Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Digitalis should be used for slowing a rapid ventricular rate in atrial fibrillation or atrial flutter unassociated with the preexcitation syndrome. Digitalis may be used to convert paroxysmal supraventricular tachycardia to sinus rhythm. Patients with the tachycardia-bradycardia syndrome should receive maintenance doses of digitalis after pacemaker implantation. Digitalis should not be used for treating CHF with normal LV systolic function unless a supraventricular tachyarrhythmia is present. Conflicting studies have been reported as to the efficacy of digoxin in the treatment of patients with CHF in sinus rhythm. Digoxin may be used for treating CHF with abnormal LV systolic function which does not respond to diuretics and ACE inhibitors or in patients unable to tolerate ACE inhibitor or other vasodilator therapy. Digitalis has a low toxic-therapeutic ratio, especially in elderly persons. Digoxin-specific Fab antibody fragments may be used for treating digitalis toxicity refractory to conventional measures with a treatment response in at least 90% of patients with advanced and potentially life-threatening digitalis toxicity.
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PMID:Clinical use of digitalis. 154 3

Although digitalis glycosides were introduced in the treatment of cardiac maladies greater than 200 years ago, controversy persists regarding the precise role of digoxin in any multidrug approach to the treatment of congestive heart failure (CHF). Despite its widespread use for more than 2 centuries, only recently have double-blind, randomized, placebo-controlled trials of digoxin therapy been conducted in patients with moderate CHF and sinus rhythm. These trials demonstrate that digoxin is superior to placebo in improving left ventricular (LV) ejection fraction, increasing exercise capacity, and preventing CHF worsening. Digoxin produces benefits similar to those seen with angiotensin converting enzyme (ACE) inhibitors with regard to clinical compensation and improvement in LV function. However, improved survival is demonstrated only in response to ACE inhibitors. The recently completed RADIANCE study addresses the value of combining digoxin with ACE inhibitor therapy in patients with mild-to-moderate CHF. Because increased mortality has been reported with the newer oral inotropic agents, it currently appears that digoxin is the only oral inotropic agent useful in clinical practice in the treatment of CHF. However, the effects of digoxin on mortality in patients with CHF remain unknown. In the large, double-blind, randomized trial conducted by the National Heart, Lung, and Blood Institute, the effects of digoxin on mortality in patients with CHF and already being treated with ACE inhibitors are currently being evaluated. Presently, based on the results of placebo-controlled studies, it appears that digoxin, alone or in combination with ACE inhibitors, is beneficial in patients with any signs or symptoms of CHF due to systolic LV dysfunction.
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PMID:Review of randomized trials of digoxin therapy in patients with chronic heart failure. 162 92

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

Patients with congestive heart failure (CHF) can be treated by diuretics, inotropic agents and vasodilators. Increased diuresis lowers left and right ventricular filling pressures but may further reduce cardiac output. Nevertheless, diuretics produce symptomatic improvement in most patients. Digoxin also has beneficial hemodynamic effects in patients with advanced CHF and sinus rhythm, but the frequency and degree of therapeutic response is inferior to that of vasodilators. Among the latter, ACE inhibitors are the most appropriate for long-term administration since they do not lead to development of tolerance and seem to improve long-term prognosis in patients with severe CHF. Newer inotropic agents have marked hemodynamic effects in the short term, but their utility for chronic treatment remains questionable. The optimum choice of drugs in various forms and stages of CHF is discussed.
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PMID:[Drug treatment of heart insufficiency]. 306 35

Both prevalence and incidence of heart failure rise with age. Diagnosis of heart failure in the older patient may be difficult because of atypical symptoms or the acceptance of symptoms as manifestations of old age. Heart failure is not a diagnosis but a syndrome. Echocardiograms should be obtained in most elderly patients to aid diagnosis and assessment. Loop diuretics, taking into account the altered homoeostasis of old age and presence of co-morbidity, are the mainstay of symptomatic treatment. ACE inhibitors are likely to benefit survival, although formal trials have failed to include many older patients. Digoxin and direct vasodilators are less well tolerated in elderly patients.
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PMID:Heart failure in the elderly patient. 754 52

Coronary artery disease, hypertension, valvular heart disease, and cardiomyopathies are the commonest causes of CHF in elderly patients. Almost half of elderly patients with CHF have normal LV ejection fraction. LV ejection fraction must be measured before knowing how to treat CHF. Underlying causes of CHF should be treated when possible. Precipitating causes of CHF should be treated. Diuretics are the first-line drug in the treatment of CHF. ACE inhibitors reduce mortality in patients with CHF and should be administered with diuretics to patients with CHF and abnormal or normal LV ejection fraction. Oral isosorbide dinitrate plus hydralazine improves survival in patients with CHF, and should be administered to patients with CHF and abnormal or normal LV ejection fraction who cannot tolerate ACE inhibitor therapy or in whom CHF persists despite therapy with diuretics plus ACE inhibitors. Digoxin should be administered to patients with a rapid ventricular rate associated with supraventricular tachyarrhythmias. Digoxin should be administered to patients with CHF in sinus rhythm and abnormal LV ejection fraction that does not respond to diuretics plus ACE inhibitors or in patients unable to tolerate ACE inhibitors or other vasodilator therapy. Digoxin should not be given to patients with CHF in sinus rhythm with normal LV ejection fraction. Calcium channel blockers are contraindicated in patients with CHF and abnormal LV ejection fraction but may be used to treat CHF with normal LV ejection fraction. The use of beta blockers in the treatment of CHF with abnormal LV ejection fraction is experimental. However, beta blockers might improve clinical symptoms in patients with CHF and normal LV ejection fraction by slowing heart rate, thereby increasing LV diastolic filling time and increasing LV end-diastolic volume. Maintenance of sinus rhythm will also increase LV diastolic filling time in patients with CHF and normal LV ejection fraction.
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PMID:Management of congestive heart failure in the elderly patient. 755 8

In his study the author deals with etiopathogenesis, diagnosis and therapy of heart failure in acute infarction of myocardium (AMI) with special attention paid to haemodynamic monitoring. The therapy of AMI is based especially on thrombolysis, or urgent revascularisation. In therapy of left ventricular failure we prefer nitrates, diuretics, and ACE-inhibitors. A severe heart failure requires haemodynamic monitoring and administration of positive inotropic substances (dopamine, dobutamine, amrinone) and sodium nitroprusside. Digoxin is indicated only in atrial fibrillation and flutter with fast response of ventricles. In cardiogenic shock it is necessary to introduce an intraaortic balloon contrapulsation and urgent revascularisation (coronary angioplasty, or aortocoronary bypass). Special attention has to be paid to the diagnosis and therapy of AMI of the right ventricle. We avoid the administration of diuretics, nitrates, or morphine which cause hypotension. The therapy is based on thrombolysis, hypotension requires volume expansion, sustained hypotension needs administration of dobutamine, and haemodynamic monitoring. In case of complete AV block, sequence atrioventricular cardiostimulation is recommended. (Ref. 11.).
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PMID:[Heart failure in acute myocardial infarct and the importance of hemodynamic monitoring]. 896 99

The effect on heart rate variability of adding digoxin to a diuretic and ACE inhibitor was studied in patients with chronic stable cardiac failure. Digoxin was found to increase heart rate variability, especially those measures of heart rate variability thought to represent parasympathetic activity. The withdrawal of digoxin led to a decrease in heart rate variability to pre-treatment levels. Whilst digoxin in standard doses does not alter prognosis in chronic cardiac failure, it does have potentially beneficial neurohumoral effects. If the increase in heart rate variability, which represents beneficial neurohumoral modulation, can be divorced from the potentially detrimental effects, perhaps by using smaller doses, then there may be a role for digoxin in the treatment of chronic cardiac failure.
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PMID:Effects of digoxin on time domain measures of heart rate variability in patients with stable chronic cardiac failure: withdrawal and comparison group studies. 908 23

Improvement of symptoms, increase in exercise capacity and prevention of disease progression are the aims of drug therapy in patients with congestive heart failure. At present only the ACE inhibitors are able to achieve all therapeutic targets and should therefore be regarded as drugs of first choice in systolic dysfunction. Diuretics are also necessary in most patients since they rapidly reduce pulmonary congestion and peripheral oedema, but have no documented beneficial long term effects on the course of CHF. Digoxin remains a useful drug to treat symptomatic patients who do not respond adequately to the combination of ACE inhibitors and diuretics, as well as in patients with atrial fibrillation. However, a reduction of mortality by digitalis glycosides cannot be expected. A new trend in the treatment of CHF is the utilisation of beta blockers. These drugs showed positive effects in chronic CHF in several studies, particularly in patients with dilated cardiomyopathy. Newer drugs such as carvedilol, seem to improve the symptoms and reduce complications even in CHF due to coronary artery disease. The role of beta blockers in the routine management of patients with heart failure requires further evaluation.
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PMID:[Drug treatment of cardiac insufficiency with systolic dysfunction]. 913 44


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