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Congestive Heart Failure (Greenwich,... Jul 2010Many of the primary clinical manifestations of heart failure are due to fluid retention and congestion, and therefore treatments targeting congestion play a central role... (Review)
Review
Many of the primary clinical manifestations of heart failure are due to fluid retention and congestion, and therefore treatments targeting congestion play a central role in heart failure management. Diuretic therapy remains the cornerstone of congestion treatment, and diuretics are prescribed to the majority of heart failure patients. Despite this ubiquitous use, there is limited evidence from prospective randomized studies to guide the use of diuretics. Some observational data have suggested that diuretics may actually be harmful in heart failure, potentially contributing to worsening renal function, neurohormonal activation, and even heart failure progression. Recent clinical trial data have provided new insights into the balance of risks and benefits from diuretics. This review describes the mechanism of action of available diuretic classes, reviews their clinical use based on current guidelines, and briefly discusses evolving alternatives to diuretic therapy in the management of congestion in heart failure patients.
Topics: Antihypertensive Agents; Blood Volume; Disease Progression; Diuretics; Heart Failure; Humans; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; Water-Electrolyte Balance
PubMed: 20653715
DOI: 10.1111/j.1751-7133.2010.00172.x -
Medicina Clinica Mar 2014Diuretics are widely recommended in patients with acute heart failure (AHF). Unfortunately, despite their widespread use, limited data are available from randomized... (Review)
Review
Diuretics are widely recommended in patients with acute heart failure (AHF). Unfortunately, despite their widespread use, limited data are available from randomized clinical trials to guide clinicians on the appropriate management of diuretic therapy. Loop diuretics are considered the first-line diuretic therapy, especially intravenous furosemide, but the best mode of administration (high-dose versus low-dose and continuous infusion versus bolus) is unclear. When diuretic resistance develops, different therapeutic strategies can be adopted, including combined diuretic therapy with thiazide diuretics and/or aldosterone antagonists. Low or "non-diuretic" doses (25-50mg QD) of aldosterone antagonists have been demonstrated to confer a survival benefit in patients with heart failure and reduced ejection fraction and consequently should be prescribed in all such patients, unless contraindicated by potassium and/or renal function values. There is less evidence on the use of aldosterone antagonists at higher or "diuretic" doses (≥ 100mg QD) but these drugs could be useful in relieving congestive symptoms in combination with furosemide. Thiazide diuretics can also be helpful as they have synergic effects with loop diuretics by inhibiting sodium reabsorption in distal parts of the nephron. The effect of diuretic therapy in AHF should be monitored with careful observation of clinical signs and symptoms of congestion. Serum electrolytes and kidney function should also be monitored during the use of intravenous diuretics.
Topics: Acute Disease; Adsorption; Diuretics; Drug Synergism; Drug Therapy, Combination; Furosemide; Heart Failure; Hemodynamics; Humans; Kidney Tubules; Mineralocorticoid Receptor Antagonists; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Sodium; Sodium Chloride Symporter Inhibitors; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 24930082
DOI: 10.1016/S0025-7753(14)70081-8 -
Clinical Journal of the American... Jan 2019
Topics: Diuretics; Heart Failure; Humans; Renal Dialysis; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 30567906
DOI: 10.2215/CJN.13361118 -
Clinical Pharmacology and Therapeutics Oct 2013Diuretics are frequently administered to relieve congestive symptoms in patients with heart failure (HF). Despite their widespread use, prospective data on the potential... (Review)
Review
Diuretics are frequently administered to relieve congestive symptoms in patients with heart failure (HF). Despite their widespread use, prospective data on the potential of diuretics to modulate HF-related morbidity and mortality are scarce. Diuretic efficacy may be limited by adverse neurohormonal activation and by "congestion-like" symptoms that may occur in the absence of fluid overload. Herein, we review the current knowledge on diuretic use and outcomes in HF.
Topics: Antidiuretic Hormone Receptor Antagonists; Diuretics; Heart Failure; Humans; Models, Biological; Practice Guidelines as Topic; Purinergic P1 Receptor Antagonists; Treatment Outcome
PubMed: 23852396
DOI: 10.1038/clpt.2013.140 -
Clinical Pharmacokinetics Mar 1996Diuretic resistance is encountered in a number of disease states, such as chronic renal failure, nephrotic syndrome, congestive heart failure (CHF) and cirrhosis.... (Comparative Study)
Comparative Study Review
Diuretic resistance is encountered in a number of disease states, such as chronic renal failure, nephrotic syndrome, congestive heart failure (CHF) and cirrhosis. Diuretic stratagems which produce sequential nephron segment blockade, and thus a synergistic diuretic response, are frequently necessary and are regularly employed in these conditions. Pharmacokinetic determinants of diuretic response, including dose administered, absolute bioavailability, and tubular transport capacity and transport rate, are reviewed here. Pharmacodynamic factors are perhaps more important to overall response, and often result in modification of the dose-response relationship; these are also reviewed here. Stratagems used to maximise the diuretic response to loop diuretics include correcting abnormal haemodynamic parameters, utilising larger doses or constant intravenous infusions, and using albumin as a vehicle to deliver the loop diuretic to the site of tubular secretion. If these measures fail, then diuretic combinations are useful. Perhaps the most effective is the combination of metolazone (a thiazide-type diuretic) and a loop diuretic. The rationale for and use of various diuretic combinations, with particular emphasis on the metolazone-loop diuretic combination, is reviewed here and applied to the major disease states associated with diuretic resistance.
Topics: Diuretics; Drug Therapy, Combination; Heart Failure; Humans; Nephrotic Syndrome
PubMed: 8882303
DOI: 10.2165/00003088-199630030-00004 -
Pediatric Nephrology (Berlin, Germany) Dec 2016Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of... (Review)
Review
Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.
Topics: Adolescent; Antihypertensive Agents; Child; Child, Preschool; Diuretics; Guidelines as Topic; Humans; Hypertension; Infant; Infant, Newborn; Thiazides
PubMed: 26983630
DOI: 10.1007/s00467-016-3334-4 -
Current Pharmaceutical Design 2017Heart failure, hypertension, cirrhosis and nephritic syndrome are among conditions that alter volume and composition of body fluids and are modulated by diuretics.... (Review)
Review
Heart failure, hypertension, cirrhosis and nephritic syndrome are among conditions that alter volume and composition of body fluids and are modulated by diuretics. Natural products are important source of diuretics and have been considered remarkable alternative with greater effectiveness and fewer side effects. However, many of these plants used in traditional medicine must be scientifically assessed about their efficacy and toxicity. Despite the large number of published articles claiming that plants or plant-derived components may act as diuretic agents, few studies have addressed the mechanism of action of medicinal plants. Thus, the aim of this review was to provide an overview of the current knowledge about the major cellular and molecular mechanisms of diuretic plants and/or their main compounds. Many well-established mechanisms (water channels, renal carriers, nitric oxide-cGMP and prostaglandin-cAMP pathways, renin-angiotensin and kinin-kallikrein systems, carbonic anhydrase, and osmotic effects), along with other newly identified targets, are connected to the diuretic activity of many natural products. However, the central path responsible for the activity of these agents remains unclear. Further studies may help clarifying the central role of each of these pathways in the pleiotropic response of these agents.
Topics: Biological Products; Diuretics; Fibrosis; Heart Failure; Humans; Hypertension; Nephrotic Syndrome; Plants, Medicinal
PubMed: 27758702
DOI: 10.2174/1381612822666161014114437 -
Journal of Cardiac Failure Nov 2011Several sets of heart failure (HF) consensus/guideline statements support the use of a flexible diuretic dosing regimen for HF outpatient management of fluid... (Review)
Review
BACKGROUND
Several sets of heart failure (HF) consensus/guideline statements support the use of a flexible diuretic dosing regimen for HF outpatient management of fluid overload-related signs and symptoms. However, despite the widespread acceptance of such an approach, the evidence supporting the effectiveness of this approach in improving clinical outcomes is unknown. The primary objective of this manuscript was to summarize and review the evidence supporting the use of a flexible diuretic regimen in the management of outpatient heart failure patients.
METHODS AND RESULTS
A systematic review was performed, and 9 studies were identified relevant to the question of flexible diuretic titration in the setting of chronic heart failure. Among the 9 studies, 5 were randomized. Three of the randomized trials included flexible diuretic titration as part of a broader multifaceted disease management program, and only 2 were designed to specifically evaluate the sole contribution of flexible diuretic titration. Collectively, data from all of the studies reviewed supported the idea that flexible and individualized diuretic dosing is potentially associated with reduced emergency room visits, reduced rehospitalization, and improved quality of life in HF patients with reduced ejection fraction.
CONCLUSIONS
To date, only 2 randomized clinical studies were identified that were designed to determine the effects of a flexible diuretic dosing regimen in outpatient HF patients with reduced ejection fraction. Data are lacking in HF patients with preserved ejection fraction. There is a critical need to test this strategy in well designed prospective randomized clinical trials.
Topics: Body Weight; Diuretics; Evidence-Based Medicine; Heart Failure; Humans; Outpatients; Practice Guidelines as Topic; Renin-Angiotensin System; Titrimetry; Treatment Outcome
PubMed: 22041332
DOI: 10.1016/j.cardfail.2011.10.001 -
British Journal of Hospital Medicine... Jul 2014
Review
Topics: Diuretics; Drug Interactions; Drug Resistance; Humans; Kidney; Renin-Angiotensin System; Sodium Chloride
PubMed: 25152940
DOI: 10.12968/hmed.2014.75.sup7.c103 -
Sports Medicine (Auckland, N.Z.) 1987Drugs that induce an increased urine flow are used both legitimately (treatment of hypertension and oedema) and otherwise (rapid weight loss) in sports and exercise.... (Review)
Review
Drugs that induce an increased urine flow are used both legitimately (treatment of hypertension and oedema) and otherwise (rapid weight loss) in sports and exercise. There are 5 major categories of diuretic drugs based on their mechanisms and loci of action. Common to all classes is hypohydration, which has been shown to have an array of adverse effects on performance, including impaired strength, power and endurance. Postural hypotension can be particularly troublesome in the elderly. Also common to all diuretics, except those interfering with the aldosterone mechanism in the distal nephron, is hypokalaemia. Severe symptomatic hypokalaemia (serum K+ concentration less than 3.0 mmol/L) is rare except in clinical situations in which additional hypokalaemic factors are present. Moderate levels of hypokalaemia (serum K+ concentration 3.0 to 3.5 mmol/L) can increase the risk of adverse reactions as has been shown in a variety of prospective clinical studies. Hypokalaemia has effects on cardiac rhythm, muscle function and integrity, local blood flow, carbohydrate metabolism, and the blood lipid profile. Performance studies generally show diminished exercise tolerance in direct proportion to the degree of hypohydration induced. This is not the case, however, in a clinical setting of compromised cardiopulmonary function, in which diuresis has direct and indirect inotropic effects which augment exercise tolerance and decrease symptoms. The ability of the carbonic anhydrase inhibitor, acetazolamide, to induce a hyperventilatory response to the obligatory metabolic acidosis is taken advantage of in mountaineering to prevent or ameliorate the symptoms of acute mountain sickness, thereby improving exercise performance at high altitude. It is suggested that in clinical situations in which the use of a diuretic is considered appropriate, every effort be made to maintain or restore the serum concentration and the total body store of potassium to normal. To some degree this can be accomplished through diet, although potassium chloride supplements or potassium-sparing diuretics or diuretic combinations may be necessary.
Topics: Diuretics; Humans; Kidney; Physical Exertion
PubMed: 3306868
DOI: 10.2165/00007256-198704040-00005