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Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs
Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully un...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305538/ https://www.ncbi.nlm.nih.gov/pubmed/37376028 http://dx.doi.org/10.3390/pharmaceutics15061579 |
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author | Jin, Qi Chen, Dandan Zhang, Xiaochun Zhang, Feng Zhong, Dongxiang Lin, Dawei Guan, Lihua Pan, Wenzhi Zhou, Daxin Ge, Junbo |
author_facet | Jin, Qi Chen, Dandan Zhang, Xiaochun Zhang, Feng Zhong, Dongxiang Lin, Dawei Guan, Lihua Pan, Wenzhi Zhou, Daxin Ge, Junbo |
author_sort | Jin, Qi |
collection | PubMed |
description | Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients. |
format | Online Article Text |
id | pubmed-10305538 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-103055382023-06-29 Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs Jin, Qi Chen, Dandan Zhang, Xiaochun Zhang, Feng Zhong, Dongxiang Lin, Dawei Guan, Lihua Pan, Wenzhi Zhou, Daxin Ge, Junbo Pharmaceutics Review Pulmonary arterial hypertension (PAH) is a malignant pulmonary vascular syndrome characterized by a progressive increase in pulmonary vascular resistance and pulmonary arterial pressure, which eventually leads to right heart failure and even death. Although the exact mechanism of PAH is not fully understood, pulmonary vasoconstriction, vascular remodeling, immune and inflammatory responses, and thrombosis are thought to be involved in the development and progression of PAH. In the era of non-targeted agents, PAH had a very dismal prognosis with a median survival time of only 2.8 years. With the deep understanding of the pathophysiological mechanism of PAH as well as advances in drug research, PAH-specific therapeutic drugs have developed rapidly in the past 30 years, but they primarily focus on the three classical signaling pathways, namely the endothelin pathway, nitric oxide pathway, and prostacyclin pathway. These drugs dramatically improved pulmonary hemodynamics, cardiac function, exercise tolerance, quality of life, and prognosis in PAH patients, but could only reduce pulmonary arterial pressure and right ventricular afterload to a limited extent. Current targeted agents delay the progression of PAH but cannot fundamentally reverse pulmonary vascular remodeling. Through unremitting efforts, new therapeutic drugs such as sotatercept have emerged, injecting new vitality into this field. This review comprehensively summarizes the general treatments for PAH, including inotropes and vasopressors, diuretics, anticoagulants, general vasodilators, and anemia management. Additionally, this review elaborates the pharmacological properties and recent research progress of twelve specific drugs targeting three classical signaling pathways, as well as dual-, sequential triple-, and initial triple-therapy strategies based on the aforementioned targeted agents. More crucially, the search for novel therapeutic targets for PAH has never stopped, with great progress in recent years, and this review outlines the potential PAH therapeutic agents currently in the exploratory stage to provide new directions for the treatment of PAH and improve the long-term prognosis of PAH patients. MDPI 2023-05-24 /pmc/articles/PMC10305538/ /pubmed/37376028 http://dx.doi.org/10.3390/pharmaceutics15061579 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Jin, Qi Chen, Dandan Zhang, Xiaochun Zhang, Feng Zhong, Dongxiang Lin, Dawei Guan, Lihua Pan, Wenzhi Zhou, Daxin Ge, Junbo Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs |
title | Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs |
title_full | Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs |
title_fullStr | Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs |
title_full_unstemmed | Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs |
title_short | Medical Management of Pulmonary Arterial Hypertension: Current Approaches and Investigational Drugs |
title_sort | medical management of pulmonary arterial hypertension: current approaches and investigational drugs |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10305538/ https://www.ncbi.nlm.nih.gov/pubmed/37376028 http://dx.doi.org/10.3390/pharmaceutics15061579 |
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