Pulmonary arterial hypertension is a rare, chronic disease characterized by progressive remodeling of the pulmonary vasculature. Historically, prognosis has been very poor with relatively low 3-year survival rates. Common symptoms include fatigue and shortness of breath upon exercise, chest pain, and syncope. Patients exhibit increased pressure and resistance in pulmonary arteries due to fibrosis, vessel narrowing, and elevated levels of vasoconstrictive agents; diagnosis is confirmed by right heart catheterization. Reduced blood flow through the pulmonary vasculature not only reduces the amount of oxygenated blood available for the systemic circulation, but increases afterload on the right ventricle and, if left untreated, ultimately causes right ventricular heart failure.
In the past, few medications were available to pulmonary arterial hypertension patients. However, recent advancements in our molecular understanding of the disease have led to the development of new therapeutic options that show promise of slowing, or in some cases reversing, disease progression. Currently available treatments have been shown to significantly improve 3-year survival rates and help promote a better quality of life for patients. While an exact molecular or genetic mechanism of disease progression is not yet known, several studies have noted the presence of dysfunctional endothelial cells and an imbalance in molecular modulators of the pulmonary vasculature. Specifically, patients exhibit chronically low levels of vasodilating agents such as prostacyclin and nitric oxide. In addition, there is a heightened vasoconstrictive effect due to elevated endothelin-1 and thromboxane A2. Drugs have been developed to target these signaling pathways and show considerable promise and efficacy for managing pulmonary hypertension in patients. Although these therapeutics have been shown to significantly improve survival rates and symptoms, many have complex and inconvenient administration protocols and a host of adverse side effects. Moreover, many require monitoring or frequent follow up visits due to their off-target effects. Recent innovative advancements in pulmonary arterial hypertension pharmaceuticals hope to deliver safe, efficacious treatment options to patients debilitated by this chronic disease.
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/26562 |
| Date | 01 November 2017 |
| Creators | Bains, Ashank |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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