Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.4.1 (phosphodiesterase)
 18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Microvascular abnormalities and fibrosis are important targets of therapy in systemic sclerosis (scleroderma). Calcium channel blockers, ACE inhibitors, sartans, phosphodiesterase-5 inhibitors and serotonin re-uptake blockers are used for Raynaud's phenomenon. Intravenous prostanoids (alprostadil, iloprost, epoprostenol, treprostinil) and endothelin receptor antagonists (bosentan, sitaxsentan, ambrisentan) show efficacy in treatment of pulmonary hypertension and distal ischemia. Successful treatment of digital ulcers secondary to systemic sclerosis was possible with sildenafil and bosentan. A platelet gel is currently in clinical trials for scleroderma-related digital ulcers. Several drugs, which directly reduce excessive production of collagens and other connective tissue proteins have been applied in systemic sclerosis. These include interferon gamma, d-penicillamine, kolchichicine, calcitriol, and imanitib. However, so far, strategies to control fibrosis by directly reducing excessive connective tissue production have been disappointing in controlled studies.
 ...
PMID:[Current treatment of systemic sclerosis. Part II. Vascular and antifibrotic treatment]. 1894 47

Current knowledge about the pathogenesis of Raynaud's phenomenon (RP) results in novel approaches for therapy. Vasospasm without endothelial damage is thought to be the main cause for primary RP. The pathogenesis of secondary forms of RP is supposed to be initiated primary by endothelial damage. The aim of the review is to present main groups of medications as well as non-pharmacological regimen, that are used for the treatment of RP. The necessity of immediate assessment and treatment in severe forms of the disease with digital ulcers is highlighted. The mild forms of primary RP can be controlled by non-pharmacologic approaches. If the effect is insufficient, medications of first choice are calcium channel blockers. In the severe forms of the disorder, intravenous infusion of prostacyclin as well as endothelin-1 receptor antagonists and specific inhibitors of phosphodiesterase-5 are the treatment of choice. Treatment in the future may include selective blockers of alpha-2c adrenergic receptors, inhibitors of protein tyrosine kinase and Rho-kinase, as well as calcitonin gene-related peptide.
 ...
PMID:New lines in therapy of Raynaud's phenomenon. 1903 2

Fibrosis, inflammation and vascular dysfunction are major features of systemic sclerosis and the multiple organ-specific complications that characterize this disease. Several manifestations of systemic sclerosis, including Raynaud's phenomenon, digital ulceration, scleroderma renal crisis and pulmonary arterial hypertension, contribute significantly to morbidity and mortality and are understood to share similarities in their underlying vasculopathy. In recent years, a number of treatment options have become available that ease the burden of these manifestations, including calcium channel blockers, angiotensin converting enzyme inhibitors, prostanoids and prostacyclin analogs, endothelin receptor antagonists, and phosphodiesterase type-5 inhibitors. Several of these treatments have demonstrated beneficial effects against more than one complication, as a result of the similarities in the pathology underlying these manifestations. However, physicians involved in the management of patients with systemic sclerosis are faced with differing levels of evidence supporting these treatments, and historically little international consensus on the treatment of some manifestations, such as digital ulcers. The aim of this article is to evaluate the level of evidence supporting each intervention in systemic sclerosis, thereby facilitating decision-making in the clinic.
 ...
PMID:The manifestations of vasculopathy in systemic sclerosis and its evidence-based therapy. 2037 46

Raynaud's phenomenon is a common condition characterized by vasospasm of the digital arteries and resulting cyanosis and redness. It often does not require pharmacologic management, but in some cases symptoms are severe and pharmacologic management is necessary. Calcium channel blockers are often used first-line, but in some patients are ineffective. Patients with severe symptoms or intolerance to available therapies have prompted exploration of alternative therapies, including endothelin antagonists, phosphodiesterase-5 inhibitors, antioxidants, newer vasodilators, statins, and botulinum toxin. These newer therapies provide the focus for this review.
 ...
PMID:Advances in the treatment of Raynaud's phenomenon. 2044 1

Pulmonary arterial hypertension (PAH) is an important complication of connective tissue diseases (CTD) and especially seen in systemic sclerosis, systemic lupus erythematosis (SLE), and mixed connective tissue disease (MCTD). In systemic sclerosis, PAH is isolated or accompanied by interstitial lung disease and currently, a major cause of mortality. It has been shown to be developed in approximately 10% of cases and annual screening with echocardiography has been recommended. Right heart catheterization is required for definite diagnosis. Limited skin involvement, late onset, Raynaud's phenomenon, digital ulcers, telangiectasias, diminished nail fold capillaries, anti-U3RNP and anticentromere antibodies are known as risk factors for PAH development in systemic sclerosis. Following diffusion lung capacity for carbon monoxide (DLCO) and pro-brain natriuretic peptide (pro-BNP) levels can be helpful for evaluating PAH development. PAH in SLE linked to antiphospholipid antibodies and Raynaud's phenomenon in some studies. MCTD is an overlap syndrome with features of systemic sclerosis, SLE, polymyositis and positive anti-U1RNP antibodies. PAH develops in 9-27% of the patients and the leading cause of mortality in patients with MCTD. Endothelin receptor antagonists, prostacyclin analogs and phosphodiesterase 5 inhibitors are being used in patients with systemic sclerosis. In SLE/MCTD patients with early diagnosis immunosuppressive treatments may be effective.
 ...
PMID:[Pulmonary arterial hypertension related to connective tissue diseases]. 2081 68

Systemic Sclerosis (SSc) is a connective tissue disorder featuring vascular alterations and an immunological activation leading to a progressive and widespread fibrosis of several organs such as the skin, lung, gastrointestinal tract, heart, and kidney. Men with SSc are at increased risk of developing erectile dysfunction (ED) because of the evolution of early microvascular tissutal damage into corporeal fibrosis. The entity of penile vascular damage in SSc patients has been demonstrated by using Duplex ultrasonography and functional infra-red imaging and it is now clear that this is a true clinical entity invariably occurring irrespective of age and disease duration and constituting the ''sclerodermic penis". Once-daily phosphodiesterase type-5 (PDE5) inhibitors improve both sexual function and vascular measures of cavernous arteries by improving surrogate markers of endothelial dysfunction, that is, plasma endothelin-1 and adrenomedullin levels, which may play a potential role in preventing progression of penile fibrosis and ED. Also, the beneficial effect of long-term PDE5i add-on therapy to SSc therapy in the treatment of Raynaud's phenomenon is described.
 ...
PMID:Penile involvement in Systemic Sclerosis: New Diagnostic and Therapeutic Aspects. 2098 15

Treatment of systemic sclerosis is based upon 3 types of medications modifiers of disease: drugs which prevent vascular damage, antifibrotric agents, and immunomodulators and immunosupressors. Drugs that prevent vascular damage such as: calcium antagonists, prostaglandins analogues, receptors of endothelin blockers (bosentan), inhibitors of angiotensin converting enzyme, receptors of angiotensin antagonists and inhibitors of 5'-phosphodiesterase have been successful in treating the Raynaud's phenomenon, renal crisis and pulmonary arterial hypertension. In contrast, the results of treatment of fibrosis are discouraging and the D-penicilamine continues being a matter of controversy. The immunosupressor therapy with cyclophosphamide and the transplant of hematopoietic cells, may be beneficial. The knowledge of the pathogenesis of systemic sclerosis to molecular level will lead to new treatment strategies.
 ...
PMID:[Treatment of systemic sclerosis]. 2179 87

Phosphodiesterase-5 inhibitors (PDE5Is) improve erectile function by enhancing nitric oxide availability in the penis and its supplying vasculature, resulting in vasodilation and increased blood flow. PDE5Is might benefit cardiovascular diseases because phosphodiesterase-5 is also located elsewhere in the body, including the pulmonary and systemic vasculature and in hypertrophied myocardium. PDE5Is are approved for pulmonary arterial hypertension, given that they improved several hemodynamic and clinical parameters in large randomized trials. Initial evidence suggests that PDE5Is benefit patients with congestive heart failure and secondary pulmonary hypertension. PDE5Is seem to improve hemodynamic and clinical parameters in patients with high-altitude pulmonary edema (HAPE) and high-altitude pulmonary hypertension. In climbers with prior episodes of HAPE, PDE5Is prevented HAPE in 2 small randomized trials. In small randomized trials of PDE5Is, patients with Raynaud's phenomenon demonstrated improved blood flow, fewer symptoms and frequency of attacks, and resolution of digital ulcers. In addition to enhancing vasodilation, PDE5Is seem to protect the myocardium through complex pathways that involve nitric oxide, cyclic guanosine monophosphate, protein kinase G, extracellular-signal-regulated kinase, B-cell lymphoma protein-2, and Rho kinase inhibition. In animal models of acute myocardial infarction, PDE5Is consistently reduced infarct size indicating cardioprotection and PDE5Is also promote reverse remodeling and reduce myocardial apoptosis, fibrosis, and hypertrophy. PDE5Is might also benefit patients with treatment-resistant hypertension, preeclampsia, or peripheral arterial disease. This review presents the pathophysiology and trial data with regard to the use of PDE5Is for cardiac diseases.
 ...
PMID:Cardiac uses of phosphodiesterase-5 inhibitors. 2219 62

Digital skin vasoconstriction on local cooling is exaggerated in primary Raynaud's phenomenon (RP) as compared with controls. A significant part of such vasoconstriction relies on the inhibition of the nitric oxide (NO) pathway. We tested the effect of the phosphodiesterase 5 (PDE5) inhibitor sildenafil, which potentiates the effect of NO, on skin blood flow. We recruited 15 patients with primary RP, performing local cooling without sildenafil (day 1), after a single oral dose of 50 mg (day 2), and after a dose of 100 mg (day 3). Skin blood flow, skin temperature, and arterial pressure were recorded, and data were expressed as cutaneous vascular conductance (CVC). Sildenafil at 100 mg, but not 50 mg, significantly lessened the cooling-induced decrease in CVC. It also increased resting CVC and skin temperature. These data suggest that 100 mg sildenafil improves digital skin perfusion during local cooling in primary RP. The benefit of sildenafil "as required" should be confirmed in a randomized, controlled trial.
 ...
PMID:Sildenafil increases digital skin blood flow during all phases of local cooling in primary Raynaud's phenomenon. 2245 96

The effects of phosphodiesterase type 5 inhibitors on vasodilation mediated via nitric oxide-cyclic guanosine monophosphate are well described. Less is known about other mechanisms through which phosphodiesterase type 5 inhibitors benefit endothelial function, including normalization of serum biomarkers, increased levels of endothelial progenitor cells, ischemia-reperfusion protection mechanisms, and other actions specific to patients with diabetes. These various mechanisms are reviewed. Their impact on several cardiovascular diseases, including erectile dysfunction, pulmonary hypertension, heart failure, high-altitude pulmonary edema, Raynaud's phenomenon, coronary artery disease, diabetes, and atherosclerosis, is presented.
 ...
PMID:Phosphodiesterase type 5 inhibitors improve endothelial function and may benefit cardiovascular conditions. 2341 May 57


<< Previous 1 2 3 4 Next >>