肺动脉高压的药物治疗

肺动脉高压(PAH)是一种由异源性疾病和不同发病机制引起的以肺动脉压力增高为表现的疾病状态。PAH的传统治疗主要集中在支持治疗及非选择性血管扩张药等基础治疗。近年来,针对其发病机制各个环节的靶向治疗逐步开展,FDA已批准6种治疗PAH的药物,分别属于前列环素类似物、内皮素受体拮抗剂和磷酸二酯酶5抑制剂。5-羟色胺受体拮抗剂、Rho激酶抑制剂、PAR-2抑制剂正处于临床前研究阶段。     

中国肺动脉高压药物治疗现状

肺动脉高压(PAH)是一类以肺血管阻力进行性升高和血管重构为特征的心肺血管疾病,最终可致右心衰竭甚至死亡。欧美有多种PAH治疗药物获得批准上市,我国PAH靶向治疗时代始于2006年,主要包括内皮素受体拮抗剂、5-型磷酸二酯酶抑制剂和前列环素类似物。本文综述中国PAH靶向药物治疗现状。     

5-羟色胺受体拮抗剂在肺动脉高压防治中的应用与展望

肺动脉高压是一组由多种病因和发病机制引起的以肺血管阻力进行性增加为特征的病理生理综合征。临床表现为右心室功能不全,预后不良,严重者可发生右心衰竭而死亡。本文主要综述了5-羟色胺与肺动脉高压的关系及5-羟色胺受体拮抗剂在肺动脉高压防治中的作用,展望了5-羟色胺受体拮抗剂可能是一类有潜力的新型治疗肺动脉高压的药物。     

肺动脉高压靶向药物治疗的新进展

肺动脉高压（PAH）是一种肺动脉循环血流受限引起肺血管阻力增高并最终导致右心衰竭的综合征,以肺小动脉的血管痉挛、内膜增生、中层肥厚、外膜增生、原位血栓形成、不同程度的炎症改变等为特征,其主要特征是肺动脉阻力进行性升高。针对PAH多种发病机制及其不同环节已开发出或正在研制针对性的靶向治疗药物,在一般治疗的同时,极大丰富了PAH药物治疗手段,改善患者预后。现就PAH靶向药物治疗的新进展进行综述。     

肺动脉高压药物治疗进展

目的:探讨肺动脉高压(pulmonary hypertension,PH)药物治疗的最新进展。方法:查阅国内外公开发表的文献,综述肺动脉高压的药物治疗进展。结果:目前肺动脉高压分为5大类,常见类型20余种。第一大类动脉型肺动脉高压(pulmonary arterial hypertension,PAH)与其他类型肺动脉高压的治疗策略有所不同,目前用于动脉型肺动脉高压治疗的药物主要有5类。结论:目前上市的相关靶向药物主要是针对动脉型肺动脉高压的治疗,这些药物都显示具有改善肺动脉高压患者的运动耐量、症状及血流动力学的作用。     

肺动脉高压治疗药物研究进展

肺动脉高压(PAH)是一类快速进展且病情严重的肺血管疾病,被称为"心血管中癌症"。在1990年前,市场上并无针对PAH治疗的有效药物,为PAH的传统药物治疗时代。1990年后,随着依前列醇的临床应用开启了PAH的靶向药物治疗时代。目前,针对PAH的三大经典途径,即一氧化氮通路、前列环素通路和内皮素受体通路的靶向药物陆续进入临床。这些药物虽无法根治PAH,但可使PAH患者的生存期得到有效延长。本文就肺动脉高压的发病机制及其治疗药物的研究进展进行综述总结,以期为PAH的临床治疗提供一些帮助。     

波生坦治疗成人肺动脉高压研究进展

肺动脉高压是临床上常见的一种致残率和致死率较高的疾病,内皮素受体拮抗剂是目前治疗肺动脉高压的常用靶向药物之一。波生坦作为第1个研发并应用于临床的内皮素受体拮抗剂,目前广泛应用于肺动脉高压的治疗。单药治疗方面,波生坦可以改善特发性肺动脉高压、结缔组织病相关性肺动脉高压患者的运动耐量、血流动力学状态和长期生存率;但其应用于先心病相关肺动脉高压患者的长期生存获益及慢性血栓栓塞性肺动脉高压患者的疗效仍缺乏证据。对于心功能Ⅲ~Ⅳ级的肺动脉高压患者,初始应用波生坦联合另一种靶向药物治疗可能优于单药治疗,而对于心功能Ⅱ~Ⅲ级的肺动脉高压患者,目前仍缺少联合用药优于单药治疗的证据。     

新作用机制肺动脉高压靶向治疗药物研究进展

肺动脉高压是一类以肺动脉渐进性闭塞导致肺血管阻力逐渐升高进而发生右心室衰竭的一种恶性肺血管疾病。随着肺动脉高压病理生理学和分子生物学等方面研究的发展,出现了许多新作用机制的肺动脉高压靶向治疗药物。本文根据国内外相关文献报道,本文将从鸟苷酸环化酶激活剂、线粒体调节剂、抗炎和免疫调节剂、酪氨酸激酶抑制剂、5-羟色胺受体拮抗剂、右心室靶向治疗药物等方面进行综述。     

潜在抗肺动脉高压新型靶向药物——伊马替尼

肺动脉高压死亡率高,目前虽然有靶向药物治疗,但仍无法治愈,患者长期预后不佳。伊马替尼作为一种酪氨酸激酶抑制剂,2002年在中国获批上市,用于治疗慢性粒细胞白血病等多种肿瘤疾病。研究发现伊马替尼除可抗肿瘤外,还可改善严重肺动脉高压患者的血流动力学和运动耐量,但安全性欠佳。随着伊马替尼靶向肺部新剂型的出现,该药有望成为抗肺动脉高压的新型靶向药物。     

肺动脉高压药物治疗研究进展

简述肺动脉高压的发病机制，阐述肺动脉高压治疗药物的开发及临床应用情况，详细介绍治疗肺动脉高压的几种新型药物。     

肺动脉高压的免疫调节治疗

肺动脉高压是临床上常见的疾病,其发病机制尚未完全清楚。免疫因素在肺动脉高压的发病机制中起重要作用。免疫抑制疗法为肺动脉高压治疗提供了新的途径。本文就机体免疫紊乱对肺动脉高压的影响机制及其免疫调节治疗的临床应用及研究现状进行综述。     

靶向药物联合介入封堵治疗动脉导管未闭合并艾森门格综合征5例效果观察

目的探讨动脉导管未闭（patent ductus arteriosus,PDA）合并艾森门格综合征（eisenmenger syndrome,ES）应用靶向药物联合介入封堵治疗的效果。方法选择2011年6月—2013年10月诊断为重度肺动脉高压（pulmonary arterial hypertension,PAH）的PDA患者5例,术前行右心导管检查肺循环血流量/体循环血流量在1.0～1.5。入院时行急性肺血管扩张试验和试封堵试验,阳性患者行介入封堵术,所有患者术后接受规范靶向药物治疗,治疗后6、12个月综合评估介入封堵治疗指征和治疗效果。结果本组随访12个月,无一例死亡,3例成功行介入封堵术,术后肺动脉压力及肺血管阻力均呈下降趋势,1例经靶向药物治疗6个月后仍无手术指征,但一般情况好转,1例接受靶向药物治疗1个月后放弃治疗,病情逐步恶化。结论经积极靶向药物、介入封堵治疗可使部分PDA合并ES患者获益。     

Systemic sclerosis-related pulmonary hypertension: unique characteristics and future treatment targets

Pulmonary arterial hypertension (PAH) is a severe vascular complication of connective tissue diseases. In the context of systemic sclerosis (SSc), PAH is a devastating disease with a dramatic impact on prognosis and survival. Despite advances in early diagnosis and the development of new targeted treatments, SSc-related pulmonary arterial hypertension (SScPAH) represents the leading cause of death in SSc patients with reported poorer response in therapy and worse prognosis compared with idiopathic PAH. Recent findings indicate that factors accounting for these differences may include cardiac involvement, pronounced autoimmune and inflammatory response and pulmonary venous vasculature remodeling. Deeper understanding of the underlying pathogenic mechanisms of pulmonary vascular disorders in SScPAH may lead to novel therapeutic strategies which are currently under investigation and may improve the outcome of these patients, for whom our therapeutic armamentarium is not effective enough. In this article we attempt to critically analyze the factors contributing to the unique phenotype of SScPAH focusing on future challenges for the design of novel targeted treatments which may alter the natural history of the disease.     

Sildenafil citrate for the treatment of pulmonary hypertension

Pulmonary arterial hypertension is a progressive disease that has a high rate of mortality. For these reasons, early treatment is essential. Treatment choices for pulmonary arterial hypertension are limited by drug tolerability, drug cost and inconvenience associated with administration techniques and dosing schedules. Therefore, a therapy that provides oral dosing with limited side effects would prove useful in managing many patients. Sildenafil citrate, the first and highly publicized oral medication to receive approval from the U.S. Food and Drug Administration for erectile dysfunction, has recently been approved for treatment of pulmonary arterial hypertension. This review summarizes the normal physiology of the pulmonary vasculature, and the pathophysiology involved in pulmonary arterial hypertension and the role of sildenafil in its treatment.     

Treprostinil therapy for pulmonary artery hypertension

Pulmonary artery hypertension is a life-threatening disease characterised by a pulmonary vasculopathy and progressive right ventricular failure. Major advances were made with the development of continuous intravenous epoprostenol (Flolan?) as a treatment modality. Nevertheless, it is far from ideal as treatment for this disease. Subcutaneous treprostinil has been FDA approved for the treatment of New York Heart Association Functional Class II – IV pulmonary artery hypertension. It is a longer acting subcutaneous prostacyclin analogue that offers an additional mode of therapy for this disease. A discussion of the pharmacology of this prostacyclin analogue as compared to its related compounds, the clinical studies which led to its approval, a review of some additional basic studies and the practical use of this drug in the treatment modalities for precapillary pulmonary artery hypertension in 2002 in light of other available therapies is discussed.     

Bosentan: a dual endothelin receptor antagonist

The peptide endothelin plays a significant role in a wide array of pathological conditions, including primary pulmonary hypertension and pulmonary arterial hypertension associated with collagen vascular disease. These are life-threatening conditions that can severely compromise the function of the lungs and heart. Inhibiting the actions of endothelin by blockade of its receptors provides a new and effective approach to therapy for patients with these conditions. Bosentan (Tracleer ) is the first orally-active dual endothelin receptor antagonist and has recently been approved in the US, Canada, Switzerland and the EU for the treatment of pulmonary arterial hypertension. Bosentan significantly improves exercise capacity, symptoms and functional status in patients with this disease and also slows clinical deterioration, which may be indicative of a delay of disease progression. Results from large-scale studies of bosentan in patients with pulmonary arterial hypertension and chronic heart failure have established its long-term safety and tolerability profiles. The introduction of the dual endothelin receptor antagonist bosentan has provided an essential treatment for pulmonary arterial hypertension and ongoing trials are evaluating its potential role in the management of other endothelin-mediated disease states.     

Treprostinil therapy for pulmonary artery hypertension

Pulmonary artery hypertension is a life-threatening disease characterised by a pulmonary vasculopathy and progressive right ventricular failure. Major advances were made with the development of continuous intravenous epoprostenol (Flolan trade mark ) as a treatment modality. Nevertheless, it is far from ideal as treatment for this disease. Subcutaneous treprostinil has been FDA approved for the treatment of New York Heart Association Functional Class II - IV pulmonary artery hypertension. It is a longer acting subcutaneous prostacyclin analogue that offers an additional mode of therapy for this disease. A discussion of the pharmacology of this prostacyclin analogue as compared to its related compounds, the clinical studies which led to its approval, a review of some additional basic studies and the practical use of this drug in the treatment modalities for precapillary pulmonary artery hypertension in 2002 in light of other available therapies is discussed.     

探究冠心病合并肺心病的临床治疗

目的通过探讨冠心病合并肺心病的临床治疗方法,旨在为临床有效治疗冠心病合并肺心病提供理论依据。方法选择2012年12月至2013年12月在我院接受治疗的冠心病合并肺心病患者86例,分成研究组和对照组,每组43例,对照组给予患者常规的治疗方式,研究组在常规治疗的基础上给予患者有针对性的治疗,统计两组患者临床疗效。结果研究组患者通过基础治疗和针对性治疗后总有效率为93.02%,对照组总有效率72.09%,研究组患者治疗的有效率显著高于对照组,且P<0.05差异显著有统计学意义。结论临床治疗时应综合考虑患者病情及时诊断并给予综合治疗,能改善患者病情临床应用价值高。     

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.     

The use of iloprost in the treatment of ‘out of proportion’ pulmonary hypertension in chronic obstructive pulmonary disease

Case Pulmonary hypertension secondary to respiratory disease most often occurs as a complication of chronic obstructive pulmonary disease, which currently constitutes one of the leading causes of death. Some patients with hypoxaemia reveal “out of proportion” pulmonary hypertension with inappropriate increase of pulmonary artery pressure. Iloprost, analogue of prostacyclin, dilates systemic vessels and pulmonary vessels in particular if administered by inhalation. It appears to be important, life-saving, complementary therapy. However, there is no evidence for its routine use in out of proportion arterial pulmonary hypertension. This case study presents a 44-year old man with chronic obstructive pulmonary disease and “out of proportion” pulmonary hypertension. We present the results of his treatment with iloprost. Conclusion In a patient with “out of proportion” pulmonary hypertension due to chronic obstructive pulmonary disease, inhaled iloprost led to improvement in clinical status and echocardiographic parameters, including a reduction of right ventricular systolic pressure.