. Drug conjugation to a water soluble polymer is a feasible approach to enhance therapeutic efficiency. Examples of carboxylate-containing polymer carriers of cisplatin and the effect of macromolecular architecture on the behavior of conjugates are discussed.
顺铂及其类似物具有毒理学不良、血液循环时间短、生物分布不特异性等缺点。此外,在生物液体中,顺铂被含氮和含硫的生物分子灭活。将药物偶联到水溶性聚合物上是一种提高治疗效率的可行方法。讨论了含羧酸的顺铂聚合物载体的实例以及大分子结构对共轭物行为的影响。
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引用次数: 2
期刊
Clinical Pharmacology & Biopharmaceutics
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