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。     

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。     

治疗肺动脉高压新药-Selexipag研究进展

肺动脉高压是以血管收缩、血管重构、平滑肌细胞增殖和原位血栓形成等为主要特征的肺小动脉异常疾病。Selexipag是一种新型口服前列环素受体激动剂,已被证明可改善Ⅱ期临床试验的血液动力学,并可减少Ⅲ期临床试验中肺动脉高压患者的疾病恶化情况。本文对其作用机制、药动学、药效学、临床试验、不良反应等方面做一综述。     

肺动脉高压的药物治疗

肺动脉高血压是以肺小动脉血管重构为特征的严重的肺循环疾病。近年来随着对肺动脉高压发病机制认识地提高,针对肺动脉高压的发病各环节的治疗,即靶向治疗取得了进展。在靶向治疗基础上,为降低单一药物的副作用及协同药物间的相互作用,联合用药成为肺动脉高压临床常用的治疗手段。     

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。     

肺动脉高压的药物治疗进展

肺动脉高压(PAH)是由多种已知或未知原因导致肺动脉压异常升高的一种威胁生命、致死率高的疾病,引起临床上的广泛关注,临床治疗药物主要包括钙离子通道阻滞剂(CCB)、前列环素、内皮素受体拮抗剂(ETRA)、磷酸二酯酶抑制剂(PDE5i)、鸟苷酸环化酶(sGC)刺激剂等,临床上已联合使用这些药物用以提高疗效,降低不良反应发...     

肺血管内皮损伤与肺动脉高压

肺动脉高压(PAH)是一组由不同病因和发病机制引起的以肺血管阻力持续增加为特征的临床综合征,潜在原因还不明确。越来越多的研究表明,肺血管内皮损伤是引起肺动脉收缩和特征性病理改变的首要因素,在PAH发生发展的不同时期,保护肺血管内皮细胞,改善内皮功能或恢复内源性血管活性物质之间的平衡,恢复血管内皮结构和功能的完整性,延缓或逆转肺血管的增殖重塑过程,已成为治疗PAH的重要目标之一。     

肺动脉高压的药物治疗进展

肺动脉高压(pulmonaryarte-rialhypertension,PAH)是以肺小动脉的血管痉挛、内膜增生和重构为主要特征的一种疾病。我国有关PAH的诊断标准为:在海平面水平呼吸空气,静息状态下肺动脉收缩压>30mmHg或者肺动脉平均压(MPAP)>20mmHg;或运动状态下MPAP>30mmHg。世界卫生组织(WHO)定义PAP的标准为:静息状态下MPAP>25mmHg或运动时MPAP>30mmHg。该病的演变呈进行性加重,升高的血管阻力增加右心室负荷,结果导致右心功能损伤、患者死亡。肺动脉高压的临床分类1998年以前肺动脉高压分为原发性肺动脉高压和继发性肺动脉高压两大类。1998年…     

肺动脉高压药物治疗新进展

肺动脉高压(PAH)传统治疗药物主要有钙拮抗剂,口服抗凝剂和前列环素类似物如依前列醇(epoprostenol)持续静脉给药。但临床疗效有限,并且使用大剂量钙拮抗剂可导致患者通气／血流比例失调。最近,对PAH的发病机理有了新的认识。新药血栓素阻断剂特波格雷(terbogrel),前列环素类似物treprostinil、贝前列素(beraprost)、伊洛前列素(iloprost)和内皮素受体阻断剂波生坦(bosentan)均已用于PAH的治疗,并取得了较好的效果。     

Treprostinil for the treatment of pulmonary hypertension

Background: Pulmonary hypertension (PH) is a severely disabling disorder characterized by sustained elevations of pulmonary arterial pressure, ultimately leading to right-heart failure and death. Pulmonary arterial hypertension (PAH) usually occurs in the absence of an evident cause (idiopathic PAH) or may be associated with connective tissue disease, HIV infection, congenital heart disease, chronic liver disease or result from the use of toxic agents and anorexigens. Objective/method: Intravenous epoprostenol has been widely used in patients with PAH, leading to long-term clinical benefits and improved survival. Epoprostenol has to be delivered through a permanently implanted Intravenous catheter. This may expose patients to potentially life-threatening complications. Thus, more stable compounds and alternative modes of prostacyclin delivery have been sought. Conclusion: Treprostinil sodium is a stable prostacyclin analogue, sharing pharmacologic actions similar to epoprostenol with comparable haemodynamic effects. Treprostinil is chemically stable at room temperature and has a long half-life (2 – 4 h), making this drug suitable for subcutaneous administration, with practical benefits in avoiding the risk of line infection and thrombosis, and cardiovascular reactions due to abrupt drug discontinuation.     

Iloprost inhalation solution for the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a condition that is characterised by increased pulmonary arterial pressure and vascular resistance that can lead to right ventricular failure and death. A variety of disturbances in pulmonary vascular endothelial and smooth muscle function are present in PAH, including reduced production of vasodilator and antiproliferative substances, such as nitric oxide and prostacyclin, and an overproduction of mitogens, such as endothelin. As a result of these observations, therapies have been developed for PAH that specifically target these pathogenic processes, including prostacyclin analogues and endothelin receptor antagonists. This article reviews iloprost inhalation solution, the most recently approved form of prostacyclin therapy that is delivered directly to the lungs by inhalation.     

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.     

Pharmacokinetic drug evaluation of selexipag for the treatment of pulmonary arterial hypertension

Introduction: Management of pulmonary arterial hypertension (PAH) remains challenging even in the contemporary era. Intravenous prostacyclin therapy, while associated with decreased mortality, has practical limitations and requires significant lifestyle modifications. The recently approved long-acting oral IP prostacyclin receptor agonist for treatment of PAH, selexipag, is a non-prostanoid agent that vasodilates, impacts remodeling (anti-proliferative), reduces endothelial cell dysfunction, inhibits platelet aggregation (anti-thrombotic), and increases right heart inotropy.

Areas covered: This review discusses the limitations of non-oral prostacyclin therapy for PAH and describes the factors which led to successful development of selexipag in in vitro and preclinical studies. We review the pharmacokinetics and pharmacodynamics of selexipag. We further discuss the methodology and results of phase II and III trials, which led to approval of selexipag for PAH management.

Expert opinion: As compared to previously developed oral prostacyclins, selexipag has limited adverse effects despite similar or better efficacy. Its final place in the treatment paradigm is not yet clear but it does represent a significant advance in the area of oral PAH therapy.     

The prostacyclin analogue treprostinil in the treatment of pulmonary arterial hypertension

Pulmonary arterial hypertension (PAH) is a rare but life‐threatening disease that progresses rapidly and is currently without a cure. Pharmacological treatments aim to slow down disease progression and to reduce symptoms by targeting the prostacyclin, the endothelin or the nitric oxide pathway. Drugs targeting the prostacyclin pathway have been shown to be favourable for PAH patients by causing vasodilatative, anti‐proliferative as well as anti‐inflammatory effects, but tend to be underused, partially due to adverse effects and difficulties associated with their intravenous administration. Treprostinil, a stable prostacyclin analogue, was FDA‐approved in 2002 to improve exercise capacity in PAH patients and is available in intravenous, subcutaneous, inhaled and oral form. The four different possible ways of administration, a long half‐life and its stability at room temperature give treprostinil an advantage over epoprostenol, iloprost and selexipag, the three other FDA‐approved drugs targeting the prostacyclin pathway. In clinical trials, treprostinil improved exercise capacity, quality of life (QOL), functional class and clinical status. While the different forms of treprostinil lead to specific complications, its general adverse effects are dizziness, nausea, pain in the jaw and extremities, diarrhoea, flushing and headache. This MiniReview will assess the benefits and drawbacks of treprostinil in the treatment of PAH by examining its specific mechanism of action and pharmacological properties, such as pharmacokinetics, pharmacodynamics, adverse effects and interactions. In addition, we will analyse and discuss results from different clinical trials, comparing treprostinil's four different forms to each other as well as to other drugs targeting the prostacyclin pathway.     

An evaluation of selexipag for the treatment of pulmonary hypertension

ABSTRACT

Introduction

Selexipag is a first-in-class, oral, long-acting, selective, non-prostanoid agonist of the prostacyclin receptor (IP receptor), indicated for the treatment of symptomatic adult pulmonary arterial hypertension (PAH). It was designed with the objective to surpass the inconveniences associated with standard prostanoid therapy, presenting fewer adverse effects and comparable hemodynamic benefits.     

New pharmacotherapy options for pulmonary arterial hypertension

Introduction: Epoprostenol was the first targeted therapy available for the treatment of pulmonary arterial hypertension (PAH). Since then great advances in our knowledge of the disease have been made and the spectrum of therapeutic options for PAH has expanded. After an overview of current available treatments, this article describes the new pharmacotherapy options and their place in the management of PAH.

Areas covered: This paper is based on a literature search and the review of studies published on PAH pharmacotherapy using the MEDLINE database.

Expert opinion: The last decade has been particularly important in PAH management with the emergence of six new molecules, the development of novel routes of administration and improvement of pharmacokinetics. Moreover, pediatric formulations have been developed. However, further research is required to inform clinicians regarding optimal choices of combination therapies (progressive add-on therapy or upfront combination therapy, selection of associated molecules regarding the patient’s profile...), to continue to improve the quality of life of patients with new drugs and to reach the ultimate goal of curing the disease.     

Notch信号通路在肺动脉高压肺血管重构中的研究进展

肺动脉高压是一种以肺动脉压力和肺血管阻力持续升高为特征,引起肺血管重构发生的心血管性疾病。Notch信号通路是一种高度保守的信号路径,主要通过调控细胞的增殖、分化及凋亡等过程,参与心血管、神经、肿瘤等疾病的发生、发展。该文主要对Notch信号通路参与肺血管重构发生的分子机制进行综述,以期为肺动脉高压的治疗提供新的策略。