Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0008031 (chest pain)
 17,248 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sitaxsentan is an orally active, selective endothelin-A receptor antagonist that may benefit patients with pulmonary arterial hypertension by blocking the vasoconstrictive effects of endothelin-A receptors, while maintaining the vasodilator and endothelin-1 clearance functions of the endothelin-B receptors. In its first randomized, placebo-controlled study, sitaxsentan improved exercise capacity assessed by the 6-min walk test, New York Heart Association functional class, cardiac index and pulmonary vascular resistance in New York Heart Association Class II, III and IV patients with idiopathic pulmonary arterial hypertension and pulmonary arterial hypertension related to connective tissue disease or congenital heart disease. Although doses of 100 and 300 mg once daily demonstrated equivalent efficacy, the lower dose had a better safety profile. Additional studies are ongoing to assess the relative safety and efficacy of 50 and 100 mg once-daily dosing. The most common side effects include rhinitis, headache, peripheral edema, chest pain, nausea, constipation, increased prothrombin time/international normalized ratio (in patients on warfarin), flushing and insomnia. As with other endothelin receptor antagonists, increases in hepatic transaminases have been observed with sitaxsentan. Initial studies using the selective oral endothelin-A receptor antagonist sitaxsentan in pulmonary arterial hypertension patients have revealed a favorable risk-benefit therapeutic profile with the 100 mg once-daily dose.
 ...
PMID:Sitaxsentan: a novel endothelin-A receptor antagonist for pulmonary arterial hypertension. 1629 89

Pulmonary arterial hypertension (PAH) is a progressive disorder with a poor prognosis. It is characterized by sustained elevation of pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR). It is defined hemodynamically by a mean PAP over 25 mm Hg, a pulmonary arterial wedge pressure of 15 mm Hg or less (which excludes left sided lesions), and a PVR of 3 or more Wood units (240 dyn.sec.cm-5). Patients are limited by exertional dyspnea, pre- or true syncope, chest pain, and edema/ascites when right heart failure supervenes. PAH afflicts predominantly young women and the diagnosis is often delayed. Three processes contribute to progressive arterial narrowing: vasoconstriction, vascular remodeling, and thrombosis in situ. The diagnosis of PAH must be confirmed and its etiology must be identified before appropriate therapy can be instituted. Right heart catheterization is necessary to establish the diagnosis, severity, and prognosis of PAH and to ascertain its etiology and to evaluate vasoreactivity, which guides therapy. Treatment of PAH includes vasodilators, supplemental O2, anticoagulation, diuretics, digoxin, intravenous inotropic therapy for decompensated right ventricular failure, and lung or combined heart-lung transplantation for those patients who continue to deteriorate with a poor quality of life despite pharmacologic therapy. Calcium channel blockers are beneficial in a small minority of patients. Prospective, controlled, randomized trials of approved vasodilator agents have enrolled a large proportion of women (70-85%). Agents such as the endothelin-1 receptor antagonist bosentan, the phosphodiesterase-5 inhibitor sildenafil, and the prostanoids have been shown to improve symptoms, exercise capacity, and, in most instances, delay clinical worsening. The clinical outcomes of patients with PAH have improved with the judicious use of contemporary therapies.
 ...
PMID:Pulmonary arterial hypertension and women. 1705 80