Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Our ability to measure precisely the pressures and flows within the glomerular microcirculation has enabled us to begin to unravel the complex relationship between systemic hypertension and kidney disease. Although a number of factors have been implicated in the development of glomerular sclerosis, one consistent finding has been that glomerular injury occurs when elevated pressures are transmitted to the glomerular capillaries. Intrarenal hypertension, in conjunction with renal hypertrophy, and, possibly, disturbances in lipid metabolism and blood coagulation constitute secondary processes through which those nephrons not severely injured by the primary renal disease are eventually destroyed. Ultimately, all renal function is lost. Clinically, increased glomerular pressure is likely to contribute to glomerular injury in those patients in whom hypertension and renal insufficiency coexist. In patients with diabetes, as yet unidentified factors cause preglomerular resistance to fall so that glomerular hypertension develops even in the absence of elevation in systemic blood pressure. Although no therapy has been proven to slow the rate of progression to end stage renal failure in humans, a number of promising interventions have been identified. These include dietary protein or salt restriction, and medication, with either converting enzyme inhibitors or calcium channel blockers.
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PMID:Impact of antihypertensive therapy on progressive kidney damage. 266 87

Renal failure is progressive irrespective of the underlying primary renal disease or continued disease activity. Intrarenal haemodynamic changes may contribute to progressive loss of renal function, and may be modified by pharmacological therapies. Angiotensin-converting enzyme (ACE) inhibitors may have a specific therapeutic advantage in the treatment of hypertension associated with progressive renal disease. We have studied the effects of an ACE inhibitor and a calcium channel blocker on systemic BP, glomerular filtration, proteinuria and histological injury in animal models of progressive renal disease (the remnant kidney and diabetes). Systemic BP was lowered similarly by each treatment in both models. Beneficial effects on renal structure, proteinuria, and glomerular filtration only occurred in the ACE inhibitor-treated animals. Intrarenal haemodynamic effects of ACE inhibitors may therefore offer an advantage over other antihypertensive agents in progressive renal disease. Where there is reduced renal perfusion, intrarenal haemodynamic effects of ACE inhibitors may lead to compromised renal function. Acute renal failure is a common consequence of ACE inhibitor therapy in patients with bilateral renal artery stenosis, or renal artery stenosis to a single functioning kidney. Acute studies have suggested that these effects are reversible; function returns following withdrawal of ACE inhibitor therapy. We examined the long-term effects of ACE inhibitor therapy in rats with the two-kidney, one-clip (Goldblatt) model of hypertension. Rats were treated for 12 months with an ACE inhibitor or a vasodilator. After 1 year of treatment the clipped kidney from the ACE inhibitor-treated rats was small, fibrotic, and had no glomerular filtration. No functional improvement of the clipped kidney occurred following ACE inhibitor withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Angiotensin-converting enzyme inhibition in renal disease; contrasting effects on renal function in renal artery stenosis and progressive renal injury. 267 36

The Working Group on Hypertension in Diabetes recommends starting pharmacologic treatment of hypertension with a small dose of a thiazide, beta-blocker, prazosin hydrochloride, angiotensin-converting enzyme inhibitor, or calcium channel blocker. Thus, these alternatives are regarded as first-line treatment in hypertensive patients with diabetes mellitus. Both thiazides and beta-blockers can cause deterioration in glycemic control and have an unfavorable influence on the lipoprotein profile. These metabolic side effects may partly counteract beneficial effects. Non-selective beta-blockers should probably be avoided in diabetic patients, since blockade of the beta-2 receptor may be associated with a compromise in peripheral blood flow and with problems associated with hypoglycemia. Cardioselective beta-blockers, which may have primary preventive effects on coronary disease, are beneficial in this patient group. In patients with non-insulin-dependent diabetes mellitus without nephropathy or overt fluid retention, diuretic therapy could be replaced by sodium restriction and/or calcium channel blocker therapy, since these agents also have a mild diuretic effect. Calcium channel blockers, angiotensin-converting enzyme inhibitors, and prazosin hydrochloride have minimal metabolic side effects, making them suitable for treatment of hypertension in this patient group.
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PMID:General considerations in selecting antihypertensive agents in patients with type II diabetes mellitus and hypertension. 268 13

The relation between hypertension, cerebrovascular disease, and heart failure in the elderly is well established. The concept that this was entirely due to hardening of the arteries and, therefore, an essential feature of aging has been revised in the last 15 years to show that there are groups of elderly people in whom hypertension is not a problem, and in this group stroke disease and heart failure are relatively uncommon. The treatment of hypertension in the elderly attracts increasing attention. The successful lowering of blood pressure in the elderly has now been reported by many authors with a variety of therapeutic agents. The case for treatment has been demonstrated in those up to 80 years of age by the European Working Party in Hypertension in the Elderly, and relevant data on compliance are also available in the older age group in the Sub-Group Analysis of the Hypertension Detection and Follow-up Programme. A similar reduction of blood pressure, both systolic and diastolic, can be safely achieved with thiazides, beta-blockade, calcium channel blockade, angiotensin-converting enzyme inhibitors, and centrally acting drugs. The differentiation between these groups is largely a matter of the side effects that occur and any concurrent existing illness from which the patient suffers, e.g., diabetes, bronchitis, heart failure, and so on. From the information available to date, the problem of choice of the most suitable drug remains a clinical decision for the prescribing doctor.
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PMID:Hypertension in the elderly. 278 25

The results of large epidemiological studies dealing with the prognosis and unfavourable outcome of essential hypertension, clearly show that the pharmacological reduction of the elevated blood pressure of hypertensive patients significantly reduces the risk of at least some major cardiovascular complications. Satisfactory antihypertensive efficacy reflects, nevertheless, merely a minimal requirement for a modern antihypertensive drug. Additional pharmacological properties, which counteract the typical concomitant diseases like CHD, heart failure and other cardiovascular complications would be desirable. In this respect, the oral CE-inhibitors captopril and enalapril offer an exciting new approach to the treatment of arterial hypertension. As the most predictive international studies on prevention of hypertension were conducted before CE-inhibitors were available, the present review evaluates the pharmacological profile of this new class of antihypertensive compounds in the light of previously available baseline drugs, including the calcium channel antagonists. Until now, captopril and enalapril have been the best investigated and documented representatives. Besides new experimental results concerning the molecular mechanism of these drugs, clinical and experimental approaches to verify protective effects on the cardiovascular and the renal system are addressed. These offer a rational basis for the preferential treatment of hypertensive patients with reduced renal function, diabetes and chronic heart failure. In addition, some distinct advantages of enalapril over captopril, resulting mainly from the long-term reduction of high blood pressure, are discussed.
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PMID:[Differential therapeutic topics in antihypertensive therapy. What can angiotensin-converting enzyme inhibitors accomplish?]. 285 Jun 83

Insulin (INS) stimulates, and diabetes inhibits, low Km cAMP phosphodiesterase (PDE). This mechanism, at least in part, accounts for the lowering of cyclic AMP levels in plasma and tissue of diabetic patients and animals. Phorbol, a tumor-promoting agent known to act through protein kinase C and calcium translocation, exhibits a powerful effect stimulating PDE in rat adipose tissue. Nifedipine, a calcium channel blocker, inhibits insulin, but not phorbol stimulated PDE. These data demonstrate new effects of inositide diacylglycerol-Ca++ pathway components on PDE and suggest some common pathways of activation of low Km cAMP PDE through insulin and phorbol esters.
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PMID:Activation of cyclic AMP phosphodiesterase by phorbol and protein kinase C pathway. 301 37

Elderly diabetic patients with hypertension present a difficult medical management problem. The guidelines published by the 1987 Working Group on Hypertension in Diabetes in the United States suggest a stepped care approach to drug therapy in these patients. The stepped care strategy is to add a series of antihypertensive medications sequentially until the blood pressure is controlled. The first step includes one of the following: thiazide diuretics, beta-blockers, alpha-adrenergic inhibitors, angiotensin converting enzyme (ACE) inhibitors or calcium channel blockers. The second step adds a second agent from the same group, while the third step adds a vasodilator and step four adds a drug like guanethidine if the combination of other drugs fails. This approach presents many perils in the aged patient with diabetes. In these patients the physician should: (1) limit the use of diuretics and beta-blockers; (2) favour the use of calcium channel blockers and ACE inhibitors; (3) use a substitution approach rather than a stepped care approach; and (4) use monotherapy if possible.
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PMID:Hypertension in the elderly diabetic: therapeutic aspects. 306 84

Hypertension combined with diabetes in the elderly is characterized by many important metabolic and cardiovascular changes, among which insulin resistance, hyperinsulinaemia and increased total peripheral resistance appear to be the most relevant. Non-insulin dependent diabetes mellitus is also characterized by insulin resistance and hyperinsulinaemia. Moreover, hyperinsulinaemia itself has been shown to increase total peripheral resistance. Hyperinsulinaemia thus seems to play a key role in the pathophysiology of hypertension in elderly diabetic subjects. Therefore elderly hypertensive diabetic patients should be treated with thiazide diuretics in low doses, calcium channel blockers and alpha-adrenergic blockers.
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PMID:Diabetes and hypertension in the elderly. 306 92

Elderly diabetics take more drugs than other groups of elderly patients. Their multiple drug use is largely explained by the drugs that they take for complications of their primary disease; these include cardiovascular drugs for macrovascular disease and antibiotics for secondary infections. They also take more drugs for control of other conditions that are etiologically associated with the development and progression of their diabetes, including antihypertensive agents, antilipemic agents and steroids, and nonsteroidal antiinflammatory drugs (NSAIDs), which are taken for relief of joint pain that is intensified by arthritic joints bearing excess weight. Drugs taken by elderly diabetics that contribute to the high prevalence of drug-nutrient interactions include those taken as antidiabetic agents, including both insulin and sulfonylureas as well as calcium channel blockers; they also include thiazides, loop diuretics, sulfa drugs, cephalosporin antibiotics, tetracyclines, antifungal agents, cholestyramine and colestipol, niacin, prednisone and other corticosteroids, and NSAIDs. These drugs and drug combinations contribute to the risk of hyperglycemia, which can cause nonketotic hyperglycemia in the elderly; to the risk of hypoglycemia, which in the elderly carries the risk of inducing pseudo-stroke; to the risk of drug-induced nutritional deficiencies from antilipemics and cephalosporins, which can induce vitamin K deficiency; to the risk of acute incompatibility reactions, including flush reactions from chlorpropamide, niacin, and calcium channel blockers; and to the risk of edema, anemia, and hyperkalemia from NSAIDs.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Drug and nutrient interactions in the elderly diabetic. 307 52

The effect of a six-week treatment by placebo, the calcium channel blocker nifedipine or the converting enzyme inhibitor captopril was assessed in normotensive patients with insulin-dependent diabetes and incipient nephropathy. In response to captopril and nifedipine, arterial pressure decreased slightly and to a similar extent. These drugs resulted in opposite effects on urinary albumin excretion (increase in urinary albumin excretion by 40% during nifedipine and decrease by 40% during captopril treatment). No change in urinary albumin excretion was observed in the placebo group. This observation of opposite changes in urinary albumin excretion in the presence of a similar fall in arterial pressure suggests that the effect of captopril and nifedipine on urinary albumin excretion results from some difference in their intrarenal action.
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PMID:Comparative effect of captopril and nifedipine in normotensive patients with incipient diabetic nephropathy. 307 98


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