血管紧张素转换酶抑制剂临床应用研究进展

自从1981年第一个口服有效的血管紧张素转换酶抑制剂（angiotensin-converting enzyme inhibitors,ACEI）--卡托普利（开搏通）被批准上市以来,该类药物的发展速度非常快。到目前为止,大约有17种药物被批准上市。不同ACEI药物有着相同的药理学作用,现已被广泛用于临床,主要用于治疗高血压、冠状动脉粥样硬化性心脏病（简称冠心病）、慢性心功能不全等心血管疾病,是治疗这些疾病的重要药物。随着研究的深入,发现该类药物对其他疾病也具有一定的治疗作用。现将近期ACEI临床应用研究进展综述如下。     

缓释片药物不可掰半服用

近年来上市的控释、缓释片剂药物越来越多。因为它能起到长效作用,减少服药次数,给病人服药带来了方便。如氨茶碱缓释片（常欣）是治疗中老年支气管哮喘、肺心病等疾病的常用药物;硝苯地平（心痛定）缓释片则常用于治疗高血压、冠心病;吗啡控释片常用于晚期癌症的口服止痛。但不少人尤其是老年人在服用这些药物时为了便于服用常将药片掰成几半,其实这是不科学的。     

缓释片药物不可掰半服用

近年来上市的控释、缓释片剂药物越来越多。因为它能起到长效作用,减少服药次数,给病人服药带来了方便。如氨茶碱缓释片（常欣）是治疗中老年支气管哮喘、肺心病等疾病的常用药物;硝苯地平（心痛定）缓释片则常用于治疗高血压、冠心病;吗啡控释片常用于晚期癌症的口服止痛。但不少人尤其是老年人在服用这些药物时为了便于服用常将药片掰成几半,其实这是不科学的。     

甘露醇可引发多种不良反应

甘露醇注射液是临床广泛用于降低颅内压、眼内压的高效脱水剂。其口服制剂有导泻作用,临床常口服给药用于治疗便秘及清洁肠道等。近几年,甘露醇静脉及口服用药的不良反应常有发生,特别是甘露醇可引起急性肾衰等严重不良反应,引起了人们的广泛关注。     

复方氟哌酸滴鼻剂的应用

氟哌酸系一氨基喹啉衍生物,是一种新型、高效、广谱抗菌药,口服该药常用于胃肠道,泌尿道、妇产科、外科手术等的感染,亦用于治疗耳鼻喉科疾病。据报道说口服给药用于治疗耳鼻喉科疾病疗效达74.5%。但口服给药副作用发生率达3.8～4.4%,甚至可发生肝肾损害等严重反应。据此,我们研制成复方氟哌酸滴鼻剂,用于治疗急慢性鼻     

美沙拉嗪联合中药灌肠治疗溃疡性结肠炎临床疗效观察简

溃疡性结肠炎（UC）是一种病因尚不十分清楚的直肠和结肠慢性非特异性炎症性疾病,病变主要累及大肠黏膜和黏膜下层,特征性表现为腹泻、腹痛、黏液脓血便[1].UC 常迁延不愈、反复发作、严重影响患者的生活质量.在临床上常用于治疗该类疾病的药物有柳氮磺胺类、类固醇激素和免疫抑制剂等,但是这些药物的临床疗效不够确切,且不良反应较大.本研究采用美沙拉嗪口服联合中药灌肠来寻求更为安全有效的治疗UC 的方法,分析报告如下.     

H_1受体阻断药可致的过敏反应

H1受体阻断药用于治疗过敏反应,但也可引起过敏反应,甚至引起过敏性休克,故在应用时应加以重视。现综述如下。1阿斯咪唑（息斯墩）一种长效新型H1受体阻断药,无嗜睡及困倦等中枢作用,现成为治疗过敏性疾病的首选口服药品。可引起算麻疹、药疹、皮疹及过敏性休克。尊麻疹常为全身大小不等的风团,同时伴有全身痉挛、头昏等;药疹则为出现在面部、前额、双眼睑的红丘疹,偶见出现在外阴、臀部的固定型紫红斑;皮疹则多出现在面部、颈部,并伴胸闷。有的病人口服数分钟后就出现过敏性休克症状［1-4］。2西替利嗪（仙特敏,斯特林）属哌嗪…     

降钙素口服制剂的研究现状

降钙素（calcitonin, CT）是一种多肽类激素,能够通过抑制破骨细胞来减少骨吸收,常用于治疗骨质疏松症、佩吉特氏病及恶性肿瘤性高血钙症。降钙素除了能作用于破骨细胞及肾小管,还有止痛作用,也可以对软骨组织起到保护作用。现今市场上主要是注射剂及喷鼻剂,因使用不方便且患者顺应性差而限制了其临床应用。相反,患者更易接受口服剂型,并且顺应性更好。本文通过查阅国内外相关文献,对降钙素的药理活性、给药途径、影响因素等方面进行综述。     

思连康治疗小儿厌食症的疗效观察

思连康为口服双歧杆菌、乳酸杆菌、肠球菌、腊样芽孢杆菌四联活菌片剂（杭州龙达新科生物制药有限公司生产）,常用于小儿及成人的肠道疾病如腹泻、便秘的辅助治疗,本人用思连康治疗小儿厌食症,收到良好的效果,先报告如下。     

醋氯芬酸新制剂的研究进展

醋氯芬酸是西班牙Prodesfarm a公司在1992年首先推向市场的一种新型的口服强效非甾体类抗炎药。它具有消炎、镇痛、解热等作用,用于缓解类风湿关节炎（RA）、骨性关节炎（OA）和强直性脊柱炎等引起的炎症和疼痛,对于扭伤、拉伤及其他软组织损伤、手术后疼痛及肿胀也非常有效,还用于其他疾病如原发性痛经及子宫附件炎等引起的疼痛。     

Role of dichloroacetate in the treatment of genetic mitochondrial diseases

Dichloroacetate (DCA) is an investigational drug for the treatment of genetic mitochondrial diseases. Its primary site of action is the pyruvate dehydrogenase (PDH) complex, which it stimulates by altering its phosphorylation state and stability. DCA is metabolized by and inhibits the bifunctional zeta-1 family isoform of glutathione transferase/maleylacetoacetate isomerase. Polymorphic variants of this enzyme differ in their kinetic properties toward DCA, thereby influencing its biotransformation and toxicity, both of which are also influenced by subject age. Results from open label studies and controlled clinical trials suggest chronic oral DCA is generally well-tolerated by young children and may be particularly effective in patients with PDH deficiency. Recent in vitro data indicate that a combined DCA and gene therapy approach may also hold promise for the treatment of this devastating condition.     

Dimethyl sulfoxide: recent pharmacological and toxicological research

A survey of the literature published in the past 2 decades on the basic pharmacology, therapeutic uses and toxicity of dimethyl sulfoxide (DMSO) is presented. A salient pharmacological action of DMSO is its ability to scavenge oxygen-free radicals implicated in xenobiotic-induced tissue damages when given before, during or several hours after the tissue insult. More trials with DMSO in diseases and conditions caused by oxygen-free radicals are warranted.     

An update on hybrid drugs in cardiovascular drug research

Background: Several different strategies are commonly used in medicinal chemistry to develop new molecules targeted at improving the current pharmacotherapy of cardiovascular diseases and hypertension. Among these, in the past years, we could observe an increasing development of new hybrid compounds in which two or more mechanisms of action are combined together to give a new pharmacological entity targeting, simultaneously, several factors involved in complex cardiovascular diseases. Objective: The aim of this review is to present the rational pharmacological bases and the chemical approaches used for the development of representative hybrid drugs. Conclusions: In this paper, some promising multi-targeted enzyme inhibitors and dual receptor antagonists are reported. Some examples of pharmacodynamic hybrids compounds, in which a suitable nitric oxide releasing functionality has been added to known cardiovascular drugs, are also shown.     

DNA存在下Cu(Ⅱ)—去甲斑螫酸络合物催化抗坏血酸氧化的动力学

在pH 7.40,20.00±0.05℃,磷酸盐缓冲液中,研究了Cu(Ⅱ)及Cu(Ⅱ)络合物的可见光谱,以及DNA存在下,Cu(Ⅱ)的去甲斑蝥酸络合物Cu(Ⅱ)/H₂DCA催化抗坏血酸(H₂A)有氧氧化动力学,检测了Cu(Ⅱ)/H₂DCA催化H₂A有氧氧化过程中·OH生成的速度。实验结果表明,在Cu(Ⅱ)/H₂DCA存在下,抗坏血酸断裂DNA链的反应体系中,存在Cu(Ⅱ)与H₂DCA和DNA的三元络合。据此,推测H₂A的催化有氧氧化对DNA链的断裂作用按特定部位的Fenton反应机理进行。该机理能够解释前文的DNA链断裂实验的所有结果。     

Dichloroacetate (DCA) dosimetry: interpreting DCA-induced liver cancer dose response and the potential for DCA to contribute to trichloroethylene-induced liver cancer

Pharmacokinetic studies with dichloroacetate (DCA) provide insights into the likelihood that trichloroethylene-induced liver cancers arise from formation of DCA as a metabolite and the mode of action by which DCA induces liver cancer. A simple physiologically based pharmacokinetic model was developed to analyze DCA blood concentration data from mice unexposed to or pre-treated with DCA. The large first pass metabolism of DCA in the liver is significantly reduced by DCA pretreatment. Because DCA inhibits its own metabolism, large increases in area under the blood concentration curve occur at lower doses than would be predicted from single-dose pharmacokinetic studies with naive mice. The dose metrics associated with the incidence of liver tumors in contrast to the multiplicity of tumors per animal may be different, suggesting potentially different roles in the cancer process for DCA versus its metabolites. By linking a model for trichloroethylene (TCE) pharmacokinetics with the DCA model, maximum levels of DCA potentially produced from TCE were estimated to be at or below the analytical chemistry detection limits. In addition, the predicted levels of DCA would be too small to produce the observed liver cancers following corn oil gavage exposure of mice to TCE.     

葛根素研究进展

葛根素具有广泛的药理作用，临床上主要用于心脑血管疾病的治疗，如心律失常、心绞病、冠心病、心肌梗死、心力衰竭、高血压、脑水肿等。本文概述了葛根素的药理作用、临床应用、制剂研究及结构修饰的研究进展。     

植物多糖在胃肠道及肝病中的新作用

The polysaccharide fraction from various herbal medicines has been well studied for its immunomodulatory action and antitumor effect, such as lentinan and lucid Ganoderma, for more than twenty years. These actions and effects may be due to stimulation of the phagocytic activity and anti-inflammatory action. It is also found to increase hematopoiesis in the bone marrow and to promote proliferation of several types of hematopoietic precursor cells. It was also found to provide radioprotective effect by improving the recovery of hematopoietic function in animals. These findings suggest that the polysaccharides from plant origins have significant pharmacological action on cells with high proliferative capacity in the body. Recently, increasing evidence implicates that vegetal polysaccharides have similar protective and repairing activities in the gastrointestinal (GI) tract as the cells in this system also have the same biological property. In this review, we would like to update and summarize findings both in animals and in human pertaining to the pharmacological actions of polysaccharides from different vegetal sources on the GI and hepatic disorders including ulcer and cancer diseases.     

Cholinesterase inhibitors: a patent review (2007 - 2011)

INTRODUCTION: Cholinesterase inhibitors participate in the maintenance of the levels of the neurotransmitter acetylcholine by inhibiting the enzymes implicated in its degradation, namely, butyrylcholinesterase and acetylcholinesterase. This pharmacological action has an important role in several diseases, including neurodegenerative diseases such as Alzheimer's. AREAS COVERED: This article reviews recent advances in the development of cholinesterase enzyme inhibitors, covering the development of new chemical entities, new pharmaceutical formulations with known inhibitors or treatments in combination with other drug families. EXPERT OPINION: The development of cholinesterase inhibitors has to face several issues, including the fact that the principal indication for these drugs, Alzheimer's disease, is not currently believed to derivate from a cholinergic deficiency, although most of the drugs clinically used for these disease are cholinesterase inhibitors. Moreover, the adverse effects found when administering cholinesterase inhibitors limit their use in other diseases, such as gastrointestinal diseases, glaucoma, or analgesia.     

Medical benefits of using natural compounds and their derivatives having multiple pharmacological actions

The multiple pharmacological actions of a unique compound are a prerequisite for classifying drugs as highly efficacious, because the multiple pharmacological actions offer the possibility of treating various symptoms of chronic diseases as described below. 1) Sustained hyperglycemia induces macrovascular and microvascular complications in type 2 diabetes mellitus. Antihyperglycemic medication and the control of postprandial hyperglycemia are essentially important for normalizing plasma glucose level. Gymnemic acid IV isolated from Gymnema sylvestre (Asclepiadaceae) leaves has antisweet, antihyperglycemic, glucose uptake inhibitory, and gut glycosidase inhibitory effects. Most of these pharmacological effects may synergistically contribute to alleviating type 2 diabetes-related symptoms. 2) Diabetic skeletal and vascular smooth muscles are hypersensitive to chemical transmitters, cytokines and autacoids. The sensitivity of neuromuscular synapses is enhanced in diabetes, which seems to be closely associated with neuropathy as one of the diabetic complications. beta-Eudesmol found in Atractylodes lancea rhizome has a desensitizing channel blocking action to nicotinic acetylcholine receptors, anti-angiogenic action in vascular endothelium, and neuronal differentiation actions. These multiple pharmacological actions are favorable for treating angiogenic diseases possibly including the complications of diabetes, namely, retinopathy and nephropathy, and cancer. 3) Nipradilol is clinically utilized as a topical antiglaucoma drug. The ocular hypotensive effects of this compound are brought about by its alpha1 and beta-adrenergic receptor blocking actions, and nitric oxide (NO) releasing action. NO directly activates cyclooxygenases. All these pharmacologic effects are beneficial for treating glaucoma. The selectivity and specificity of drug action are required for treating acute diseases, infections or for acting as useful reagents. The pleiotropic actions of natural compounds and their derivatives serve as important clues for developing new drugs for various chronic diseases.