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

The possibilities for therapy in the field of severe cardiac insufficiency have been extended in recent years by the introduction of novel agents endowed with a positive inotropic action. These substances may be arranged in two large classes: sympathomimetic agents and "non sympathomimetic--non digitalis-like" inotropic agents. The stimulant action of noradrenaline, adrenaline and isoproterenol on beta-adrenergic myocardial receptors has been clearly demonstrated but the usefulness of these medicines is limited by their positive chronotropic and arrhythmogenic actions. Dopamine and dobutamine have proved to be very useful in the treatment of patients in intensive care units. However, the exclusively intravenous route of administration limits their importance to the medium or long term. Several compounds, which are active by the oral route, have been the subject of therapeutic trials for the short or medium term. The problems posed by their use result, in the first place, from an insufficient understanding of their mechanism of action. Some of them (pirbuterol, salbutamol, terbutaline, penoterol) seem to act preferentially on B2 adrenergic receptors and the haemodynamic effect results, in part or predominantly, from the vasodilator action which they cause. On the other hand, other agents (prenalterol, ICI 108-87) show a relative selectivity for B1 adrenergic receptors. Ibopamine exerts its action on B1 receptors and dopaminergic receptors. A second problem concerns the hypothetical character of their long term therapeutic activity. A major problem in the use of several of these sympathomimetic agents in chronic treatment is the appearance of a desensitization of the beta receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[New cardiotonic agents]. 293 98

Beta-adrenergic agonists can progressively lose their efficacy during chronic therapy in patients with heart failure. Ibopamine is a new dopamine derivative, active on dopaminergic and beta-adrenergic receptors, whose hemodynamic activity has been acutely demonstrated. To assess whether any attenuation of its efficacy occurs, the variations of the cardiac output induced during chronic therapy were monitored by impedance cardiography in 15 patients with dilated cardiomyopathy who showed a significant increase of the cardiac output (20.7 +/- 10.0%) after acute ibopamine administration. The efficacy of ibopamine was also assessed after 6 and 12 months of therapy by echocardiography, exercise testing, and 24-hour dynamic electrocardiogram (EKG) monitoring. The cardiac output response to ibopamine did not show any significant attenuation (range 15% to 19%) in the evaluations at 1, 2, 3, 4, 8, and 12 months of therapy. No significant change, was noted, after 6 and 12 months, in the exercise capacity (505 vs. 602 and 604 seconds) and the fractional shortening (16.2 vs. 18.3 and 18.5) without any change of the diastolic diameter. Ventricular arrhythmias were significantly reduced after 6, but not 12, months of therapy. No significant change in the New York Association (NYHA) functional class was noted at 6 and 12 months of therapy (2.4 +/- 5 vs. 2.3 +/- 7 and 2.4 +/-0.6, respectively). Our results show that ibopamine can maintain its hemodynamic activity even during chronic therapy.
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PMID:Lack of tolerance development during chronic ibopamine administration to patients with congestive heart failure. 315 8

The effects of a new orally effective dopamine-like derivative, ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on the cardiovascular system were investigated in anesthetized dogs. Ibopamine increased dose-dependently stroke volume index, cardiac index, left ventricular pressure, its first derivative: dP/dt, peak velocity left ventricular ejection and renal blood flow. After beta-blockade the positive inotropic effect of ibopamine is inhibited. Total peripheral resistance and renal vascular resistance decreased after ibopamine. Urine output was increased dose-dependently, reaching 115% after ibopamine 8 mg/kg intraduodenally. Coronary and femoral flows and resistance did not change after administration of 4 and 8 mg/kg. Only very high doses (24 mg/kg) caused an increase in flow and resistance. Mesenteric flow decreased transiently and then returned to the previous level or increased considerably over the basal figures when a high dose was used. No significant changes or fall in heart rate were observed with doses up to 16 mg/kg and no significant changes in pulmonary resistance were noted. The data obtained from the present investigation show, however, that oral ibopamine is capable of producing most of the effects induced by intravenously given dopamine in anesthetized dogs. Ibopamine's cardiac and renal effects may open new prospects for the long-term treatment of chronic heart failure in human subjects.
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PMID:Effects of ibopamine on systemic, pulmonary and regional hemodynamics. Experimental investigations in anesthetized dogs. 370 41

The activity of ibopamine (SB-7505), the 3,4-diisobutyryl ester of N-methyldopamine, on myocardial contractility and systemic and renal hemodynamics was investigated in the anesthetized dog with experimental infarction, instrumented with catheters and electromagnetic flowmeters. Ibopamine, given by the intraduodenal route at a dose of 24 mg/kg, was effective in improving the hemodynamic parameters depressed by myocardial infarction, in particular myocardial contractility and renal hemodynamics. In eliciting such activity which resembles that developed by dopamine in similar experimental conditions, ibopamine seems to meet the requirements of an orally active pharmacological agent useful in the therapy of acute heart failure.
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PMID:Effects of ibopamine on acute cardiac failure following experimental coronary occlusion in dogs. 370 44

The sympathetic nervous system is under extraordinarily complex modulation, involving numerous presynaptic and postsynpatic control mechanisms. These highly conserved and very redundant control mechanisms allow for the sympathetic nervous system to adapt quickly and precisely to altered environmental stress or conditions. Heart failure (HF) is characterized by excessive sympathetic activity, with both enhanced "spillover" and reduced clearance of norepinephrine (NE). The normal inhibitor control mechanisms appear faulty, with unleashed sympathetic activity likely contributing to the pathophysiology of the clinical syndrome and being associated with excessive mortality. Attempts to attenuate pharmacologically the release or "spillover" of NE from sympathetic neurons in HF has remained an attractive therapeutic strategy, and various alpha 2 adrenergic agonists and dopaminergic agents have been studied in several small clinical trials. Agents designed to activate both presynaptic (DA2) and postsynaptic or vascular (DA1) receptors have demonstrated promise. Ibopamine, a prodrug that is converted metabolically to epinine, a DA1 > DA2 agonist, has potential for selective vasodilation of mesenteric, renal, cerebral, and coronary vascular beds while reducing NE release and aldosterone activity. Preliminary clinical trials with ibopamine are encouraging, but placebo-controlled multicenter studies will be necessary to establish its role in the treatment of HF.
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PMID:Receptor systems involved in norepinephrine release in heart failure: focus on dopaminergic systems. 774 93

Ibopamine is the prodrug of epinine or N-methyl dopamine. Ibopamine stimulates the DA1 and DA2 dopaminergic receptors, the beta 1 and beta 2 adrenoceptors, and the alpha 1 and alpha 2 adrenoceptors. Ibopamine has varying degrees of affinity for these various families, being the highest for the dopamine receptors and the lowest for the alpha adrenergic receptors. In the clinical setting, there is a dose-related hemodynamic and neurohormonal response. In patients with heart failure (HF), low doses appear to exert beneficial neurohormonal, hemodynamic, and renal effects, without increased inotropic effects. However, at higher doses (> 200 mg) ibopamine exerts effects that do not appear to be clinically useful in long-term treatment of chronic HF. Several small trials have suggested a benefit of ibopamine on exercise performance in patients with mild to moderate HF. On the basis of these studies, ibopamine is now being used in Europe to treat patients with mild to moderate congestive heart failure (CHF). At doses of 100 or 200 mg/t.i.d., there has been no evidence of significant safety problems. Ibopamine may have a role in the treatment of patients with more severe left ventricular dysfunction who remain symptomatic despite therapy with diuretics and angiotensin-converting enzyme (ACE) inhibitors. Preliminary data suggest the drug is well tolerated in this setting and can decrease sympathetic stimulation. Large placebo-controlled trials will assess the benefits of the optimal dose of the drug when added to ACE-inhibitor therapy, and the effect on survival.
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PMID:Neurohormonal and hemodynamic effects of ibopamine. 774 94

Ibopamine, the most widely studied dopaminergic drug for the treatment of chronic heart failure, appears to have beneficial hemodynamic, renal, and neurohormonal effects in this setting. Angiotension-converting enzyme (ACE) inhibitors have become the recommended standard treatment for chronic heart failure; however, some patients may benefit from additional drugs to improve their symptoms and functional capacity. Ibopamine may be effective as an additive drug for patients with chronic heart failure. It is also possible that ibopamine will improve survival in these patients. Large-scale trials are needed to assess the effects on morbidity and mortality when ibopamine is added to ACE inhibitors, diuretics, and possibly digitalis.
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PMID:Clinical efficacy of ibopamine in patients with chronic heart failure. 774 95

The indications for digitalis glycosides in the treatment of congestive heart failure with sinusrhythm have been disputed since early in this century. In the last decade several well designed studies have been published that have established the effectiveness of digitalis in this condition. However, new groups of drugs have been introduced in the treatment of heart failure and have been compared with digitalis. Ibopamine appeared to be an effective alternative for digitalis in patients with heart failure of low NYHA class. Because of their proven favourable effect on patient survival, ACE inhibitors are replacing digitalis as first-line drug--after diuretics--in the treatment of congestive heart failure. In this review of the literature the present place of digitalis in the treatment of heart failure is discussed.
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PMID:Digitalis in congestive heart failure. 783 Aug 50

Ibopamine is an orally administered dopamine agonist which is rapidly converted to its active metabolite epinine by esterase hydrolysis. Ibopamine acts predominantly as a vasodilator and inhibitor of neuroendocrine activation in congestive heart failure, but also has mild positive inotropic effects at higher doses. The beneficial effects on cardiac and systemic haemodynamic parameters seen in short term studies have been maintained in predominantly noncomparative trials for up to 1 year, and improvements in New York Heart Association (NYHA) functional class and clinical symptoms have been observed in patients with congestive heart failure of varying severity. In double-blind studies conducted in small numbers of patients, the efficacy of ibopamine was comparable to that of digoxin, captopril, enalapril and hydrochlorothiazide. Ibopamine can successfully replace treatment with intravenous dopamine in patients with severe heart failure, and is effective and well tolerated when administered in combination with digoxin, diuretics and/or angiotensin converting enzyme (ACE) inhibitors. Ibopamine has shown no detrimental effects on renal function, few adverse effects on neurohormonal parameters and has demonstrated no significant proarrhythmic properties at therapeutic doses in patients with congestive heart failure. No adverse metabolic effects were observed during ibopamine therapy in patients with diabetes mellitus, nor did ibopamine have detrimental effects in patients with chronic obstructive pulmonary disease. While reliable evidence is required concerning effects on mortality before the role of ibopamine can be clearly defined, the drug appears to be a useful agent for combination with conventional therapies in treating patients with mild to severe congestive heart failure.
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PMID:Ibopamine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic use in congestive heart failure. 790 58

The effect of ibopamine and furosemide in 130 patients with NYHA Class I and II heart failure were studied in a parallel, double-blind, randomized placebo-controlled multi-centre trial. Ibopamine 200 mg b.i.d. was compared to furosemide 40 mg q.d. and placebo. A 1- to 2-week single-blind run-in period was followed by an 8-week double-blind treatment period. Reproducible treadmill exercise test times with the modified Naughton-Balke protocol were required for randomization. Exercise times increased significantly in comparison to the placebo group after 8 weeks of therapy for both the furosemide group (1.2 min, P < 0.035) and the ibopamine group (1.3 min, P < 0.025). Neither furosemide nor ibopamine affected quality of life assessments. Adverse clinical experiences were generally mild and similar in frequency amongst the three treatment groups. The results of this study show the usefulness of both ibopamine and furosemide as monotherapy in patients with mild congestive heart failure.
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PMID:The effects of oral ibopamine in patients with mild heart failure--a double blind placebo controlled comparison to furosemide. The Ibopamine Study Group. 822 57


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