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

Levosimendan, a pyridazinone-dinitrile derivative, is a calcium sensitiser with additional action on adenosine triphosphate (ATP)-sensitive potassium channels. It is used intravenously (IV) for the treatment of decompensated cardiac failure. At therapeutic doses, levosimendan exhibits enhanced contractility with no increase in oxygen demands. It also produces antistunning effects without increasing myocardial intracellular calcium concentrations or prolonging myocardial relaxation. Levosimendan also causes coronary and systemic vasodilation. In patients with decompensated congestive heart failure (CHF), IV levosimendan significantly reduced the incidence of worsening CHF or death. IV levosimendan significantly increased cardiac output or cardiac index and decreased filling pressure in the acute treatment of stable or decompensated CHF in large, double-blind, randomised trials and after cardiac surgery in smaller trials. Levosimendan is well tolerated, with the most common adverse events (headache, hypotension, nausea) being secondary to vasodilation. It has not been shown to be arrhythmogenic. Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole.
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PMID:Levosimendan. 1136 86

The study demonstrates that clinical-radiological causes and outcome of cardio-embolic infarcts in a population-based study correspond to a well-identified stroke pattern. Cardio-embolic infarcts was diagnosed in 882 cases (37.9%) of 2,330 consecutive first-ever stroke patients included in a prospective population-based stroke registry over a 14-year period (1985-1997). Thirty-three criteria out of 98 were introduced into a monovariate analysis and the significant variable were introduced into a multivariate analysis to identify significant criteria to define stroke patterns in cardio-embolic infarction. Cardiac sources of embolus included atrial arrhythmia, valvular heart disease (19%), and cardiac failure (18%). Patients with cardio-embolic infarction showed a significantly higher rate of female predominance (p < 0.001), history of ischemic heart disease (p < 0.001), acute stroke onset (p < 0.05), headache (p < 0.05), previous treatment by anti-platelets and anti-K-vitamin (p < 0.001), Wernicke aphasia (p < 0.001), severe deficit (p < 0.001) and death (p < 0.001). After a logistic procedure, female gender and ischemic heart disease were the two independent risk factors associated with cardio-embolic stroke. Cardio-embolic stroke is a specific subtype of stroke with its own clinical, radiological, etiological and prognostic characteristics. In the acute stage, it is necessary to identify quickly this type of stroke because of severe prognosis and appropriate treatment.
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PMID:Stroke patterns in cardio-embolic infarction in a population-based study. 1142 6

Although the biological effects of adrenomedullin (AM) and PAMP have been reported extensively in animal studies and from in-vitro experiments, relatively little information is available on responses to the hormone administered to man. This review summarizes data from the few studies carried out in man. In healthy volunteers, i.v. infusion of AM reduces arterial pressure, probably at a lower rate of administration than is required to elicit other responses. AM stimulates heart rate, cardiac output, plasma levels of cAMP, prolactin, norepinephrine and renin whilst inhibiting any concomitant response in plasma aldosterone. Little or no increase in urine volume or sodium excretion has been observed. Patients with essential hypertension differ only in showing a greater fall in arterial pressure and in the development of facial flushing and headache. In patients with heart failure or chronic renal failure, i.v. AM has similar effects to those seen in normal subjects but also induces a diuresis and natriuresis, depending on the dose administered. Infusion of AM into the brachial artery results in a dose-related increase in forearm and skin blood flow, more prominent and more dependent on endogenous nitric oxide in healthy volunteers than in patients with cardiac failure. When infused into a dorsal hand vein, AM partially reversed the venoconstrictor action of norepinephrine. Although much more information is required to clarify the role of AM under physiological and pathophysiological circumstances, it is clear that it has prominent hemodynamic and neurohormonal effects, though generally lesser urinary effects when administered short-term in doses sufficient to raise its levels in plasma to those seen in a number of clinical disorders. The only study of PAMP in man showed that its skeletal muscle vasodilator potency, when infused into the brachial artery of healthy volunteers, was less than one hundredth that of AM, and it was without effect on skin blood flow.
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PMID:Bioactivity of adrenomedullin and proadrenomedullin N-terminal 20 peptide in man. 1175 60

B-type or brain natriuretic peptide (BNP) is a balanced vasodilator with no inotropic nor chronotropic properties. Plasma levels can be used in diagnosis and prognosis of patients with heart failure, hypertension, myocardial infarction, right ventricular dysfunction and cor pulmonale. Intravenous therapy with BNP (nesiritide) in nearly 1000 patients demonstrated significant dose-dependent reductions in pulmonary capillary wedge pressure and systemic vascular resistance, as well as increased cardiac index. Compared to dobutamine, it is not pro-arrhythmic and has no effect on heart rate. Compared to standard therapy, it improves dyspnea by 3 h of therapy and leads to fewer headaches and arrhythmias than the commonly used intravenous agents nitroglycerin and dobutamine, respectively. Current research suggests an important role for use of nesiritide in the treatment of decompensated heart failure.
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PMID:BNP in decompensated heart failure: diagnostic, prognostic and therapeutic potential. 1175 93

CGRP is a potent vasodilator that has been shown to have a physiological and/or pathological role in neurogenic inflammation, headaches including migraine, thermal injury, circulatory shock, pregnancy and menopause, hypertension and heart failure and is known to be cardioprotective. CGRP is also a positive inotrope and increases heart rate. Clinical trials have shown beneficial effects of the vasodilatory action of CGRP in hypertension, angina, heart failure, Raynaud's disease and venous stasis ulcers. However, the clinical potential of CGRP is limited as it has to be given by infusion and is quickly broken down. Oral long acting CGRP-mimetics may have potential in disorders in which CGRP has been shown to be beneficial. CGRP-mimetics include capsaicin/vanilloid receptor agonists and gene transfer of an adenoviral vector that encodes prepro-CGRP. CGRP inhibitors have therapeutic potential in conditions in which excessive CGRP-mediated vasodilatation is present; neurogenic inflammation, migraine and other headaches, thermal injury, circulatory shock and flushing in menopause. CGRP inhibitors include capsaicin, antagonists at capsaicin/vanilloid receptors, civamide, CGRP receptor antagonists and 5-HT1D-receptor agonists. Drugs that are 5-HT1D-receptor agonists, the 'triptans' are already commonly used in migraine and the first small molecule CGRP antagonist, BIBN4096BS, is under clinical investigation for the treatment of migraine.
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PMID:Migraine and beyond: cardiovascular therapeutic potential for CGRP modulators. 1177 40

The uses, pharmacology, clinical efficacy, dosage and administration, adverse effects, and drug interactions of hawthorn are discussed. Hawthorn (Crataegus oxyacantha) is a fruit-bearing shrub with a long history as a medicinal substance. Uses have included the treatment of digestive ailments, dyspnea, kidney stones, and cardiovascular disorders. Today, hawthorn is used primarily for various cardiovascular conditions. The cardiovascular effects are believed to be the result of positive inotropic activity, ability to increase the integrity of the blood vessel wall and improve coronary blood flow, and positive effects on oxygen utilization. Flavonoids are postulated to account for these effects. Hawthorn has shown promise in the treatment of New York Heart Association (NYHA) functional class II congestive heart failure (CHF) in both uncontrolled and controlled clinical trials. There are also suggestions of a beneficial effect on blood lipids. Trials to establish an antiarrhythmic effect in humans have not been conducted. The recommended daily dose of hawthorn is 160-900 mg of a native water-ethanol extract of the leaves or flowers (equivalent to 30-169 mg of epicatechin or 3.5-19.8 mg of flavonoids) administered in two or three doses. At therapeutic dosages, hawthorn may cause a mild rash, headache, sweating, dizziness, palpitations, sleepiness, agitation, and gastrointestinal symptoms. Hawthorn may interact with vasodilating medications and may potentiate or inhibit the actions of drugs used for heart failure, hypertension, angina, and arrhythmias. The limited data about hawthorn suggest that it may be useful in the treatment of NYHA functional class II CHF.
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PMID:Hawthorn: pharmacology and therapeutic uses. 1188 7

Erectile dysfunction (ED) in men is amenable to correction with Viagra in a majority of patients. The accumulated experience of prescribing Viagra across the broad continuum of men suffering from ED is sufficient for a meaningful assessment of the safety of Viagra in clinical practice. The use of Viagra necessitates caution in cardiac failure and when used within six months of acute myocardial infarction and stroke. It is inadvisable in patients with unstable angina pectoris. The co-administration of Viagra with organic nitrates, for example, glyceryl trinitrate or isosorbide dinitrate, is unsafe. The relative contraindications to Viagra in cardiovascular disease are uncontrolled hypertension and impaired cardiac reserve. With respect to interactions with other drugs, the potential influence on the metabolism of Viagra by medications that affect the cytochrome-P-450 system does not translate into clinical effects. The vasodilatory properties of sildenafil citrate are largely responsible for unwanted effects. The most common side effects are headache, flushing (due to vasodilation), and dyspepsia (due to relaxation of the smooth muscle of the gastroesophageal sphincter with reflux). In the recommended single-dose range (25-100 mg), the use of Viagra for erectile dysfunction, in the absence of contraindications, is extremely safe provided the drug is taken under proper conditions.
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PMID:The clinical safety of viagra. 1207 89

Levosimendan is one of the first agents of a new class of drugs known as calcium sensitizers. These drugs are believed to increase cardiac contractility by sensitizing cardiac myofibrils to calcium, and may therefore be of clinical benefit in the treatment of low-cardiac output states, particularly congestive heart failure. In addition to sensitizing troponin to intracellular calcium, levosimendan has been shown to inhibit phosphodiesterase III, which may contribute to its positive inotropic effect, and open adenosine triphosphate (ATP)-sensitive potassium channels (K(ATP)), which may produce vasodilation. Unlike currently available intravenous inotropes, levosimendan does not increase myocardial oxygen utilization, has not been shown to be proarrhythmic, and has been used effectively in the presence of beta-blocking medications. Levosimendan also has not been shown to impair ventricular relaxation, which was an initial concern with this class of drugs. Clinical studies of levosimendan have demonstrated short-term hemodynamic benefits of levosimendan over both placebo and dobutamine. While large-scale, long-term morbidity and mortality data are scarce, the Levosimendan Infusion versus Dobutamine in severe low-output heart failure (LIDO) study suggested a mortality benefit of levosimendan over dobutamine up to 180 days after treatment. Clinical studies comparing levosimendan with other positive inotropes, namely milrinone, are lacking. Levosimendan treatment appears to be well-tolerated, with the primary adverse events being headache and hypotension. No clinically significant drug-drug interactions have been reported with levosimendan to date. The clinical future of levosimendan will depend on the results of larger, ongoing clinical trials.
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PMID:Levosimendan: a unique approach to the treatment of heart failure. 1214 86

Nesiritide, a recombinant human B-type natriuretic peptide, is the first in a new drug class for the treatment of decompensated heart failure. The drug binds to receptors in the vasculature, kidney, adrenal gland, and brain, and overcomes resistance to endogenous BNP present in patients with CHF. Nesiritide administration leads to a rapid and balanced vasodilatory effect, which results in a significant decrease in right and left ventricular filling pressures and systemic vascular resistance and at the same time in an increase in stroke volume and cardiac output without a change in heart rate. These early hemodynamic changes result in a rapid improvement in symptoms of heart failure. In addition, nesiritide lowers aldosterone, catecholamines, and endothelin-1 levels and its effect on the kidney leads to an increased natriuresis and diuresis without effect on serum potassium or renal function. Prior to its approval for clinical use, nesiritide was studied in 10 different clinical trials involving 941 patients with moderate and severe CHF, including elderly patients, patients with both systolic and diastolic dysfunction, and patients with arrhythmias, renal insufficiency, and acute ischemic syndrome. In comparative studies with available vasoactive therapies frequently used for treatment of patients with decompensated heart failure, nesiritide was proven comparable in efficacy to inotropic drugs such as dobutamine, but superior in safety. In a recent study, nesiritide was found to be more effective and better tolerated than the vasodilator, nitroglycerin. The most common side effects expected with the use of nesiritide are headaches and decrease in blood pressure. At the recommended dose of nesiritide, headache was reported during the first 24 hours of treatment in 8% of patients and symptomatic hypotension in 4% of patients, compared to 20% and 5% in nitroglycerin-treated patients.
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PMID:Nesiritide: a new drug for the treatment of decompensated heart failure. 1223 67

Pulmonary edema is the primary danger in cardiac patients who undergo abortion by intra-amniotic instillation of hypertonic saline solution. The intra-amniotic saline has not been considered safe for induction of abortion in the 2nd trimester of pregnancy due to either immediate or late complications. Side effects range from vomiting, diarrhea, and headaches to severe septicaemea, convulsions, hemorrhage, disseminated intra-vascular coagulation, and pulmonary edema. Pulmonary edema is often unanticipated in women with "tight" mitral stenosis which was unrecognized in pregnancy. Organic lesion in the heart is often undetected prior to instillation of hypertonic saline which could subsequently cause cardiac failure and lung edema.
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PMID:Unanticipated complications of intra amniotic saline. 1233 31


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