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)

Inhaled beta(2)-adrenoceptor agonists (beta(2)-agonists) are the most commonly used asthma medications in many Western countries. Minor adverse effects such as palpitations, tremor, headache and metabolic effects are predictable and dose related. Time series studies suggested an association between the relatively nonselective beta-agonist fenoterol and asthma deaths. Three case-control studies confirmed that among patients prescribed fenoterol, the risk of death was significantly elevated even after controlling for the severity of asthma. The Saskatchewan study not only found an increased risk of death among patients dispensed fenoterol, but also suggested this might be a class effect of beta(2)-agonists. However, in subsequent studies, the long-acting beta(2)-agonist salmeterol was not associated with increased asthma mortality. In a case-control study blood albuterol (salbutamol) concentrations were found to be 2.5 times higher among patients who died of asthma compared with controls. It is speculated that such toxic concentrations could cause tachyarrhythmias under conditions of hypoxia and hypokalemia. The risk of asthma exacerbations and near-fatal attacks may also be increased among patients dispensed fenoterol, but this association may be largely due to confounding by severity. Although salmeterol does not appear to increase the risk of near-fatal attacks, there is a consistent association with the use of nebulized beta(2)-agonists. Nebulized and oral beta(2)-agonists are also associated with an increased risk of cardiovascular death, ischemic heart disease and cardiac failure. Caution should be exercised when first prescribing a beta-agonist for patients with cardiovascular disease. A potential mechanism for adverse effects with regular use of beta(2)-agonists is tachyphylaxis. Tachyphylaxis to the bronchodilator effects of long-acting beta(2)-agonists can occur, but has been consistently demonstrated only for formoterol (eformoterol) a full agonist, rather than salmeterol, a partial agonist. Tachyphylaxis to protection against induced bronchospasm occurs with both full and partial beta(2)-agonists, and probably within a matter of days at most. Underlying airway responsiveness to directly acting bronchoconstricting agents is not increased when the bronchodilator effect of the regular beta(2)-agonist has been allowed to wear off, although there may be an increase in responsiveness to indirectly acting agents. While there has been speculation that underlying airway inflammation in asthma may be made worse by regular use of short-acting beta(2)-agonists, in contradistinction, a number of studies have shown that long-acting beta(2)-agonists have positive anti-inflammatory effects. An Australian Cochrane Airways Group systematic review of the randomized, controlled trials of short-acting beta-agonists found only minimal and clinically unimportant differences between regular use and use as needed. Regular short-acting treatment was better than placebo. However, a subsequent systematic review has found that regular use of long-acting beta-agonists had significant advantages over regular use of short-acting beta-agonists. More studies and data are needed on the regular use of beta(2)-agonists in patients not taking inhaled corticosteroids, and in potentially vulnerable groups, such as the elderly and those with particular genotypes for the beta-receptor, who might be more prone to adverse effects.
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PMID:Adverse effects of beta-agonists: are they clinically relevant? 1471 95

This case report discusses the cause of death in a 3-year-old child who survived a high dose (20 mg x kg-1 x h-1) of propofol, infused over a period of 15 h, following which the patient developed a combined respiratory and metabolic acidosis, the oxygenation remaining normal. Bronchospasm was assumed to be the cause of hypercapnia. At this time the doctors in charge did not think of a possible side-effect of propofol. The administration of propofol was interrupted, the patient recovered within 13 h from the acidosis, woke up and required further sedation. A supposedly entirely safe infusion of 4 mg x kg-1 x h-1 propofol, as recommended in the literature for up to 48 h, was administered. After only 8 h intractable bradycardic dysrhythmias occurred. Although pharmacokinetic studies have pointed to a possible accumulation of propofol during continuous infusions, an interruption of an infusion for several hours has been considered sufficient for practically total clearance of the drug from the body. In this case re-exposure with a recommended dose of propofol was accompanied by bradycardia and dysrythmias that proved to be resistant to therapy and led to fatal cardiac insufficiency with a functioning artificial pacemaker in place. This case raises concerns about the safety of long-term infusions of propofol for sedation in children and possibly also in adults.
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PMID:Death after re-exposure to propofol in a 3-year-old child: a case report. 1499 68

Beta-adrenoceptor antagonists ("beta-blockers") are one of the most widely used classes of drugs in cardiovascular medicine (hypertension, ischaemic heart disease and increasingly in heart failure) as well as in the management of anxiety, migraine and glaucoma. Where known, the mode of action in cardiovascular disease is from antagonism of endogenous catecholamine responses in the heart (mainly at beta1-adrenoceptors), while the worrisome side effects of bronchospasm result from airway beta2-adrenoceptor blockade. The aim of this study was to determine the selectivity of beta-antagonists for the human beta-adrenoceptor subtypes. (3)H-CGP 12177 whole cell-binding studies were undertaken in CHO cell lines stably expressing either the human beta1-, beta2- or the beta3-adrenoceptor in order to determine the affinity of ligands for each receptor subtype in the same cell background. In this study, the selectivity of well-known subtype-selective ligands was clearly demonstrated: thus, the selective beta1 antagonist CGP 20712A was 501-fold selective over beta2 and 4169-fold selective over beta3; the beta2-selective antagonist ICI 118551 was 550- and 661-fold selective over beta1 and beta3, respectively, and the selective beta3 compound CL 316243 was 10-fold selective over beta2 and more than 129-fold selective over beta1. Those beta2-adrenoceptor agonists used clinically for the treatment of asthma and COPD were beta2 selective: 29-, 61- and 2818-fold for salbutamol, terbutaline and salmeterol over beta1, respectively. There was little difference in the affinity of these ligands between beta1 and beta3 adrenoceptors. The clinically used beta-antagonists studied ranged from bisoprolol (14-fold beta1-selective) to timolol (26-fold beta2-selective). However, the majority showed little selectivity for the beta1- over the beta2-adrenoceptor, with many actually being more beta2-selective. This study shows that the beta1/beta2 selectivity of most clinically used beta-blockers is poor in intact cells, and that some compounds that are traditionally classed as "beta1-selective" actually have higher affinity for the beta2-adrenoceptor. There is therefore considerable potential for developing more selective beta-antagonists for clinical use and thereby reducing the side-effect profile of beta-blockers.
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PMID:The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. 1565 28

Atrial cardiocytes in the heart of mammals produce in a regulated manner the polypeptide hormones atrial natriuretic factor (ANF, ANP) and brain natriuretic peptide (BNP). The biological actions of ANF and BNP are similar; they include the modulation of systems that tend to increase extracellular fluid volume and blood pressure, such as the renin-angiotensin system and the sympathetic nervous system. Additionally, both hormones have potent growth-regulating properties. ANF and BNP signal by activating membrane-bound guanylyl cyclase receptors, leading to an increase in intracellular cGMP and thus affecting the activity of cGMP-regulated enzymes and ion channels. Under chronic hemodynamic overload, cardiac ANF and BNP synthesis and secretion are increased. This increase is viewed as a cardioprotective mechanism, given the beneficial effects of ANF and BNP on cardiac preload, afterload and cardiovascular growth. As discussed in this review, some basic facts regarding the synthesis and secretion of ANF and BNP and their peripheral effects remain to be clarified. Nevertheless, at the clinical level, the elevation of circulating ANF and BNP in heart failure or following acute coronary syndromes has been shown to have diagnostic and prognostic implications. Moreover, these peptides themselves hold promise as therapeutic agents in the treatment of heart failure. Additional pharmaceutical applications might be gleaned from current preclinical and clinical studies showing beneficial effects of ANF or BNP in the treatment of hypertension, bronchospasm and in tissue remodeling following acute myocardial infarction.
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PMID:The endocrine function of the heart. 1626 46

B-type natriuretic peptide (BNP) is an endogenous cardiac neurohormone, produced in the ventricles in response to pressure and volume elevation. Nesiritide is identical to endogenous BNP and is synthesized using recombinant DNA technology. It is currently used in the treatment of acute decompensated heart failure. In clinical trials, nesiritide has been shown to decrease pulmonary capillary wedge pressure, pulmonary artery pressure, right atrial pressure, and systemic vascular resistance, as well as increase cardiac index and stroke volume index. Infusions of nesiritide have led to increased diuresis and natriuresis. Patients treated with nesiritide have reported improvements in global clinical status, dyspnea, and fatigue. Therapy with nesiritide has resulted in decreased plasma renin, aldosterone, norepinephrine, and endothelin-1 levels, as well as reduced ventricular ectopy and ventricular tachycardia. Heart rate variability also improved with nesiritide. Patients with acute coronary syndromes, serious arrhythmia, renal disease, diastolic dysfunction, or vasopressor dependence have been safely managed with nesiritide. Early treatment with nesiritide in the emergency department may lead to decreased length of hospital stay and reduced readmission rates compared to standard care. Outpatient serial infusions of nesiritide in severe heart failure patients on optimal medical therapy may result in improved clinical status, increased ejection fraction, reduced aldosterone and endothelin-1 levels, and decreased hospitalizations. Potential future uses of nesiritide include treatment of acute coronary syndromes, pulmonary hypertension, bronchospasm in chronic lung disease, and as antifibrotic/anti-remodeling therapy or bridge to cardiac transplant. The possibility of subcutaneous injections of nesiritide has been studied in both animals and humans.
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PMID:Nesiritide: past, present, and future. 1633 35

Extensive randomised clinical trial data support the view that beta-blockers have a significant impact on the prognosis of patients with cardiovascular disease, especially those with coronary artery disease and chronic heart failure. Unfortunately, this essential treatment is often withheld from patients with asthma and from some patients with Chronic Obstructive Pulmonary Disease (COPD). The principal concern, a concern supported by a number of guidelines, is that beta-blockers may precipitate severe and potentially fatal bronchospasm. However, a number of studies, culminating in a recent meta-analysis, show that cardioselective beta-blockers are not only safe but are beneficial in patients with co-existing airways and coronary disease. In this article we review the evidence supporting the position that cardioselective beta-blockers, when introduced with care in both community and hospital settings, are safe in patients with mild airways disease and can significantly improve prognosis.
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PMID:Beta-blocker therapy of cardiovascular diseases in patients with bronchial asthma or COPD: the pro viewpoint. 1670 34

The aim of this study was to identify the classic autopsy signs of drowning in post-mortem multislice computed tomography (MSCT). Therefore, the post-mortem pre-autopsy MSCT- findings of ten drowning cases were correlated with autopsy and statistically compared with the post-mortem MSCT of 20 non-drowning cases. Fluid in the airways was present in all drowning cases. Central aspiration in either the trachea or the main bronchi was usually observed. Consecutive bronchospasm caused emphysema aquosum. Sixty percent of drowning cases showed a mosaic pattern of the lung parenchyma due to regions of hypo- and hyperperfused lung areas of aspiration. The resorption of fresh water in the lung resulted in hypodensity of the blood representing haemodilution and possible heart failure. Swallowed water distended the stomach and duodenum; and inflow of water filled the paranasal sinuses (100%). All the typical findings of drowning, except Paltau's spots, were detected using post-mortem MSCT, and a good correlation of MSCT and autopsy was found. The advantage of MSCT was the direct detection of bronchospasm, haemodilution and water in the paranasal sinus, which is rather complicated or impossible at the classical autopsy.
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PMID:Drowning--post-mortem imaging findings by computed tomography. 1776 53

Up to 1 in 25 people in Europe and the USA have stable angina, with symptoms that may limit function and quality of life. Beta-blockers are usually used in initial symptomatic treatment, but may cause unwanted effects. They are also contraindicated in some patients (e.g. those with uncontrolled heart failure, severe peripheral vascular disease) and should be avoided in patients with asthma or a history of reversible obstructive airways disease or bronchospasm. Ivabradine (Procoralan-Servier) is the first in a new class of specific heart rate-reducing drugs and is licensed for the "symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm, who have a contra-indication or intolerance for beta-blockers". Here we consider the place of ivabradine in the management of patients with stable angina.
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PMID:Ivabradine for stable angina? 1898 82

Nesiritide, recombinant human B-type natriuretic peptide, is an intravenous vasodilator that is used to treat acutely decompensated heart failure. In addition to its modest diuretic and natriuretic properties, nesiritide reduces intracardiac filling pressures, increases cardiac index and improves symptoms. Long-term safety data are accruing, and a number of ongoing clinical trials will explore the potential benefit of nesiritide in a variety of clinical situations: peri-operative cardiac surgery, serial out-patient infusions, continuous out-patient or pretransplant infusions, and infusions in patients with pulmonary hypertension, bronchospasm, renal insufficiency, and acute coronary syndromes. Alternative delivery methods also are under development.
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PMID:Current and future uses of nesiritide. 1980 59

Apical ballooning syndrome (ABS) is increasingly diagnosed in critical care settings. Widespread application of echocardiography and cardiac enzyme testing has increased its recognition. Our experience of 4 subjects illustrates the association of ABS with a wide spectrum of acute pulmonary disorders seen in critical care settings. All had ABS proven by normal coronary angiogram and subsequent normalization of left ventricular dysfunction. Bronchospasm due to chronic obstructive pulmonary disease exacerbation or cardiac failure warrants the use of beta agonists. ABS, on the other hand, being caused by excess sympathetic activity could potentially improve with beta blockade. Coexistence of ABS and pulmonary disease in critical-care settings presents unique therapeutic challenges and outcomes can be optimized by judicious use of available medical options.
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PMID:Therapeutic challenges in combined apical ballooning syndrome and acute pulmonary decompensation. 1982 94


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