流感疫苗及抗流感病毒药物的临床应用

1流感疫苗接种疫苗是预防流感的主要措施。在接种流感疫苗后2~3周,通常可以获得免疫力,当机体接触到疫苗所针对的流感病毒时就可以启动保护性免疫反应。目前用于生产疫苗的流感病毒是经鸡胚培养获得的,从筛选用于制备疫苗的病毒到生产出流感疫苗需要6~8个月。每年分布在82个国家的110个国家流感监测中心和4个世界卫生组织的流感实验室对全球流感病毒的变化趋势进行监测,由WHO根据监测所得资料分析在下个冬季最可能导致流行的毒株,分析结论将指导疫苗的生产。全球现具备3亿支流感疫苗的年生产能力,主要在澳大利亚、加拿大、法国、德国、意…     

抗心律失常药物的临床应用

心律失常的临床表现差异很大，有的心律失常无临床意义，有的则影响健康并危及生命。因而要先考虑需要药物治疗时，以选用何种药物为最佳选择。要熟知所选药物的分类、药效学及其对心脏电生理的影响。     

流感病毒诱导细胞凋亡及抗流感药物的研究进展

流感病毒是造成人类流行性感冒的病原体，目前仍常有流行。现认为流感病毒诱导宿主细胞凋亡（apoptosis）是流感病毒诱导细胞死亡的重要机制，并与其致病性息息相关。流感病毒的防治主要有流感疫苗和抗流感药物。中草药治疗流感效果肯定、毒副作用小、价格低廉，现广泛地用于临床。[第一段]     

抗血小板药物研究进展及临床应用情况

正心脑血管疾病和外周动脉血管病变的发病率在我国有逐年上升趋势,抗血小板药物的应用在其预防和治疗中起到了相当重要的作用。目前的抗血小板类药物包括:(1)阿司匹林;(2)噻吩吡啶类药;(3)血小板膜糖蛋白(GPⅡb/Ⅲa)受体拮抗剂;(4)选择性的增加血小板内环磷酸腺苷(cAMP)的药物;(5)P_2Y_(12)拮抗剂。现就常用抗血小板药物作用的机理及其在心脑血管领域的应用现状、进展作一综述。1抗血小板药物的作用机理1.1阿司匹林研究发现小剂量阿司匹林通过不可逆地乙酰化血小板环氧化酶,主要是乙酰化环氧化酶-(COX-1)丝氨酸530位点,抑制TXA_2的形成~([1])。乙酰水杨酸分别     

抗血小板药物

抗血小板药物杨福英（空军广州医院，广州５１０６０２）抗血小板药物（血小板功能抑制剂）是一组通过不同机制和途径以抑制血小板聚集和／或活化，并能阻止血小板参与血栓形成的药物。血小板具有粘附、聚集、释放功能，但在正常血液循环中，血小板不发生聚集，只有在聚集...     

抗贫血药物的临床应用

<正> 贫血的种类很多,如缺铁性贫血,溶血性贫血,再生障碍性贫血,骨髓病性贫血,巨幼红细胞性贫血,红细胞内在缺陷或外因影响所致贫血等等。根据不同原因不同发病机制使用不同药物不同方法的针对性治疗,才能取得予期的效果。如果笼统地使用所谓的“补血药”来治疗各种原因的贫血,疗效是不确切的甚至是无效的,现就常用的抗贫血药物予以介绍。一、铁剂:缺铁性贫血是最常见的一类贫血,因而使用铁剂治疗缺铁性贫血是经常遇到并且有确实疗效的。铁的代谢:铁存在于人体所有组织细胞中,它不仅是红细胞合成血红蛋白的主要原料,而且还广泛存在于细胞氧化过程中的许多酶中,成为许多氧化还原酶的组成成分,铁对于生命的重要由此也可明确了。成年人体内铁的总量男性为50mg/kg体重,女性35mg/kg体重。铁大部分存在于血红蛋白中,占体内铁总量的57％,贮存铁约占铁总量的1/3。肌红蛋白含铁占9％,还有少量铁     

抗高血压药物的临床应用

目前，临床常用的抗高血压药物主要有以下8大类。现将其应用和评价简要介绍如下，供参考。     

抗心律失常药物的选择

药物用于心律失常的治疗有近百年的历史，但迄今仍未找到一种既有有效控制心律失常又不增加患者死亡率的理想药物。因此，当前药物治疗的关键是要合理地使用抗心律失常药物，尽可能发挥药物的治疗效能，降低不良反应。     

抗血小板药物的临床应用

AssessmentoftheBasicStudyandClinicalUseofAnti－PlateletsDrugsYangXuryi（ShanghaiInstituteofCardiovascularDiseases,200032）临床用药血小板与动脉粥样硬化的发生有关,并在动脉血栓形成中起着关键性的作用。近几年来,由于血小板生化、生理物理、病生和临床医学的进展推动抗血小板药物药理的进展,在药物作用机理和临床疗效方面,获取了新的认识和临床验证。三血小板粘聚功能的机制微循环要维持正常血液灌注,必须具备正常流态门owcondition或flowstatus）,影响血液流态的因素很多,例如微血管功能、微血管壁、血流内无形成…     

Detection of the Antiviral Drug Oseltamivir in Aquatic Environments

Oseltamivir (Tamiflu®) is the most important antiviral drug available and a cornerstone in the defence against a future influenza pandemic. Recent publications have shown that the active metabolite, oseltamivir carboxylate (OC), is not degraded in sewage treatment plants and is also persistent in aquatic environments. This implies that OC will be present in aquatic environments in areas where oseltamivir is prescribed to patients for therapeutic use. The country where oseltamivir is used most is Japan, where it is used to treat seasonal flu. We measured the levels of OC in water samples from the Yodo River system in the Kyoto and Osaka prefectures, Japan, taken before and during the flu-season 2007/8. No OC was detected before the flu-season but 2–58 ng L⁻¹ was detected in the samples taken during the flu season. This study shows, for the first time, that low levels of oseltamivir can be found in the aquatic environment. Therefore the natural reservoir of influenza virus, dabbling ducks, is exposed to oseltamivir, which could promote the evolution of viral resistance.     

A Drug-Disease Model Describing the Effect of Oseltamivir Neuraminidase Inhibition on Influenza Virus Progression

A population drug-disease model was developed to describe the time course of influenza virus with and without oseltamivir treatment and to investigate opportunities for antiviral combination therapy. Data included viral titers from 208 subjects, across 4 studies, receiving placebo and oseltamivir at 20 to 200 mg twice daily for 5 days. A 3-compartment mathematical model, comprising target cells infected at rate β, free virus produced at rate p and cleared at rate c, and infected cells cleared at rate δ, was implemented in NONMEM with an inhibitory Hill function on virus production (p), accounting for the oseltamivir effect. In congruence with clinical data, the model predicts that the standard 75-mg regimen initiated 2 days after infection decreased viral shedding duration by 1.5 days versus placebo; the 150-mg regimen decreased shedding by an additional average 0.25 day. The model also predicts that initiation of oseltamivir sooner postinfection, specifically at day 0.5 or 1, results in proportionally greater decreases in viral shedding duration of 5 and 3.5 days, respectively. Furthermore, the model suggests that combining oseltamivir (acting to subdue virus production rate) with an antiviral whose activity decreases viral infectivity (β) results in a moderate additive effect dependent on therapy initiation time. In contrast, the combination of oseltamivir with an antiviral whose activity increases viral clearance (c) shows significant additive effects independent of therapy initiation time. The utility of the model for investigating the pharmacodynamic effects of novel antivirals alone or in combination on emergent influenza virus strains warrants further investigation.     

Oseltamivir inhibits H7 influenza virus replication in mice inoculated by the ocular route

The majority of human infections associated with H7 influenza viruses have resulted in ocular and not respiratory disease. While oseltamivir has been prescribed to individuals presenting with conjunctivitis following H7 virus exposure, it is unknown if oseltamivir inhibits virus replication in ocular tissue. We demonstrate that H7 viruses possess sensitivity to neuraminidase inhibitors and that administration of oseltamivir before ocular virus challenge in mice inhibits H7N7 and H7N3 virus replication in ocular and respiratory tissues.     

Oseltamivir (Tamiflu) and its potential for use in the event of an influenza pandemic

Recent cross species transmission of avian influenza has highlighted the threat of pandemic influenza. Oseltamivir (Tamiflu) has been shown to be effective in the treatment and prevention of epidemic influenza infection in adults, adolescents and children (> or = 1 year). Although oseltamivir has not been approved for prophylactic use in children, it has been shown to be effective. Oseltamivir is also active against avian influenza virus strains. Evidence suggests that lower doses or shorter durations of treatment/chemoprophylaxis other than those approved may not be effective and may contribute to emergence of viral resistance. Safety data from dose ranging studies show that 5 day courses of 150 mg twice daily for treatment and 6 week courses of 75 mg twice daily for prophylaxis were as well tolerated as the approved dose regimens. The use of oseltamivir in a pandemic is influenced by the goals of the pandemic plan developed by the responsible Government and Health Authority. To optimize use of antiviral medications, processes will be needed to collect, collate and report outcome data from treated patients and/or from use for chemoprophylaxis of pandemic influenza during the first-wave outbreaks. If oseltamivir is included in a national or regional pandemic plan, stockpiling of the material, either in the form of capsules or the bulk active pharmaceutical ingredient will be necessary. In the absence of a stockpile, there is no guarantee that an adequate supply of oseltamivir will be available.     

Progress on baculovirus-derived influenza vaccines

The baculovirus insect cell production technology allows for rapid vaccine production and is particularly suitable for influenza vaccines where annual adjustment of the composition is required. Recombinant hemagglutinin produced using this technology is safe, immunogenic and effective in preventing cell-culture confirmed influenza in individuals; recombinant neuraminidase may play a role as an additive to improve the currently licensed influenza vaccines. Universal vaccine candidates, such as matrix protein M2 and nucleocapsid protein, are yet to enter the clinic whereas the first pandemic influenza virus-like particle (VLP) vaccine candidate is in clinical development. This review presents an overview of the use of this production system for the development of various influenza vaccine targets, including hemagglutinin, neuraminidase, M2, nucleoprotein and VLPs containing multiple influenza proteins. The development progress and the advantages and disadvantages of each vaccine candidate are discussed.     

Nonclinical Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in the Central Nervous System

Oseltamivir, a potent and selective inhibitor of influenza A and B virus neuraminidases, is a prodrug that is systemically converted into the active metabolite oseltamivir carboxylate. In light of reported neuropsychiatric events in influenza patients, including some taking oseltamivir, and as part of a full assessment to determine whether oseltamivir could contribute to, or exacerbate, such events, we undertook a series of nonclinical studies. In particular, we investigated (i) the distribution of oseltamivir and oseltamivir carboxylate in the central nervous system of rats after single intravenous doses of oseltamivir and oseltamivir carboxylate and oral doses of oseltamivir, (ii) the active transport of oseltamivir and oseltamivir carboxylate in vitro by transporters located in the blood-brain barrier, and (iii) the extent of local conversion of oseltamivir to oseltamivir carboxylate in brain fractions. In all experiments, results showed that the extent of partitioning of oseltamivir and especially oseltamivir carboxylate to the central nervous system was low. Brain-to-plasma exposure ratios were approximately 0.2 for oseltamivir and 0.01 for oseltamivir carboxylate. Apart from oseltamivir being a good substrate for the P-glycoprotein transporter, no other active transport processes were observed. The conversion of the prodrug to the active metabolite was slow and limited in human and rat brain S9 fractions. Overall, these studies indicate that the potential for oseltamivir and oseltamivir carboxylate to reach the central nervous system in high quantities is low and, together with other analyses and studies, that their involvement in neuropsychiatric events in influenza patients is unlikely.Oseltamivir (Tamiflu; F. Hoffmann-La Roche Ltd.) is an orally administered antiviral drug for the treatment and prophylaxis of influenza A and B viruses. Following the oral administration of oseltamivir phosphate, the prodrug is converted by esterases to the active metabolite oseltamivir carboxylate (OC) (7). In influenza patients, OC selectively binds and potently inhibits the neuraminidase (NA) enzymes that are present on all influenza A and B viruses and are essential for the release of progeny viruses from infected host cells (20). In clinical studies, this action reduces the severity and duration of the symptoms of influenza virus in individuals with clinical illness or prevents the onset of symptoms in those with asymptomatic disease (24).Recently, an increase in reports of neuropsychiatric adverse events (NPAEs) in influenza patients who were and were not exposed to oseltamivir was identified (29). The reporting frequency indicates that these events were rare. The majority of reports originated from Japan and usually involved children or young adolescents. No causal link with oseltamivir therapy could be identified, but the reports generated renewed interest in the central nervous system (CNS) tolerability profile of oseltamivir (5, 21). In response to these events, Roche, the manufacturer of oseltamivir, initiated a comprehensive safety review to firmly establish the nature of the reported events and investigate potential links with oseltamivir therapy (29). The review involved the assessment of all spontaneously reported NPAEs in the Roche Global Safety Database, review of the existing preclinical and clinical data sets, and assessment of epidemiological databases for information on the incidence of NPAEs in patients with and without influenza virus and/or drug exposure. From this comprehensive analysis, it was concluded that the incidence of NPAEs in patients with influenza virus receiving oseltamivir was no higher than that in those who had not received oseltamivir (1, 31) and that there was no plausible mechanism by which oseltamivir or OC could induce or exacerbate NPAEs (29).In addition to the above-mentioned clinical safety review, a series of nonclinical in vitro and in vivo studies was performed with the objective of characterizing the distribution of oseltamivir and OC to the CNS, the active export of oseltamivir and OC from the CNS, and the conversion from oseltamivir to OC, including the potential for intracerebral conversion. The present article addresses the conduct and outcomes of these pharmacokinetic investigations.     

Oseltamivir in seasonal,pandemic, and avian influenza: a comprehensive review of 10-years clinical experience

Oseltamivir (Tamiflu®; F. Hoffmann-La Roche Ltd, Basel, Switzerland) is an orally administered antiviral for the treatment and prevention of influenza A and B infections that is registered in more than 100 countries worldwide. More than 83 million patients have been exposed to the product since its introduction. Oseltamivir is recommended by the World Health Organization (WHO) for use in the clinical management of pandemic and seasonal influenza of varying severity, and as the primary antiviral agent for treatment of avian H5N1 influenza infection in humans. This article is a nonsystematic review of the experience gained from the first 10 years of using oseltamivir for influenza infections since its launch in early 2000, emphasizing recent advances in our understanding of the product and its clinical utility in five main areas. The article reviews the pharmacokinetics of oseltamivir and its active metabolite, oseltamivir carboxylate, including information on special populations such as children and elderly adults, and the co-administration of oseltamivir with other agents. This is followed by a summary of data on the effectiveness of oseltamivir treatment and prophylaxis in patients with all types of influenza, including pandemic (H1N1) 2009 and avian H5N1 influenza. The implications of changes in susceptibility of circulating influenza viruses to oseltamivir and other antiviral agents are also described, as is the emergence of antiviral resistance during and after the 2009 pandemic. The fourth main section deals with the safety profile of oseltamivir in standard and special patient populations, and reviews spontaneously reported adverse event data from the pandemic and pre-pandemic periods and the topical issue of neuropsychiatric adverse events. Finally, the article considers the pharmacoeconomics of oseltamivir in comparison with vaccination and usual care regimens, and as a component of pandemic influenza mitigation strategies.     

输血传播病毒的研究进展

输血是临床治疗的一种方法,在患者大量出血的紧急情况下,可挽救人的生命.但输血也有风险,会造成输血传染病的发生.引起输血传染病的病毒有巨细胞病毒、朊病毒、西尼罗病毒、切昆贡亚热病毒、登革热病毒、人类疱疹病毒8型、人类嗜T淋巴细胞病毒等,其通过输血传播的问题已引起国际输血医疗界的广泛关注.本文就这些病毒的致病机制、流行趋势...