Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

Query: EC:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary arterial hypertension (PAH) is a disease characterized by an elevation in pulmonary artery pressure that can lead to right ventricular failure and death. Conventional treatment is based on non-specific drugs (warfarin, oxygen, diuretics). Pure vasodilators like calcium channel antagonists have little or no effect on the vast majority of patients. Although there is no cure for PAH, newer medical therapies have been shown to improve a variety of clinically relevant end-points including survival, functional class, exercise tolerance, haemodynamics, echocardiographic parameters and quality of life measures. Intravenous prostacyclin, was the first introduced drug for treatment of PAH and remains the first-line treatment for the most severe patients. Since then the list of approved drugs for PAH has expanded to include prostacyclin analogues with differing routes of administration, a dual endothelin receptor antagonist, and a phosphodiesterase-5 inhibitor. Novel drugs have also shown promise in experimental trials and are likely to be added to the list of options. This article reviews the current treatments strategies for PAH.
...
PMID:Current pharmacological treatment of pulmonary arterial hypertension. 1869 Aug 74

Pulmonary arterial hypertension (PAH) is a devastating disease that is characterized by a high mortality. The pathogenesis of PAH is multifactorial. In addition to hereditary factors (e. g., BMPR2 mutations), numerous environmental factors may trigger the onset and progression of the disease. An imbalance between vasoconstrictive and vasodilative factors leads to vasoconstriction in the pulmonary circuit, resulting in an increase of pulmonary vascular resistance and pulmonary artery pressure. Alterations of several signaling pathways (i. e.; endothelin, nitric oxide and prostacyclin pathways) contribute to an increase of pulmonary vascular tone, and these pathways represent the targets of the current therapeutic interventions. However, PAH is increasingly recognized as a chronic proliferative disease particularly of the small pulmonary arteries, that is primarily characterized by morphological changes of the vascular wall ("vascular remodeling"). These changes are particularly induced by peptide growth factors such as platelet-derived growth factor (PDGF) that elicit their signals via activation of membrane-bound receptor tyrosine kinases (RTK). Accordingly, there is both experimental and clinical evidence for a therapeutic efficacy of tyrosine kinase inhibitors (TKI), which provide the basis for "reverse remodeling" strategies and indeed represent a promising novel approach for the treatment of PAH. Epidermal growth factor (EGF), soluble guanylate cyclase (sGC), and phosphodiesterase type 1 (PDE1) may represent additional future target molecules. PAH leads to progressive right heart failure which determines the outcome of PAH patients. The pathomechanisms of right heart failure should therefore also be considered for the development of novel therapeutic concepts.
...
PMID:[Novel concepts in the pathobiology of pulmonary arterial hypertension]. 1881 87

Pulmonary arterial hypertension (PAH) is a progressive albeit rare long-term complication of HIV infection, which has gained importance following the improved survival of HIV-infected patients with the use of HAART. The clinical and pathological findings in PAH associated with HIV infection (HIV-PAH) share many features with the idiopathic form of the disease. HIV-PAH is associated with a particularly poor prognosis and decreased survival compared with HIV-infected patients without this complication, and patients with HIV-PAH tend to die from the effects of PAH rather than as a result of their HIV infection. Prompt diagnosis and effective treatment of PAH in HIV-infected patients is therefore essential. There are currently only limited data regarding the efficacy of PAH therapies in HIV-PAH. Treatment with epoprostenol has been reported to provide benefit in some cases, but is associated with a range of problems linked to the need for continuous intravenous infusion. The dual endothelin receptor antagonist bosentan has proved to be effective in HIV-PAH without affecting the control of HIV infection, and has the benefit of oral administration. Other PAH therapies including prostacyclin analogs, phosphodiesterase type 5 inhibitors and selective endothelin receptor antagonists have yet to be trialed in this setting. Taking into account currently available data and clinical experience, a treatment algorithm for HIV-PAH based on that defined in treatment guidelines for other forms of PAH is suggested.
...
PMID:HIV-related pulmonary arterial hypertension: clinical presentation and management. 1884 23

Pulmonary arterial hypertension is a progressive, fatal disease. Current treatments including prostanoids, endothelin-1 (ET-1) antagonists, and phosphodiesterase (PDE) inhibitors, have sought to address the pulmonary vascular endothelial dysfunction and vasoconstriction associated with the condition. These treatments may slow the progression of the disease but do not afford a cure. Future treatments must target more directly the structural vascular changes that impair blood flow through the pulmonary circulation. Several novel therapeutic targets have been proposed and are under active investigation, including soluble guanylyl cyclase, phosphodiesterases, tetrahydrobiopterin, 5-HT2B receptors, vasoactive intestinal peptide, receptor tyrosine kinases, adrenomedullin, Rho kinase, elastases, endogenous steroids, endothelial progenitor cells, immune cells, bone morphogenetic protein and its receptors, potassium channels, metabolic pathways, and nuclear factor of activated T cells. Tyrosine kinase inhibitors, statins, 5-HT2B receptor antagonists, EPCs and soluble guanylyl cyclase activators are among the most advanced, having produced encouraging results in animal models, and human trials are underway. This review summarises the current research in this area and speculates on their likely success.
...
PMID:Therapeutic targets in pulmonary arterial hypertension. 1901 Mar 50

Pulmonary arterial hypertension (PAH), previously known as primary pulmonary hypertension, is characterized by a progressive increase in pulmonary vascular resistance leading to right ventricular failure and death. Recently dramatic advance in medical therapy including prostanoids, endothelin-receptor antagonists, phosphodiesterase 5 inhibitors, has occurred, and American College of Chest Physicians(ACCP) Evidence-Based Clinical Practice Guidelines have been proposed, followed by several guidelines for treatment of pulmonary hypertension in our country. Additionally several reports have provided utility of combination therapy. This article summarizes recent medical therapy for PAH including updated ACCP guidelines in 2007, further advance, and recommended therapeutic approach for PAH, available in our country.
...
PMID:[Recommended guideline for the use of medical therapy in pulmonary hypertension]. 1905 32

Pulmonary arterial hypertension (PAH) is serious and a progressive disease with relatively poor prognosis if not identified and treated early in children. In pediatric age group, the transition of the pulmonary circulation from fetal life to neonatal period plays a pivotal role to maintain the pulmonary vascular resistance to be low. In children with iPAH, acute drug response to vasodilator is more prominent than that in adult. But, prognosis is relatively poor. Recently, phosphodiesterase (PDE) 5 inhibitor (sildenafil, Viagra) and endothelin receptor antagonist (bosentan, Tracleer) in addition to prostacyclin used as a combination therapy can be used for this age population. The 5-year survival has been improved to > 80%. In this chapter, we focus on pathophysiological aspects and treatment strategy of idiopathic PAH, familial PAH, and PAH in the neonate (ex. PPHN).
...
PMID:[Pulmonary arterial hypertension in pediatric age]. 1905 42

Pulmonary arterial hypertension (PAH) has evolved from an untreatable condition to a disease for which several classes of drugs have now been approved, including various prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Because the pathogenesis of pulmonary hypertension is increasingly understood, various new substances are now under clinical investigation, including serotonin antagonists, vasoactive intestinal peptide, stimulators of soluble guanylate cyclase and tyrosine kinase inhibitors. Several of these compounds hold promise for the future therapy of PAH, especially as regression of pulmonary vascular remodeling appears to become a realistic possibility with the combination of established and novel treatments.
...
PMID:Novel approaches to the pharmacotherapy of pulmonary arterial hypertension. 1912 10

Pulmonary arterial hypertension (PAH) is characterized by vasoconstriction, in situ thrombosis, and vascular remodeling of small pulmonary arteries inducing increased pulmonary arterial resistance. Conventional treatment is based on life style modification and nonspecific treatment (warfarine, diuretics, oxygen). Calcium channel blockers are vasodilatators that have been shown to be of great efficacy in a very specific subpopulation of patients with PAH. For the majority of patients, specific PAH therapies are still lacking. Numerous studies evaluating prostacyclin agonists, endothelin-receptor antagonists, and phosphodiesterase type 5 inhibitors are now available to guide therapeutic choices. Despite those important advances there is still no cure for PAH. Fortunately, research is ongoing and many drugs show promises.
...
PMID:Therapeutic advances in pulmonary arterial hypertension. 1912 76

Pulmonary arterial hypertension is a progressive, symptomatic, and ultimately fatal disorder for which substantial advances in treatment have been made during the past decade. Effective management requires timely recognition and accurate diagnosis of the disorder and appropriate selection among therapeutic alternatives. Despite progress in treatment, obstacles remain that impede the achievement of optimal outcomes. The current article provides an overview of the pathobiologic mechanisms of pulmonary arterial hypertension, including genetic substrates and molecular and cellular mechanisms, and describes the clinical manifestations and classification of pulmonary arterial hypertension. The article also reviews established approaches to evaluation and treatment, with emphasis on the appropriate application of calcium channel blockers, prostacyclin analogues, endothelin receptor antagonists, and phosphodiesterase 5 inhibitors. In addition, the authors discuss unresolved issues that may complicate patient management, such as the clinical importance of mild or exercise-related pulmonary arterial hypertension, and they identify avenues by which treatment may advance in the future through the use of combination treatment, outcomes assessment, and exploration of alternative pharmacologic strategies.
...
PMID:Pulmonary hypertension: diagnosis and management. 1918 54

Pulmonary arterial hypertension (PAH) is often treated with endothelin (ET) receptor blockade or phosphodiesterase-5 (PDE5) inhibition. Little is known about the specific effects on right ventricular (RV) function and metabolism. We determined the effects of single and combination treatment with Bosentan [an ET type A (ET(A))/type B (ET(B)) receptor blocker] and Sildenafil (a PDE5 inhibitor) on RV function and oxidative metabolism in monocrotaline (MCT)-induced PAH. Fourteen days after MCT injection, male Wistar rats were orally treated for 10 days with Bosentan, Sildenafil, or both. RV catheterization and echocardiography showed that MCT clearly induced PAH. This was evidenced by increased RV systolic pressure, reduced cardiac output, increased pulmonary vascular resistance (PVR), and reduced RV fractional shortening. Quantitative histochemistry showed marked RV hypertrophy and fibrosis. Monotreatment with Bosentan or Sildenafil had no effect on RV systolic pressure or cardiac function, but RV fibrosis was reduced and RV capillarization increased. Combination treatment did not reduce RV systolic pressure, but significantly lowered PVR, and normalized cardiac output, RV fractional shortening, and fibrosis. Only combination treatment increased the mitochondrial capacity of the RV, as reflected by increased succinate dehydrogenase and cytochrome c oxidase activities, associated with an activation of PKG, as indicated by increased VASP phosphorylation. Moreover, significant interactions were found between Bosentan and Sildenafil on PVR, cardiac output, RV contractility, PKG activity, and mitochondrial capacity. These data indicate that the combination of Bosentan and Sildenafil may beneficially contribute to RV adaptation in PAH, not only by reducing PVR but also by acting on the mitochondria in the heart.
...
PMID:Endothelin receptor blockade combined with phosphodiesterase-5 inhibition increases right ventricular mitochondrial capacity in pulmonary arterial hypertension. 1939 50


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

---