UMLS:C0020538 - FACTA Search

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Query: UMLS:C0020538 (hypertension)
170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metformin (dimethyl-biguanide) is an oral antidiabetic drug, which decreases hepatic glucose production (gluconeogenesis) and increases peripheral glucose uptake by muscles. Metformin is a first-line drug in the treatment of overweight and obese type 2 diabetic patients, offering a selective pathophysiological approach by its effect on insulin resistance. It has been shown in a number of studies to improve clinical outcomes in type 2 diabetic patients. It has been demonstrated in a number of studies that metformin has multiple biological effects - it has been shown to have platelet antiaggregating effects, to reduce the rate of formation of advanced glycation end products (AGEs) and to decrease the cellular oxidative reactions, thus demonstrating the antioxidant effects of the drug, which may largely explain its vascular protective effect. A number of studies have established the favorable effect of metformin on body weight, insulin resistance, hyperinsulinaemia, lipid parameters (total cholesterol, HDL-cholesterol, LDL-cholesterol, triglycerides), arterial hypertension, fibrinolysis, endothelial dysfunction. Thus metformin appears to have a broad set of pharmacological properties, making the drug potentially applicable even in nondiabetic situations such as obesity, extreme insulin resistance with acanthosis nigricans, polycystic ovary syndrome, etc. Metformin has been demonstrated in the Diabetes Prevention Program to be a drug with great potential in preventing the conversion of IGT to type 2 diabetes. Thus, metformin appears to be a drug with multiple therapeutic effects far beyond its effect on lowering blood glucose in diabetes mellitus.
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PMID:Current indications for metformin therapy. 1552 5

Type 2 diabetes is a serious, costly, and increasingly common disease. Several conditions commonly seen in family medicine settings confer increased risk of developing diabetes. Among these conditions are impaired glucose tolerance, impaired fasting glucose, obesity, gestational diabetes, hypertension, hyperlipidemia, and menopause. We here present the results of a systematic review of the literature examining the evidence for different strategies aimed at preventing type 2 diabetes in patients with these conditions. The strongest evidence supports an intensive lifestyle intervention designed to induce modest weight loss. The greatest degree of prevention, based on lesser quality evidence, may be imparted by bariatric surgery. Metformin and troglitazone have appreciable evidence in specific populations, and orlistat and acarbose have slightly less evidence among obese patients, for preventing diabetes. Ramipril, captopril, losartan, pravastatin, and estrogens show some very preliminary promise for preventing diabetes in patients treated for hypertension, hyperlipidemia, and menopause, but each needs a more rigorous evaluation. Although more questions remain to be answered, family physicians now have tools available to help our patients lead lives free of diabetes.
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PMID:Preventing type 2 diabetes mellitus. 1570 62

Patients with type 2 diabetes mellitus have a greater risk of cardiovascular disease than nondiabetic individuals. These patients are often insulin resistant and have an associated clustering of risk factors that contribute to cardiovascular disease. The risk factors include dyslipidemia, hypertension, altered hemostasis, and chronic inflammation. A primary objective in the management of type 2 diabetes mellitus is normalization of blood glucose levels; however, some of the oral drugs used to control blood glucose levels have significant effects on these risk factors. In this article, we review the current data involving the modification of these cardiovascular risk factors by the biguanide (metformin), the thiazolidinediones (troglitazone, rosiglitazone, and pioglitazone), the alpha-glucosidase inhibitors (miglitol, acarbose), and the insulin secretagogs (glyburide [glibenclamide], glipizide, chlorpropamide, tolbutamide, tolazamide, glimepiride, repaglinide, and nateglinide). Generally, the thiazolidinediones improve hemostasis and endothelial function and reduce blood pressure, while having variable effects on dyslipidemia. Metformin improves dyslipidemia and altered hemostasis and decreases plasma C-reactive protein levels with little or no effect on blood pressure. Data on the effects of the alpha-glucosidase inhibitors and insulin secretagogs are sparse; however, these drugs appear to have little or no effect on cardiovascular risk factors.
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PMID:Cardiovascular risk factors associated with insulin resistance: effects of oral antidiabetic agents. 1590 Dec 7

Because management of type 2 diabetes mellitus usually involves combined pharmacological therapy to obtain adequate glucose control and treatment of concurrent pathologies (especially dyslipidaemia and arterial hypertension), drug-drug interactions must be carefully considered with antihyperglycaemic drugs. Additive glucose-lowering effects have been extensively reported when combining sulphonylureas (or the new insulin secretagogues, meglitinide derivatives, i.e. nateglinide and repaglinide) with metformin, sulphonylureas (or meglitinide derivatives) with thiazolidinediones (also called glitazones) and the biguanide compound metformin with thiazolidinediones. Interest in combining alpha-glucosidase inhibitors with either sulphonylureas (or meglitinide derivatives), metformin or thiazolidinediones has also been demonstrated. These combinations result in lower glycosylated haemoglobin (HbA(1c)), fasting glucose and postprandial glucose levels than with either monotherapy. Even if modest pharmacokinetic interferences have been reported with some combinations, they do not appear to have important clinical consequences. No significant adverse effects, except a higher risk of hypoglycaemic episodes that may be attributed to better glycaemic control, occur with any combination. Challenging the classical dual therapy with sulphonylurea plus metformin, there is a recent trend to use alternative dual combinations (sulphonylurea plus thiazolidinedione or metformin plus thiazolidinedione). In addition, triple therapy with the addition of a thiazolidinedione to the metformin-sulphonylurea combination has been recently evaluated and allows glucose targets to be reached before insulin therapy is considered. This triple therapy appears to be safe, with no deleterious drug-drug interactions being reported so far.Potential interferences may also occur between glucose-lowering agents and other drugs, and such drug-drug interactions may have important clinical implications. Relevant pharmacological agents are those that are widely coadministered in diabetic patients (e.g. lipid-lowering agents, antihypertensive agents); those that have a narrow efficacy/toxicity ratio (e.g. digoxin, warfarin); or those that are known to induce (rifampicin [rifampin]) or inhibit (fluconazole) the cytochrome P450 (CYP) system. Metformin is currently a key compound in the pharmacological management of type 2 diabetes, used either alone or in combination with other antihyperglycaemics. There are no clinically relevant metabolic interactions with metformin, because this compound is not metabolised and does not inhibit the metabolism of other drugs. In contrast, sulphonylureas, meglitinide derivatives and thiazolidinediones are extensively metabolised in the liver via the CYP system and thus, may be subject to drug-drug metabolic interactions. Many HMG-CoA reductase inhibitors (statins) are also metabolised via the CYP system. Even if modest pharmacokinetic interactions may occur, it is not clear whether drug-drug interactions between oral antihyperglycaemic agents and statins may have clinical consequences regarding both efficacy and safety. In contrast, a marked pharmacokinetic interference has been reported between gemfibrozil and repaglinide and, to a lesser extent, between gemfibrozil and rosiglitazone. This leads to a drastic increase in plasma concentrations of each antihyperglycaemic agent when they are coadministered with the fibric acid derivative, and an increased risk of adverse effects. Some antihypertensive agents may favour hypoglycaemic episodes when co-prescribed with sulphonylureas or meglitinide derivatives, especially ACE inhibitors, but this effect seems to result from a pharmacodynamic drug-drug interaction rather than from a pharmacokinetic drug-drug interaction. No, or only modest, interferences have been described with glucose-lowering agents and other pharmacological compounds such as digoxin or warfarin. The effects of inducers or inhibitors of CYP isoenzymes on the metabolism and pharmacokinetics of the glucose-lowering agents of each pharmacological class has been tested. Significantly increased (with CYP inhibitors) or decreased (with CYP inducers) plasma levels of sulphonylureas, meglitinide derivatives and thiazolidinediones have been reported in healthy volunteers, and these pharmacokinetic changes may lead to enhanced or reduced glucose-lowering action, and thus hypoglycaemia or worsening of metabolic control, respectively. In addition, some case reports have evidenced potential drug-drug interactions with various antihyperglycaemic agents that are usually associated with a higher risk of hypoglycaemia.
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PMID:Drug interactions of clinical importance with antihyperglycaemic agents: an update. 1596 7

Nowadays, about 6-8% of the German population suffers from diabetes mellitus mostly type 2 but in patients with angiopathies about 30% have known diabetes and a further 30% have newly diagnosed diabetes or impaired glucose tolerance. Therefore diagnosis and therapy of glucose impairment play a central role for management of these patients. The antidiabetic therapy for secondary prevention of cardiovascular disease has to be embedded in a multifactorial concept with management of hypertension, hyperlipidemia and hypercoagulability. The management of diabetes following guidelines is a stepwise therapy with lifestyle interventions (diet, exercise) and oral drugs or insulin. Metformin has shown favorable outcome in overweight patients if aware of side effects; insulin is a safe drug in multimorbid patients and with planned interventions or operations. We are awaiting the results of multiple endpoint studies with newer antidiabetic drugs which may change our current concept of management of diabetes mellitus in these patients in the near future.
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PMID:[Management of diabetes mellitus in patients with angiopathies]. 1641 60

AMP-activated protein kinase (AMPK) is tightly regulated by the cellular AMP:ATP ratio and plays a central role in regulation of energy homeostasis and metabolic stress. Metformin has been shown to activate AMPK. We hypothesized that metformin may prevent nuclear factor kappaB (NF-kappaB) activation in endothelial cells exposed to inflammatory cytokines. Metformin was observed to activate AMPK, as well as its downstream target, phosphoacetyl coenzyme A carboxylase, in human umbilical vein endothelial cells (HUVECs). Metformin also dose-dependently inhibited tumor necrosis factor (TNF)-alpha-induced NF-kappaB activation and TNF-alpha-induced IkappaB kinase activity. Furthermore, metformin attenuated the TNF-alpha-induced gene expression of various proinflammatory and cell adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1, in HUVECs. A pharmacological activator of AMPK, 5-amino-4-imidazole carboxamide riboside (AICAR), dose-dependently inhibited TNF-alpha- and interleukin-1beta-induced NF-kappaB reporter gene expression. AICAR also suppressed the TNF-alpha- and interleukin-1beta-induced gene expression of vascular cell adhesion molecule-1, E-selectin, intercellular adhesion molecule-1, and monocyte chemoattractant protein-1 in HUVECs. The small interfering RNA for AMPKalpha1 attenuated metformin or AICAR-induced inhibition of NF-kappaB activation by TNF-alpha, suggesting a possible role of AMPK in the regulation of cell inflammation. In light of these findings, we suggest that metformin attenuates the cytokine-induced expression of proinflammatory and adhesion molecule genes by inhibiting NF-kappaB activation via AMPK activation. Thus, it might be useful to target AMPK signaling in future efforts to prevent atherogenic and inflammatory vascular disease.
Hypertension 2006 Jun
PMID:Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. 1663 95

Nonalcoholic steatohepatitis (NASH), which is considered the hepatic manifestation of the metabolic syndrome is an increasingly cause of chronic liver disease in Japan. NASH is finally lead to liver cirrhosis and hepatocellular carcinoma as viral hepatitis, therefore, medical treatment should be considered, when NASH occurs. Treatment of patients with metabolic syndrome has been focused on the management of associated conditions such as obesity, hyperlipidemia, hypertension and hyperinsulinemia. Insulin resistance, that could accelerate liver inflammation and fibrosis by up-regulation of TNFa seems to be most important factor in many cases of NASH. The insulin-sensitizing drugs, which were biguanides (metformin) and thiazolidinediones (pioglitazone) have been shown to correct not only insulin resistance but also steatosis and inflammation in the liver. Metformin and pioglitazone might be useful drugs against NASH, however further investigations were needed.
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PMID:[Insulin sensitizer--anti-diabetic drugs, metformin and pioglitazone that can improve insulin resistance]. 1676 25

Metabolic and non metabolic cardiovascular risk factors tend to cluster in the same individual. The association of the cardiovascular risk factors is referred as metabolic syndrome (MS). This syndrome is associated with an increased risk of accelerated atherosclerosis and cardiovascular events. The cluster of cardiovascular risk factors of the MS includes: insulin resistance with or without glucose intolerance or diabetes, abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, a proinflammatory and prothrombotic state. MS is one of the major issues in the management of cardiovascular disease because of its epidemic proportion and its impact on increasing risk of developing both cardiovascular disease and type 2 diabetes. The main therapeutic goal in the management of patients with the MS is to reduce risk for clinical cardiovascular events and to prevent type 2 diabetes. In particular, for individuals with established diabetes, risk factors management must be intensified to reduce their higher cardiovascular risk. Lifestyle changes have a critical role in the clinical management of the risk factors predisposing to MS, such as overweight/obesity, physical inactivity. A large body of evidence suggests the use of Metformin and Acarbose for the treatment of the syndrome as these drugs have consistently shown to reduce cardiovascular events and mortality. Most anti-hypertensive drugs have unfavorable metabolic profile while b-blockers, centrally acting agents and drugs targeting the renin angiotensin system should always be considered for the treatment of hypertension in patients with MS.
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PMID:Metabolic syndrome. 1685 17

The number of diabetics will increase almost 70% in developed countries during the next 20 years: peripheral arterial disease is a common and costly complication. The incidence of cardiovascular disease (mortality and morbidity) due to atherosclerosis, is higher among patients with diabetes than in those without diabetes. Intensive management of diabetes, including glycaemic control, treatment of hypertension and dyslipidemia, as well as nonpharmacological interventions, decreases both micro- and macrovascular complications. Aspirin and clopidogrel have less antiplatelet effect in patients with diabetes. Metformin therapy is considered a risk factor for lactic acidosis if not withdrawn 2 days before angiography, but this risk is extremely low in patients with normal renal function. Peri-operative hyperglycaemia and large fluctuations in plasma glucose increase postoperative mortality and morbidity and careful measures are required to minimise these effects.
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PMID:Diabetes care for patients with peripheral arterial disease. 1736 40

The leaves of some mistletoes, specifically Loranthus micranthus Linn, Tapinanthus dodoneifolius (DC) Danser and Globimetula cupulata (DC) Van Tieghem (family: Loranthaceae), are used traditionally in Nigerian folk medicine to manage, control and/or treat a plethora of human ailments, including diabetes mellitus and hypertension. In order to scientifically appraise some of the folkloric, ethnomedical uses of Globimetula species, the present study was undertaken to investigate the hypoglycaemic and hypotensive effects of Globimetula cupulata aqueous leaf extract (GCE, 50-800 mg/kg po) in rat experimental paradigms. The hypoglycaemic effect of the plant extract was examined in normal (normoglycaemic) and diabetic (hyperglycaemic) rats using a streptozotocin (STZ)-induced diabetes model. Normotensive Wistar and hypertensive Dahl salt-sensitive rats were used to investigate the hypotensive (antihypertensive) effect of the plant extract. Metformin (MFM, 500 mg/kg po) was used as the reference hypoglycaemic agent for comparison. Acute oral administrations of G cupulata aqueous leaf extract (GCE, 50-800 mg/kg po) caused dose-related, significant (p < 0.05-0.001) hypoglycaemia in normal and STZ-treated diabetic rats. Furthermore, acute intravenous administrations of GCE (50-800 mg/kg iv) produced dose-dependent, significant reductions (p < 0.05-0.001) in systemic arterial blood pressure and heart rates of the normotensive and hypertensive rats used. Although the exact hypoglycaemic and hypotensive mechanisms of action of the plant extract still remain speculative, it is unlikely that the extract induced hypotension in the mammalian experimental animal model via cholinergic mechanisms, since its cardiovascular effects were resistant to atropine pretreatment. However, the findings of this experimental study indicated that Globimetula cupulata aqueous leaf extract possesses hypoglycaemic and hypotensive properties. This therefore lends pharmacological support to the folkloric, ethnomedical uses of the plant in the management and/ or control of diabetes mellitus and hypertension among the Yoruba-speaking people of western Nigeria.
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PMID:Hypoglycaemic and hypotensive effects of Globimetula cupulata (DC) Van Tieghem (Loranthaceae) aqueous leaf extract in rats. 1739 89

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