Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) Pulmonary hypertension is a progressive disorder characterised by abnormally high pulmonary artery pressure, leading to right ventricular failure and death, generally after a few years. (2) Treatment usually combines an anticoagulant, oxygen therapy, a diuretic and, sometimes a calcium channel blocker. Efficacy is poorly documented but appears to be limited. Long-term treatment with epoprostenol (prostacyclin), given as a continuous intravenous infusion via a central catheter and pump improves the quality of life of patients with severe pulmonary hypertension (NYHA classes III and IV, associated with discomfort during daily activities or even at rest). The impact of this treatment on survival seems to depend on the type of pulmonary hypertension: benefits were seen in a trial in patients with idiopathic pulmonary hypertension, while there was no effect in another trial in patients with pulmonary hypertension associated with scleroderma. Epoprostenol causes numerous adverse effects, some of which can be severe. (3) Marketing authorisation was recently granted in Europe for oral bosentan therapy for pulmonary arterial hypertension severe enough to restrict daily activities. (4) Two placebo-controlled trials lasting 12 to 16 weeks included 32 and 213 patients who responded inadequately to calcium channel blockers. They showed that the 6-minute walking distance improved by a median of 76 metres and 44 metres, respectively. In the trial with 213 patients, 42% of patients in the bosentan group and 30% of those in the placebo group were improved according to the NHYA scale. No impact on survival was observed in these short trials. (5) A trial in 33 patients showed no difference in symptom improvement between groups treated with intravenous epoprostenol + oral bosentan or intravenous epoprostenol + oral placebo. (6) Two adverse effects require monitoring, namely anemia and elevated transaminase activity. Bosentan carries a risk of multiple pharmacokinetic interactions and is teratogenic in animals. Women taking bosentan cannot use hormone-based contraception, because of a pharmacokinetic interaction. (7) In practice, oral bosentan improves symptoms in patients whose daily activities are restricted by pulmonary arterial hypertension. Bosentan is easy to use, making it an option before continuous intravenous epoprostenol infusion, even though it may not be as effective.
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PMID:Bosentan: new preparation. Pulmonary hypertension: an option before epoprostenol infusion. 1587 38

In addition to its potent vasoconstricting effect, endothelin (ET)-1 induces proliferation of pulmonary vascular cells and appears to play a pathogenic role in the development of pulmonary arterial hypertension (PAH). Blockade of the ET receptors has been proposed for the treatment of this condition. Bosentan (Tracleer, Actelion Pharmaceuticals), an oral ETA/ETB receptor antagonist, has been shown to improve exercise capacity, quality of life, haemodynamics and time to clinical worsening of patients with PAH in short-term placebo-controlled trials. These improvements were sustained, and a long-term observational study on idiopathic PAH patients suggested a favourable effect on survival in this subset. In the present report, the pharmacology, clinical efficacy and safety profile of bosentan are summarised. The place of bosentan among the current therapies available for the treatment of PAH is also discussed.
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PMID:Treatment of pulmonary arterial hypertension with bosentan: from pathophysiology to clinical evidence. 1601 84

For patients with pulmonary arterial hypertension (PAH) two first line therapies - iloprost inhalation (Ventavis) and bosentan (Tracleer) -- are available in Germany. A third substance, sildenafil, is already approved in the US and will be approved for this indication in the European Union soon. Patients with PAH can be stabilized or improved with a specific mono-therapy for a limited period of time only. Therefore, the question arises when and how to initiate treatment escalation. The available data from controlled clinical trials are insufficient to give a definite answer to these questions. Moreover, it is still unclear which combination of the above mentioned substances may be superior in the treatment of PAH. On the other hand, combination therapy is already reality in clinical practice. Based on this background experts from specialized centers dealing with PAH discussed the scientific basis of the role of combination therapy in PAH patients during a workshop held on April 22/23. 2005 in Wiesbaden. The goal of this workshop was to formulate a common position with regard to combination therapy of PAH on the basis of the available scientific data and clinical experience.
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PMID:[A role for combination therapy in pulmonary arterial hypertension]. 1622 88

In view of the shortcomings of the current system for postmarketing drug surveillance that is based on voluntary spontaneous adverse drug reaction (ADR) reporting, new approaches are needed. We describe an approach involving a combination of limited distribution, patient and physician education, as well as a novel pharmaco-vigilance system that is capable of promoting the safe and adequate use of a new drug. Importantly, it provides the possibility of calculating true ADR occurrence rates, as the exposed population (denominator) and the number of patients with events (numerator) are known. These measures were taken for the oral dual endothelin ET(A)/ET(B) antagonist bosentan (Tracleer). In recent guidelines issued by the European Society of Cardiology, American College of Chest Physicians and the WHO, this drug is considered as first-line oral treatment for the treatment of pulmonary arterial hypertension, a devastating orphan disease associated with a poor prognosis. Bosentan was approved in 2001/2 on the basis of two pivotal studies that showed improved exercise capacity and haemodynamic parameters while delaying time to clinical worsening. Elevations in serum liver aminotransferase levels of >3 times the upper limit of normal were noted in 10.2% of patients (placebo-subtracted incidence). Therefore, liver function tests have to be performed on a regular basis. In addition, bosentan has potential as a teratogen. In the US, a controlled distribution network for bosentan (Tracleer) Access Program [T.A.P.]) and the development of a patient database to follow patients was set up. Accompanied by comprehensive physician and patient education programmes, T.A.P. was developed to provide a mechanism to assist with the primary risk management goals for bosentan therapy, namely pregnancy prevention and liver enzyme monitoring and prevention of hepatic injury. In Europe, the Tracleer) Excellence (TRAX PMS) database is a novel European non-interventional, prospective, internet-based surveillance system initiated by the manufacturer in cooperation with the European Medicines Agency. It collected potential safety signals associated with bosentan use including adverse events, elevations of liver aminotransferase levels, other abnormal laboratory values, death and hospitalisation. TRAX PMS has accrued 79% of all known patients in the EU and the data provide supportive 'real-life' evidence on the long-term safety of bosentan. The two different systems had similar goals and outcomes. The data received concerning thousands of patient-years of use have confirmed the clinical trial results regarding product safety and the favourable benefit/risk ratio of bosentan, especially with regard to known type A adverse events. The clinical monitoring algorithm has also been confirmed. In addition, no rare type B events were uncovered despite the increased reporting rate. These systems might serve as templates for future pharmaco-vigilance efforts regarding drugs that require particular safety attention.
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PMID:Risk management strategies in the postmarketing period : safety experience with the US and European bosentan surveillance programmes. 1623 52

There is conflicting evidence regarding the effect of endothelin-1 (ET-1) on platelets. Some studies show that ET-1 activates platelets, others show platelet inhibition with ET-1 and some studies did not detect an effect of ET-1. These conflicting results may be due to complex interactions between platelet ET(A) and ET(B) receptors. ET-1 antagonism may emerge as an important therapeutic strategy in the management of several vascular disorders. However, to date the only prescribed ET-1 antagonist is bosentan for pulmonary arterial hypertension. Bosentan is a 'dual' ET-1 antagonist (i.e. it acts on both ET(A) and ET(B) receptors). Whether this action involves an effect on platelets remains to be established. In this review some of the studies describing the effect of ET-1 on human platelets are discussed. Vascular diseases where ET-1 is implicated are also considered.
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PMID:Endothelin-1 and human platelets. 1624 83

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries. It induces a fixed pulmonary arterial obstruction, persistent elevation of pulmonary arterial resistance, and eventually right heart failure. Conventional therapy is based on simple measures (exercise limitation) and nonspecific treatments (warfarin, diuretics, and oxygen). Pure vasodilators, such as calcium channel blockers, are effective only in a minority of patients who have an acute response to vasodilator testing. Intravenous prostacyclin (epoprostenol) and endothelin receptor blockers have vasodilator and antiproliferative properties. Epoprostenol therapy has significantly improved PAH prognosis and remains the first-line treatment for patients with the most severe disease. Bosentan is an interesting first-line treatment for NYHA functional class III patients. Availability of novel specific drugs (endothelin receptor type A antagonists, prostacyclin analogues, type 5 phosphodiesterase inhibitors) is opening new perspectives in PAH treatment. The long-term benefit of these drugs remains to be evaluated and their respective place in treatment of these patients is still uncertain. The evolution of therapy from vasodilators to antiproliferative agents reflects the advancement in our understanding of the mechanisms mediating pulmonary arterial hypertension.
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PMID:[Treatment of pulmonary arterial hypertension]. 1630 76

Bosentan (Tracleer), an orally administered dual endothelin (ET)(A) and ET(B) receptor antagonist, is indicated in the treatment of pulmonary arterial hypertension (PAH). The efficacy of oral bosentan 125 mg twice daily in improving exercise capacity has been demonstrated in well designed trials in adult patients with idiopathic PAH or PAH associated with connective tissue disease or congenital systemic-to-pulmonary shunts, and in other trials in patients with idiopathic PAH or PAH associated with congenital heart disease or HIV infection. The beneficial effects of first-line bosentan treatment may be maintained for up to 1 year in patients with idiopathic PAH or PAH associated with connective tissue disease. Despite the potential for treatment-related teratogenicity and hepatotoxicity, long-term data indicate that bosentan is generally well tolerated at the approved dosages. Although well designed trials are required to establish the efficacy of bosentan versus or in combination with other specific PAH therapies, especially sildenafil, the convenient oral administration and lack of serious injection-related adverse effects may render bosentan preferable to other PAH therapies. Preliminary data indicate that bosentan may be effective in pediatric PAH patients, although randomized trials are required. Furthermore, bosentan may be a useful option for the prevention of digital ulcer development in patients with systemic sclerosis. Thus, in accordance with current clinical guidelines, bosentan is a convenient, effective, and generally well tolerated agent for use in the first-line treatment of class III PAH or second-line treatment of class IV PAH.
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PMID:Bosentan: a review of its use in pulmonary arterial hypertension and systemic sclerosis. 1678 Mar 92

Male heterozygous Ren-2 transgenic rats and Hannover Sprague-Dawley rats fed a normal or high-salt diet were either untreated or treated with the nonselective receptor ET(A)/ET(B) receptor blocker bosentan or the selective ET(A) receptor blocker, ABT-627, known as atrasentan. Survival rate was partly increased by bosentan and fully normalized by atrasentan. Bosentan did not significantly influence the course of hypertension in TGR, whereas atrasentan significantly decreased BP on both diets. Atrasentan substantially reduced proteinuria, cardiac hypertrophy, glomerulosclerosis and left ventricular ET-1 tissue concentration on both diets. Our data indicate that ET(A) receptor blockade is superior to nonselective blockade in attenuating hypertension, end-organ damage and improving survival rate.
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PMID:Early-onset endothelin receptor blockade in hypertensive heterozygous Ren-2 rats. 1680 27

The natural history of congenital heart disease (CHD) with left to right shunt and high pulmonary blood flow, is characterized by development of severe Pulmonary Artery Hypertension (PAH); this condition usually contraindicates any type of surgical or interventional cardiac correction because of bad results. We here report the case of an adult patient with a patent ductus arteriosus and severe PAH, treated uneventfully with a staged combined therapy: Bosentan for 3 months and then percutaneous closure with amplatzer duct occluder (AGA Med. Co. Golden Valley, MN). The patient showed a dramatic improvement both of pulmonary hemodynamics and functional capacity at 8 months follow up confirming the efficacy of pulmonary vasodilator therapy in PAH associated to congenital heart disease.
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PMID:Combined endothelin receptor antagonist and transcatheter interventional therapy of patent ductus arteriosus with severe pulmonary artery hypertension. 1687 49

Pulmonary arterial hypertension (PAH) with coexisting portal hypertension has been defined as portopulmonary hypertension (PPHTN). It is often related to liver cirrhosis of various aetiologies and is associated with a high mortality rate. Endothelin-1 (ET) is supposed to play an important role in the pathogenesis of PAH as well as portal hypertension. Therefore, therapy with an ET(A)/ET(B) receptor antagonist might be of use in the treatment of PPHTN. We report the case of a 76-year-old male with liver cirrhosis owing to chronic hepatitis C virus infection and PPHTN who was treated with the dual ET(A)/ET(B) receptor antagonist bosentan. The patient showed remarkable improvement of 6-min walking distance from 300 to 480 m after 2 weeks and to 540 m after 14 weeks, respectively. In addition, a significant decline of N-terminal pro B-type natriuretic peptide fraction (NT-proBNP) from 4928 ng mL(-1) to 640 ng mL(-1) was observed. Bosentan might be a promising new therapeutical option for patients suffering from PPHTN.
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PMID:Bosentan treatment of portopulmonary hypertension related to liver cirrhosis owing to hepatitis C. 1691 14


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