Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.15.1 (ACE)
 18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Primary pulmonary hypertension is a rare but difficult-to-manage condition. Adequate clinical trials of agents used in its treatment have not been performed. A variety of drugs have been reported to provide benefit in patients with primary pulmonary hypertension, including beta-adrenoceptor agonists, alpha-adrenoceptor antagonists, and vasodilators such as isosorbide dinitrate, diazoxide, hydralazine, angiotensin converting enzyme inhibitors, prostaglandins and calcium antagonists. Calcium antagonists appear to offer the most promise, although treatment failures have occurred with them as well as with all other drugs used in this condition. In the absence of a specific treatment for primary pulmonary hypertension, several of the agents listed above should be tried before accepting therapeutic failure. Invasive investigation is necessary to adequately monitor the acute response to therapy. Whether combination therapy with 2 or more drugs might improve the response to treatment is an area worthy of further research.
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PMID:Drug treatment of primary pulmonary hypertension. 286 78

We compared immunoreactivity for angiotensin converting enzyme (ACE) in pulmonary artery and lung parenchymal tissues (obtained at the time of resection for lung transplantation) from eight patients with Stage IV primary pulmonary hypertension (PPH) with the reactivity in similar tissues from eight normal donors. ACE immunoreactivity was markedly and consistently increased in the endothelium and subendothelial neointimal regions of elastic pulmonary arteries from patients with PPH as compared with normal pulmonary arteries. Immunoreactivity in normal muscular pulmonary arteries was usually less than in surrounding capillary endothelial cells, whereas it was usually of comparable intensity with that in surrounding alveolar capillaries in muscular pulmonary arteries of patients with PPH. These observations suggest that ACE may be involved in the pathogenesis of vascular remodeling associated with neointimal formation in pulmonary arteries.
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PMID:Angiotensin converting enzyme expression in primary pulmonary hypertension. 888 12

Various drugs are associated with adverse respiratory disorders (ARDs) ranging in severity from mild, moderate to severe and even fatal. Cardioselective and nonselective beta-blockers, calcium antagonists and dipyridamole can induce asthma. ACE inhibitors are mainly associated with cough. Amiodarone is related to a form of interstitial pneumonitis (IP) which can be fatal, tocainidine and flecainidine to a form of IP, and hydrochlorothiazide to a form of IP and pulmonary oedema. Antiasthmatic drugs can be associated with a paradoxical bronchospasm, while leukotriene antagonists are linked to the development of Churg-Strauss syndrome. Nonsteroidal anti-inflammatory drugs including aspirin (acetylsalicylic acid) may induce asthma. Gold is mainly related to IP, penicillamine to IP, systemic lupus erythematosus, bronchiolitis obliterans, and Goodpasture's syndrome. Acute respiratory reactions to nitrofurantoin include dyspnoea, cough, IP, and pleural effusion while IP and fibrosis are common in chronic reactions. Other antibacterials mainly evoke pneumonitis, pulmonary infiltrates and eosinophilia, and bronchiolitis obliterans. ARDs are similar for most categories of cytotoxic agents, with chronic pneumonitis and fibrosis being the most common. Noncardiogenic pulmonary oedema occurs as the most common respiratory complication in opioid agonist addiction. Psychotropic drugs such as phenothiazides, butyrophenones and tricyclic antidepressants can also induce pulmonary oedema. Oral contraceptives may produce asthma exacerbation, while long term use and/or high doses of postmenopausal hormone replacement therapy increase the risk of asthma. Bromocriptine is mainly associated with pleural effusion, while methysergide is usually associated with pleural effusion and fibrosis. Some anorectic agents have been linked to the development of primary pulmonary hypertension. The possibility of the occurrence of ARDs should be taken into account in each individual patient. Although in most cases the adverse effects are unpredictable, they can be reduced to a minimum or prevented if some drugs are avoided or stopped in time.
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PMID:Drug-induced respiratory disorders: incidence, prevention and management. 1094 76

Endogenous peptidases participate in a major way in the formation of peptide pressor substances such as angiotensin II (A II) and endothelin (ET) as well as in the degradation of depressor substances, e.g. atrial natriuretic peptide (ANP) or bradykinin. They include on the one hand the angiotensin converting enzyme (ACE) and endothelin converting enzyme (ECE), on the other hand kinase II for bradykinin and neutral endopeptidase 24.11 (NEP) for ANP. Inhibition of these enzymatic reactions leads to a decline of vasopressors A II and ET and conversely delays the break-down of vasodilatating bradykinin and ANP. The main haemodynamic consequence of this double inhibition is a reduced peripheral vascular resistance and decline of the blood pressure. The concurrent block of both systems (dual inhibition) is more effective than the isolated block of one substance. The first dual endopeptidase inhibitors were ACE inhibitors blocking the conversion of angiotensin I to A II and inhibiting at the same time the degradation of bradykinin by kininase II which is identical with ACE. At present further substances were synthetized with a dual inhibitory effect e.g. on ECE and on NEP (phosphoramidone, thiorphan, ecadatril etc.). Under experimental conditions they have a long-term antihypertensive effect on the vascular wall and heart muscle. The development of another dual ACE and NEP inhibitor has reached already the stage of clinical tests and the first clinical studies. The preparation omapatrilate in amounts of 2.5-80 mg significantly reduced the BP in a dose-dependent way in mild and medium advanced essential hypertension. Normalization of the blood pressure, i.e. a drop below 140/90 mm Hg, was achieved with omapatrilate monotherapy in as many as 83% of patients with hypertension stage I and in 53% patients with essential hypertension stage II. The drop of blood pressure after 20-80 mg/day depended on the degree of hypertension and was comparable or better than monotherapy with lisonopril 20 mg/day or amlodipine 10 mg/day. Treatment with omapatrilate was well tolerated. Dual peptidase inhibitors interfering with the formation of pressor substances and with the degradation of depressor substances seem to be a perspective class of antihypertensives also useful in the treatment of other cardiovascular diseases (heart failure, primary pulmonary hypertension). Before its final inclusion in the therapeutic pattern, further comparative and clinical mortality studies must be implemented.
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PMID:[Dual endopeptidase inhibitors--a new direction in the development of hypertensive agents]. 1104 16

Systemic sclerosis (SSc) is responsible for fibrosis of the dermis and other organs as well as vascular abnormalities. While the pathogenesis of SSc is continually being better understood, there is still no single therapeutic agent that has been shown to increase survival in a prospective randomized trial. Traditional medications such as colchicine and D-penicillamine are disappointing in clinical practice, and the latter one failed to clearly show benefit when tested in a prospective placebo controlled trial comparing conventional high dose versus low dose. Conversely, new disease modifying agents are emerging such as cyclophosphamide (CYC) in interstitial pulmonary disease and stem cell autograft after high dose CYC therapy in patients who develop visceral involvement in the three first years of evolution of the disease. Organ specific therapy may show dramatic benefit, such as angiotensin converting enzyme inhibitors in renal crisis and epoprostenol in primary pulmonary hypertension. We will try to review disease modifying agents available in SSc and emphasize new therapeutic agents that are currently being evaluated, including vasodilators, anti-inflammatory, anti-fibrosing agents and immunosuppressive molecules.
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PMID:[Long-term treatments for systemic sclerosis: what are the perspectives?]. 1221 93

No single therapeutic agent has been shown to increase survival of patients with systemic scleroderma in a prospective randomized trial. Drugs as colchicine and D-penicillamine are disappointing. Conversely, disease modifying agents are emerging such as cyclophosphamide in interstitial pulmonary disease, and stem cell autograft after high dose cyclophosphamide therapy in patients who develop visceral involvement in the three first years of evolution of the disease is under study. Organ specific therapy may show significant benefit, such as angiotensin converting enzyme inhibitors in renal crisis and epoprostenol in primary pulmonary hypertension.
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PMID:[Treatment of scleroderma]. 1253 69

Treatment of systemic sclerosis has been somewhat haphazard and treatment has often been "borrowed" from the experience gained from treating other connective tissue diseases. There was a period of time that was focused mainly on organ-specific manifestations of systemic sclerosis and some advance in preventing vital organ damage (such as renal crisis) was achieved. The vast improvement in mortality from the use of ACE inhibitors raises one's hopes for other effective therapeutic interventions. At this juncture, the evidence is strong that the ACE inhibitors that are used in scleroderma renal crisis are disease-modifying, even without proving it by a randomized controlled trial. The evidence is strong that the use of epoprostenol for primary pulmonary hypertension is life-saving; however, whether epoprostenol is life-saving in the pulmonary hypertension in scleroderma remains to be proven. There are suggestions that bosentan (for the pulmonary hypertension of scleroderma), cyclophosphamide (for SSc alveolitis), stem cell transplant, interferon-gamma (for interstitial pulmonary fibrosis), and methotrexate (for the skin thickening of diffuse scleroderma) may improve organ function or functional activities, but whether they are truly disease-modifying remains to be proven. As we increase our understanding of the pathophysiology of systemic sclerosis and we learn how better to design trials for systemic sclerosis, we may be more successful in developing optimal disease-modifying therapy. Although the treatment of systemic sclerosis remains difficult, there are an increasing number of potentially effective regimens that are undergoing clinical investigations. A rational approach to therapy seems possible, based on a hypothesis of the pathogenesis of systemic sclerosis. Thus, there is accumulating evidence that supports the use of prostacyclin derivatives to treat systemic sclerosis, some evidence that antifibrotic regimens may be effective, and moderate evidence that immunosuppression also may be effective in certain stages of this disease.
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PMID:Update on disease-modifying antirheumatic drugs in the treatment of systemic sclerosis. 1284 2