Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011881 (diabetic nephropathy)
 10,836 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This manuscript will highlight the major elements of the recently published sixth Joint National Committee (JNC-6) report. First, a 3-tiered classification of overall cardiovascular risk is provided as a guide to the institution of therapy with either lifestyle modifications or antihypertensive drugs. Second, the need for prevention is stressed. Third, guidelines for the effective use of appropriate lifestyle modifications are provided. Fourth, a 3-pronged pathway for the choice of critical therapy is provided: one for uncomplicated hypertensive; another for those with "compelling" indications for specific drugs, including the presence of diabetic nephropathy, congestive heart failure, post-myocardial infarction or systolic hypertension in the elderly; the third for those with concomitant conditions that may be either favorably or unfavorably affected by specific types of drugs. In addition, the report emphasizes the need to achieve the goal of less than 140/90 mmHg by a progressive process of therapy and, if necessary, referral to a hypertension specialist. Recommendations are made for improved adherence to therapy, therapy of resistant hypertension and hypertensive crises.
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PMID:The 6th joint national committee report (JNC-6): new guidelines for hypertension therapy from the USA. 965 20

Blockade of the renin-angiotensin system with angiotensin-converting enzyme (ACE) inhibitors is now recognized as an effective approach for the treatment of hypertension and congestive heart failure. In addition, ACE inhibitors are very effective for the prevention of chronic renal failure. Today, it is possible to antagonize the effects of angiotensin II more specifically using AT1 receptor antagonists. Several non-peptide, orally active angiotensin II receptor antagonists have recently been developed clinically. These new molecules are as effective as ACE inhibitors, calcium antagonists and beta-blockers at reducing blood pressure in hypertensive patients. Furthermore, they appear to have similar systemic and renal hemodynamic properties in patients with congestive heart failure and renal diseases. Now, several large clinical trials such as the LIFE, the RENAAL and the ELITE II studies are under way to investigate the long-term benefits of one of these compounds in hypertension, heart failure and type II diabetic nephropathy.
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PMID:[Angiotensin II AT1 receptor antagonists: clinical development and future perspectives]. 977 27

Blockade of the renin-angiotensin system is now recognized as an effective approach to the treatment of hypertension and congestive heart failure. Today, it is possible to antagonize the effects of angiotensin II more specifically by blocking its receptors by using nonpeptide receptor antagonists. These compounds that first have been used to recognize the various subtypes of angiotensin II receptors are now available clinically. Four of them have recently been launched on the market and several others are preregistered for the treatment of hypertension. These new molecules are as effective as ACE inhibitors, calcium antagonists and beta-blockers in lowering blood pressure in hypertensive patients. When compared to ACE inhibitors, they appear to have comparable favorable effects on systemic and renal hemodynamic properties. One of the major characteristics of angiotensin II receptor antagonists as a class is the excellent tolerability with an incidence of side effects that is generally similar to that of placebo. Large clinical trials are now underway to demonstrate the long-term benefits of these agents in hypertension, heart failure and type II diabetic nephropathy.
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PMID:Angiotensin II receptor antagonists in hypertension. 983 93

Angiotensin I-converting enzyme (ACE) inhibitors are commonly used for the treatment of hypertension, progressive chronic renal disease, diabetic nephropathy, and congestive heart failure. Because angiotensin II acts through membrane bound type 1 (AT1) and type 2 (AT2) receptors, ACE inhibitors and angiotensin II-receptor antagonists have distinct effects. ACE inhibitors inhibit production of angiotensin II thus suppressing the action of angiotensin II on both AT1 and AT2. In contrast, the effect of AT1-receptor antagonists is to selectively block the activation of the AT1 receptor. This AT1-receptor blockade leaves the AT2 receptors unopposed to elevated levels of endogenous angiotensin II. Thus, there may be an advantage of AT1-receptor blockade over ACE inhibition in the management of a variety of chronic vascular diseases, including chronic glomerulonephritis and other glomerular diseases. In a clinical trial candesartan, an AT1-receptor antagonist, effectively lowered urinary protein excretion in patients with chronic glomerular nephritis. Evidence indicates that functionally active AT1 receptors, as well as AT2 receptors, are present in both afferent and efferent arteriole of the glomerulus, and that angiotensin II induces afferent and efferent arteriolar dilatation via AT2 receptors.
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PMID:Effects of candesartan on the proteinuria of chronic glomerulonephritis. 1007 22

The renin-angiotensin-aldosterone system (RAAS) plays an important role in both the short-term and long-term regulation of arterial blood pressure, and fluid and electrolyte balance. The RAAS is a dual hormone system, serving as both a circulating and a local tissue hormone system (i.e., local mediator) as well as neurotransmitter or neuromediator functions in CNS. Control of blood pressure by the RAAS is exerted through multiple actions of angiotensin II, a small peptide which is a potent vasoconstrictor hormone implicated in the genesis and maintenance of hypertension. Hypertension is a primary risk factor associated with cardiovascular, cerebral and renal vascular disease. One of the approaches to the treatment of hypertension, which may be considered as a major scientific advancement, involves the use of drugs affecting the RAAS. Pharmacological interruption of the RAAS was initially employed in the late 1970s with the advent of the angiotensin converting enzyme (ACE) inhibitor, captopril. ACE inhibitors have since gained widespread use in the treatment of mild to moderate hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathy. As the roles of the RAAS in the pathophysiology of several diseases was explored, so did the realization of the importance of inhibiting the actions of angiotensin II. Although ACE inhibitors are well tolerated, they are also involved in the activation of bradykinin, enkephalins, and other biologically active peptides. These actions result in adverse effects such as cough, increased bronchial reactivity, and angioedema. Thus, the goal of achieving a more specific blockade of the effects of angiotensin II than is possible with ACE inhibition. The introduction of the nonpeptide angiotensin II receptor antagonist losartan in 1995 marked the achievement of this objective and has opened new vistas in understanding and controlling the additional biological effects of angiotensin II. Complementary investigations into the cloning and sequencing of angiotensin II receptors have demonstrated the existence of a family of angiotensin II receptor subtypes. Two major types of angiotensin II receptors have been identified in humans. The type 1 receptor (AT1) mediates most known effects of angiotensin II. The type 2 receptor (AT2), for which no precise function was known in the past, has gained importance recently and new mechanisms of intracellular signalling have been proposed. This review presents recent advances in angiotensin II receptor pharmacology, molecular biology, and signal transduction, with particular reference to the AT1 receptor. Excellent reviews have appeared recently on this subject.
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PMID:Angiotensin II receptors-antagonists, molecular biology, and signal transduction. 1009 99

The advent of the ACE inhibitors has been one of the major developments in cardiovascular pharmacology this century. Aside from their role as potent anti-hypertensive drugs with few adverse effects, ACE inhibitors have numerous other effects that have only been partially explained. Antihypertensive therapy is the most effective treatment in patients with diabetic nephropathy, postponing the development of end-stage renal failure. Although this effect can apparently be obtained with all antihypertensives (except nifedipine), recent meta-analyses have indicated that the beneficial effects of ACE inhibitors on proteinuria and preserved renal function are greater than with other drugs. In nondiabetic patients, treatment with ACE inhibitors may delay or prevent the development of congestive heart failure following acute myocardial infarction. Whether this also occurs in diabetic patients is still unknown, but subgroup analysis of existing studies and controlled clinical trials in this area should be encouraged. In conclusion, ACE inhibitors are the only drugs that have been proven, in controlled clinical trials, to be effective in preventing progression from micro-albuminuria to overt nephropathy. Furthermore, they are more effective in diminishing albuminuria at low levels of blood pressure reduction compared with other antihypertensives. In comparison with beta-blockers, ACE inhibitors have the advantage that they do not mask the subjective symptoms of hypoglycaemia, nor do they affect the serum lipid profile.
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PMID:ACE inhibitors in patients with diabetes mellitus. Clinical and economic considerations. 1016 Feb 52

Blockade of the renin-angiotensin system is recognized as an effective approach for the treatment of hypertension and congestive heart failure. It is possible to antagonize the effects of angiotensin II (AngII) by blocking its receptors, using nonpeptide receptor antagonists. Six angiotensin receptor blockers (ARB) have been approved for the treatment of hypertension: losartan, valsartan, irbesartan, candesartan, telmisartan, and eprosartan. These new drugs are highly selective for the AT1 receptor subtype and induce dose-dependent inhibition of the BP response to exogenous AngII. Numerous double-blind, placebo-controlled studies have demonstrated that ARB are efficacious for treating mild, moderate, and severe hypertension. When compared with other classes of antihypertensive agents, ARB are as effective as angiotensin-converting enzyme inhibitors, calcium antagonists, thiazide diuretics, and beta-blockers. One advantage of ARB as a class is their excellent tolerability and side effect profile. Several large clinical trials of ARB are now under way to demonstrate their benefits in hypertension, heart failure, and type II diabetic nephropathy.
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PMID:Comparative antihypertensive effects of angiotensin II receptor antagonists. 1020 83

Inhibitors of angiotensin converting enzyme (ACE inhibitors) have been introduced more than fifteen years ago into the treatment of hypertension, congestive heart failure, myocardial infarction and diabetic nephropathy. The therapeutic success is related to their action in reduction of plasma and tissue angiotensin II concentrations and potentiation of endogenous kinins. They are able to improve myocardium metabolic status, prevent cardiac hypertrophy, limit myocardial infarct size, and thus prevent heart failure. Since 1987 ACE inhibitors are introduced in the clinical practice in our clinic. We introduced the therapy with lisinopril (Lopril), in 70% of patients among 2855 patients that were admitted in Coronary Care Unit in 1997 and 1998. Lisinopril was introduced as soon as the patient was admitted, together with fibrinolitic, Heparin and Aspirin therapy. Since that time we noticed decrease in postinfarction heart failure in comparison to previous years. We recommend permanent therapy with a small doses of ACE inhibitors in patients with heart infarction.
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PMID:[Converting enzyme inhibitors in acute myocardial infarct and heart failure]. 1035 28

Achieving the optimal outcome in hypertensive patients requires the selection and use of appropriate strategies to lower the blood pressure and reduce the patient's risk of cardiovascular events such as stroke and coronary heart disease. It also requires ongoing monitoring of the patient to ensure that the desirable end-points of treatment are being met, and that the heart, kidneys and other sites are being effectively protected from potential complications. Current guidelines on the treatment of hypertension continue to emphasise the use of low dose diuretics as appropriate first-line therapy whenever pharmacological intervention is indicated, except where there are positive indications (e.g. coexisting congestive heart failure or diabetic nephropathy) for other classes of drugs. Diuretics have repeatedly been shown to reduce the morbidity and mortality associated with hypertension, both in the elderly and in younger adults, and their combination with other antihypertensive agents (when clinically indicated) permits the use of lower total dosages. The thiazide-related diuretic indapamide has been reported to have a number of advantages over the thiazides, including minimal or no adverse influence on plasma lipids and glucose metabolism, or on kidney function in patients with renal insufficiency. It has also been found to produce regression of left ventricular hypertrophy, which is now accepted as an important objective of antihypertensive therapy. The recently developed sustained release (SR) formulation of indapamide allows use of a lower daily dosage of the drug, thereby improving its efficacy:safety ratio in comparison with immediate release formulations. Clinical studies have confirmed the efficacy of indapamide SR 1.5 mg daily in lowering elevated blood pressure, and this formulation can be considered an appropriate choice whenever a diuretic is indicated for the treatment of hypertension, including elderly hypertensives and, because of its metabolic 'neutrality', hypertensive patients with diabetes.
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PMID:Concluding remarks. Pursuit of the optimal outcome in hypertension. 1049 31

The purpose of this study was, using consensus methodology, to document current understanding of contrast media nephrotoxicity (CMN) and to identify areas where there is disagreement or confusion. To draw up guidelines for avoiding CMN based on the current understanding of the condition established by the survey. One hundred sixty-four statements were mailed to 148 members of the European Society of Urogenital Radiology (ESUR) and to 48 experts in the field of CMN. They were asked about the definition, clinical features, predisposing factors and pathophysiology of CMN and about prophylactic measures. The importance of the statements was rated on a scale from 1 to 10 (1 least important, 10 most important). Fifty-three members (38%) and 23 experts (48%) responded. Both groups considered that an increase in serum creatinine that peaks within 3-4 days and a decrease in creatinine clearance are the most important (rating > 7) features of CMN. Enzymuria was not considered important (rating < 6). Pre-existing renal insufficiency, diabetic nephropathy, dehydration, congestive heart failure, concurrent administration of nephrotoxic drugs and the dose and type of contrast media were considered to be risk factors. Reduction in renal perfusion and damage to tubular cells were considered the main factors in the pathophysiology of CMN (rating > 6). Hydration and the use of low osmolar contrast media were thought to minimize the incidence of CMN (rating > 6). The majority of the responders (84.6% of members and 95.5% of experts) believe that the incidence of CMN in patients with normal renal function is less than 5%. Of the members, 62.5%, and 35.3% of experts, believe that the incidence of CMN is 20-30% in the presence of risk factors. There was disagreement about the definition of CMN, the threshold dose of contrast media above which renal complications may develop, the safe period between repeat injections, the relevance of contrast media renal retention shown on CT and whether contrast media have long-term effects on renal function. The survey showed good understanding of CMN among those who answered the questionnaires, although areas of disagreement remain which require further research. Simple guidelines are proposed.
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PMID:Contrast-media-induced nephrotoxicity: a consensus report. Contrast Media Safety Committee, European Society of Urogenital Radiology (ESUR). 1243 87


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