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)

The phosphodiesterase-5 (PDE-5) inhibitor, sildenafil, has been reported to produce sustained pulmonary vasodilatation in patients with pulmonary hypertension (PH). Recently, vardenafil, a more potent and selective PDE-5 inhibitor than sildenafil, has been approved for the treatment of erectile dysfunction. However, the long-term effects of oral vardenafil in patients with PH are unknown. We studied five consecutive patients with PH; one with primary pulmonary hypertension, two with chronic pulmonary thromboembolism, one with Eisenmenger syndrome (ventricular septal defect) and one with secondary pulmonary hypertension after a ventricular septal defect closure operation. In an acute hemodynamic trial, vardenafil (5 mg) significantly decreased both the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) with an increase in cardiac output. In a chronic hemodynamic trial, the maintenance dose of vardenafil (10 to 15 mg) for 3 months significantly decreased the PVR, but not the SVR, with a 20.7% reduction of the PVR/ SVR ratio. Plasma brain natriuretic peptide (BNP) levels were also significantly decreased after 3 months. This pilot study demonstrates that long-term oral vardenafil therapy may be a safe and effective treatment for patients with PH.
...
PMID:Long-term vardenafil therapy improves hemodynamics in patients with pulmonary hypertension. 1675 46

Pulmonary hypertension is a serious disorder, difficult to treat especially in the severe forms. The treatment consists mainly of calcium channel blockers, anti-coagulation, intravenous epoprostenol, inhaled nitric oxide and recent agents as bosentan and sildenafil. Sildenafil, a phosphodiesterase 5 specific inhibitor, has been largely evaluated in primary pulmonary hypertension, and in some cases of secondary pulmonary hypertension including parenchymal and thromboembolic diseases; it has not yet been evaluated in severe pulmonary hypertension with elevated pre-capillary resistance in operated mitral stenosis. We report the cases of two patients operated from mitral valve replacement for severe mitral stenosis with elevated pre-capillary resistance, where oral sildenafil, introduced empirically immediately after the surgical procedure at the dose of 50 mg/d, permitted a significant decrease in pulmonary pressures and resistances, allowing a rapid withdrawal of nitric oxide and reducing therefore hospitalization time in the intensive care unit. We think that this simple treatment, with or without association to nitric oxide, should be generalized to persistent pulmonary hypertension following cardiac surgery.
...
PMID:[Beneficial effect of sildenafil following surgery for mitral stenosis complicated by pre-capillary pulmonary hypertension: report of two cases]. 1707 67

The prevalence of pulmonary arterial hypertension (PAH) in congenital heart anomalies is rising, because an increasing proportion of these patients now reach adulthood. However, morbidity and mortality rates in these patients are modified by the existing cardiac anomaly and thus differ from idiopathic pulmonary hypertension (IPAH). There are, in addition to Eisenmenger's syndrome, special forms such as local PAH or hemodynamically relevant increased pulmonary vascular resistance associated with a dysfunctional or absent right ventricle. In all these forms of PAH it is the therapeutic aim to achieve pulmonary vascular dilatation to reduce symptoms of right ventricular stress and to increase pulmonary blood flow and raise systemic oxygen supply. Just as in IPAH, intravenous, inhaled or oral medications--prostanoids, endothelin-receptor inhibitors, phosphodiesterase-5 inhibitors--are being used with increasing success.
...
PMID:[Pulmonary hypertension in congenital heart disease]. 1713 97

Since the discovery of sildenafil in 1989 as a highly selective inhibitor of the phosphodiesterase type-5 (PDE-5) receptor, 2 additional PDE-5 inhibitors, tadalafil and vardenafil, have emerged as safe and effective treatments of erectile dysfunction (ED). Enzymes in the PDE family catalyze the hydrolysis of the intracellular signaling molecules cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP), which is the second messenger of nitric oxide (NO) and a principal mediator of smooth muscle relaxation and vasodilation. Sildenafil was initially introduced for clinical use as the result of extensive research on chemical agents targeting PDE-5 that might potentially be useful in the treatment of coronary heart disease. Erection is largely a hemodynamic event, which is regulated by vascular tone and blood flow balance in the penis. Endothelial dysfunction, an early component of atherosclerosis, may inhibit a vascular event such as erection and is rarely confined to the arteries supplying blood to the penis, but more likely occurs throughout the vascular bed. In addition to the effects of the NO-cGMP signaling pathway on cavernosal smooth muscle, clinical findings have suggested that vascular tone in the pulmonary, coronary, and other vascular tissues expressed by PDE-5 is also influenced by this signal transduction mechanism. This has led to the emergence of novel therapeutic indications for sildenafil over a range of cardiovascular conditions that are either well-established risk factors or comorbidities with ED. Recently, the U.S. Food and Drug Administration approved sildenafil as an orally active therapy for the treatment of primary pulmonary hypertension. The drug will be marketed under the trade name of Revatio, not Viagra, the name used for the ED indication. The approved dose for primary pulmonary hypertension is 20 mg 3 times daily.
...
PMID:Type 5 phosphodiesterase inhibitors in the treatment of erectile dysfunction and cardiovascular disease. 1730 94

The incidence of pulmonary vascular disorders is significantly increased in patients with liver disease. Intrapulmonary shunting with hypoxemia in patients with liver disease is diagnosed as hepatopulmonary syndrome (HPS), whereas precapillary pulmonary vessel obliteration is identified as portopulmonary hypertension (PPHTN). Because the symptoms of liver disease can mimic those of pulmonary vascular disease, all patients with hepatic failure should be screened for these two diseases. Pulse oximetry effectively screens for hypoxemia associated with HPS, whereas an elevated right ventricular systolic pressure estimated by echocardiography identifies patients at risk of having PPHTN. Liver transplantation is the only effective medical therapy for HPS. However, those who have a resting arterial oxygenation less than 50 mm Hg or a shunt measured by scintigraphic perfusion greater than 20% have an unacceptably high mortality rate following surgery. Compared with HPS, there are more therapeutic options that can bridge patients with PPHTN to transplantation. Drugs used to manage idiopathic pulmonary hypertension have shown promise in the treatment of PPHTN. Prostanoids, endothelin receptor antagonists, and phosphodiesterase-5 inhibitors have improved transplant survival. Despite treatment, however, perioperative mortality for patients with PPHTN remains high. Even with successful transplantation, HPS and PPHTN can persist or develop de novo. Long-term follow-up and surveillance of liver transplant recipients is thus indicated to identify HPS and PPHTN following surgery.
...
PMID:Hepatopulmonary syndrome and portopulmonary hypertension. 1748 15

Hepatopulmonary syndrome (HPS) is found in 4-47% of patients with cirrhosis and is characterized by intrapulmonary vascular dilatations especially in the basal parts of the lung. Liver injury and/or portal hypertension trigger the release of endothelin-l, TNF-alpha, cytokines and mediate vascular shear stress and release of nitric oxide and carbon monoxide, all contributing to intrapulmonary vasodilation. Severe HPS increases mortality (30%) after liver transplantation, especially if Pa O2 is below 50 mmHg. The diagnosis is made by calculating the alveolar-arterial oxygen gradient and by performing a contrast echocardiography. Medical therapy fails and the only long-term treatment available is liver transplantation. More than 85% experience significant improvement or complete resolution in hypoxaemia, but this may take more than 1 year. Portopulmonary hypertension (PPHT) occurs in 2-8% of the patients with cirrhosis. Imbalance between vasodilating (decreased pulmonary expression of eNOS and prostacyclin I2) and vasoconstrictive agents (increased expression of ET-1 and angiotensin 1) may be responsible for misguided angiogenesis and pulmonary hypertension. The diagnosis is made by performing an echocardiography and a right heart catheterisation when systolic pulmonary artery pressure is higher than 30 mmHg on echocardiography. Although prostacyclin analogues are efficacious, adverse effects in terms of safety, tolerability and drug delivery occur. Bosentan is probably the therapy of choice for patients with PPHT because it decreases pulmonary but can also diminish portal hypertension. Sildenafil, a phosphodiesterase-5 inhibitor is used for idiopathic pulmonary hypertension, however, it should be used cautiously in patients with portal hypertension as it may increase portal hypertension by splanchnic vasodilation.
...
PMID:Hepatopulmonary syndrome and portopulmonary hypertension: what's new? 1771 35

Pulmonary hypertension (PH) is a hemodynamic state characterized by elevation in the mean pulmonary arterial pressure and pulmonary vascular resistance leading to right ventricular failure and premature death. PH can be the result of a variety of diseases of different etiologies. Pulmonary arterial hypertension (PAH) should be distinctly differentiated from pulmonary venous hypertension (PVH) as a result of left heart disease. PAH is commonly caused by or associated with an underlying pulmonary, cardiac, or systemic disease (APAH). In the absence of an identifiable etiology or associated underlying disease, PAH is referred to as idiopathic (IPAH). IPAH, formerly known as primary pulmonary hypertension (PPH), is a rare disease most commonly seen in women of childbearing age. Presenting symptoms and signs are nonspecific and include dyspnea on exertion, fatigue, and a loud pulmonary component of the second heart sound. Transthoracic Doppler echocardiography is an excellent noninvasive test to detect the presence of pulmonary hypertension, although every patient should receive a right heart catheterization to confirm the diagnosis. A detailed work up, including laboratory tests and imaging studies, is also indicated to rule out known causes of pulmonary hypertension. Several targeted treatment options have become available in recent years and include parenteral and inhaled prostanoids, oral endothelin receptor antagonists, and oral phosphodiesterase type-5 inhibitors. As a result of their complex care, patients should be referred to centers with expertise in pulmonary hypertension.
...
PMID:Pulmonary hypertension: evaluation and management. 1800 30

Pulmonary hypertension leading to right heart failure can be related to primary lung disease or hypoventilation. Idiopathic pulmonary hypertension is a progressive disease with poor prognosis. Therapy of idiopathic pulmonary hypertension includes: oxygen, calcium channel blockers, diuretics, anticoagulants, prostanoids, endothelin receptor antagonists and phosphodiesterase-5 inhibitors. Patients with pulmonary arterial hypertension (PAH) and pulmonary hypertension due to chronic thrombotic or embolic disease should be treated with vasodilatators. The potent vasodilatators are: prostacyclin PGI2, prostacyclin analogue and endothelin receptor antagonists. For patients with idiopathic PAH classified as NYHA III (New York Heart Association) bosentan is recommended, whereas for patients classified as NYHA IV--epoprostenol. Combination therapy is an emerging therapeutic option in PAH. In BREATH-2 (Bosentan Randomised Trial of Endothelin Antagonist Therapy for PAH) study the efficacy and safety of combining bosentan and epoprostenol given orally was investigated. No significant difference was established between treatment groups in 6-minutes walking distance or NYHA functional class. However other study investigating the combination of bosentan and prostacyclin analogue showed clinical improvement. Additional bosentan therapy may also reduce the epoprostenol dose and therefore decrease its side-effects. Interventional procedures: atrial septostomy and lung transplantation are indicated in patients with advanced NYHA class III and IV symptoms and refractory to available medical treatment. However, currently no management potent enough to cure pulmonary arterial hypertension is available. The introduction of new class of drugs allowed for the improvement of quality of life and overall survival. The choice of drug depends on a variety of factors including accessibility, approval status and patient's preferences.
...
PMID:[Treatment of pulmonary hypertension]. 1854 Jan 80

Despite the importance of the pulmonary circulation as a determinant of exercise capacity in health and disease, studies into the regulation of pulmonary vascular tone in the healthy lung during exercise are scarce. This review describes the current knowledge of the role of various endogenous vasoactive mechanisms in the control of pulmonary vascular tone at rest and during exercise. Recent studies demonstrate an important role for endothelial factors (NO and endothelin) and neurohumoral factors (noradrenaline, acetylcholine). Moreover, there is evidence that natriuretic peptides, reactive oxygen species and phosphodiesterase activity can influence resting pulmonary vascular tone, but their role in the control of pulmonary vascular tone during exercise remains to be determined. K-channels are purported end-effectors in control of pulmonary vascular tone. However, K(ATP) channels do not contribute to regulation of pulmonary vascular tone, while the role of K(V) and K(Ca) channels at rest and during exercise remains to be determined. Pulmonary hypertension is associated with alterations in pulmonary vascular function and structure, resulting in blunted pulmonary vasodilatation during exercise and impaired exercise capacity. Although there is a paucity of studies pertaining to the regulation of pulmonary vascular tone during exercise in idiopathic pulmonary hypertension, the few studies that have been performed in models of pulmonary hypertension secondary to left ventricular dysfunction suggest altered control of pulmonary vascular tone during exercise. Since the increased pulmonary vascular tone during exercise limits exercise capacity, future studies are needed to investigate the vasomotor mechanisms that are responsible for the blunted exercise-induced pulmonary vasodilatation in pulmonary hypertension.
...
PMID:Control of pulmonary vascular tone during exercise in health and pulmonary hypertension. 1858 25

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


<< Previous 1 2 3 4 Next >>

---