UMLS:C0018801 - FACTA Search

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Query: UMLS:C0018801 (heart failure)
72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Angiotensin II receptor blockers (ARBs) represent a new class of effective and well tolerated orally active antihypertensive agents. Recent clinical trials have shown the added benefits of ARBs in hypertensive patients (reduction in left ventricular hypertrophy, improvement in diastolic function, decrease in ventricular arrhythmias, reduction in microalbuminuria, and improvement in renal function), and cardioprotective effect in patients with heart failure. Several large long-term studies are in progress to assess the beneficial effects of ARBs on cardiac hypertrophy, renal function, and cardiovascular and cerebrovascular morbidity and mortality in hypertensive patients with or without diabetes mellitus, and the value of these drugs in patients with heart disease and diabetic nephropathy. The ARBs specifically block the interaction of angiotensin II at the AT1 receptor, thereby relaxing smooth muscle, increasing salt and water excretion, reducing plasma volume, and decreasing cellular hypertrophy. These agents exert their blood pressure-lowering effect mainly by reducing peripheral vascular resistance usually without a rise in heart rate. Most of the commercially available ARBs control blood pressure for 24 h after once daily dosing. Sustained efficacy of blood pressure control, without any evidence of tachyphylaxis, has been demonstrated after long-term administration (3 years) of some of the ARBs. The efficacy of ARBs is similar to that of thiazide diuretics, beta-blockers, angiotensin-converting enzyme inhibitors or calcium channel blockers in patients with similar degree of hypertension. Higher daily doses, dietary salt restriction, and concomitant diuretic or ACE inhibitor administration amplify the antihypertensive effect of ARBs. The ARBs have a low incidence of adverse effects (headache, upper respiratory infection, back pain, muscle cramps, fatigue and dizziness), even in the elderly patients. After the approval of losartan, five other ARBs (candesartan cilexetil, eprosartan, irbesartan, telmisartan, and valsartan) and three combinations with hydrochlorothiazide (irbesartan, losartan and valsartan) have been approved as antihypertensive agents, and some 28 compounds are in various stages of development. The ARBs are non-peptide compounds with varied structures; some (candesartan, losartan, irbesartan, and valsartan) have a common tetrazolo-biphenyl structure. Except for irbesartan, all active ARBs have a carboxylic acid group. Candesartan cilexetil is a prodrug, while losartan has a metabolite (EXP3174) which is more active than the parent drug. No other metabolites of ARBs contribute significantly to the antihypertensive effect. The variation in the molecular structure of the ARBs results in differences in the binding affinity to the receptor and pharmacokinetic profiles. The differences observed in lipid solubility, absorption/distribution, plasma protein binding, bioavailability, biotransformation, plasma half-life, and systemic elimination influence the time of onset, duration of action, and efficacy of the ARBs. On the basis of the daily mg dose, the antihypertensive potency of the ARBs follows the sequence: candesartan cilexetil > telmisartan approximately = losartan > irbesartan approximately = valsartan > eprosartan. After oral administration, the ARBs are rapidly absorbed (time for peak plasma levels = 0.5-4 h) but they have a wide range of bioavailability (from a low of 13% for eprosartan to a high of 60-80% for irbesartan); food does not influence the bioavailability, except for valsartan (a reduction of 40-50%) and eprosartan (increase). A limited dose-peak plasma levels/areas under the plasma level-time curve proportionality is observed for some of the ARBs. Most of these drugs have high plasma protein binding (95-100%); irbesartan has the lowest binding among the group (90%). The steady-state volumes of distribution vary from a low of 9 L (candesartan) to a high of 500 L (telmisartan). (ABSTRACT TRUNCATE
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PMID:Clinical pharmacokinetics of angiotensin II (AT1) receptor blockers in hypertension. 1085 85

Since the publication of the Agency for Health Care Policy and Research Guidelines for treatment of heart failure, a number of new agents have been investigated for this indication. beta-Blockers have now been shown to improve outcomes in mild to moderate heart failure when added to standard therapy. Angiotensin II receptor antagonists have also been investigated and show promise. In general, calcium channel blockers are second- or third-line agents in patients refractory to other therapy. Investigational agents including spironolactone may also hold promise for future therapy.
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PMID:Pharmacotherapy of systolic heart failure: a review of recent literature and practical applications. 1090 4

Angiotensin II receptor blockers represent a class of effective and well tolerated orally active antihypertensive drugs. Activation of AT(1) receptors leads to vasoconstriction, stimulation of the release of catecholamines and antidiuretic hormone and promote growth of vascular and cardiac muscle. AT(1) receptor blockers antagonise all those effects. Losartan was the first drug of this class marketed, shortly followed by valsartan, irbesartan, telmisartan, candesartan, eprosartan and others on current investigation. All these drugs have the common properties of blockading the AT(1) receptor thereby relaxing vascular smooth muscle, increase salt excretion, decrease cellular hypertrophy and induce antihypertensive effect without modifying heart rate or cardiac output. Most of the AT(1) receptor blockers in use controlled blood pressure during the 24 h with a once-daily dose, without evidence of producing tolerance to the antihypertensive effect and being with low incidence of side effects even at long term use. Monotherapy in mild-to-moderate hypertension controls blood pressure in 40 to 50% of these patients; when a low dose of thiazide diuretic is added, 60-70% of patients are controlled. The efficacy is similar to angiotensin-converting enzyme (ACE) inhibitors, diuretics, calcium antagonists and beta-blocking agents. AT(1) receptor blockers are specially indicated in patients with hypertension who are being treated with ACE inhibitors and developed side effects such as, cough or angioedema. The final position in the antihypertensive therapy in this special population and other clinical situations, such as left ventricular hypertrophy, heart failure, diabetes mellitus and renal disease, has to be determined in large prospective clinical trials, some of which are now being conducted and seem promising.
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PMID:Angiotensin II receptor antagonists role in arterial hypertension. 1198 4

Angiotensin II receptor antagonists (AAIIs) are the most specific inhibitors of the renin-angiotensin-aldosterone system. There are two types of angiotensin II (Ang II) receptors, the AT(1) receptor, which is responsible for all the classical physiological properties of Ang II, and the AT(2) receptor, whose function in humans remains unclear. The different AAIIs used in clinical practice vary depending on their pharmacodynamic and pharmacokinetic properties, and, for some of them, depending on their metabolism in vivo into an active metabolite. AAIIs are relatively well tolerated, and, unlike angiotensin-converting enzyme inhibitors (ACEIs), do not induce cough. AAIIs are indicated in mild, moderate and severe essential hypertension, where their efficacy has been proven in many studies. The maximal antihypertensive effect is obtained in a few days or weeks, and is somewhat retarded when compared with ACEIs. Their effect is independent of age and sex, but does depend to a certain extent on ethnic origin, since Afro-American patients are less sensitive to AAIIs than Caucasians. In general, the antihypertensive and haemodynamic response to blockers of the renin-angiotensin system is potentiated in presence of a negative salt balance and attenuated in case of a positive salt balance. This means that AAII efficiency is improved by salt depletion induced by a salt-free diet or thiazide diuretics. AAIIs induce short-term improvement of haemodynamic parameters in cardiac insufficiency. Several ongoing clinical trials have been designed to compare their efficacy in cardiac insufficiency and myocardial infarction with those of reference treatments. Valsartan has been recently shown to improve morbimortality in patients with cardiac insufficiency and receiving a conventional treatment including an ACEI. It has been convincingly shown that blockade of the renin-aldosterone system by ACEIs decreases proteinuria and slows down the progression of renal insufficiency, especially in type 2 diabetic nephropathy. Recent trials have shown that AAIIs share the same properties as ACEIs in these indications. It appears that the beneficial effect of AAIIs and ACEIs is not entirely explained by the blood pressure lowering effect of these drugs. AAII administration increases renin release and Ang II production, which may overcome Ang II blockade. On this basis, the combination of an AAII and an ACEI has been proposed to achieve a maximal renin-angiotensin system blockade. Several experimental studies in animals and preliminary clinical studies all indicate that the combination of the two drugs may be more beneficial than either drug used alone in hypertension, cardiac insufficiency and post-myocardial infarction. Clinical trials are necessary to further document the putative advantages of such a combined therapy. The future of AAIIs depends on the following: progress made in the understanding of the molecular and cellular activities of angiotensin (angiotensin receptor signalling, receptor dimerisation, presence of other angiotensin receptor subtypes, role of AT(2) receptor, etc.);a comprehensive view of the role of the local renin system in various organs (local generation and effect of Ang II on cellular proliferation, fibrosis, inflammation, angiogenesis, etc.);predictability of the response to AAII treatment (genetic predisposition to AAII treatment, in conjunction with environmental factors); andresults of the ongoing clinical trials designed to assess the long-term effects of AAIIs in cardiovascular mortality and morbidity, in comparison with reference treatments.
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PMID:[Angiotensin II receptor blockers: current status and future prospects]. 1203 89

The renin-angiotensin-aldosterone system plays a key role in the regulation of fluid and electrolyte balance. Angiotensin-converting enzyme inhibitors inhibit angiotensin-converting enzyme and have been shown to be effective in many cardiovascular diseases. They should be considered for the treatment of hypertension in patients with heart failure, previous myocardial infarction, diabetes, or proteinuria. There are a number of side-effects associated with angiotensin-converting enzyme inhibitors, especially persistent dry cough. Angiotensin II receptor antagonists (sartans) provide a more specific blockade of the renin-angiotensin-aldosterone system and are associated with fewer side-effects, including cough. Their long-term efficacy and tolerability in the treatment of patients with hypertension has, however, yet to be established. Periodic monitoring of renal function and electrolytes is required in patients treated with an angiotensin-converting enzyme inhibitor or a sartan.
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PMID:Blockade of the renin-angiotensin system. 1205 64

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

Evidence from large, randomized, controlled clinical trials supports the use of angiotensin-converting enzyme (ACE) inhibitors, beta blockers, and spironolactone to reduce mortality and morbidity. Despite these effective therapies, event rates related to heart failure remain high. Although ACE inhibitors reduce angiotensin II production, they do not fully suppress the increased angiotensin II production in heart failure. Angiotensin II receptor blockers (ARBs) directly block the effect of angiotensin II, derived from any source, at the receptor level and have the potential to be as effective or even more effective than ACE inhibitors. The results of a number of clinical studies have demonstrated ARBs are effective and well tolerated. However, no studies have demonstrated a convincing decrease in mortality with ARB use, although a decrease has been observed for heart failure hospitalization. The results from further studies are awaited to clarify the role of ARBs in the treatment of heart failure.
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PMID:The role of angiotensin II receptor blockers in the treatment of heart failure patients. 1255 75

Angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors have been shown to reduce morbidity and mortality in patients with heart failure, but their inhibitory actions on angiotensin I-induced increases in blood pressure in heart failure are not clear. Angiotensin I blocking and cardioprotective properties of the angiotensin II receptor blocker candesartan and the angiotensin-converting enzyme inhibitor quinapril were studied in a rat model of dilated cardiomyopathy after autoimmune myocarditis. Low-dose candesartan (0.5 mg/kg) showed the same angiotensin I blocking action as high-dose quinapril (20 mg/kg) in rats with heart failure. Twenty-eight days after immunization, surviving Lewis rats (43/58, 74%) were divided into three groups and given quinapril at 20 mg/kg per day (group Q, n = 14), candesartan at 0.5 mg/kg per day (group C, n = 14) or vehicle alone (group V, n = 15). After oral administration for 1 month, four of 15 (27%) rats in group V and two of 14 (14%) in group C died. None of the animals in group Q died. Although angiotensin II levels of the blood and the left ventricle in group V [367 +/- 26 and 437 +/- 18% versus normal rats (group N)] were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 +/- 32 and 169 +/- 53%, both p < 0.01). The left ventricular end-diastolic pressure and the area of myocardial fibrosis were lower, and the first derivative +/-dP/dt was higher in group Q (7.0 +/- 1.7 mmHg, 9 +/- 3% and +3451+/- 170/-3182 +/- 186 mmHg/s, respectively) than in group V (16.7 +/- 1.3 mmHg, 36 +/- 6% and +2601 +/- 235/-2156 +/- 257 mmHg/s, respectively) and in group C (11.2 +/- 2.0 mmHg, 26 +/- 4% and +3063 +/- 164/-2734 +/- 174 mmHg/s, respectively). Although levels of expression of transforming growth factor beta1 and collagen III mRNA in groupV (367 +/- 26 and 437 +/- 18% versus group N) were significantly higher than those in group N (both p < 0.01), they were reduced in group Q (88 +/- 32 and 169 +/- 53%, both p < 0.01). These results suggested that although low-dose candesartan can block increases in blood pressure with circulating angiotensin I to the same extent as high-dose quinapril, it does not confer sufficient protection against injury from the renin-angiotensin system in heart failure.
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PMID:Comparative effects of angiotensin II receptor blockade (candesartan) with angiotensin-converting enzyme inhibitor (quinapril) in rats with dilated cardiomyopathy. 1269 79

The blockade of the renin-angiotensin system in the heart failure using ACE inhibitors, based on numerous clinical studies, demonstrated significant decrease in morbidity and mortality in the patients. Discovery of angiotensin II receptor antagonists brought about a new possibility of blockade of the rennin-angiotensin system. The blockade of the renin-angiotensin system with angiotensin II receptor antagonists should have been more effective and comprehensive than that induced by ACE inhibitors. However, the first studies with angiotensin II receptor antagonists in heart failure did not confirm that the antagonists are superior in reducing mortality and hospitalization in patients with heart failure when compared with ACE inhibitors. For the time being, the ACE inhibitors remain the current therapy of choice in treating heart failure. Angiotensin II receptor antagonists are a reasonable alternative in patients who cannot be treated with ACE inhibitors because of adverse effects. Clinical studies currently under way with angiotensin II receptor antagonists may alter these conclusions.
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PMID:[Angiotensin II antagonists in the treatment of cardiac decompensation]. 1282 85

Heart failure is a common and costly medical condition. Ischemic heart disease and hypertension account for most cases of heart failure in developed countries. Estimates of the one-year mortality rates for patients with New York Heart Association (NYHA) Class II, III, and IV are 10%, 20%, and 40%, respectively. Angiotensin-converting enzyme (ACE) inhibitors reduce mortality of heart failure patients by approximately 25% (odds ratio 0.77, 95% CI 0.67 0.88). Larger doses of ACE inhibitors are more effective in preventing hospitalization than are lower doses. Angiotensin II receptor blockers (ARBs) are an alternative for patients who cannot tolerate ACE inhibitors because of their side effects (e.g., cough). Evidence for benefits of using combination of ACE inhibitors and ARBs is encouraging, but requires further study. For patients who cannot tolerate either ACE inhibitors or ARBs, vasodilator therapy with hydralazine and nitrates will probably provide benefit. (Diuretic therapy, while a mainstay of heart failure treatment, is primarily used for symptom relief.) There is also evidence that spironolactone reduces mortality (relative risk reduction 30%, 95% CI 18 40%) for patients with NYHA class III and IV heart failure. When administering spironolactone to heart failure patients, monitoring for hyperkalemia is essential. After two centuries of use, randomized controlled trials have finally demonstrated that digoxin is effective in preventing hospitalizations (relative risk reduction 28%, 95% CI 21 34%). There is now overwhelming evidence that beta-blockers are safe for heart failure patients but that they reduce the risk of death for these patients by approximately 30%. In addition to these medical interventions, heart failure patients may also benefit from a number of non-pharmacological interventions.
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PMID:A review of heart failure treatment. 1477 Feb 50

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