Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0018801 (heart failure)
 72,216 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carvedilol, a new beta-blocker with vasodilating properties due to alpha 1-blockade, was investigated in preparations of human ventricular myocardium. Carvedilol demonstrated a high affinity and is a slightly beta 1-selective competitive beta-blocking agent, with a KD for beta 1-receptors of approximately 4-5 nM and a mild selectivity for beta 1 vs. beta 2 receptors of 6- to 39-fold, depending on the method employed to assess subtype potency. In addition, carvedilol was also a potent alpha 1-blocking agent, with a beta 1:alpha 1 blocking relative potency of 1.7-fold. In human lymphocytes containing beta 2-receptors and in human myocardial membranes containing both beta 1- and beta 2-receptors carvedilol exhibited the unique property of guanine nucleotide modulatable binding. Despite this, no intrinsic sympathomimetic activity of carvedilol was detected in preparations of isolated human heart or in myocardial membranes. Vasodilation related to alpha 1-blockade and the lack of intrinsic activity should translate into improved tolerability and good efficacy in the treatment of heart failure.
 ...
PMID:Effects of carvedilol on adrenergic receptor pharmacology in human ventricular myocardium and lymphocytes. 135 Apr 78

Several studies in the past have shown the long-term beneficial effects of beta-blockers in congestive heart failure. Despite the interest in this mode of therapy, their clinical application has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show any improvements with standard beta-blocker therapy. Carvedilol, a new, non-selective beta-blocking agent with concurrent alpha-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischaemic heart disease. All had resting left ventricular ejection fraction less than or equal to 45% and were maintained on diuretic therapy. Acute haemodynamic measurements were made after intravenous carvedilol (2.5-7.5 mg) and also after chronic therapy for 8 weeks (carvedilol 12.5-50 mg b.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study and 5 were withdrawn. Symptomatic and haemodynamic improvement was demonstrated in 11 of the 12 patients after 8 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Can intravenous beta blockade predict long-term haemodynamic benefit in chronic congestive heart failure secondary to ischaemic heart disease? A comparison between intravenous and oral carvedilol. 135 Apr 92

Carvedilol is a dual-acting drug designed to produce two complementary effects: beta-blockade and vasodilation. These effects are induced in the same dose range, a prerequisite for utilizing both properties in an appropriate manner. The vasodilation is mediated predominantly by specific alpha 1-adrenoceptor blockade. At markedly higher concentrations, additional vasodilating actions besides alpha 1-blockade can be observed. These effects resemble those of Ca(2+)-antagonistic properties. However, they do not contribute to the acute blood pressure-lowering activity of carvedilol but may be responsible for the increased blood flow to specific organs. At beta-blocking doses, carvedilol reduces the regional and systemic vascular resistance in various experimental models, healthy volunteers, and in patients with cardiovascular diseases such as hypertension, coronary artery disease, and heart failure. The profile of carvedilol thus insures beneficial treatment of hemodynamic disorders characterized by increased sympathetic tone and increased vascular resistance.
 ...
PMID:Vasodilatory action of carvedilol. 137 50

Several studies have demonstrated the long-term beneficial effects of beta-blockers in the treatment of congestive heart failure. Despite interest in this mode of therapy, clinical application of beta-blockers has been limited due to their negative inotropic effect. A subset of the heart failure patients do not show improvements with standard beta-blocker therapy. Carvedilol, a new nonselective beta-blocking agent with concurrent alpha-blocking properties, was evaluated in 17 patients with chronic heart failure secondary to ischemic heart disease. All had resting left ventricular ejection fraction less than or equal to 45% and were maintained on diuretic therapy. Acute hemodynamic measurements were made after administration of intravenous carvedilol (2.5-7.5 mg) and after chronic therapy for 8 weeks (12.5 to 50 mg b.i.d.). Radionuclide ventriculography, ambulatory intra-arterial blood pressure monitoring, and right heart catheterization were performed before and after 8 weeks of chronic therapy. Twelve patients completed the study (five were withdrawn). Symptomatic and hemodynamic improvements were demonstrated in 11 of the 12 patients after 8 weeks of therapy.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Can intravenous beta-blockade predict long-term hemodynamic benefit in chronic congestive heart failure secondary to ischemic heart disease? A comparison of intravenous with oral carvedilol. 137 53

Recent studies have shown that beta-blockers may be effective in the management of heart failure. However, negative inotropic effects of these agents may offset the beneficial properties of up-regulation of the beta-receptors and reduction in myocardial oxygen demand. Carvedilol is a new drug which possesses a balanced combination of vasodilatation and beta-blockade. Previous studies have shown that carvedilol may have beneficial effects on left ventricular function in patients with ischemic heart disease. We have performed a preliminary study to address the safety and acute effects of intravenous carvedilol in 17 patients with chronic congestive heart failure secondary to ischemic heart disease. Acute hemodynamic changes were monitored by right heart catheterization and arterial cannulation. Ejection fraction was also monitored by radionuclide ventriculography. Significant reductions in heart rate (79 +/- 14 to 72 +/- 12 beats/min, p less than 0.001) systolic and diastolic blood pressure (137 +/- 20/72 +/- 8 to 119 +/- 19/66 +/- 8 mm Hg, p less than 0.001 and p less than 0.01), systemic vascular resistance (1766 +/- 367 to 1518 +/- 377 dynes/s/cm-5/m2, p less than 0.001) and pulmonary artery wedge pressure (20 +/- 8 to 15 +/- 7 mm Hg, p less than 0.001) were observed. Ejection fraction increased significantly from 24 to 28% (p less than 0.001) but there was little change in cardiac index or stroke volume index. The peak changes occurred at 10 min and the effect on pulmonary wedge pressure was maintained up to 30 min. No adverse effects were noted. The improvements in left ventricular filling pressure and systolic function, and the reduction in sympathetic activity may combine to produce an important therapeutic advantage in congestive heart failure. Further studies with this interesting agent are recommended.
 ...
PMID:The effects of intravenous carvedilol, a new multiple action vasodilatory beta-blocker, in congestive heart failure. 172 73

Carvedilol is an arylethanolamine that is a racemic mixture of 2 enantiomers. The S-(-)-enantiomer has beta-adrenoceptor blocking activity, while the racemate also has alpha 1-receptor blocking activity due to the activity of the R-(+)-enantiomer. The drug is rapidly absorbed and undergoes extensive first-pass metabolism in the liver. It reaches a peak concentration 1 to 2 hours postdose and has an elimination half-life of about 4 to 7 hours. Absorption is delayed by food. The drug is highly lipophilic and is highly protein bound. The drug is metabolised by the liver, with some metabolites having biological activity. The pharmacokinetic profile is not altered in the elderly or in patients with renal disease. However, bioavailability of the oral medication is greatly increased in patients with liver disease. Carvedilol lowers blood pressure as a result of its beta-blocking and vasodilatory activity. The reduction in blood pressure is similar to that achieved with other antihypertensive drugs, and there are no adverse effects on renal or cerebral blood flow. Carvedilol has been used in small numbers of patients with cardiac failure. It reduces left ventricular hypertrophy and has no significant adverse metabolic effects.
 ...
PMID:Clinical pharmacokinetics and pharmacodynamics of carvedilol. 791 79

Risk factors in elderly hypertensives: Recent large-scale clinical trials have shown that antihypertensive treatment in the elderly produces meaningful reductions in strokes and other cardiovascular events. However, the treatment of hypertension in older patients is often complicated by the presence of concomitant disorders. Clinical and silent myocardial ischemia, as well as left ventricular hypertrophy and both systolic and diastolic left ventricular dysfunction, frequently coexist with hypertension. Additional clinical considerations in elderly hypertensives include a high prevalence of abnormal lipid and glucose metabolism and a tendency toward decreased renal function. Effects of different antihypertensive drugs: Although diuretics and conventional beta-blockers have been used as first-line drugs in the major clinical trials, some of their effects on metabolic parameters and on the myocardium can make them inappropriate in some patients. Newer drug classes, including angiotensin converting enzyme (ACE) inhibitors, calcium-channel blockers and, more recently, alpha 1-adrenergic blockers are effective alternatives. Dual-acting beta-blockers offer an important new approach for treating hypertension in elderly patients. Effects of carvedilol: Carvedilol possesses both beta- and alpha 1-blocking activity and appears to exhibit calcium channel blocking activity in animals. The alpha 1-blocking properties of this drug help to produce a desirable hemodynamic profile and facilitate appropriate blood pressure and heart rate responses to exercise. Carvedilol does not appear to adversely affect left ventricular systolic function and, in selected patients with heart failure, has been shown to increase the ejection fraction.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Antihypertensive treatment with a dual-acting beta-blocker in the elderly. 810 39

beta-adrenoceptor-blocking drugs, first introduced for the treatment of symptomatic angina pectoris, have been found effective across the whole spectrum of ischaemic disease. Labetalol was the first combined-action beta-blocking drug to be described and was shown to be capable of increasing exercise tolerance in patients with angina pectoris. Carvedilol also possesses a peripheral vasodilating action mainly due to an alpha 1-adrenoceptor blockade. Haemodynamic studies with carvedilol in patients with ischaemic heart disease have shown a reduction in peripheral vascular resistance in contrast to propranolol which increases systemic resistance and reduces cardiac output. Additionally, in ischaemic heart failure there is evidence of improved myocardial function, as shown by an increase in ejection fraction, after the administration of carvedilol. Carvedilol has been shown to improve exercise tolerance in patients with angina pectoris and reduce the occurrence of episodes of silent myocardial ischaemia. Carvedilol, unlike many beta-blocking drugs, does not adversely affect the plasma lipid profile qualitatively or quantitatively. In contrast to many non-selective beta-blocking drugs, carvedilol has a more favourable haemodynamic profile, and its lack of adverse influence on the plasma lipid profile may be important in its long-term use.
 ...
PMID:Carvedilol in ischaemic heart disease. 810 63

Sustained oral treatment with beta blockers has been shown to improve symptoms in patients with chronic heart failure. In non-placebo-controlled trials, the administration initially of a low dose, gradually increased over a period of weeks has been demonstrated to improve both symptoms, exercise capacity and left-ventricular ejection fraction. The rationale for this treatment is the enhanced adrenergic stimulation present in heart failure which results in decreased sensitivity and density of myocardial beta-receptors. Beta blockers may decrease this pathological adrenergic drive. Carvedilol, in addition to its beta-blocking properties, is a vasodilator and is theoretically more suitable than earlier compounds of its potential to further decrease left-ventricular afterload. Recent studies have demonstrated symptomatic improvement with carvedilol in patients with heart failure, and a multicentre trial has been designed to evaluate its efficacy and safety.
 ...
PMID:Carvedilol in heart failure. 810 65

Carvedilol is a non-selective beta-adrenoceptor antagonist with vasodilating properties which has been shown to be effective in the management both of hypertension and of stable angina pectoris. In order to explore its wider efficacy in patients with manifest heart failure, a preliminary study was performed in patients with chronic stable angina pectoris accompanied by abnormal left ventricular wall motion, but without overt heart failure (mean ejection fraction < 40%). Six patients were given carvedilol 25 mg b.i.d. for 2 weeks followed by 50 mg b.i.d. for a further 2 weeks according to a single-blind placebo-controlled protocol. At the end of the 4 week period of treatment, in four patients left ventricular wall motion was improved, in two it was unchanged, and in none was there any deterioration; mean ejection fraction increased from 40 to 48%. These results prompted a further study in 17 patients with chronic ischaemic heart failure. The haemodynamic and clinical responses to intravenous carvedilol followed by the oral drug (50 mg b.i.d.) for 8 weeks were studied. There was an improvement in all haemodynamic variables, although postural hypotension necessitated withdrawing two patients, and clinical deterioration was evident in two others. The beneficial effects of carvedilol were considered to be related to the combined reduction in afterload and inhibition of neurohumeral activation. These results have been confirmed in placebo-controlled, double-blind studies.
 ...
PMID:Vasodilating beta-blockers in heart failure. 852 82


1 2 3 4 5 6 7 8 9 10 Next >>