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

Angiotensin converting enzyme (ACE) inhibition and digoxin may be used in the management of heart failure. Digoxin increases myocardial contractility in vitro, and has a modest but durable beneficial effect in congestive heart failure due to impaired left ventricular systolic function. ACE inhibitors have clear beneficial effects in all grades of heart failure and, in addition, modify the natural history and reduce mortality. Comparative studies in mild to moderate heart failure reveal a tendency towards greater benefits and tolerability of ACE inhibitors over digoxin. ACE inhibition is indicated, in conjunction with diuretic therapy, for all grades of heart failure. Digoxin is best reserved for patients with atrial fibrillation and a rapid ventricular response, and for those whose heart failure is not controlled with an ACE inhibitor plus a diuretic. In patients with heart failure following myocardial infarction, digoxin is of modest benefit. Digoxin should be administered slowly and carefully to avoid acute vasoconstriction and toxicity. Provisional data suggest ACE inhibitors are also beneficial in these patients. However, the results of clinical trials presently in progress are required to clarify their role following myocardial infarction.
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PMID:Angiotensin converting enzyme inhibitors versus digoxin for the treatment of congestive heart failure. 137 44

Despite extensive clinical experience the role of digoxin is still not well defined. In patients with atrial fibrillation digoxin is beneficial for ventricular rate control. For patients in sinus rhythm and heart failure the situation is less clear. Digoxin has a narrow therapeutic:toxic ratio and concentrations are affected by a number of drugs. Also, digoxin has undesirable effects such as increasing peripheral resistance and myocardial demands, and causing arrhythmias. There is a paucity of data from well-designed trials. The trials that are available are generally small with limitations in design and these show variation in patient benefit. More convincing evidence is required showing that digoxin improves symptoms or exercise capacity. Furthermore, no trial has had sufficient power to evaluate mortality. Pooled analysis of the effects of other inotropic drugs shows an excess mortality and there is a possibility that digoxin may increase mortality after myocardial infarction (MI). Angiotensin-converting enzyme (ACE) inhibitors should be used first as they are safer, do not require blood level monitoring, modify progression of disease, relieve symptoms, improve exercise tolerance and reduce mortality. Caution should be exercised in using digoxin until large mortality trials are completed showing either benefit or harm. Until then digoxin should be considered a third-line therapy.
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PMID:Heart failure: to digitalise or not? The view against. 144 52

Electrolyte abnormalities are a frequent and potentially hazardous complication in patients with heart failure. This may be due to the pathophysiological alterations seen in the heart failure state leading to neurohumoral activation (stimulation of the renin-angiotensin-aldosterone system, sympathoadrenergic stimulation), and due to the complications of therapy with diuretics, cardiac glycosides or ACE inhibitors. Patients with heart failure may exhibit hyponatremia due to a decrease in water excretion, which may be related to the enhanced release of both angiotensin and vasopressin and can be exaggerated by diuretic therapy. Along with potassium and calcium, magnesium influences cardiovascular function. Magnesium and potassium deficiencies play an important role in the development of cardiac arrhythmias. Magnesium is essential for the maintenance of intracellular potassium concentration. Although there are conflicting data regarding the prevalence of hypomagnesemia in patients with chronic heart failure (the values range from 7-37%), multiple studies have documented lower magnesium concentrations in patients with heart failure than in normal controls. As magnesium and potassium are mainly intracellular ions, measurements in serum or plasma are of limited value to assess magnesium status. There was no correlation between the intracellular electrolyte content and the electrolyte levels in plasma, either for mononuclear cells or erythrocytes or for myocardial and skeletal muscle. Loop diuretics (e.g. furosemide) are supposed to cause a substantial loss of both magnesium and potassium in the plasma and intracellular space. The potassium-sparing diuretics amiloride and triamterene are reported to also exert magnesium-sparing effects. Recently, ACE inhibitors have been documented to have important magnesium-conserving actions, possibly via their effect on glomerular filtration. Hyperkalemia, secondary to the use of ACE inhibitors in patients with heart failure, is well documented. Digoxin directly limits the renal tubular reabsorption of magnesium, therefore increasing magnesium excretion. Low magnesium and potassium concentrations increase cardiac glycoside toxicity. In contrast, elevated levels of magnesium decrease the sensitivity of human myocardium to antiarrhythmogenic actions of cardiac glycosides, without affecting maximally developed tension. Moreover, magnesium increases binding affinity of cardiac glycosides to the receptor. The antiarrhythmic action of magnesium is suspected to be mediated by a reduced sensitivity to electrophysiological changes induced by Ca2+, thus indicating Ca2+ antagonistic properties of magnesium. Magnesium deficiency has also been implicated in sudden death, notably in patients with congestive heart failure. Therefore, when treating congestive heart failure, one must consider how to prevent depletion of electrolytes or how to replete potassium and magnesium in deficiency states.
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PMID:Heart failure and electrolyte disturbances. 150 35

Digoxin was administered to an 18-day-old infant who showed evidence of cardiac failure. When a Doppler echogram revealed a patent ductus, indomethacin was administered for medical management. Therapeutic digoxin doses then resulted in toxic serum concentrations of 8.2 ng/ml. Serum creatinine rose accordingly. Although this patient did not manifest signs of digoxin toxicity, practitioners should be alerted to the potential complications of these commonly used agents.
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PMID:Increase in serum digoxin concentrations after indomethacin therapy in a full-term neonate. 151 32

This article reviews evidence that the reflex control of the cardiovascular system provided by negative feedback mechanisms is impaired in congestive heart failure (CHF). The impairment involves vagal and sympathetic modulation of the heart exerted by arterial baroreceptors. It also affects baroreceptor control of blood pressure and peripheral vascular resistance, as well as the cardiopulmonary receptor's ability to modulate sympathetic activity. The degree of such impairment is most marked in severe CHF but is also apparent, to a minor degree, in mild heart failure. Reflex impairment is due to a reduction in the receptor signal, but other factor under investigation are probably also involved. Digoxin and other pharmacologic treatments of CHF improve reflex function, thereby facilitating a reduction in the elevated sympathetic activity and a stepping up of the reduced vagal activity typical of CHF. This may be relevant to a patient's prognosis.
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PMID:Reflex cardiovascular control in congestive heart failure. 162 89

The purpose of this study was to confirm that an agent, which increases diastolic [Ca2+]i, namely digoxin, depresses cardiac performance, mitochondrial activity, and glycolysis in chronic alcohol-treated and myopathic hearts, and that an agent, which lowers diastolic [Ca2+]i, namely isoproterenol, activates cardiac performance, mitochondrial activity, and glycolysis in these animals. Energy levels, glycolysis, mitochondrial activity, hemodynamics, and cAMP were studied in isolated hearts from three groups of animals, i.e., 9-month control hamsters, hamsters given 50% alcohol until 9 months of age, and 6-month-old cardiomyopathic hamsters in heart failure. Isolated hearts were perfused with either a control medium, a medium containing isoproterenol, digoxin, or digoxin + isoproterenol. Measurement of phosphomonoester sugars, and glucose-6-phosphate, were used to assess glycolytic activity. Oxygen consumption was used to analyze mitochondrial activity. All hearts perfused with either isoproterenol or isoproterenol + digoxin showed an increase in developed pressure, rate-pressure-product, and a decrease in end-diastolic pressure. Isoproterenol activated mitochondrial activity and glycolysis in hearts from myopathic and chronic alcohol hamsters. Based on 31P-NMR studies, isoproterenol or isoproterenol + digoxin improved the over-all energy state of hearts from cardiomyopathic hamsters, but not hearts from control and chronic alcohol hamsters. Digoxin alone augmented the rate-pressure-product and oxygen consumption in control hearts but not hearts from myopathic and chronic alcohol hamsters. Digoxin caused an increase in end-diastolic pressure in myopathic and chronic alcohol hearts but not control hearts. Digoxin depressed glycolysis and worsened the energy state in hearts from cardiomyopathic and chronic alcohol hamsters, but not hearts from control hamsters. In conclusion digoxin, but not isoproterenol nor isoproterenol + digoxin, depressed cardiac performance and glycolysis as well as high energy phosphates in cardiomyopathic and chronic alcohol hearts. Isoproterenol added to digoxin negated the adverse effects of digoxin in cardiomyopathic and chronic alcohol hearts.
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PMID:Activation of glycolysis with isoproterenol but not digoxin reverses chronic alcohol depression in hamster hearts. 162 50

We tested whether digoxin would limit tissue hypoxia during severe anemia by improving peripheral O2 distribution or decreasing O2 demands. Hematocrit (Hct) was reduced in eight control and eight digoxin-treated pigs from 27-28% to 17-18, 11-12, and 7-8%. Whole body and hindlimb blood flow, O2 transport, O2 extraction, and O2 consumption and serum catecholamines (epinephrine and norepinephrine) were determined at each Hct. Arterial and femoral venous lactate and O2 deficit were obtained to reflect tissue hypoxia. Cardiac output was significantly greater (P less than 0.05) with digoxin, as expected, but there were no differences in hindlimb blood flow. Also, whole body and hindlimb O2 extractions were equal in both groups for similar levels of O2 transport, suggesting that digoxin did not alter the relationship of O2 flow to metabolism in regional circulations. As whole body O2 consumption fell, controls accumulated more (P less than 0.05) O2 deficit and arterial lactate than the digoxin group. Furthermore, the slope demonstrating the linear increase of lactate with respect to O2 deficit was much steeper in controls (y = 1.11 + 0.06x) than in digoxin (y = 1.36 + 0.02x), suggesting that there were differences in the degree of tissue hypoxia for comparable O2 deficit. This may be attributed to the marked differences in catecholamine response: epinephrine was higher in controls at Hct of 7-8% and norepinephrine was higher at Hcts of 11-12 and 7-8%. Digoxin may have inhibited the release of catecholamine or reduced the stimulus for catecholamine secretion during anemia. We speculate that digoxin markedly improved the balance between peripheral O2 supply and demand during anemia by inhibiting catecholamine thermogenesis, thereby decreasing O2 demands. This may explain some of the salutary effects of glycosides in high-output cardiac failure with normal ventricular function.
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PMID:Oxygen transport during anemic hypoxia in pigs: effects of digoxin on metabolism. 163 60

Poisoning is a significant problem in the elderly. The majority of poisonings in older people are unintentional and may result from dementia and confusion, improper use of the product, improper storage or mistaken identities. Depression is also common in the elderly and suicide attempts are more likely to be successful in this age group. The elderly patient's recuperative abilities may be inadequate as a result of numerous factors including impaired hepatic or renal function as well as chronic disease processes. General management of poisoning in the elderly parallels management of younger adults, but it is especially important to ascertain underlying medical conditions and concurrent medications. In most poisonings, activated charcoal and cathartic are sufficient. Haemodialysis or haemoperfusion may be required at lower plasma drug concentrations in elderly patients. While the specific indications for antidotes are the same for all age groups, dosage alterations and precautions may need to be considered in the elderly. Drugs most often implicated in poisonings in the elderly include psychotherapeutic drugs, cardiovascular drugs, analgesics and anti-inflammatory drugs, oral hypoglycaemics and theophylline. Cardiovascular and neurological toxicities occur with overdoses of neuroleptic drugs and, more frequently and severely, with cyclic antidepressants. Patients with pre-existing cardiovascular disease are at particular risk of worsening ischaemic heart disease and congestive heart failure. Benzodiazepines only appear to produce significant toxicity during long term administration or in combination with other CNS depressants. Digoxin can cause both chronic and acute intoxication, most seriously cardiac toxicity including severe ventricular arrhythmias, second or third degree heart block or severe refractory hyperkalaemia. Immune Fab antibody is indicated for the management of digoxin toxicity, although patients dependent on the inotropic effect of digoxin may develop heart failure after digoxin Fab antibody administration. Nitrates can cause toxicity including headache, vomiting, hypotension and tachycardia from excessive sublingual, transdermal or intravenous doses. Conduction disturbances and hypotension occur with overdoses of antihypertensive drugs; these effects are mild with angiotensin converting enzyme (ACE) inhibitors, occasionally severe with beta-blockers and of significant concern with calcium channel antagonists. The elderly commonly use aspirin and other salicylates, are more likely to develop chronic intoxications to these agents, and are more susceptible to severe complications such as pulmonary oedema. Salicylate poisoning, recognition of which is often delayed, should be considered in elderly patients with neurological abnormalities or breathing difficulties, especially in the setting of acid-base abnormalities. The clinical effects of NSAID overdose are mild and usually involve the central nervous system and gastrointestinal tract.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poisoning in the elderly. Epidemiological, clinical and management considerations. 179 7

Digoxin is one of the most frequently prescribed drugs, particularly in the elderly population where there is an increased prevalence of atrial fibrillation and cardiac failure. The drug has a narrow therapeutic range and has gained a reputation for producing adverse effects in older patients. The more frail elderly patients with coexistent disease, often taking other treatments, are more at risk from digoxin toxicity due to inappropriate dosing, noncompliance, or increased sensitivity to digoxin resulting from pharmacokinetic or pharmacodynamic interactions. Application of basic pharmacological principles may be helpful in anticipating these problems. Elderly patients more commonly receive digoxin than younger patients, which in part accounts for the higher rates of toxicity in this group. Numerous components contribute to the development of toxicity, and diagnosis of toxicity is difficult in this age group. The measurement of serum concentrations can contribute to the clinical diagnosis. A major problem is the accurate diagnosis of digoxin toxicity which may have numerous nonspecific clinical manifestations, many of which are related to coexisting disease in elderly patients. This diagnostic imprecision is well recognised but has been helped by the introduction of serum digoxin measurement. However, reliance on serum concentrations should not replace clinical judgement, since these do not always correlate with toxicity. The apparently decreasing incidence of toxicity over recent years probably reflects several factors: the improvement in digoxin formulations, awareness of digoxin pharmacology, utilisation of serum concentrations, and the realisation that digoxin withdrawal is a viable proposition in elderly patients. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin overdose, especially in the elderly population.
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PMID:Digoxin toxicity in the aged. Characterising and avoiding the problem. 179 26

The clinical literature on the subject of inotropic therapy of heart failure, particularly use of digitalis glycosides, is full of contradictions. Most of this disparity can be accounted for if not reconciled by taking the methodology of the clinical trials into consideration. Because drug interventions may produce subtle effects requiring a subjective determination, the questions being asked in these studies cannot be answered without removing as many sources of bias as possible from the patient management and data analysis. If a study has not been adequately randomized, double-blinded, and placebo-controlled, the clinical findings will be inconclusive at best. Systolic myocardial dysfunction plays a pivotal role in the pathogenesis of CHF in many patients and is a prerequisite for the use of cardiotonic drugs. Although the clinical signs of heart failure may be relieved initially by diuretics and vasodilators, compensation may require the addition of a positive inotrope, particularly in advanced cases. In veterinary medicine, the choice of positive inotrope is limited to digoxin, digitoxin, dobutamine, or amrinone. Digoxin possesses superior pharmacokinetics and is the cardiac glycoside of choice for use in the dog. Dobutamine and amrinone are more potent inotropes, but since they must be administered by continuous intravenous infusion, their use is limited to critical care therapy. At the present time, only digoxin can be administered orally for sustained long-term maintenance therapy. Milrinone, a more potent derivative of amrinone, also offers this option, but it has not been available since its brief trial debut as an investigational drug. None of the nonglycoside alternatives couples the benefits of positive inotropic and negative chronotropic effects. Consequently, digoxin remains the mainstay for chronic inotropic support of the heart. Atrial fibrillation with a rapid ventricular response rate is the prime indication for digoxin. In the last few years, evidence from methodologically sound clinical trials on humans has also restored faith in the efficacy of digoxin for treating heart failure in patients with normal sinus rhythm. From these studies, the profile of a digitalis responsive heart failure patient has emerged. Digoxin is most likely to be efficacious when heart failure is associated with chronic, severe ventricular systolic dysfunction, which has resulted in ventricular dilatation. The most reliable clinical marker is the presence of a third heart sound (gallop rhythm). Although the patients in the worst heart failure generally have the shortest survival time, they may also have the most dramatic short-term clinical benefit. However, once cardiac reserve is exhausted in the terminal stages of failure, cardiotonic stimulation ceases to be effective.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Efficacy of inotropic support of the failing heart. 194 98


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