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Deutsche Medizinische Wochenschrift... Mar 2019The treatment of generalized edema includes primarily the treatment of the underlying disease as well as the sodium restriction. Often, however, the volume balance alone...
The treatment of generalized edema includes primarily the treatment of the underlying disease as well as the sodium restriction. Often, however, the volume balance alone can not be controlled satisfactorily. Commonly, diuretics are used for the treatment of chronic heart failure, liver cirrhosis, nephrotic syndrome and renal failure. Diuretics are well documented effective and necessary drugs for the treatment of hypervolemia. From a symptomatic point of view, they are indispensable for cardiac decompensation and they have a firm place in the treatment of hypertension. Due to the different effects as well as pharmacological differences, diuretics can be used for differential therapeutics. The therapy can be associated with side effects. Sequential nephron blockade may be useful in diuretic resistance, but evidence in controlled trials is still lacking. This review provides an overview of the mechanisms, diuretic use and diuretic resistance.
Topics: Diuretics; Edema; Heart Diseases; Humans; Hypertension
PubMed: 30870869
DOI: 10.1055/a-0661-4426 -
Kidney360 May 2022Despite the incompletely understood multiple etiologies and underlying mechanisms, cardiorenal syndrome is characterized by decreased glomerular filtration and sodium... (Review)
Review
Despite the incompletely understood multiple etiologies and underlying mechanisms, cardiorenal syndrome is characterized by decreased glomerular filtration and sodium avidity. The underlying level of renal sodium avidity is of primary importance in driving a congested heart failure phenotype and ultimately determining the response to diuretic therapy. Historically, mechanisms of kidney sodium avidity and resultant diuretic resistance were primarily extrapolated to cardiorenal syndrome from non-heart failure populations. Yet, the mechanisms appear to differ between these populations. Recent literature in acute decompensated heart failure has refuted several classically accepted diuretic resistance mechanisms and reshaped how we conceptualize diuretic resistance mechanisms in cardiorenal syndrome. Herein, we propose an anatomically based categorization of diuretic resistance mechanisms to establish the relative importance of specific transporters and translate findings toward therapeutic strategies. Within this categorical structure, we discuss classic and novel mechanisms of diuretic resistance.
Topics: Cardio-Renal Syndrome; Diuretics; Heart Failure; Humans; Sodium; Sodium Potassium Chloride Symporter Inhibitors
PubMed: 36128483
DOI: 10.34067/KID.0006372021 -
Cardiology in ReviewDecompensated heart failure accounts for approximately 1 million hospitalizations in the United States annually, and this number is expected to increase significantly in...
Decompensated heart failure accounts for approximately 1 million hospitalizations in the United States annually, and this number is expected to increase significantly in the near future. Diuretics provide the initial management in most patients with fluid overload. However, the development of diuretic resistance remains a significant challenge in the treatment of heart failure. Due to the lack of a standard definition, the prevalence of this phenomenon remains difficult to determine, with some estimates suggesting that 25-30% of patients with heart failure have diuretic resistance. Certain characteristics, including low systolic blood pressures, renal impairment, and atherosclerotic disease, help predict the development of diuretic resistance. The underlying pathophysiology is likely multifactorial, with pharmacokinetic alterations, hormonal dysregulation, and the cardiorenal syndrome having significant roles. The therapeutic approach to this common problem typically involves increases in the diuretic dose and/or frequency, sequential nephron blockade, and mechanical fluid movement removal with ultrafiltration or peritoneal dialysis. Paracentesis is potentially useful in patients with intra-abdominal hypertension.
Topics: Atherosclerosis; Diuretics; Heart Failure; Humans
PubMed: 32282394
DOI: 10.1097/CRD.0000000000000310 -
European Journal of Medicinal Chemistry Dec 2020Diuretics are the first-line therapy for widespread cardiovascular and non-cardiovascular diseases. Traditional diuretics are commonly prescribed for treatment in... (Review)
Review
Diuretics are the first-line therapy for widespread cardiovascular and non-cardiovascular diseases. Traditional diuretics are commonly prescribed for treatment in patients with hypertension, edema and heart failure, as well as with a number of kidney problems. They are diseases with high mortality, and the number of patients suffering from heart and kidney diseases is increasing year by year. The use of several classes of diuretics currently available for clinical use exhibits an overall favorable risk/benefit balance. However, they are not devoid of side effects. Hence, pharmaceutical researchers have been making efforts to develop new drugs with a better pharmacological profile. High-throughput screening, progress in protein structure analysis and modern methods of chemical modification have opened good possibilities for identification of new promising agents for preclinical and clinical testing. In this review, we provide an overview of the medicinal chemistry approaches toward the development of small molecule compounds showing diuretic activity that have been discovered over the past decade and are interesting drug candidates. We have discussed promising natriuretics/aquaretics/osmotic diuretics from such classes as: vasopressin receptor antagonists, SGLT2 inhibitors, urea transporters inhibitors, aquaporin antagonists, adenosine receptor antagonists, natriuretic peptide receptor agonists, ROMK inhibitors, WNK-SPAK inhibitors, and pendrin inhibitors.
Topics: Animals; Diuretics; Drug Development; Humans; Molecular Structure; Structure-Activity Relationship
PubMed: 33007663
DOI: 10.1016/j.ejmech.2020.112855 -
Current Heart Failure Reports Apr 2017The burden of heart failure in the United States is growing rapidly to epic proportions with serious clinical implications for patients and economic strain for... (Review)
Review
PURPOSE OF REVIEW
The burden of heart failure in the United States is growing rapidly to epic proportions with serious clinical implications for patients and economic strain for healthcare systems. One of the most common reasons for hospitalization in acute decompensated heart failure (ADHF) is excess volume accumulation which leads to untoward symptoms including dyspnea,orthopnea, and edema.
RECENT FINDINGS
Over the past several decades, there has been great interest in exploring various decongestive strategies in order to achieve symptomatic improvement and favorable clinical outcomes. These include different modalities of loop diuretic administration, the adjunctive use of non-loop diuretics, and other diuretic sparing strategies. Herein, we provide an appraisal of these decongestive strategies and discuss novel concepts predicting clinical outcomes based on diuretic response and decongestive adequacy while discussing commonly encountered problems such as worsening renal function in ADHF.
Topics: Acute Disease; Diuretics; Heart Failure; Humans; Kidney Diseases; Sodium Potassium Chloride Symporter Inhibitors; Treatment Outcome; United States
PubMed: 28243969
DOI: 10.1007/s11897-017-0319-y -
Journal of Veterinary Internal Medicine Jan 2023Diuretics, such as furosemide, are routinely administered to dogs with congestive heart failure (CHF). Traditionally, dose and determination of efficacy primarily are... (Review)
Review
Diuretics, such as furosemide, are routinely administered to dogs with congestive heart failure (CHF). Traditionally, dose and determination of efficacy primarily are based on clinical signs rather than quantitative measures of drug action. Treatment of human CHF patients increasingly is guided by quantification of urine sodium concentration (uNa) and urine volume after diuretic administration. Use of these and other measures of diuretic responsiveness is associated with decreased duration of hospitalization, complication rates, future rehospitalization, and mortality. At their core, loop diuretics act through natriuresis, and attention to body sodium (Na) stores and handling offers insight into the pathophysiology of CHF and pharmacology of diuretics beyond what is achievable from clinical signs alone. Human patients with low diuretic responsiveness or diuretic resistance are at risk for difficult or incomplete decongestion that requires diuretic intensification or other remedial strategies. Identification of the specific etiology of resistance in a patient can help tailor personalized interventions. In this review, we advance the concept of loop diuretic responsiveness by highlighting Na and natriuresis. Specifically, we review body water homeostasis and congestion in light of the increasingly recognized role of interstitial Na, propose definitions for diuretic responsiveness and resistance in veterinary subjects, review relevant findings of recent studies, explain how the particular cause of resistance can guide treatment, and identify current knowledge gaps. We believe that a quantitative approach to loop diuretic usage primarily involving natriuresis will advance our understanding and care of dogs with CHF.
Topics: Humans; Animals; Dogs; Sodium Potassium Chloride Symporter Inhibitors; Heart Failure; Diuretics; Furosemide; Sodium; Dog Diseases
PubMed: 36408832
DOI: 10.1111/jvim.16590 -
BMJ Open Jun 2023We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
We sought to validate, or refute, the common belief that bedtime diuretics are poorly tolerated due to nocturia.
DESIGN
Prespecified prospective cohort analysis embedded within the randomised BedMed trial, in which hypertensive participants are randomised to morning versus bedtime antihypertensive administration.
SETTING
352 community family practices across 4 Canadian provinces between March 2017 and September 2020.
PARTICIPANTS
552 hypertensive patients (65.6 years old, 57.4% female) already established on a single once-daily morning antihypertensive and randomised to switch that antihypertensive to bedtime. Of these, 203 used diuretics (27.1% thiazide alone, 70.0% thiazide/non-diuretic combinations) and 349 used non-diuretics.
INTERVENTION
Switching the established antihypertensive from morning to bedtime, and comparing the experience of diuretic and non-diuretic users.
PRIMARY AND SECONDARY OUTCOME MEASURES
Primary outcome: Adherence to bedtime allocation time at 6 months (defined as the willingness to continue with bedtime use, not an assessment of missed doses). Secondary 6-month outcomes: (1) nocturia considered to be a major burden and (2) increase in overnight urinations/week. All outcomes were self-reported and additionally collected at 6 weeks.
RESULTS
At 6 months: Adherence to bedtime allocation time was lower in diuretic users than non-diuretic users (77.3% vs 89.8%; difference 12.6%; 95% CI 5.8% to 19.8%; p<0.0001; NNH 8.0), and more diuretic users considered nocturia a major burden (15.6% vs 1.3%; difference 14.2%; 95% CI 8.9% to 20.6%; p<0.0001; NNH 7.0). Compared with baseline, diuretic users experienced 1.0 more overnight urinations/week (95% CI 0.0 to 1.75; p=0.01). Results did not differ between sexes.
CONCLUSIONS
Switching diuretics to bedtime did promote nocturia, but only 15.6% found nocturia a major burden. At 6 months, 77.3% of diuretic users were adherent to bedtime dosing. Bedtime diuretic use is viable for many hypertensive patients, should it ever become clinically indicated.
TRIAL REGISTRATION NUMBER
NCT02990663.
Topics: Humans; Female; Aged; Male; Diuretics; Antihypertensive Agents; Prospective Studies; Nocturia; Canada; Hypertension; Cohort Studies; Sodium Chloride Symporter Inhibitors; Thiazides
PubMed: 37280022
DOI: 10.1136/bmjopen-2022-068188 -
Acta Medica Portuguesa Mar 2023Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute... (Review)
Review
Acute heart failure is a frequent cause of hospital admission in Portugal, and has an increasing tendency given the aging population. Although most admissions for acute heart failure are caused by congestive conditions, not all patients have a congestive phenotype, reflecting the complexity of a process with multiple pathophysiological pathways. The use of diuretics, usually loop diuretics, is the mainstay of treatment for congestion. However, many patients develop resistance, thus constituting a challenge with no consensual solution to date, despite extensive debate over the years. Despite its frequent use in clinical practice, the co-administration of albumin and furosemide remains controversial in the management of patients with acute heart failure, hypoalbuminemia, and diuretic resistance. This review addresses the pathophysiological mechanisms of congestion in patients with acute heart failure and explores the theoretical basis that supports the co-administration of albumin and furosemide in this clinical context. It is intended to clarify the potential benefit of the combined approach in this specific population and identify possible gaps in the literature that could be the subject of future studies.
Topics: Humans; Furosemide; Diuretics; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Albumins
PubMed: 36762993
DOI: 10.20344/amp.17714 -
European Journal of Preventive... Oct 2023Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a...
Fluid retention is a major determinant of symptoms in patients with heart failure (HF), and it is closely associated with prognosis. Hence, congestion represents a critical therapeutic target in this clinical setting. The first therapeutic strategy in HF patients with fluid overload is optimization of diuretic intervention to maximize water and sodium excretion. When diuretic therapy fails to relieve congestion, renal replacement therapy represents the only alternative option for fluid removal, as well as a way to restore diuretic responsiveness. On this background, the pathophysiology of fluid balance in HF is complex, with heart, kidney, and lung being deeply involved in volume regulation and management. Therefore, the interplay between these organs should be appreciated and considered when fluid overload in HF patients is targeted.
Topics: Humans; Heart Failure; Heart; Kidney; Water-Electrolyte Balance; Diuretics
PubMed: 37819223
DOI: 10.1093/eurjpc/zwad166 -
British Journal of Hospital Medicine... Dec 2023Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect...
Thiazide diuretics exert a natriuretic and diuretic effect by inhibiting sodium reabsorption in the distal convoluted tubule. Furthermore, thiazide diuretics affect renal calcium handling by increasing calcium reabsorption, leading to hypocalciuria. The effect that thiazide diuretics exert on parathyroid hormone secretion is controversial. Some studies found parathyroid hormone levels were suppressed with the use of thiazide diuretics, while others found that thiazides were associated with initial parathyroid hormone suppression followed by raised parathyroid hormone levels. This makes the relationship between thiazide diuretics and primary hyperparathyroidism interesting. If a patient is taking thiazide diuretics, this may make it harder to establish the aetiology of hypercalcaemia and may unmask normocalcaemic or mild primary hyperparathyroidism. Thiazide diuretics may have a beneficial role in the diagnosis of patients with concomitant hyperparathyroidism and hypercalciuria by distinguishing secondary hyperparathyroidism caused by hypercalciuria from normocalcaemic primary hyperparathyroidism. In addition, thiazide diuretics may have a role in managing patients with primary hyperparathyroidism who have an indication for parathyroidectomy in view of significant hypercalciuria, but are unfit for surgery.
Topics: Humans; Sodium Chloride Symporter Inhibitors; Calcium; Hyperparathyroidism, Primary; Hypercalciuria; Diuretics; Parathyroid Hormone
PubMed: 38153014
DOI: 10.12968/hmed.2023.0228