Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Congestive heart failure (CHF) is growing epidemiologic and clinical problem, and is the only common cardiovascular condition that is increasing in incidence, prevalence and mortality. During last years numerous clinical trial have been conduced evaluating the effect of various treatment procedures on clinical endpoints in patients with CHF. The major risk factor for CHF are hipertension and atherosclerotic vascular diseases, and now it is clear that aggressive treatment of hypertension and hyperlipidemia can be effective in preventing CHF. Treatment strategies for CHF are aimed at preventing and delaying progression of the disease and improving survival. In the treatment of CHF diuretics are at present the first drugs line for patients with fluid retention and are necessary to relieve symptoms but cannot halt progression or improve the prognosis of CHF. Angiotensin-converting enzyme inhibitors (ACE inhibitors) therapy has been shown to decrease mortality and progression of CHF and should be used early in patients with left ventricular dysfunction whether they have symptomatic or asymptomatic CHF. Digoxin therapy is associated with decrease in the risk of worsening CHF irrespective of rhythm, systolic function, severity of CHF or therapy with ACE inhibitors. In patients with symptomatic CHF due to systolic dysfunction the addition of diuretics and digoxin appears to reducing worsening CHF without improving survival. Other than digoxin oral inotropic agents (amrinone, pimobendan, vesnarinone, ibopamine) increase mortality in patients with CHF and have not improved symptom status and other clinical endpoints during long-term therapy. Hydralazine and isosorbide dinitrate administrated in combination are less effective alternative to ACE inhibitors. Beta-blockers and particular carvedilol may prolong survival and decrease worsening CHF when used in combination with digoxine, diuretics and ACE inhibitors. Beta-blockers therapy improve hemodynamics, LVEF and functional status patients with CHF and the ideal candidate for this therapy is stable patients with NYHA II-III CHF due to nonischemic cause. Calcium antagonists do not appear to be useful in patients with CHF, although amlodipine and mibefradil appears to be safe for treatment of angina or hypertension in this group. On the basis of current data, antiarrhythmic agents should not be given to patients with CHF free from arrhythmia but those with sustained ventricular tachycardia or ventricular fibrillation amiodaron appears to be safe.
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PMID:[Trends in pharmacological treatment of congestive heart failure]. 1036 2

Digoxin prevents ouabain-induced hypertension in rats. In the present study, we tested whether this effect of digoxin depends on its sensitizing effect on baroreflex function or is due to an antagonistic action on exogenous ouabain or endogenous ouabain-like activity ("ouabain") in the brain. In Wistar rats, resting mean arterial pressure (MAP) was significantly increased by long-term subcutaneous (SC) ouabain (75 microg/d) plus high salt (8%) intake for 12 days (but not after only 5 days). In rats with chronic sinoaortic denervation (SAD), MAP was increased within 5 days of ouabain treatment to the same extent as MAP after 12 days of treatment in intact rats. The effect of ouabain and high salt was prevented when digoxin was given SC concomitantly via osmotic minipump (200 microg x kg(-1) x d(-1)). Resting MAP was not changed in rats treated with digoxin alone. In a second set of rats with chronic SAD or sham surgery, high salt intake was given for 14 days, with or without SC digoxin (200 microg x kg(-1) x d(-1)) or intracerebroventricular (ICV) antibody Fab fragments (200 microg/d), which bind "ouabain" with high affinity. On day 14, MAP, central venous pressure, heart rate, and renal sympathetic nerve activity were recorded in conscious rats at rest and in response to air-jet stress, IV phenylephrine and nitroprusside, and acute volume expansion with 5% dextrose IV. In rats with SAD versus sham surgery, high salt significantly increased resting MAP as well as excitatory responses of MAP, heart rate, and renal sympathetic nerve activity to air stress. These effects of high salt in rats with SAD were prevented by digoxin or Fab fragments. Arterial baroreflex function was blunted but cardiopulmonary baroreflex function was not affected in rats with SAD. Digoxin and Fab fragments had no effects on either function. In an in vitro assay for the inhibitory effects on Na+, K(+)-ATPase activity, 20 ng of ouabain caused 29% inhibition, but 20 ng of ouabain plus 13 or 53 ng of digoxin caused only 16% or 4% inhibition, respectively. These data indicate that the arterial baroreflex opposes sympathoexcitatory responses to ouabain and "ouabain" in the brain, thereby delaying ouabain- and preventing high salt-induced hypertension in Wistar rats. In addition to possible effects on the arterial baroreflex, digoxin appears to act centrally to prevent the sympathoexcitatory and pressor effects of increased brain "ouabain" or ouabain.
Hypertension 1999 Oct
PMID:Digoxin prevents ouabain and high salt intake-induced hypertension in rats with sinoaortic denervation. 1052 51

Physicians must aggressively treat heart failure in the early stages to prevent disease progression and improve survival. Early treatment implies early diagnosis of left ventricular (LV) dysfunction, before the onset of symptoms. Patients with risk factors for the development of heart failure, especially coronary disease or hypertension, should undergo echocardiography to evaluate LV function. Patients with LV systolic dysfunction should be further evaluated to determine the type of cardiac dysfunction, uncover correctable etiologic factors, determine prognosis, and guide treatment. Angiotensin-converting enzyme (ACE) inhibitors and beta-adrenergic blocking drugs improve survival and are integral to the treatment plan. Physicians should prescribe an ACE inhibitor as initial therapy for all patients with LV systolic dysfunction unless there are specific contraindications. The combination of hydralazine and isosorbide dinitrate is an acceptable alternative therapy for patients who cannot take ACE inhibitors. Diuretics should be used if there are signs or symptoms of volume overload. Beta-adrenergic blocking drugs should be added to therapy in stable patients with mild to moderate heart failure after optimal treatment with ACE inhibitors, diuretics, or other vasodilators. Digoxin should be used routinely in patients with severe heart failure and should be added to therapy in patients with mild to moderate heart failure who remain symptomatic despite optimal doses of ACE inhibitors and diuretics. Spironolactone should be added, but electrolytes should be closely monitored. Warfarin anticoagulation should be considered in patients with a left ventricular ejection fraction (LVEF) of 35% or less. Until survival data exist, angiotensin receptor blockers (ARBs) should not be used as initial therapy or as sole therapy but can be used for ACE-intolerant patients or can be added to standard heart failure therapy. Outpatient use of intravenous inotropic therapy should be avoided. Patients with severe heart failure should have peak oxygen consumption measured to quantify functional impairment, determine prognosis, and identify the need for advanced heart failure therapy. Patients who remain symptomatic while receiving optimal standard therapy should be referred early to a specialized heart failure center.
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PMID:Chronic Heart Failure. 1109 88

Underlying causes and precipitating causes of congestive heart failure (CHF) should be treated when possible. Older persons with CHF and normal left ventricular (LV) ejection fraction should have maintenance of sinus rhythm, treatment of hypertension and myocardial ischemia, slowing of the ventricular rate below 90 beats/minute, and reduction of salt overload. First-line drug treatment in the management of these persons is the use of loop diuretics combined with beta blockers as tolerated. Angiotensin-converting enzyme (ACE) inhibitors should be administered if CHF persists despite diuretics and beta blockers. If persons are unable to tolerate ACE inhibitors because of cough, rash, or altered taste sensation, angiotensin II type 1 receptor antagonists should be given. If CHF persists despite diuretics, beta blockers, and ACE inhibitors or the person is unable to tolerate beta blockers, ACE inhibitors, and angiotensin II type 1 receptor antagonists, isosorbide dinitrate plus hydralazine should be administered. Calcium channel blockers should be used if CHF persists despite administration of diuretics and the person is unable to tolerate beta blockers, ACE inhibitors, angiotensin II type 1 receptor antagonists, and isosorbide dinitrate plus hydralazine. Digoxin, beta blockers, verapamil, and diltiazem may be used to slow a rapid ventricular rate in persons with supraventricular tachyarrhythmias. Digoxin should not be used in persons with CHF in sinus rhythm with normal LV ejection fraction.
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PMID:Left ventricular diastolic heart failure with normal left ventricular systolic function in older persons. 1157 22

Diastolic heart failure is predominantly a disease of the elderly: at the age of 70 years, almost half of all patients with heart failure have diastolic heart failure. Hypertension and obesity are common underlying disorders in patients with diastolic heart failure. Patients with diastolic heart failure have an equal, or only slightly better, prognosis in terms of mortality compared to patients with systolic heart failure. Echocardiography can distinguish diastolic heart failure from systolic heart failure. Patients with heart failure and a normal ejection fraction almost certainly have a diastolic dysfunction. There is a lack of reliable data about the optimal medicinal treatment strategy for patients with diastolic heart failure. Angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, and (non-dihydropyridine) calcium antagonists have therapeutic potential. Digoxin may be contraindicated.
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PMID:[Diastolic heart failure]. 1470 11

Digoxin-specific Fab (Digibind) is a mixture of antidigoxin Fab fragments prepared from sheep sera and is used as a treatment for digoxin poisoning. Digoxin-specific Fab has been shown to neutralize an endogenous Na+/K+ ATPase inhibitor (endogenous digoxin-like Na+/K+ ATPase regulatory factor; EDLF) in rats and humans and to lower blood pressure. Although the exact structure of EDLF is unknown, compounds identical to or structurally related to ouabain, bufalin, and marinobufagenin have been detected in mammalian plasma. In this study, some structural characteristics of EDLF were inferred from the ability of digoxin-specific Fab to neutralize the Na+/K+ ATPase inhibitory activity of several known cardenolides and bufodienolides. Additional structural information was obtained from [3H]ouabain binding and enzyme-linked immunosorbent assay experiments. Digoxin-specific Fab had the ability to interact to some extent with all of the cardenolides and bufodienolides tested. However, digoxin-specific Fab was more than 20-fold more potent in neutralizing ouabain and bufalin than marinobufagenin. The antihypertensive effect of digoxin-specific Fab seen in preeclampsia and animal models of hypertension may therefore be due to a molecule identical to or structurally similar to ouabain or bufalin.
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PMID:Characterization of the neutralizing activity of digoxin-specific Fab toward ouabain-like steroids. 1498 68

Optimal outpatient treatment of systolic heart failure has three goals that should be pursued simultaneously: (1) control of risk factors for the development and progression of heart failure, (2) treatment of heart failure, and (3) education of patients. Control of risk factors includes treating hypertension, diabetes, and coronary artery disease, and eliminating the use of alcohol and tobacco. All patients with heart failure should be taking an angiotensin-converting enzyme (ACE) inhibitor or angiotensin-receptor blocker. In the absence of contraindications, an ACE inhibitor is preferred. In most patients, physicians should consider adding a beta blocker to ACE-inhibitor therapy. In patients with severe heart failure, spironolactone is a useful addition to baseline drug therapy, as is carvedilol (substitute carvedilol if patient is already taking a beta blocker). Patients with stable heart failure should be encouraged to begin and maintain a regular aerobic exercise program. Digoxin therapy may reduce the likelihood of hospitalization but does not reduce mortality. It must be monitored closely, with a target dosage level of 0.5 to 1.1 ng per mL. Symptoms may be controlled with the use of diuretics and restricted dietary sodium. Finally, patient education, with the patient's active participation in the care, is a key strategy in the management of heart failure. Periodic follow-up between scheduled office visits, which is essential in the long-term management of heart failure, may include telephone calls from the office nurse, maintenance of a daily symptom and weight diary, and participation in a disease-management program.
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PMID:Outpatient treatment of systolic heart failure. 1622 19

Atrial fibrillation (AF) is the most common complication following coronary artery bypass graft surgery (CABG). Post-CABG AF occurs most commonly on the second postoperative day and declines in incidence thereafter. A number of risk factors have been found to be associated with a higher frequency of post-CABG AF. These risk factors include advanced age, a prior history of AF, hypertension, and heart failure. Postoperative complications--including low cardiac output, use of an intra-aortic balloon pump, pneumonia, and prolonged mechanical ventilation--are also associated with higher rates of post-CABG AF. Post-CABG AF increases the risk of stroke, and the length and cost of hospitalization. Prophylactic administration of conventional beta-adrenoceptor antagonists (beta-blockers) or sotalol produces a consistent and significant reduction in the incidence of post-CABG AF; however, results with prophylactic amiodarone or magnesium are less consistent. Termination of post-CABG AF, once it occurs, can be accomplished with a number of antiarrhythmic agents. Ibutilide has been the most widely studied agent for this indication. Sotalol is not indicated for cardioversion of AF and has not been studied in the post-CABG setting. Electrical cardioversion and biatrial pacing have also been used to terminate post-CABG AF. Ventricular rate is best controlled with beta-blockers and calcium channel antagonists. Esmolol has a rapid onset of action and is easily titrated to effect. Digoxin can control the ventricular rate, but has a slow onset of action. There are limited data available to guide decisions regarding the optimal management of post-CABG AF.
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PMID:Pharmacological management of atrial fibrillation following cardiac surgery. 1625 24

The incidence and prevalence of atrial fibrillation are increasing because of both population ageing and an age-adjusted increase in incidence of atrial fibrillation. Deciding between a rate control or rhythm control approach depends on patient age and comorbidities, symptoms and haemodynamic consequences of the arrhythmia, but either approach is acceptable. Digoxin is no longer a first-line drug for rate control: beta-blockers and verapamil and diltiazem control heart rate better during exercise. Anti-arrhythmic drugs have only a 40%-60% success rate of maintaining sinus rhythm at 1 year, and have significant side effects. The selection of optimal antithrombotic prophylaxis depends on the patient's risk of ischaemic stroke and the benefits and risks of long-term warfarin versus aspirin, but is independent of rate or rhythm control strategy. Ischaemic stroke risk is best estimated with the CHADS2 score (Congestive heart failure, Hypertension, Age > or = 75 years, Diabetes, 1 point each; prior Stroke or transient ischaemic attack, 2 points). For patients with valvular atrial fibrillation or a CHADS(2) score > or = 2, anticoagulation with warfarin is recommended (INR 2-3, higher for mechanical valves) unless contraindicated or annual major bleeding risk > 3%. Aspirin or warfarin may be used when the CHADS(2) score = 1. Aspirin, 81-325 mg daily, is recommended in patients with a CHADS(2) score of 0 or if warfarin is contraindicated. Stroke rate is similar for paroxysmal, persistent, and permanent atrial fibrillation, and probably for atrial flutter.
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PMID:Atrial fibrillation. 1730 23

Cardiac glycosides have been used for decades to treat congestive heart failure. The recent identification of cardiotonic steroids such as ouabain, digoxin, marinobufagenin, and telocinobufagin in blood plasma, adrenal glands, and hypothalamus of mammals led to exciting new perspectives in the pathology of heart failure and arterial hypertension. Biosynthesis of ouabain and digoxin occurs in adrenal glands and is under the control of angiotensin II, endothelin, and epinephrine released from cells of the midbrain upon stimulation of brain areas sensing cerebrospinal Na(+) concentration and, apparently, the body's K(+) content. Rapid changes of endogenous ouabain upon physical exercise may favor the economy of the heart by a rise of intracellular Ca(2)(+) levels in cardiac and atrial muscle cells. According to the sodium pump lag hypothesis, this may be accomplished by partial inhibition of the sodium pump and Ca(2+) influx via the Na(+)/Ca(2+) exchanger working in reverse mode or via activation of the Na(+)/K(+)-ATPase signalosome complex, generating intracellular calcium oscillations, reactive oxygen species, and gene activation via nuclear factor-kappaB or extracellular signal-regulated kinases 1 and 2. Elevated concentrations of endogenous ouabain and marinobufagenin in the subnanomolar concentration range were found to stimulate proliferation and differentiation of cardiac and smooth muscle cells. They may have a primary role in the development of cardiac dysfunction and failure because (i) offspring of hypertensive patients evidently inherit elevated plasma concentrations of endogenous ouabain; (ii) such elevated concentrations correlate positively with cardiac dysfunction, hypertrophy, and arterial hypertension; (iii) about 40% of Europeans with uncomplicated essential hypertension show increased concentrations of endogenous ouabain associated with reduced heart rate and cardiac hypertrophy; (iv) in patients with advanced arterial hypertension, circulating levels of endogenous ouabain correlate with BP and total peripheral resistance; (v) among patients with idiopathic dilated cardiomyopathy, high circulating levels of endogenous ouabain and marinobufagenin identify those individuals who are predisposed to progressing more rapidly to heart failure, suggesting that endogenous ouabain (and marinobufagenin) may contribute to toxicity upon digoxin therapy. In contrast to endogenous ouabain, endogenous marinobufagenin may act as a natriuretic substance as well. It shows a higher affinity for the ouabain-insensitive alpha(1) isoform of Na(+)/K(+)-ATPase of rat kidney tubular cells and its levels are increased in volume expansion and pre-eclampsia. Digoxin, which is synthesized in adrenal glands, seems to counteract the hypertensinogenic action of ouabain in rats, as do antibodies against ouabain, for example, (Digibind) and rostafuroxin (PST 2238), a selective ouabain antagonist. It lowers BP in ouabain- and adducin-dependent hypertension in rats and is a promising new class of antihypertensive medication in humans.
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PMID:Endogenous and exogenous cardiac glycosides and their mechanisms of action. 1761 Mar 45


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