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Thiazide diuretics were the first tolerated efficient antihypertensive drugs that significantly reduced cardiovascular morbidity and mortality in placebo-controlled clinical studies. Although these drugs today still are considered a fundamental therapeutic tool for the treatment of hypertensive patients, the following considerations should be taken into account. Although there are some indications that chlorthalidone can offer additional advantages as compared with other compounds, a recent meta-analysis of placebo-controlled trials suggested that the beneficial effects of thiazide diuretics could be a class effect. Thiazide diuretics must be used at appropriate and/or optimal doses to achieve the optimal antihypertensive effect with the smallest occurrence of side effects, including alterations in glucose and lipid profiles and hypokalemia. Moreover, because thiazide diuretics can increase the incidence of new-onset diabetes, especially when combined with beta blockers, caution is advised in using these drugs above all in patients who are at high risk for developing diabetes, in whom thiazide diuretics should be used at the lowest active dose and possibly in combination with drugs that block the renin-angiotensin system. Finally, the current debate on whether thiazide diuretics are the first-choice drug for most patients with uncomplicated hypertension, as stated in the Seventh Joint National Committee Report, or are included in the major classes of antihypertensive agents that are suitable for initiation and maintenance of therapy, as reported in the European Society of Hypertension-European Society of Cardiology Guidelines, derives from different interpretations of controlled clinical trial data on drug class comparison and of cost-benefit analyses. However, considering that the benefit of antihypertensive drugs seems to be due principally to BP lowering per se without definitive evidence of the superiority of a particular drug class and that there is no cost-benefit analysis showing the superiority of thiazide diuretics, it is believed that these drugs should not be considered as the only first-choice drug but included among first-choice drugs.
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PMID:Thiazide diuretics in the treatment of hypertension: an update. 1656 43

Lowering blood pressure (BP) in hypertensive patients reduces morbidity and mortality. However the long-term safety of some antihypertensive agents was a matter of concern. Diuretic, the gold standard treatment in hypertension may impair glucose tolerance and thereby accelerate the development of diabetes mellitus. It was also associated with increased cardiovascular mortality in diabetic patients. However, recent evidence showed that low-medium dose of thiazide diuretic especially when given in combination with potassium sparing agent is effective in reducing BP and cardiovascular morbidity and mortality. Beta blockers are less effective than other antihypertensive agents in the elderly. Therefore they may be appropriate as a first choice in young and middle-age hypertensives, and in those with fast heart rate, but they should not be considered appropriate as the first-line therapy in the elderly with uncomplicated hypertension. Several years ago a plethora of publications showed that short-acting calcium antagonists may increase the risk for myocardial infarction and cancer. A few years ago two studies showed that calcium antagonists are less effective than angiotensin converting enzyme inhibitors in preventing cardiovascular events in diabetic hypertensive patients. However, recent results from large prospective randomized studies showed that calcium antagonists reduce cardiovascular morbidity and mortality in diabetic and non-diabetic hypertensive patients. Some investigators have suggested that angiotensin receptor blockers (ARBs) may increase the risk of myocardial infarction in hypertensive patients. However, recent meta analyses refuted this conclusions and showed that ARBs are probably as effective as other antihypertensive agents in prevention of myocardial infarction. Despite the concern that has been raised regarding the long-term safety of some antihypertensive agents, it is clear that lowering BP is safe and beneficial.
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PMID:Long-term safety of antihypertensive therapy. 1686 47

Beta-blockers are less beneficial than other antihypertensive drugs in the elderly with hypertension. All elderly patients in Ontario, Canada (population over 3.5 million elderly) without co-morbidities who were first treated for hypertension with a beta-blocker were studied in a retrospective population-based cohort study (1994-2002) to determine the characteristics of those prescribed beta-blockers. Of the 194,761 patients in our cohort, 25 485 (13%) were prescribed a beta-blocker as their first antihypertensive agent. On multivariate analysis, factors significantly associated with being prescribed a beta-blocker as first-line therapy included male sex (adjusted odds ratio (OR) 1.06 [95% CI 1.03-1.09] vs women), younger age (adjusted OR 1.67 [95% CI 1.55-1.79] for patients aged 66-69 vs those aged 85 or older), residence in a long-term care facility (adjusted OR 1.19 [95% CI 1.04-1.35] vs living in the community) and lower socioeconomic status (adjusted OR 1.07 [95% CI 1.02-1.12], for lowest quintile vs highest quintile). Patients with diabetes were substantially less likely to be prescribed beta-blockers (adjusted OR 0.42 [95% CI 0.40-0.44]). Greater efforts are required to educate physicians to select other drugs for initial therapy in older patients with uncomplicated hypertension.
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PMID:Use of beta-blockers for uncomplicated hypertension in the elderly: a cause for concern. 1728 45

The blood pressure (BP) goals set by hypertension management guidelines (<140/90 mm Hg in uncomplicated hypertension; <130/80 mm Hg in type 2 diabetes or kidney disease) are not being achieved in a high proportion of patients, partly because monotherapy is insufficient in many patients. In particular, patients with uncontrolled moderate or severe hypertension and/or associated cardiovascular risk factors remain at high risk for cardiovascular events and hypertensive emergency. In recognition of the urgency of treating moderate and severe hypertension, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) advocates the initial use of 2-drug therapies in patients with systolic BP levels >20 mm Hg above goal or diastolic BP level >10 mm Hg above goal. Regimens should usually include a thiazide diuretic and, for patients with diabetes or kidney disease, an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. Recently, clinical trial data have shown that first-step antihypertensive treatment of moderate and severe hypertension with carefully chosen fixed-dose combinations provides a high rate of BP goal achievement, a simplified dosing regimen, and superior tolerability compared with monotherapy.
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PMID:Emerging insights in the first-step use of antihypertensive combination therapy. 1804 7

Beta-blockers have long being used as first-line therapy for hypertension as their use had resulted in a reduction in cardiovascular morbidity and mortality in controlled clinical trials. A recent meta-analysis comparing beta-blockers to all other anti-hypertensive drugs taken together has found that stroke reduction was sub-optimal. Specifically, atenolol was associated with a 26% higher risk of stroke compared with other drugs. Several reasons may explain the less favourable outcomes with beta-blocker therapy. These include some adverse metabolic abnormalities such as dyslipidaemia and new-onset diabetes, and less effective reduction of central aortic compared with brachial blood pressure. Newer beta-blockers such as carvedilol or nebivolol are better tolerated. These beta-blockers have a vasodilating effect, which may beneficially affect systolic blood pressure in the aorta. Their long-term cardiovascular outcome in hypertension is still not known. Further studies would be required to show that stroke is adequately reduced by these newer beta-blockers. In conclusion, beta-blockers should not be the first drugs of choice in the management of uncomplicated hypertension. They may be used in addition to other antihypertensive agents to achieve blood pressure goals. However, in patients with angina pectoris, a previous myocardial infarction, heart failure and certain dysrhythmias, beta-blockers still play an important role.
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PMID:Should beta-blockers still be used as initial antihypertensive agents in uncomplicated hypertension? 1807 10

Hypertension is a major risk factor for cardiovascular morbidity and mortality and currently has been estimated at 30% of the US population. Of these, only 36.8% have their blood pressure reduced to recommended levels of lower than 140/90 mmHg for uncomplicated hypertension, or less than 130/80 mmHg for patients with diabetes mellitus or renal disease. Since monotherapy controls blood pressure in less than 50% of treated hypertensive patients, combination therapy is often required to bring blood pressure to the recommended levels of the 7th Joint National Committee report. One of the most effective and widely used combinations is the combination of an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker with hydrochlorothiazide (HCTZ). Aliskiren, a new blocker of the renin-angiotensin system has been developed and approved by the US FDA on 18th January 2008 for the treatment of hypertension. Aliskiren is a direct inhibitor of renin, the rate-limiting enzyme for the production of angiotensin II, a powerful vasoconstrictive peptide. Several randomized clinical trials have demonstrated that aliskiren administered in single daily doses of 150, 300 or 600 mg alone and in combination with HCTZ 12.5 and 25 mg is effective in lowering blood pressure, and is safe and well tolerated. In this article, the pharmacokinetic and pharmacodynamic profile and the clinical application of aliskiren alone and in combination with HCTZ will be discussed.
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PMID:Aliskiren-hydrochlorothiazide combination for the treatment of hypertension. 1832 92

Blacks have the highest rates of hypertension and cardiovascular disease, with earlier onset, greater severity, and more target organ damage including coronary disease, heart failure, stroke, and end-stage renal disease. A major reason is the greater prevalence of other cardiovascular disease risk factors, particularly obesity, inactivity, and diabetes mellitus, along with socioeconomic differences, adherence, and achievement of goals. This review focuses on the burden of cardiovascular disease in blacks. Therapeutic lifestyle changes and pharmacologic interventions to decrease clinical events in this high-risk group are described. Intensive blood pressure control is a primary means of "stopping the clock" in the progression of cardiovascular disease and renal disease. Thiazide diuretics remain primary first-step agents, especially for uncomplicated hypertension; calcium channel blockers are also efficacious. However, renin-angiotensin system modulators may also be beneficial, especially with a diuretic, considering the high prevalence in this group of patients of compelling indications for use of such agents.
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PMID:Cardiovascular disease in blacks: can we stop the clock? 1845 98

The incidence of hypertension continues to increase worldwide and, according to recent estimates, its incidence is approximately 30% of the U.S. population. However, the control of blood pressure (BP) to recommended levels of < 140/90 mmHg for uncomplicated hypertension, recommended in the 7th Report of the Joint National Committee (JNC-7) on Prevention, Detection, Evaluation and Treatment of High Blood Pressure, remains low at 36.8%. Because the level of BP is directly related to cardiovascular and stroke morbidity and mortality, aggressive treatment and control of hypertension are strongly indicated. Since monotherapy alone is not effective for the control of stage 2 hypertension, fixed-dose combination therapy with two complementary drugs has been recommended by the JNC-7 guidelines as initial therapy for subjects with diastolic BP > or = 100 mmHg and systolic BP > or = 160 mmHg. There are several fixed-dose combination preparations already available, each with its individual indications. The recently FDA-approved fixed-dose combinations of amlodipine with either olmesartan or valsartan are very effective in treating hypertension and are safe and well tolerated. In addition to reducing BP, these new fixed-dose combinations have also demonstrated significant reductions in the inciendence of edema associated with amlodipine monotherapy, which makes them more acceptable to patients. In addition, due to the metabolic neutrality of both component drugs, these preparations are preferable for the treatment of hypertensive patients with diabetes or the metabolic syndrome, in addition to other cardiovascular risk factors.
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PMID:Amlodipine/ARB fixed-dose combinations for the treatment of hypertension: focus on amlodipine/olmesartan combination. 1859 98

Although beta-blockers have been previously shown to effectively reduce blood pressure (BP) and have been used for hypertension treatment for over 40 years, their effect on cardiovascular morbidity and mortality in hypertensive patients remains controversial and its use in uncomplicated hypertension is currently under debate. However, data on the above field derive mainly from studies which were conducted with older agents, such as atenolol and metoprolol, while considerable pharamacokinetic and pharmacodynamic heterogeneity is present within the class of beta-blockers. Carvedilol, a vasodilating non-cardioselective beta-blocker, is a compound that seems to give the opportunity to the clinician to use a cardioprotective agent without the concerning hemodynamic and metabolic actions of traditional beta-blocker therapy. In contrast with conventional beta-blockers, carvedilol maintains cardiac output, has a less extended effect on heart rate and reduces BP by decreasing vascular resistance. Further, several studies has shown that carvedilol has a beneficial or at least neutral effect on metabolic parameters, such as glycemic control, insulin sensitivity, and lipid metabolism, suggesting that they could be used in subjects with the metabolic syndrome or diabetes without negative consequences. This article summarizes the distinct pharmacologic, hemodynamic, and metabolic properties of carvedilol in relation to conventional beta-blockers, attempting to examine the potential use of this agent for hypertension treatment.
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PMID:Carvedilol in hypertension treatment. 1862 77

The present report highlights the key messages of the 2009 Canadian Hypertension Education Program (CHEP) recommendations for the management of hypertension and the supporting clinical evidence. In 2009, the CHEP emphasizes the need to improve the control of hypertension in people with diabetes. Intensive reduction in blood pressure (to less than 130/80 mmHg) in people with diabetes leads to significant reductions in mortality rates, disability rates and overall health care system costs, and may lead to improved quality of life. The CHEP recommendations continue to emphasize the important role of patient self-efficacy by promoting lifestyle changes to prevent and control hypertension, and encouraging home measurement of blood pressure. Unfortunately, most Canadians make only minor changes in lifestyle after a diagnosis of hypertension. Routine blood pressure measurement at all appropriate visits, and screening for and management of all cardiovascular risks are key to blood pressure management. Many young hypertensive Canadians with multiple cardiovascular risks are not treated with antihypertensive drugs. This is despite the evidence that individuals with multiple cardiovascular risks and hypertension should be strongly considered for antihypertensive drug therapy regardless of age. In 2009, the CHEP specifically recommends not to combine an angiotensin-converting enzyme inhibitor with an angiotensin receptor blocker in people with uncomplicated hypertension, diabetes (without micro- or macroalbuminuria), chronic kidney disease (without nephropathy [micro- or overt proteinuria]) or ischemic heart disease (without heart failure).
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PMID:2009 Canadian Hypertension Education Program recommendations: the scientific summary--an annual update. 1941 57


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