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

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

Pulmonary hypertertension (PHT) is a rare disease defined by increased resistance of the pulmonary arteries inevitably leading to right heart failure if specific treatment is not given. This disease can occur sporadically (idiopathic or primary PHT), within a familial context (familial PHT, BMPR2 gene mutation), or occur as a complication of other diseases (connective tissue disease, congenital cardiomyopathy, human immunodeficiency virus infection, portal hypertension, use of anorexigenic agents). The incidence of primary PHT is 2 million cases per year, probably an underestimation due to the low specificity of clinical signs, predominantly exercise-induced dyspnea. Recent therapeutic advances (prostacyclin and endothelin receptor antagonists administered in continuous infusion) have improved the prognosis of this orphan disease. Inhaled iloprost and type 5 phosphodiesterase inhibitors should be evaluated for this indication. Lung transplantation is reserved for patients unresponsive to medical treatment.
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PMID:[Pulmonary hypertension: from genetics to treatments]. 1554 47

Sildenafil, a phosphodiesterase type-5 inhibitor, offers potential to treat pulmonary hypertension associated with a variety of conditions. We assessed the early impact of sildenafil on a cohort of patients referred to our unit who had severe pulmonary hypertension secondary to chronic thromboembolic disease which was not amenable to pulmonary thromboendarterectomy and who also had coexisting left ventricular dysfunction. Six patients were studied. Diagnosis of pulmonary embolic disease was made by ventilation perfusion scanning and/or CT pulmonary angiography. All patients were anticoagulated with oral coumarin derivatives and none were considered suitable for pulmonary thromboendarterectomy. Pulmonary hypertension was diagnosed by right heart catheterisation and each patient had Medical Research Council (MRC) dyspnoea score and New York Heart Association (NYHA) class noted and 2D echocardiography prior to commencement of sildenafil 50 mg three times a day. After 6 weeks of sildenafil therapy, right heart catheterisation and 2D echocardiography were repeated, and MRC dyspnoea score, NYHA class and exercise capacity were recorded. All patients demonstrated an improvement in mean pulmonary artery pressure, mean pulmonary capillary wedge pressure, MRC dyspnoea score, NYHA class and gas transfer. No adverse effects of sildenafil were noted. Our data suggests that sildenafil is an effective and well-tolerated therapy for patients with severe pulmonary hypertension associated with pulmonary thromboembolic disease and impaired left ventricular function, producing beneficial effects as early as 6 weeks.
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PMID:Early haemodynamic benefit of sildenafil in patients with coexisting chronic thromboembolic pulmonary hypertension and left ventricular dysfunction. 1572 48

By 2020, chronic obstructive pulmonary disease (COPD) will become the third leading cause of mortality and fifth leading cause of disability worldwide. Although traditionally therapeutic nihilism has dominated the approach to the management of COPD patients, it is becoming increasingly clear that COPD is a highly preventable and treatable condition. Smoking cessation is the most important therapy because it is the only intervention that has been shown to modify the accelerated decline in lung function that is characteristic of COPD. Domiciliary oxygen therapy for those who are hypoxemic at rest results in improved survival. Vaccinations and immunizations against influenza and pneumococcus should be encouraged. Bronchodilators are used for symptomatic relief. Recent introduction of long-acting bronchodilators facilitates good control of dyspnea with once or twice daily dosing. In conjunction with inhaled corticosteroids, they appear to produce added clinical benefits. Pulmonary rehabilitation and lung transplantation are other therapeutic options for select groups of patients. Many promising compounds are in various stages of development as future therapies in COPD. Drugs such as phosphodiesterase 4 inhibitors, tyrosine kinase blockers and peroxisome proliferator-activated gamma receptor agonists show great promise as disease-modifying agents in COPD.
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PMID:Therapeutic options for chronic obstructive pulmonary disease: present and future. 1574 84

We hypothesized that chronic oral administration of the phosphodiesterase-5 inhibitor sildenafil could improve the exercise capacity and pulmonary hemodynamics in patients with pulmonary arterial hypertension (PAH) on the basis of previous short-term studies. We tested this hypothesis in 14 subjects with PAH, including seven patients with the idiopathic form and seven patients with atrial septal defects, but no other congenital heart abnormalities. Patients were subjected to a 6-min walk test and dyspnea was graded according to the Borg scale. Pulmonary flow and pressures were measured by Doppler echocardiography. Patients were given sildenafil, 75 mg orally three times a day, and followed up for 1 year. Sildenafil therapy resulted in the following changes: increase in the 6-min walk distance from a median value of 387 m (range 0 to 484 m) to 462 m (range 408 to 588 m; P < 0.01), improvement of the Borg dyspnea score from 4.0 (median value) to 3.0 (P < 0.01), and increased pulmonary flow (velocity-time integral) from a median value of 0.12 (range 0.08 to 0.25) to 0.23 (range 0.11 to 0.40; P < 0.01) with no changes in pulmonary pressures. In one patient with pulmonary veno-occlusive disease diagnosed by a lung biopsy, sildenafil had a better effect on the pulmonary wedge pressure than inhaled nitric oxide (15 and 29 mmHg, respectively, acute test). He walked 112 m at baseline and 408 m at one year. One patient died at 11 months of treatment. No other relevant events occurred. Thus, chronic administration of sildenafil improves the physical capacity of PAH patients and may be beneficial in selected cases of veno-occlusive disease.
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PMID:One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease. 1578 29

Inhaled nitric oxide (iNO) has been shown to be a potent and selective vasodilator in pulmonary arterial hypertension (PAH). However, the clinical experience in prolonged treatment is limited. We assess the safety and effectiveness of long-term administration of iNO in severe PAH. Two female patients were admitted to our hospital because of severe dyspnea (World Health Organization functional class IV) and hypoxemia. They were diagnosed with PAH (primary and secondary to congenital heart disease) and treated with iNO for 2 years. The delivery system consisted of an NO tank of 800 ppm, a modified gas-pulsing device, and nasal cannulas. On iNO treatment the patients showed remarkable improvement of symptoms, oxygenation and 6-min walk distance. After 16 months the patients began to experience a progressive rebound of symptoms. A phosphodiesterase type 5 inhibitor (dipyridamole) was added to iNO. This intervention proved useful in improving clinical deterioration and hemodynamics. This is the first study reporting 2-year iNO therapy in 2 patients with primary and secondary pulmonary hypertension. The combination of dipyridamole with iNO augments the pulmonary vasodilatation and may be useful in managing PAH.
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PMID:Long-term inhaled nitric oxide plus dipyridamole for pulmonary arterial hypertension. 1608 87

Pulmonary hypertension is a severe life-limitating disease often affecting younger patients. The connection between HIV infection and the development of pulmonary hypertension is well documented. The underlying pathobiology still remains unclear. Given that the prognosis of HIV infection has been improved by highly active antiretroviral therapy (HAART), severe pulmonary hypertension is becoming a life-limiting factor.HIV patients suffering from exercise-induced dyspnea should be tested for pulmonary hypertension, if other pulmonary or cardiac disorders (e. g., restrictive or obstructive ventilation disorders, pneumonia, coronary heart disease) can be excluded. The incidence of pulmonary hypertension is 1,000 times higher in HIV patients as compared to the general population. Estimated numbers of unreported cases are not included.A suspected diagnosis of pulmonary hypertension can be substantiated by noninvasive diagnostic methods (e. g., echocardiography), however, right heart catheterization remains the diagnostic gold standard. As new therapeutic options with prostanoids, endothelin antagonists, and phosphodiesterase-5 inhibitors are now available, early and accurate diagnosis is essential.
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PMID:[HIV-associated pulmonary hypertension ]. 1617 Jun 78

Systolic pulmonary arterial hypertension (PAH) was diagnosed in a 15-year-old intact male Yorkshire terrier presented for progressive dyspnoea and coughing. Several examinations were performed (thoracic radiographs, faecal analysis, heartworm antigen test, tracheal fluoroscopy, abdominal ultrasound, complete blood cell count, urine and serum biochemistry) but the PAH remained of unknown origin. Despite medical treatment (diuretics and angiotensin-converting enzyme inhibitor), cardiovascular and respiratory signs dramatically worsened over a 1-month period, with several daily syncope, cyanosis and tachypnoea at rest requiring permanent oxygen therapy. Oral tadalafil (Cialis), a new long-acting phosphodiesterase-5 inhibitor, belonging to the same family as sildenafil (Viagra), was added to the background therapy. The condition of the dog improved quickly (< 24 h), and short-term follow up (7 days) showed a decrease in systolic pulmonary arterial pressure up to 26 mmHg concomitant with the disappearance of all respiratory and cardiac signs of PAH (cyanosis, syncope and tachypnoea). This case is of interest because it concerns the first reported short-term use of tadalafil in canine PAH. However, long-term studies with a large number of diseased animals are now required before prescription by general practitioners could be recommended.
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PMID:Efficacy of oral tadalafil, a new long-acting phosphodiesterase-5 inhibitor, for the short-term treatment of pulmonary arterial hypertension in a dog. 1653 28

Chronic obstructive pulmonary disease (COPD) is a progressive disease of the airways that is triggered primarily by smoking. It manifests clinically with dyspnea, cough and sputum production, all of which become aggravated with disease progression. The only intervention that can halt the decline in lung function in COPD is smoking cessation--other interventions and therapeutic treatments can only slow down the progression of the disease. Pharmacologic treatment of stable COPD consists primarily of bronchodilators, which are used for relieving symptoms and reducing lung function decline, and corticosteroids, which are used for minimizing the associated inflammation. Methylxanthines are non-selective phosphodiesterase (PDE) inhibitors with bronchodilatory and anti-inflammatory effects; however, their use in COPD and other respiratory conditions is limited by their narrow therapeutic index and poor safety profile. Cilomilast and roflumilast are selective PDE4 inhibitors that are currently in pre-registration and phase III clinical trials, respectively, for the treatment of COPD (cilomilast and roflumilast) and asthma (roflumilast).
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PMID:Roflumilast for the treatment of chronic obstructive pulmonary disease. 1672 16

Acral ulcers in patients with progressive systemic sclerosis (PSS) are often recalcitrant to therapy. Sildenafil, an inhibitor of phosphodiesterase-5, dilates small arteries by increasing endothelial cGMP. Oral administration of sildenafil to a 35-year-old white male patient suffering from incapacitating PSS with severe pulmonary arterial hypertension and acral ulcers induced a clinically significant reduction in dyspnea and increase in walking distance within one week as well as complete and long-lasting healing of all ulcers within five weeks. This case demonstrates the efficacy of sildenafil in the treatment of scleroderma-associated refractory acral ulcers.
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PMID:[Fast and efficient healing of scleroderma-associated acral ulcers with sildenafil]. 1761 9

A 7-month-old male Papillon was presented to us with mild dyspnea, cyanosis and a diastolic murmur detected by cardiac auscultation. Echocardiography revealed severe pulmonary arterial hypertension (PH), and administration of 1 mg/kg of oral sildenafil, a phosphodiesterase type 5 (PDE5) inhibitor, twice daily was initiated. Exercise capacity, cyanosis, dyspnea and cardiac murmur were improved after therapy for 4 weeks. PCV was remarkably high (74%) after therapy for 3 years, however, increasing the dose of sildenafil decreased this value (60%). Follow-up after therapy for 4 years revealed that treatment with oral sildenafil only continued to provide the dog with an excellent quality of life, without any side effects.
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PMID:A case of long-term sildenafil therapy in a young dog with pulmonary hypertension. 1798 97


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