医药信息

诺华公司推翻欧洲人用医药产品委员会(CHMP)对酒石酸卡巴拉汀的负面评价CHMP对酒石酸卡巴拉汀(rivastigmine tartrate,Exelon)的负面评价被诺华公司成功推翻后,该机构目前同意推荐Exelon作为帕金森病相关痴呆症的治疗用药。据悉,40％的帕金森病患者有不同程度的痴呆症状。     

2022年《医药导报》各期药物专栏要目

第1期真实世界药物评价,第2期肺动脉高压药物治疗,第3期恶性肿瘤免疫治疗热点聚焦,第4期器官移植与精准药物治疗,第5期共晶药物研究,第6期药物治疗管理,第7期上市药品安全性评价,第8期肠道菌群与中药研究,第9期中药药理研究,第10期精神科和心理疾病,第11期纳米药物,第12期新医改与药事管理,若投专栏稿件,请至少在该期出版前8个月将稿件通过《医药导报》杂志官方网站(www.yydbzz.com)在线投稿系统投稿,以便及时送审和处理稿件。谢谢!     

EMEA又公布了两个有关生物仿制药的指南

欧洲医药局（EMEA）又公布了两个有关生物仿制药的CHMP（人用医药产品委员会）指南草案，涉及促红细胞生成素和细胞集落刺激因子（rG—CSF）。指南中涉及非临床及临床问题，并解释了CHMP审评所要求的研究和文件。指南的关键内容是可比较性，即如何显示生物仿制药相对于参照产品的可比较性。     

新型抗肺动脉高压药PRX-08066的临床试验获阳性结果

肺动脉高压表现为高血压和给肺提供血液的肺动脉发生结构变化。根据一份Datamonitor调查报告，慢性阻塞性肺病（COPD）病人中约有20％患有肺动脉高压，即全球约有150万肺动脉高压患者。COPD病人通常使用多种药物或1种B2激动剂与1种皮质类固醇的复方产品（如葛兰素史克公司的沙美特罗＋氟替卡松复方产品Advair／Seretide）治疗，而用于治疗肺动脉高压的药物包括内皮素受体拮抗剂，如Gilead科学公司产品安生坦（ambrisentan，Letairis）和Actelion公司产品波生坦（bosentan，Tracleer）。     

欧洲人用医疗产品委员会向欧盟委员会推荐批准数种药物

据中国医药报讯：欧洲人用医疗产品委员会（CHMP）近日向欧盟委员会推荐一批药物可以通过批准，其中Amgen公司和GSK公司的产品名列榜首。Amgen得到CHMP推荐的产品是骨质疏松症治疗药Prolia，该药可用于绝经后妇女防止骨折，也可用于罹患前列腺癌的男性患者——这类患者随着体内激素水平的减少而导致骨质流失．从而也会增加骨折的风险。     

抗肺动脉高压药物研究进展

肺动脉高压是一种慢性心肺系统疾病,既可能是多种不明病因引起的原发性疾病,也可能是心肺功能异常相关疾病的并发症,其病理机制至今未明,病因复杂,死亡率高。目前临床上治疗药物有限,而且治疗效果差、不良反应多,急需疗效更好、更安全的药物。该文通过对文献调研和分析,总结以肺动脉高压和其他适应症为主的上市药物抗肺动脉高压的研究进展与作用缺陷,并提出抗肺动脉高压药物研发的问题,以期为今后肺动脉高压治疗药物的研究提供参考。     

基于临床指南的肺动脉高压住院患者用药分析及评价

目的 基于临床指南分析肺动脉高压住院患者在某心血管病专科医院的用药情况，为肺动脉高压靶向药物的临床合理使用提供参考。方法 选取某院2021年诊断为肺动脉高压的住院患者数据，对其用药情况进行统计，计算药物限定日剂量(DDDs)、日用药金额(DDc)、药物利用指数(DUI)等。结果 纳入研究患者1866例，肺动脉高压靶向药物销售金额排名第四，使用频次排名第八，其中DDDs最高的药物是马昔腾坦片，DDDs最小的药物是司来帕格片，DDc最高的药物是司来帕格片，DDc最低的是他达拉非片；仅他达拉非片的DUI>1。结论 肺动脉高压患者用药种类繁多，经药品集中采购肺动脉高压靶向药物价格趋于合理，减轻患者经济压力，但仍有一定下降空间。     

澳大利亚药物警戒指南简介

澳大利亚药物警戒指南是澳大利亚于2003年7月颁布的药品安全与评价部门对已注册申请者的药物警戒职责的管理要求,是针对报告已经注册的医药产品的不良反应(ADR)而制定的.文件中有关"产品"和"已注册的医药产品"是指由澳大利亚药品管理局(TGA)的药品安全与评价部门(DSEB)负责管理的注册医药产品.     

黄酮类化合物抗肺动脉高压的研究进展

黄酮类化合物是一类多酚类化合物,根据其化学结构可分为黄酮醇、黄酮、黄烷酮、异黄酮、儿茶素、花青素和查耳酮。研究表明,黄酮类化合物具有抗氧化、抗炎、心血管保护、抗肿瘤、抗病毒、抗过敏等多种药理作用。该文查阅了近年来国内外研究文献,对黄酮类化合物抗肺动脉高压的作用及其机制进行综述,旨在为肺动脉高压的治疗提供新的候选药物及治疗途径。     

三联靶向药物治疗肺动脉高压的循证证据与时机选择

肺动脉高压(PAH)是一类以肺小动脉重构为主要病变的慢性进展性的恶性疾病,表现为肺血管阻力增加、肺动脉压力升高,最终导致右心衰竭甚至死亡.目前治疗PAH的药物主要针对内皮素通路、一氧化氮通路和前列环素通路三大途径,PAH的治疗策略是根据PAH患者的风险评估制定个体化治疗方案,使患者尽早达到并维持低危状态.目前指南推荐初...     

Overview of treprostinil sodium for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension is a life-threatening disorder that refers to a group of diseases characterized by an abnormal elevation of the blood pressure within the pulmonary circulation due to a vasculopathy of the pulmonary microcirculation (1). If left untreated, the overall prognosis of pulmonary arterial hypertension is poor, with a 5-year survival rate of 34%. The most common cause of death is progressive right-sided heart failure (2). There is no pharmacologic cure for pulmonary arterial hypertension, and a team approach is required for the proper care of these patients (3). Treatment is directed at improving clinical symptoms, increasing exercise tolerance and extending survival. Until just a few years ago, standard treatment options for the treatment of pulmonary arterial hypertension were limited and included coumarin derivatives, calcium channel blockers, diuretics, digoxin and oxygen supplementation (4). In the last decade, the therapeutic options for pulmonary arterial hypertension have made considerable advances. In at least three major randomized controlled trials, the continuous intravenous infusion of epoprostenol, a synthetic salt of prostacyclin with potent vasodilatory ability, has been shown to improve exercise tolerance, hemodynamics, survival and quality of life in patients with New York Heart Association (NYHA) functional classes III and IV with either primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma (5-9). Epoprostenol has now become a mainstay therapy in the long-term treatment of primary pulmonary hypertension or pulmonary arterial hypertension associated with scleroderma. Nevertheless, epoprostenol is far from an ideal form of therapy. Issues such as the short half-life of the drug, need for continuous central intravenous access and significant side effects have led to the development of more stable prostacyclin analogues as alternative therapies for primary pulmonary hypertension. These alternative therapies include iloprost (inhaled delivery) and treprostinil (subcutaneous delivery). As a result, the Food and Drug Administration (FDA) recently approved treprostinil for the treatment of pulmonary arterial hypertension in patients with NYHA classes II-IV. This review will offer a discussion of the basic pharmacology of treprostinil, its similarities to and differences from epoprostenol, the animal studies as well as the initial investigational studies leading to its FDA approval, and clinical uses of the drug alone or in combination with newer therapies directed at pulmonary arterial hypertension developed over the last decade.     

Role of the serotonin transporter in pulmonary arterial hypertension

Pulmonary arterial hypertension is a disease in which pulmonary arterial pressure is raised, leading to right heart failure. Survival is poor despite current therapeutic strategies. The ‘serotonin hypothesis of pulmonary arterial hypertension’ arose in the 1960s following an ‘epidemic’ of pulmonary arterial hypertension in women taking the indirect serotinergic agonist aminorex as an anorexigen. In the 1980s, the hypothesis was revisited following the occurrence of pulmonary arterial hypertension associated with the use of fenfluramines as anorexigens; these are also indirect serotinergic agents. Research has identified changes in serotonin synthesis, serotonin receptor activation and serotonin uptake via the serotonin transporter in experimental and clinical pulmonary arterial hypertension. This review will discuss our current understanding of this serotonin hypothesis with particular reference to the role of the serotonin transporter.     

Current medical treatment of pulmonary arterial hypertension

Primary pulmonary hypertension is a rare disease of the pulmonary vasculature manifested by dyspnea on exertion, syncope, and signs and symptoms of right heart failure. In the absence of adequate treatment, primary pulmonary hypertension has a grave prognosis, with a median survival of 2.8 years. Pulmonary arterial hypertension develops in association with known risk factors and predisposing clinical conditions, and shares many clinical, pathological and therapeutic characteristics with primary pulmonary hypertension. Therapeutic choices in pulmonary arterial hypertension depend on the etiology of the disease, severity of functional impairment and hemodynamic response following acute vasodilator administration during right heart catheterization. Agents currently approved for the specific treatment of pulmonary arterial hypertension are continuous intravenous epoprostenol, subcutaneous treprostinil and oral bosentan. A small group of patients who demonstrate true acute vasoreactivity at right heart catheterization may be chronically treated with oral calcium channel blockers. In addition, most patients with pulmonary hypertension receive conventional treatment, represented by anticoagulants, diuretics, inotropic medication or oxygen supplementation. Treatment of pulmonary arterial hypertension has significantly altered the natural course of the disease, with pronounced symptomatic, functional and survival benefit. Current clinical research focuses on the discovery of new targets of therapy and the use of a combination treatment approach, which will offer hope and valuable insight into the pathogenetic basis of this devastating illness.     

组织多普勒TDI-Tei指数评价先天性心脏病患者右心室功能的价值

目的探讨组织多普勒TDI-Tei指数评价先天性心脏病患者右心室功能的临床应用价值。方法选取60例先天性心脏病患者,根据肺动脉压力升高情况分为3组：重度肺动脉高压组（〉80mm Hg）11例,轻中度肺动脉高压组（40~80mm Hg）23例和无肺动脉高压组（〈40mm Hg）26例,每位患者分别在术前、术后1周、术后3个月、术后6个月4个时期,应用组织多普勒法测定右室TDI-Tei指数并进行对比研究。结果手术前,与无肺动脉高压组相比较,轻中度肺动脉高压组和重度肺动脉高压组右室TDI-Tei指数均升高（P〈0.05,P〈0.01）。与术前比较,无肺动脉高压组术后1周右室TDI-Tei指数无明显变化,轻中度肺动脉高压组术后1周右室TDI-Tei指数下降（P〈0.05）;重度肺动脉高压组术后1周TDI-Tei指数下降不明显,术后3个月和6个月均明显下降（均P〈0.05）。各组测得的TDI-Tei指数与肺动脉收缩压呈良好的相关性。结论组织多普勒TDI-Tei指数可较敏感地反映先天性心脏病患者的右心室功能变化,结合肺动脉收缩压,是可用于动态、长期评价右心室整体功能的较好指标。     

Sildenafil citrate for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension is a life-threatening, progressive disease that is characterised by an increase of pulmonary artery pressure leading to right heart failure and death. Conventional therapy (e.g., anticoagulants, diuretics, cardiac glycoside) has until recently represented the mainstay of pulmonary arterial hypertension treatment, but newer specific therapies have become available in the meantime. Among them, are the endothelin receptor antagonists (e.g., bosentan), prostacyclin and prostanoid derivatives (e.g., epoprostenol, iloprost, beraprost, treprostinil) or phosphodiesterase-5 inhibitors (e.g. sildenafil citrate). Sildenafil citrate has recently been approved for pulmonary arterial hypertension therapy, and the two discussed clinical studies assessed its safety and efficacy.     

Calcium Channel Blockers and Pulmonary Hypertension

Abstract: In vascular smooth muscle from the pulmonary circulation, potassium evoked contractions are abolished in calcium-free medium and by calcium channel blockers (CCB). Noradrenaline, histamine, and serotonin induced contractions are partly resistant. Pulmonary arterial hypertension may occur both as a primary disorder and secondary to cardiac and pulmonary diseases; in both types there may be a component of pulmonary arterial vasoconstriction. In animal models, hypoxic pulmonary hypertension is counteracted by CCBs, nifedipine being particular effective. In patients with this disorder, CCBs also seem able to lower pulmonary arterial pressure and vascular resistance, but no controlled trials documenting their clinical efficacy have been performed. This is valid also for primary pulmonary hypertension, where some of the CCBs may have clinical value.     

Novel therapeutics for the treatment of paediatric pulmonary arterial hypertension

The treatment of paediatric pulmonary arterial hypertension is challenging due to the serious nature of the disease, its rapid progression and the limited treatment options available. However, recent advances in the treatment of pulmonary arterial hypertension may offer significant improvements for patients suffering from this condition. Novel treatment options include prostacyclin analogues and endothelin receptor antagonists. A comprehensive review of the newer agents, with an emphasis on the pathobiology/pathophysiology of pulmonary arterial hypertension provides insight into future management of paediatric pulmonary arterial hypertension.     

Rho-kinase inhibitors show promise in pulmonary hypertension

In pulmonary arterial hypertension, it is necessary to obtain a vasodilation that is selective for the pulmonary circulation. Ras human orthologue (Rho)/Rho-kinase-mediated Ca2+ sensitisation plays a central role in mediating the sustained vasoconstriction and increased vasoreactivity in the rat hypoxic model of pulmonary hypertension. Rho-kinase inhibitors (Y-27632 and/or fasudil) have been shown to reduce pulmonary arterial pressure in three rat models of pulmonary hypertension. The first clinical study to report the effects of a Rho-kinase inhibitor in pulmonary hypertension enrolled nine patients with severe pulmonary hypertension. Fasudil hydrochloride 30 mg for 30 min i.v. caused a slight decrease in the mean pulmonary artery pressure and increase in the cardiac index but neither of these responses was significant. However, fasudil caused a significant decrease in pulmonary vascular resistance. Rho-kinase inhibitors may be useful in pulmonary hypertension, and should undergo further development for this indication.     

Novel therapeutics for the treatment of paediatric pulmonary arterial hypertension

The treatment of paediatric pulmonary arterial hypertension is challenging due to the serious nature of the disease, its rapid progression and the limited treatment options available. However, recent advances in the treatment of pulmonary arterial hypertension may offer significant improvements for patients suffering from this condition. Novel treatment options include prostacyclin analogues and endothelin receptor antagonists. A comprehensive review of the newer agents, with an emphasis on the pathobiology/pathophysiology of pulmonary arterial hypertension provides insight into future management of paediatric pulmonary arterial hypertension.     

Rho-kinase inhibitors show promise in pulmonary hypertension

In pulmonary arterial hypertension, it is necessary to obtain a vasodilation that is selective for the pulmonary circulation. Ras human orthologue (Rho)/Rho-kinase-mediated Ca²⁺ sensitisation plays a central role in mediating the sustained vasoconstriction and increased vasoreactivity in the rat hypoxic model of pulmonary hypertension. Rho-kinase inhibitors (Y-27632 and/or fasudil) have been shown to reduce pulmonary arterial pressure in three rat models of pulmonary hypertension. The first clinical study to report the effects of a Rho-kinase inhibitor in pulmonary hypertension enrolled nine patients with severe pulmonary hypertension. Fasudil hydrochloride 30 mg for 30 min i.v. caused a slight decrease in the mean pulmonary artery pressure and increase in the cardiac index but neither of these responses was significant. However, fasudil caused a significant decrease in pulmonary vascular resistance. Rho-kinase inhibitors may be useful in pulmonary hypertension, and should undergo further development for this indication.