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

Pulmonary arterial hypertension is a rare disease that is characterized by increased pulmonary vascular resistance and right heart failure. Recent advances in the understanding of pulmonary arterial hypertension have been translated into effective therapies tested in clinical trials. These trials have used surrogate end points as the primary outcomes of interest. However, it is not clear which potential surrogate end points are reliable and valid for studying pulmonary arterial hypertension. Identification of suitable end points not only would help investigators design appropriate clinical trials but would assist clinicians in caring for this patient population. Hemodynamic, echocardiographic, neurohormone, and exercise measures hold some promise as potential surrogate end points for clinical trials of therapy for pulmonary arterial hypertension. Hemodynamic measures have the most evidence to support their use. Functional studies, such as the distance walked in 6 minutes, also may be meaningful. We present the available data as well as the strengths and weaknesses of each metric. Further studies should focus on validating the most promising of these surrogate end points, so that future investigators, subjects, and patients may benefit from the advantages they confer on clinical trials and patient care.
 ...
PMID:Surrogate end points for pulmonary arterial hypertension. 1545 83

Patients with unpalliated complex cyanotic congenital heart may have significant morbidity resulting from severe pulmonary hypertension. In late stages, medical management is often difficult, and worsening right heart failure is resistant to medication. The risk of complications and early death can be averted by detailed evaluation and prompt intervention to identify the reversible elements that compound their physiology. It is vital to address any treatable issue to improve a patient's quality of life while awaiting heart-lung transplantation. Our case is a good example of such an approach, where the identification and treatment of reversible pulmonary venous hypertension in the background of irreversible pulmonary arterial hypertension, by offloading the left atrium by atrial septostomy and stent implantation, resulted in significant improvement in the quality of life for the patient.
 ...
PMID:A novel use of atrial septostomy and stent implantation in a patient with complex cyanotic congenital heart disease and severe pulmonary hypertension. 1549 37

New drugs for pulmonary arterial hypertension have shown efficacy in randomized controlled trials. Endothelin receptor antagonists (ERA) and prostanoids are most important for clinical practice. Bosentan represents the first approved orally active therapy for PAH. Besides its hepatotoxicity it is mostly well tolerated. The first approved prostanoid, epoprostenol, is currently first choice only for decompensated right heart failure in PAH. It has to be delivered continuously intravenously and is prone to complications, side effects and very high costs. Alternatively, subcutaneous treprostinil can be applied. It is less risky and expensive but may cause local pain at the infusion site. Inhaled iloprost combines the features of a prostanoid with pulmonary and intrapulmonary selectivity. Alternatively, iloprost is being used as continuous intravenous infusion. The phosphodiesterase-5 inhibitor sildenafil was effective in two randomized controlled trials but has not been approved for PAH therapy.
 ...
PMID:[Therapy of pulmonary arterial hypertension]. 1570 89

Idiopathic pulmonary arterial hypertension is a rare but serious and life-threatening disease that leads to right heart failure and death within 2.8 years without specific treatment. This review focuses on the stable prostacyclin analog iloprost, its biologic action and pharmacology and, finally, on its clinical development, efficacy and safety in patients with idiopathic pulmonary arterial hypertension, which led to its approval for this indication. Furthermore, this review assesses the role of iloprost compared with other newly developed drugs, such as the endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil, as well as other modes of application of prostacyclin and its analogs for the treatment of idiopathic pulmonary arterial hypertension. Based on the different modes of action of these substances, a combination of these treatments could be most promising for the future.
 ...
PMID:Iloprost for idiopathic pulmonary arterial hypertension. 1585 95

(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.
 ...
PMID:Bosentan: new preparation. Pulmonary hypertension: an option before epoprostenol infusion. 1587 38

Sildenafil and inhaled nitric oxide (iNO) relax smooth muscle by inhibiting the degradation and stimulating the production of cyclic guanosine monophosphate, respectively. We compared the acute pulmonary vasodilator effects of sildenafil, iNO, and epoprostenol and asked whether the combination of iNO with sildenafil had additive pulmonary vasodilator effects. We assessed the effects of extended use of sildenafil in a small cohort of patients. Twenty patients with pulmonary arterial hypertension underwent an acute vasodilator trial with sildenafil (all patients), iNO and iNO plus sildenafil (11), and epoprostenol (19). We also provided sildenafil to patients who were ineligible for, or had clinical deterioration on epoprostenol, treprostinil, or bosentan. Mean+/-se pulmonary artery pressure dropped by 13+/-3%, 19+/-4%, 14+/-3%, and 26+/-4% with epoprostenol, iNO, sildenafil, and iNO+sildenafil, respectively. Cardiac index increased with epoprostenol and sildenafil. A correlation was found between the effects of iNO and epoprostenol. Nine out of ten patients who were started on long-term sildenafil treatment alone or in combination with other vasodilators had symptomatic improvement. Three died of right heart failure. In conclusion, sildenafil is a potent acute pulmonary vasodilator, an effect that is potentiated by combination with iNO. Long-term therapy of pulmonary hypertension with sildenafil alone or in combination with other agents appears to be safe and well tolerated.
 ...
PMID:Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. 1732 34

Patients with portal hypertension may develop pulmonary complications such as hepatopulmonary syndrome (HPS) or portopulmonary hypertension (PPHT). PPHT is defined as elevated pulmonary pressure, elevated pulmonary vascular resistance, a normal pulmonary capillary wedge pressure, and portal hypertension in the absence of other known causes pulmonary hypertension. Various factors such as hyperdynamic circulation, volume overload, and circulating vasoactive mediators are suspected to be involved in the pathogenesis of PPHT. The prognosis of patients with severe PPHT is significantly reduced due to the risk of right heart failure. In patients with moderate to severe PPHT liver transplantation is associated with a significantly increased mortality. The chief symptom of PPHT may be dyspnoe in the presence of typical histomorphological alterations comparable with idiopathic pulmonary hypertension. Continuous intravenous application of prostacyclin is currently regarded as the treatment of choice for patients with severe PPHT. Inhaled prostacyclin or its analogue iloprost or oral treatment with the endothelin-receptor antagonist bosentan may be promising alternatives which should be further investigated in randomized controlled trials.
 ...
PMID:[Portopulmonary hypertension]. 1600 50

Chronic cor pulmonale involves the enlargement of the right ventricle as a result of pulmonary hypertension due to pulmonary disorders involving the lung parenchyma, bellows function, or ventilatory drive. The right ventricular hypertrophy that occurs in chronic cor pulmonale is a direct result of chronic hypoxic pulmonary vasoconstriction and subsequent pulmonary artery hypertension, leading to increased right ventricular work and stress. We discuss methods by which hypoxic vasoconstriction and reduction in the pulmonary vascular bed lead to the development of pulmonary artery hypertension. This article reviews the interaction of the pulmonary vasculature and right ventricle in the non-diseased state as well as during disease exacerbations. Ventricular dependence and its contribution to the pathophysiology of right ventricular failure are also reviewed. In addition, we provide an overview of specific disease states that can result in the development of chronic cor pulmonale including chronic obstructive pulmonary disease (COPD), interstitial lung disease, sleep apnea, alveolar hypoventilation disorders, and primary pulmonary hypertension. We also review the current diagnostic studies used to evaluate and study cor pulmonale.
 ...
PMID:Cor pulmonale: an overview. 1608 45

Pulmonary artery hypertension (PAH) is the primary cardiovascular complication encountered in chronic obstructive pulmonary disease (COPD). Cor pulmonale can range clinically from mild changes in right ventricular function to frank right heart failure. The prevalence of PAH increases as COPD worsens, and the development of PAH and cor pulmonale appears to affect survival of patients with COPD. Potential causes proposed to explain the development of PAH in COPD include gas exchange abnormalities, destruction of the pulmonary vascular bed, alterations in respiratory mechanics, changes in intrinsic pulmonary vessel tone, and increased blood viscosity. Standard clinical evaluation, including history, physical examination, spirometry, electrocardiography, and chest radiography, is generally inadequate in identifying right ventricular dysfunction. Noninvasive techniques, such as echocardiography, radionuclide ventriculography, and magnetic resonance imaging, have largely replaced invasive pulmonary artery catheterization in the initial assessment of cor pulmonale. The goals of therapy consist of attenuation of PAH, enhancement of right ventricular function, alleviation of clinical symptoms, and improvement in survival. The agents that have been most extensively evaluated for these purposes include oxygen, vasodilators, theophylline, and inotropic medications.
 ...
PMID:Pulmonary hypertension and cor pulmonale in COPD. 1608 47

Surgical and interventional therapies for pulmonary arterial hypertension (PAH) in appropriately selected patients have the potential to dramatically improve or, in some cases, cure PAH. These include atrial septostomy, a palliative procedure or bridge to transplantation in patients with refractory right heart failure, pulmonary thromboendarterectomy for pulmonary hypertension associated with chronic thromboembolic disease, and closure of congenital systemic-pulmonary shunts in patients with PAH but without significant pulmonary vascular disease. Lung transplantation should be considered for patients with all forms of PAH who demonstrate advanced or progressive disease.
 ...
PMID:Surgical and interventional therapies for pulmonary arterial hypertension. 1612 19


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>