Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Bosentan: a dual endothelin receptor antagonist. 1208 9

Endothelin receptor antagonism has emerged as an important therapeutic strategy in pulmonary arterial hypertension (PAH). Laboratory and clinical investigations have clearly shown that endothelin (ET)-1 is overexpressed in several forms of pulmonary vascular disease and likely plays a significant pathogenetic role in the development and progression of pulmonary vasculopathy. Oral endothelin receptor antagonists (ERAs) have been shown to improve pulmonary hemodynamics, exercise capacity, functional status, and clinical outcome in several randomized placebo-controlled trials. Bosentan, a dual-receptor antagonist, is approved by the U.S. Food and Drug Administration for class III and IV patients with PAH, based on two phase III trials. In addition to its efficacy as sole therapy, bosentan may have a role as part of a combination of drugs such as a prostanoid or sildenafil. The selective endothelin receptor-A antagonists sitaxsentan and ambrisentan are currently undergoing investigation.
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PMID:Endothelin receptor antagonists in pulmonary arterial hypertension. 1519 80

Endothelin receptor antagonism has emerged as an important therapeutic approach in pulmonary arterial hypertension (PAH). Bench to bedside scientific research has clearly shown that endothelin-1 (ET-1) is over-expressed in several forms of pulmonary vascular disease and plays an important pathogenetic role in the development and progression of PAH. Oral endothelin receptor antagonists (ERAs) have been shown to improve exercise capacity, functional status, pulmonary hemodynamics, and delay the time to clinical worsening in several randomized placebo-controlled trials. Bosentan, the first oral ERA, was approved in 2001 and since that time it has established a strong record of safety and efficacy in PAH. More recently, two additional ERAs, ambrisentan and sitaxsentan, have been approved for use. The objective of this review is to evaluate the available evidence supporting the efficacy, pharmacology, safety and tolerability, and patient-focused perspectives for bosentan, the first approved ERA for PAH. Ongoing and forthcoming randomized trials are also highlighted including the application of bosentan in combination with other PAH therapies.
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PMID:Safety and tolerability of bosentan in the management of pulmonary arterial hypertension. 1992 Sep 27