Drugs in other drugs: a new look at drugs as fragments

The authors of this review have examined the complete set of marketed drugs, with regards to looking for structural similarities between drugs. By comparing the structures of all drugs, it has been established how many times one marketed drug occurred as a substructure within another marketed drug. A total of 209 from 1386 marketed drugs sized between 100 and 1500 Da (i.e. 15% of the 1386 total) are contained within other drugs, differing by one or more continuous chemical fragment, and as many as 418 drugs from the total of 1386 (i.e. 30%) contain other drugs as substructure fragments. Many smaller drugs occur in multiple larger drugs. Most of the small changes tend to retain primary indicated pharmacology, whereas larger changes more often lead to different primary pharmacology. We identify a subset of drugs that can be used in fragment-based drug discovery strategies. In addition, the analysis enhances understanding of marketed drug space from the chemical building-block perspective.     

Second international symposium on drugs as discriminative stimuli

Epinephrine produced a dose-dependent stimulation of ureogenesis. Epinephrine action was unaffected by the β-adrenergic antagonist propranolol but was blocked by the α-adrenergic antagonists prazosin and yohimbine. Prazosin was approximately 3 orders of magnitude more potent than yohimbine, indicating that the adrenoceptor involved in this action is of the α₁-subtype.     

Squeezing the balloon: international drugs policy

Recent experience of supply reduction activities in a major opium-producing country, Pakistan, is reviewed. It is concluded that international efforts to reduce the supply of illicit drugs are ineffective, inadvertently promote use of more dangerous forms of drugs and exacerbate health problems in supplier countries. In addition, source country supply reduction activities are associated with serious unintended negative consequences, including corruption and poor governance in supplier countries. This leads to a vicious circle as these adverse social consequences make it harder to restrict drug production.     

Availability and timing of new drugs in Israel: analysis and international comparison

Whereas the latest data suggest that the number of new chemical entities (NCE) launches worldwide may be on the increase, both recent and longer term data show a decline in the rate of NCE introductions into Israel. In terms of percentage availability, only 30% of NCEs available worldwide during 1978-1987 were introduced in Israel during the same period, compared with 42% for the U.S.A. In both countries there has been a decreasing percentage availability since 1983/84. The percentage availability of commercially significant NCEs was greater (47%) compared to all NCEs introduced in Israel. Whereas in the U.S.A. the lower the therapeutic rating the higher the proportion of NCEs, in Israel the B- and C-rated drugs were equally represented. NCEs with an A-rating had a similar share of all NCEs (ca 15%) in both countries. The average time lag for NCEs launched worldwide to reach Israel during 1978-1987 was 4 to 5 years, but in recent years there has been a considerable decline. Commercially significant NCEs introduced in Israel had on average a shorter time lag of 0.5 years than the average for all NCEs introduced. In spite of a preponderance of NCEs first launched in the U.S.A. there was on average a slight relative lag into the U.S.A. compared to Israel. This was probably due to there being a number of NCEs first introduced in Israel with a long delay before they were subsequently approved in the U.S.A.(ABSTRACT TRUNCATED AT 250 WORDS)     

Drugs in the peri-operative period: 4--Cardiovascular drugs

Many patients undergoing elective surgery will be taking medicines for cardiovascular disorders. Here, in the fourth and final article in our series on drug therapy in the peri-operative period, we review the management of patients taking certain antithrombotic, antihypertensive, anti-anginal or anti-arrhythmic drugs.     

Emergency room injury presentations as an indicator of alcohol-related problems in the community: a multilevel analysis of an international study

OBJECTIVE: This study describes and examines the development of surrogate measures of acute alcohol-related injury for use in the evaluation of community-based prevention initiatives. METHOD: An international collaborative study of alcohol and injury, the Emergency Room Collaborative Alcohol Analysis Project (ERCAAP), provided a subset of data on 8580 emergency room (ER) presentations from five countries and 28 ER facilities. RESULTS: Presentations most likely to be alcohol related were those made between 12:00 AM and 4:59 AM (56%), on Fridays, Saturdays or Sundays (26%); and those among injured persons who were male (28%), who were aged between 18 and 45 years (24%) or who were unmarried (24%). Multilevel logistic regression models confirmed the significance of the above variables as predictors of alcohol involvement prior to the injury event. The strongest predictor variable was presentation between 12 midnight and 4:59 AM with an odds ratio of 4.92 (Wald Test chi2 = 397.6, p < .001). Being male had an odds ratio of 3.01 (Wald Test chi2 = 247.25, p < .001), and presenting on a Friday, Saturday or Sunday night had an odds ratio of 1.50 (Wald Test chi2 = 49.6, p < .001), whereas being under 45 (odds ratio [OR] = 1.20, p < .05) and being unmarried (OR = 1.2, p < .01) were less strong predictors. Combining all these values for variables raised the probability of prior alcohol involvement in such injury presentations to 0.65, although only 3.37% of all cases met these criteria, limiting applicability of this combined variable as a surrogate measure for intervention studies. Probabilities of prior alcohol involvement are presented with other combinations of values for the predictor variables. CONCLUSIONS: Frequency of nighttime injury presentations to ER facilities, particularly by men, can be used as a reliable surrogate measure of alcohol-related injuries for various epidemiological and evaluation purposes.     

Drugs of Dependence Monitoring System: an effective check of the movements of certain drugs in Australia

For the past 13 years the Commonwealth Department of Health has operated a computerized monitoring system which records the movements throughout Australia of selected legal drugs with abuse potential. The Drugs of Dependence Monitoring System is designed to prevent diversion to the illicit market. From the moment of import or manufacture, every movement of the selected drug is monitored until the drug reaches the final distributor, in most cases a pharmacy, a veterinarian or a hospital. Approximately 300,000 movements are checked each year. All drugs used in Australia, which are covered by the Single Convention on Narcotic Drugs, 1961, and the 1971 Convention on Psychotropic Substances are included in the system. Reports are generated on quantities imported, exported, locally produced, used in manufacture and distributed. The result is that the risk of diversion has been reduced to a minimum. Information obtained from the system has proved of considerable assistance in fulfilling Australia's international treaty obligations.     

Nornostocine congeners as potential anticancer drugs: An overview

The naturally occurring phyco-constituent nostocine A, bearing the pyrazolotriazine scaffold in its structural frame, belongs to an organic class of pharmacologically curious candidates with a remarkable anticancer activity. This review summarizes the chemistry of numerous synthetic strategies of demethylated nostocine as “nornostocine derivatives,” in which the substitutes are connected to a few functionalities with the pyrazolotriazine moiety at N-1, C-3, and C-5 positions. These strategies may provide a framework to design and develop a novel potent anticancer drug candidate(s) with an augment of structure activity relationship related to anticancer activities.     

国际疾病分类(ICD-10)与临床疾病诊断存在问题的探析

目的：探讨临床医生对疾病诊断更标准化、规范化，适应国际疾病分类(ICD-10)在临床的应用。方法：分析我院2002年以来，应用国际疾病分类过程中与临床疾病诊断之间存在的问题。结果：存在主要疾病诊断选择错误，滥用“术后”作第一诊断，没有写“组织类型”肿瘤的诊断，随意用症状和体征代替诊断，没有写外部原因中毒或损伤的疾病的问题。并对存在问题提出几点改进建议。结论：临床疾病诊断的标准化和规范化，可增加编码正确率，提高国际疾病分类水平。     

英国癌症药物基金补偿品种的特征分析及启示

目的:通过对英国癌症药物基金(Cancer Drugs Fund,CDF)纳入补偿的抗癌药物品种进行分析,为我国探索建立包括抗癌药、罕见病用药在内的特殊品种独立基金补偿模式的品种遴选提供参考.方法:基于英国国家卫生和临床技术优化研究所公布的技术评估指南与国民健康服务体系中列出的英国癌症药物基金清单,对27个癌症治疗药物...     

Chiral discrimination and enantioselective analysis of drugs: an overview

Molecular recognition of different enantiomers of a drug has become of increasing importance in the last decade due to the racemic switch strategy adapted by the pharmaceutical industry. Different analytical techniques to carry out enantioselective analysis of chiral compounds have been suggested in the literature. In the following, a brief overview of different techniques used for enantioselective analysis is given. Challenging aspects of these techniques, such as the quality of analytical information received from each technique, advantages, and disadvantages are discussed. Alternatives (enantioselective membranes, amperometric biosensors, molecularly imprinted polymers (MIPs)), capable of meeting the requirements of industrial processes, in terms of productivity, cost-effectiveness, and environmental issues are critically reviewed.