Effect of colour of drugs: systematic review of perceived effect of drugs and of their effectiveness.

OBJECTIVE: To assess the impact of the colour of a drug''s formulation on its perceived effect and its effectiveness and to examine whether antidepressant drugs available in the Netherlands are different in colour from hypnotic, sedative, and anxiolytic drugs. DESIGN: Systematic review of 12 published studies. Six studies examined the perceived action of different coloured drugs and six the influence of the colour of a drug on its effectiveness. The colours of samples of 49 drugs affecting the central nervous system were assessed using a colour atlas. MAIN OUTCOME MEASURES: Perceived stimulant action versus perceived depressant action of colour of drugs; the trials that assessed the effect of drugs in different colours were done in patients with different diseases and had different outcome measures. RESULTS: The studies on perceived action of coloured drugs showed that red, yellow, and orange are associated with a stimulant effect, while blue and green are related to a tranquillising effect. The trials that assessed the impact of the colour of drugs on their effectiveness showed inconsistent differences between colours. The quality of the methods of these trials was variable. Hypnotic, sedative, and anxiolytic drugs were more likely than antidepressants to be green, blue, or purple. CONCLUSIONS: Colours affect the perceived action of a drug and seem to influence the effectiveness of a drug. Moreover, a relation exists between the colouring of drugs that affect the central nervous system and the indications for which they are used. Research contributing to a better understanding of the effect of the colour of drugs is warranted.     

Molecular dynamics simulation as a tool for assessment of drug binding property of human serum albumin

Human serum albumin (HSA) is a major plasma protein and binding of drugs with this plasma protein has a great importance. It possess esterase activity which can cleave the drugs containing ester bond and thus, can regulate the effect of drugs. Till date no systematic study has been done to analyse binding of such drugs and to compare the results with the drugs which do not have ester bond. Therefore, in the present study two different categories—ester and non-ester drugs have been considered to analyse their interaction with HSA at two principle drug binding sites using molecular modelling tools. It is observed that the drugs irrespective of ester or non-ester nature prefer either Sudlow site I or II by hydrogen bond and hydrophobic interactions. The information obtained from the study can assist to study pharmacokinetics of the drugs and that in turn will help in noval drug discoveries.     

Blood pressure and heart rate and withdrawal of antihypertensive drugs.

The immediate effects on heart rate and blood pressure of withdrawing antihypertensive drugs were studied over three-day periods in 26 patients. Four groups of drugs were studied. After withdrawal all patients taking clonidine showed a considerable increase in heart rate and blood pressure with intense ectopic activity. Patients taking postganglionic neurone-blocking drugs showed a similar but less pronounced reaction with increased ventricular ectopic activity. No alarming reactions were seen after withdrawal of methyldopa or beta-blocking drugs. Methyldopa and, especially, beta-blocking drugs are less likely to produce withdrawal reactions than clonidine or the postganglionic neurone-blocking drugs, and patients taking these drugs are therefore less likely to suffer violent reactions if they forget to take their tablets.     

A systematic analysis of FDA-approved anticancer drugs

Background

The discovery of novel anticancer drugs is critical for the pharmaceutical research and development, and patient treatment. Repurposing existing drugs that may have unanticipated effects as potential candidates is one way to meet this important goal. Systematic investigation of efficient anticancer drugs could provide valuable insights into trends in the discovery of anticancer drugs, which may contribute to the systematic discovery of new anticancer drugs.

Results

In this study, we collected and analyzed 150 anticancer drugs approved by the US Food and Drug Administration (FDA). Based on drug mechanism of action, these agents are divided into two groups: 61 cytotoxic-based drugs and 89 target-based drugs. We found that in the recent years, the proportion of targeted agents tended to be increasing, and the targeted drugs tended to be delivered as signal drugs. For 89 target-based drugs, we collected 102 effect-mediating drug targets in the human genome and found that most targets located on the plasma membrane and most of them belonged to the enzyme, especially tyrosine kinase. From above 150 drugs, we built a drug-cancer network, which contained 183 nodes (150 drugs and 33 cancer types) and 248 drug-cancer associations. The network indicated that the cytotoxic drugs tended to be used to treat more cancer types than targeted drugs. From 89 targeted drugs, we built a cancer-drug-target network, which contained 214 nodes (23 cancer types, 89 drugs, and 102 targets) and 313 edges (118 drug-cancer associations and 195 drug-target associations). Starting from the network, we discovered 133 novel drug-cancer associations among 52 drugs and 16 cancer types by applying the common target-based approach. Most novel drug-cancer associations (116, 87%) are supported by at least one clinical trial study.

Conclusions

In this study, we provided a comprehensive data source, including anticancer drugs and their targets and performed a detailed analysis in term of historical tendency and networks. Its application to identify novel drug-cancer associations demonstrated that the data collected in this study is promising to serve as a fundamental for anticancer drug repurposing and development.

     

Reasons for failure of antihypertensive treatment.

One hundred patients whose hypertension was originally well controlled were carefully screened when a routine clinic visit showed that their blood pressure was above 170/100 mm Hg. Simple misconceptions accounted for 75 failures: 38 did not know they had to continue their drugs, 14 thought they should not take antihypertensive drugs if they had not had a meal, 13 did not know which drugs controlled their blood pressure, and 10 believed it was better not to take their drugs on clinic days. Eleven patients were using racemic alpha-methyldopa, which was ineffective; 11 others said they could not afford the drugs; only three intentionally stopped their drugs because of unpleasant side effects. Patients need to be thoroughly informed about their treatment and the number of drugs kept to a minimum.     

Identification of lysosomotropic compounds based on the distribution and size of lysosomes

Lysosomal accumulation of drugs with their specific physicochemical properties is of key importance to drug distribution in the body. Several attempts have been made to treat various human diseases by employing the accumulation of lysosomal drugs, and many methods to identify lysosomal accumulation of drugs have been proposed. Among those, the use of high-content screening has increased tremendously because of improved efficiency and accuracy as well as the development of automatic image acquisition and analytical techniques. Conventional methods to identify lysosomal accumulation of drugs by evaluating changes in the lysosomal area are unable to maximize the advantages of phenotypic high-content screening. Lysosomal distribution and the size of lysosomes are affected by lysosomal accumulating drugs. Therefore, we present image acquisition conditions and analytical methods to utilize lysosomal distribution and size as parameters for identifying lysosomal accumulating drugs. These two parameters will help to improve the reliability of the screening methods for identifying lysosomal accumulation of drugs by maximizing usage of information from image-based screening.     

甲胎蛋白携带药物靶向治疗肿瘤

甲胎蛋白(alpha fetoprotein,AFP)是一种在胎儿发育时期高表达的蛋白质,它又是一种穿梭蛋白质,能够将营养物质输送给胚胎细胞.相似的是,在肝癌等恶性肿瘤发展时期,肿瘤细胞也高表达AFP及其受体,它们通过AFP受体摄取AFP及其运载的物质.因此,可以将AFP与抗癌药物结合,选择性攻击肿瘤细胞.AFP与药物...     

Current status and perspectives of biopharmaceutical drugs

Since the first approval of recombinant human insulin three decades ago, more than 150 biopharmaceutical drugs have been marketed, and some of them became blockbuster drugs in market size. The patent expiration of the oldest biopharmaceutical drugs resulted in the development of biosimilar drugs. However the short serum half-life of biopharmaceutical drugs incurs a frequent injection to maintain a target clinical outcome in patients. The other major critical concern of biopharmaceutical drugs is immunogenicity producing anti-drug antibodies. These antibodies may reduce clinical efficacy by neutralizing biological activity, and may not only cause a severe allergic reaction but also other serious adverse reactions by blocking endogenous proteins. In order to improve pharmaceutical properties and reduce immunogenicity, the next generation biobetter drugs were achieved by glycoengineering technology, pegylation technology and protein engineering technology. Other biobetter drugs having optimized binding sites were also generated by in vitro display technology. Many of those biobetter drugs have been developed and/or are under development, and come into the clinical field in the near future.     

Treatment of alcoholism; problems arising from the substitution of other drugs in therapy

Of the 139 patients admitted to hospital for chronic alcoholism, 32 had been taking other drugs also, and 17 were addicted to the drugs. Of the 32 patients, 16 used barbiturates, and 8 were addicted. Five took large amounts in suicidal attempt. Ten patients combined still other drugs with alcohol and barbiturates; and seven of them were addicted to barbiturates. Of the six patients combining alcohol with drugs other than barbiturates, two were addicted to the use. Of the 16 patients who used drugs other than barbiturates, eight used one or more opiates such as meperidine, morphine, codeine or dihydromorphinone. Four used stimulants such as benzedrine or dexedrine, alone or in combination. Still other drugs were used in some combination by 32 patients.     

Combination of Two but Not Three Current Targeted Drugs Can Improve Therapy of Chronic Myeloid Leukemia

Chronic myeloid leukemia (CML) is a cancer of the hematopoietic system and has been treated with the drug Imatinib relatively successfully. Drug resistance, acquired by mutations, is an obstacle to success. Two additional drugs are now considered and could be combined with Imatinib to prevent resistance, Dasatinib and Nilotinib. While most mutations conferring resistance to one drug do not confer resistance to the other drugs, there is one mutation (T315I) that induces resistance against all three drugs. Using computational methods, the combination of two drugs is found to increase the probability of treatment success despite this cross-resistance. Combining more than two drugs, however, does not provide further advantages. We also explore possible combination therapies using drugs currently under development. We conclude that among the targeted drugs currently available for the treamtent of CML, only the two most effective ones should be used in combination for the prevention of drug resistance.     

当前我国畜牧业抗菌药应用与耐药性应对趋势

抗菌药在现代农业和医学中发挥了举足轻重的作用,然而,随着民众对食品安全和生态环保意识的逐渐增强,抗菌药物的使用愈发受关注。如何科学合理使用抗菌药,确保动物安全健康,防止药物残留超标,进而实现畜牧业绿色发展是当前研究的重要课题。本文结合当前畜牧业抗菌药使用现状,从四个方面分析了滥用抗菌药的危害,并归纳总结了耐药机制研究进展,最后提出抗菌药替代策略,旨在为畜牧业抗菌药安全使用和抗菌药替代技术研发提供参考。     

靶向共价键药物的研究进展

药物与靶标的结合是启动药理作用的本源,共价键药物是以共享电子的方式来实现与靶标的结合,其中大多为抗感染、抗肿瘤以及心脑血管、神经系统和代谢类药物。简介共价键药物与非共价键药物的区别以及既往的重磅级共价键药物与靶标的结合特点,分类综述靶向共价键药物的理性设计及与靶标的结合反应。     

Kinetics and mechanisms of cholesterol esterase inhibition by cardiovascular drugs in vitro

Cardiovascular drugs such as lovastatin, simvastatin, amlodipine besylate, nifedipine, and hydralazine hydrochloride inhibit cholesterol esterase (CEase) in vitro. In the present paper, an attempt was made to determine kinetically the reaction mechanism for CEase inhibition by these drugs. The inhibition constant, Ki, for the mixed-type inhibition of CEase by these drugs in the presence of triton-X-100 or taurochloate were measured. Moreover, the pKi values were correlated with the molecular weights of these drugs. In conclusion, the fact that these drugs lower cholesterol levels in the plasma low-density lipoprotein may be partially due to the CEase inhibition by these drugs.     

某三级甲等医院营养类药物使用情况调查

目的:通过对某三级甲等医院2012年全年处方进行分析,调查营养类药物使用情况。方法:通过回顾性方法、Microsoft Excel 2007、SPSS 16.0对数据进行分析。结果:肠内营养乳剂(TP)使用量最大;葡萄糖注射液(20 ml)使用量排名第一;脑外科应用营养类药物比较多;肠外营养类药物的发放量大于肠内营养类药物,差异具有统计学意义(P0.05);营养类药物应用年龄区间大,男女比例约为1:1。结论:本研究调查此三级甲等医院营养类药物的使用情况,为医生、患者和医院管理者在选择营养类药物提供了参考,为我国基本药物目录修改提供了依据。     

固体药物多晶型的研究进展

多晶型现象在固体药物中普遍存在,多晶型是影响固体药物质量和疗效的重要因素之一。在固体药物早期研究与开发阶段进行多晶型研究具有十分重要的意义。本文归纳总结了有关药物晶型研究进展,讨论了固体药物晶型的研究意义、主要的技术手段、晶型药物对生物利用度的影响、晶型的工艺控制以及预测等。     

Enhancement of gastrointestinal absorption of poorly water soluble drugs via lipid based systems

Development of knowledge on lipids has attracted the scientific community for the effective utilization of the natural and synthetic lipids. Bioavailability of poorly water soluble drugs from gastrointestinal tract (GIT) can be enhanced by formulating the drugs in lipid based formulations. This formulation can increase the dissolution of poorly water soluble drugs, and facilitates the formation of solubilized phases from which absorption may occur. The enhanced solubility of lipophilic drugs from lipid-based systems will not necessarily arise directly from the administered lipid, but most likely from the intra luminal processing to which they are subjected prior to absorption. This review will focus on assessment of lipid-based formulations of drugs with a consideration of how gastrointestinal physiology, the choice of lipids and their formulation attribute and the mode of lipid digestion in the GIT influence the bioavailability of lipophilic drugs.     

Analytical methodologies for metallomics studies of antitumor Pt-containing drugs

Pt-containing drugs are nowadays essential components in cancer chemotherapy. However, drug resistance and side effects limit the efficiency of the treatments. In order to improve the response to Pt-based drugs, different administration strategies or new Pt-compounds have been developed with little success. The reason for this failure could be that the mechanism of action of these drugs is not completely understood. In this way, metallomics studies may contribute to clarify the interactions of Pt-containing drugs within the organism. This review is mainly focused on the role of Analytical Chemistry on the study of the interactions between Pt-based drugs and biomolecules. A summary of the analytical techniques and the most common sample treatment procedures currently used in metallomics studies of these drugs is presented. Both are of paramount importance to study these complex samples preserving the drug-biomolecule interaction. Separation and detection techniques must be carefully selected in order to achieve the intended goals. The use of multidimensional hyphenated techniques is usually necessary for a better understanding of the Pt-based drugs interactions in the organism. An overview of Pt-drugs biological interactions is presented, considering the different sample matrices and the drugs course through the organism. Samples analysed in the included studies are blood, urine, cell cytosol, DNA as well as the drugs themselves and their derivatives. However, most of these works are based on in vitro experiments or incubations of standards, leading in some cases to contradictory results depending on the experimental conditions used. Though in vivo experiments represent a great challenge due to the high complexity and the low concentrations of the Pt-adducts in real samples, these studies must be undertaken to get a deeper understanding of the real interactions concerning Pt-containing drugs.     

ADC药物的抗体组成及其作用靶点研究进展*

抗体药物偶联物(antibody-drug conjugates,ADC)是一类由单克隆抗体和小分子细胞毒性药物通过连接子偶联而成的新型生物治疗药物。与传统的细胞毒药物相比,ADC具有靶向性强、毒副作用小等优势,在临床上展现较好的治疗潜力。其中,抗体部分通过与肿瘤细胞表面的靶向抗原结合,精准地将小分子细胞毒性药物递送至肿瘤部位,从而实现肿瘤特异性杀伤效果,是影响ADC疗效的核心要素之一。对近年来ADC药物中抗体的组成及其作用靶点的研究进展进行了综述。