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:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The coexistence of diabetes mellitus in hypertensive patients doubles the number of cardiovascular events (relative risk: 1.73-2.77) and cardiovascular mortality (relative risk: 2.25-3.66). Therapeutic interventions concentrating on elevated blood glucose alone for prevention of late complications were not effective in essential reduction of cardiovascular morbidity and mortality. For that reason therapies, focussing on other macrovascular risk factors, did increase significantly in the last decade. Strategies for reduction of the macrovascular risk include the aggressive treatment of hypertension. In the now published hypertension intervention studies in diabetic patients many different objectives were studied. As we already know, lowering of blood pressure does reduce cardiovascular risk. The optimal blood pressure threshold is not known yet, but of major interest. To find the most effective antihypertensive agent and the most effective combination therapy for diabetic patients, the most frequently used antihypertensive agents were compared with each other. Very interesting are the special effects of some substances, which exceed the lowering of blood pressure, like effects on the endothelinn or on coagulation disturbances. These protective and antiatherosclerotic effects could possibly get relevance even in normotensive patients. Concerning this special question, ACE-inhibitors and Angiotensin II receptor antagonists are getting more and more in the focus of interest and seem to be superior compared to other substances. Concluding the existing evidence from hypertension studies the following recommendations can be deduced: Diabetic patients with at least one additional cardiovascular risk factor should get an ACE-inhibitor in combination with other antihypertensive agents or as monotherapy. For combination therapy all the available antihypertensive agents are appropriate and can lower blood pressure adequately.
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PMID:[Reduction of cardiovascular morbidity and mortality by combined antihypertensive drug therapy in patients with type 2 diabetes mellitus]. 1209 90

The ideal antihypertensive drug should be effective in reducing blood pressure, but have a low incidence of adverse effects. Angiotensin II receptor blockers, such as eprosartan, are as effective as ACE inhibitors in reducing blood pressure, but lack the main adverse effect of ACE inhibitors, namely cough. Eprosartan has been shown to be well tolerated with a placebo-like adverse-effect profile. When given as monotherapy it is effective in reducing blood pressure; however, some patients require additional blood pressure control, which may be provided by combination therapy. Indeed, the combination of eprosartan and the thiazide diuretic hydrochlorothiazide has been shown to be effective in further reducing blood pressure in patients not optimally responding to eprosartan monotherapy. This article reviews the safety and tolerability of eprosartan in combination with hydrochlorothiazide from 17 studies of 1899 patients with hypertension and normotensive volunteers. Of these studies, four were controlled with patients receiving a fixed-dose combination, six were long-term, open-label, and another four were controlled studies with hydrochlorothiazide being given to eprosartan non-responders. The other three studies included healthy subjects receiving the combination of eprosartan and hydrochlorothiazide. There was a high completion rate in all studies evaluated. Most of the patients receiving eprosartan 600mg in combination with hydrochlorothiazide 12.5mg daily completed the studies, which supports acceptance of this combination therapy by patients. The most frequently reported adverse events in these combination studies were headache, dizziness, myalgia, and upper respiratory tract infection in patients with hypertension. The majority of adverse events were mild to moderate in intensity, and were not considered to be related to study treatment. The adverse event that was more common in patients receiving combination therapy compared with those receiving monotherapy was dizziness. This adverse event may be due to hydrochlorothiazide as it has previously been observed in patients taking thiazide diuretics. In healthy volunteers, the most frequently reported adverse events were headache, dizziness, and upper respiratory tract infection. However, none of these adverse events were considered related to study medication. In summary, the combination of eprosartan/hydrochlorothiazide is well tolerated, both as short- and long-term therapy, with most adverse events occurring early. The most frequent adverse events were headache, dizziness, and upper respiratory infection, which would be expected based on the safety profile of each of the components. Therefore, the combination of eprosartan with hydrochlorothiazide can be effectively and safely used in patients not adequately responding to eprosartan monotherapy.
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PMID:Safety and tolerability of eprosartan in combination with hydrochlorothiazide. 1211 44

Angiogenesis, cellular growth and invasion of a cancer cell are attractive targets for new treatment strategies of malignancies in recent years. The evidences are accumulating that ACE inhibitors and angiotensin II type 1 antagonists could be novel anti-angiogenic, anti-invasive, and even anti-growth agents against neoplastic tissues: The renin-angiotensin system promotes angiogenesis directly or indirectly and growth of neoplastic cell. Some tumors carry angiotensin II type 1 receptors. Angiotensin II antagonists and angiotensin-I-converting enzyme inhibitors have shown some anti-neoplastic actions. Angiotensin II receptor blocker losartan antagonises platelets, which are thought to modulate via vascular endothelial growth factor. They may even protect the patient from the major toxicity of chemotherapy and/or radiotherapy, myelotoxicity, enabling us to give higher doses and end up with higher success rate. We believe that these agents can be useful on clinical grounds and suggest their incorporation into clinical studies.
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PMID:Old antihypertensives as novel antineoplastics: angiotensin-I-converting enzyme inhibitors and angiotensin II type 1 receptor antagonists. 1220 67

Cardiovascular disease is common, affecting an increasing number of persons as the population ages. To combat this growing health problem, physicians use a multitude of medications in the treatment of their patients. Although pharmacologic therapy greatly enhances quality of life for a majority of patients, there is always the potential for an unfavorable reaction. For example, cardiovascular drugs can induce a vast array of adverse dermatologic responses. This article reviews the various cutaneous reaction patterns that can occur as a result of treatment with class III, IV, and other antiarrhythmic agents, ACE inhibitors, Angiotensin II receptor blockers, and diuretics.
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PMID:Adverse dermatologic effects of cardiovascular drug therapy: part II. 1221 92

Angiotensin II receptor blockers (ARBs) directly inhibit the angiotensin II type 1 receptors, which suppresses the renin-angiotensin-aldosterone system (RAAS). Six ARBs are approved in Canada for the treatment of hypertension, none are yet approved for the treatment of heart failure (HF). Evidence comparing ARBs to angiotensin converting enzyme inhibitors (ACEIs) in HF is still limited. A recent meta-analysis of 17 clinical trials could not confirm that ARBs are superior to ACEIs in reducing either mortality or hospitalization in HF patients. ARBs may be used as an alternative in HF patients intolerant of ACEIs. A meta-analysis indicates that, compared to using an ACEI alone, adding an ARB to an ACEI carries the potential for additional benefits in terms of reduced hospitalization, but not mortality. However, the FDA determined there is currently insufficient evidence of such additional benefit when valsartan is combined to an ACEI in patients with HF.
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PMID:Heart failure: is there a role for angiotensin II receptor blockers? 1224 2

Recently, both researchers and clinicians have focused their attention to the blockade of the renin-angiotensin system (RAS). Their efforts resulted in discovery of ACE inhibitors. ACE inhibitors proved to be effective antihypertensive drugs. However, their excellent antihypertensive efficacy has been limited by frequent occurrence of adverse effects, among which cough occupies a prominent place. Angiotensin II receptor antagonists could completely block RAS, having significantly less adverse effects than ACE inhibitors. Clinical studies have demonstrated that angiotensin II receptor antagonists are equally effective in the treatment of hypertension as diuretics, beta blockers, calcium antagonists and ACE inhibitors. Also the studies showed angiotensin II receptor antagonists to have an additional advantage, i.e. the frequency of their adverse effects matches that of placebo. All today available angiotensin II receptor antagonists--losartan, valsartan, irbesartan, candesartan, eprosartan, and telmisartan--equally lower both systolic and diastolic pressure. This new class of drugs can be used as monotherapy or can be combined with other antihypertensive drugs, especially with diuretics. Trials now underway will demonstrate whether angiotensin II receptor antagonists can prevent target-organ damage and reduce cardiovascular morbidity and mortality.
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PMID:[Role of angiotensin II antagonists in the treatment of hypertension]. 1237 64

The continued poor rates of blood pressure (BP) control to the recommended target BP of <140/90 mm Hg in patients with hypertension indicate a persistent need for improved antihypertensive therapy. Angiotensin II receptor blockers (ARBs) constitute the newest approved class of antihypertensive agents. As with angiotensin converting enzyme inhibitors, ARBs block the renin-angiotensin-aldosterone system, but do so through a more specific mechanism. Angiotensin converting enzyme inhibitors block the conversion of angiotensin I to angiotensin II, but angiotensin II may be produced by several alternate pathways. Angiotensin II receptor blockers, by contrast, inhibit the binding of angiotensin II to the angiotensin II type 1 (AT1) receptor, independent of the pathway of angiotensin II production. Comparative safety and efficacy trials indicate that ARBs are similar to other antihypertensive drugs in terms of BP-lowering effectiveness and have superior tolerability. Olmesartan medoxomil is the newest and one of the most effective of the ARBs. In controlled trials, it has been shown to provide 24-h BP control with antihypertensive efficacy at least as good as that of the calcium channel blockers amlodipine besylate and felodipine and the beta-blocker atenolol. In a comparative study, olmesartan medoxomil demonstrated significantly greater reductions in diastolic BP than did three other leading ARBs-losartan potassium, irbesartan, and valsartan. With the convenience of placebo-like tolerability and once-daily dosing, combined with excellent antihypertensive efficacy, olmesartan medoxomil may be a useful addition to our management of hypertension.
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PMID:Strategies to meet lower blood pressure goals with a new standard in angiotensin II receptor blockade. 1238 91

Diabetes mellitus is the most common cause of end-stage renal disease in the United States, accounting for about 50% of all new cases. Although we previously established the renoprotective benefits of angiotensin converting enzyme (ACE) inhibitors in patients with coexisting hypertension and type 1 diabetes, evidence of the renoprotective effect of ACE inhibitors in patients with type 2 diabetes is less clear. We conducted the Irbesartan Diabetic Nephropathy Trial (IDNT) to determine whether the angiotensin II receptor blocker (ARB) irbesartan slows the progression of nephropathy in patients with type 2 diabetes independently of its blood pressure (BP)-lowering effect. In this randomized, controlled trial, we found that irbesartan was associated with a 20% reduction in the risk for the primary composite end point (doubling of the baseline serum creatinine concentration, development of end-stage renal disease, or death from any cause) compared with placebo (P =.02) and a 23% reduction compared with amlodipine therapy (P =.006). These results were not explained by differences in the BP that was achieved. In a separate study, losartan was shown to reduce the risk for progression of renal disease in patients with type 2 diabetic nephropathy. Angiotensin II receptor blocker therapy has also been demonstrated to slow the progression to overt nephropathy when initiated early in the course of type 2 diabetic renal disease (ie, in patients with microalbuminuria). Based on these studies, ARBs are clearly effective in protecting against the progression of nephropathy due to type 2 diabetes. This protection is independent of their BP-lowering effect. Preclinical studies with the newest ARB, olmesartan medoxomil, suggest that this agent may provide renoprotective benefits as well.
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PMID:The role of angiotensin II receptor blockers in preventing the progression of renal disease in patients with type 2 diabetes. 1238 93

Percutaneous transluminal coronary angioplasty (PTCA) and stent implantation are useful techniques for treating patients with coronary atherosclerosis. However, the long-term efficacy of these treatment is limited by vascular restenosis, which occurs after these procedures. Although ACE inhibitor cilazapril prevented the neointimal hyperplasia of rat carotid artery after balloon injury, it did not lead to prevention of restenosis after PTCA in human studies (MERCATOR and MARCATOR). Angiotensin II receptor blocker, candesartan, inhibited the neointimal formation after balloon injury in both rat and dog. Val-PREST trial showed that valsartan reduced the in-stent restenosis rate after stent implantation. The inhibition of renin-angiotensin system by angiotensin II receptor blocker may help to prevent restenosis after angioplasty.
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PMID:[Preventing effect of angiotensin II receptor blocker on neointimal hyperplasia after vascular injury]. 1239 91

Some antihypertensive agents may be capable of reducing chronic renal insufficiency (CRI) progression because they halt some of the pathogenic mechanisms involved in renal damage. Although this effect seems to be partially independent of BP reduction, it is still unclear whether these drugs are really superior to other antihypertensive agents when the BP values recommended by the present guidelines are actually achieved. This is particularly true when considering that, in published trials, target and achieved BP values were constantly higher than those nowadays recommended. Furthermore, in the majority of these studies, patients treated with ACE-inhibitors (ACE-I) or Angiotensin II receptor antagonists (ATIIRA) achieved lower BP values than those in control groups and BP values during 24 h were not recorded. Anyway, taking into account the role of baseline and follow-up BP values, the treatment effect remained significant in almost all of the multivariate models. These findings suggest that the renoprotective effect of these agents (ACE-I, ATIIRA) is partially independent of better BP control. However, caution should be paid in attributing true biologic renoprotective properties to drugs just on the basis of statistical adjustments of BP values, although robustly performed, without being aware of what those BP values actually reflect.
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PMID:Is it the agent or the blood pressure level that matters for renal protection in chronic nephropathies? 1246 14


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