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European Heart Journal Aug 2023
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Metolazone; Heart Failure
PubMed: 37572039
DOI: 10.1093/eurheartj/ehad463 -
Revista Portuguesa de Cardiologia :... Sep 2023Acute heart failure (HF) decompensation generally manifests with signs and symptoms of congestion that strongly predict poor poor patient outcome. Loop diuretics are the... (Review)
Review
Acute heart failure (HF) decompensation generally manifests with signs and symptoms of congestion that strongly predict poor poor patient outcome. Loop diuretics are the cornerstone of therapy to counteract fluid overload and are widely used for acute management and chronic stabilization of HF. However, a diminished response to loop diuretics is a common problem, affecting the patient's clinical course and potentially prolonging hospitalization. Diuretic resistance is defined as failure to decongest despite appropriate and escalating loop diuretic therapy. We propose a protocol for the management of diuretic resistance. The initial approach should include an assessment of causes of pseudo-diuretic resistance. Adjustments to loop diuretic therapy, such as increasing doses and frequency of administration and sequential nephron blockade, may be successful. For hospitalized patients with progressive disease there are more invasive methods for fluid removal. Switching from oral to intravenous loop diuretics is essential to avoid variable absorption and for symptomatic relief. Extracorporeal ultrafiltration is also an option since this technique is highly effective at removing plasma fluid from blood. While extracorporeal ultrafiltration is an invasive solution, peritoneal dialysis is a home-based, intermittent therapeutic option that can enable efficient management of fluid overload, preventing HF-related hospital admission, and improving quality of life. As a last resort for fluid removal, a peritoneal dialysis regimen should fully exploit its decongestive properties and should be tailored to the patient's characteristics and clinical needs.
Topics: Humans; Diuretics; Sodium Potassium Chloride Symporter Inhibitors; Ultrafiltration; Quality of Life; Heart Failure
PubMed: 36948455
DOI: 10.1016/j.repc.2022.05.012 -
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 Cardiology Reports Aug 2019To discuss the current definition as well as recommendations for diagnosis and treatment of resistant hypertension (RH) based on the 2018 American Heart Association... (Review)
Review
PURPOSE OF REVIEW
To discuss the current definition as well as recommendations for diagnosis and treatment of resistant hypertension (RH) based on the 2018 American Heart Association (AHA) guidelines and recent literature.
RECENT FINDINGS
RH is defined as uncontrolled blood pressure (BP) on ≥ 3 anti-hypertensives, one of which should be a diuretic, prescribed at maximally tolerated doses and appropriate dosing frequency. The diagnosis of RH requires exclusion of white coat effect and medication non-adherence, underscoring the importance of out-of-office BP measurements. Secondary causes of hypertension must be excluded in all patients with RH. A step-wise approach to treatment focusing on lifestyle modifications and medication optimization can be effective in > 50% of the patients with RH. Device-based interventional therapies for RH are currently investigational. Out-of-office BP measurements are central to the diagnosis of RH. Medication optimization is successful in most patients. Further studies are needed to define the role of device-based interventions.
Topics: Antihypertensive Agents; Blood Pressure; Blood Pressure Determination; Blood Pressure Monitoring, Ambulatory; Diuretics; Humans; Hypertension; Practice Guidelines as Topic
PubMed: 31471727
DOI: 10.1007/s11886-019-1209-6 -
Nefrologia 2022To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria. (Review)
Review
OBJECTIVE
To assess the effects of pharmacological interventions in patients with idiopathic hypercalciuria.
METHODS
We performed a search of multiple databases, trial registries, grey literature and conference proceedings up to October 2019. We included randomized and quasi-randomized controlled trials that examined any pharmacological intervention for preventing complications of idiopathic hypercalciuria (given for at least four months and six of follow-up). The primary outcomes were stone-free patients, urinary symptoms and severe adverse events.
RESULTS
We included five RCTs (n=446 patients, all adults, 4 in individuals with kidney stones and 1 in postmenopausal women with osteoporosis). Diuretics were likely to increase the number of stone-free patients (RR 1.61, 95% CI 1.33-1.96, moderate quality of evidence (QoE)); 274 more stone-free patients/1000 patients treated (95% CI: 148-432) and produced a slight decrease in the stone formation rate (mean difference -0.18, 95% CI -0.30 to -0.06, low QoE); 180 fewer stones/year/1000 patients treated (95% CI: 300 r to 60). No data on urinary symptoms were reported. The association between diuretic use and severe adverse events was uncertain (RR 5.00, 95% CI 0.60-41.88, very low QoE); 4 more severe adverse events/1000 patients treated (95% CI: 0 fewer to 39 more).
CONCLUSIONS
The addition of diuretics to a normal or modified diet probably reduces the number of stone recurrences and may decrease the stone formation rate. It is uncertain whether diuretics increase the occurrence of severe adverse events. There were no studies investigating other outcomes or in children.
Topics: Child; Adult; Humans; Female; Hypercalciuria; Kidney Calculi; Diuretics; Osteoporosis
PubMed: 36792305
DOI: 10.1016/j.nefroe.2021.04.014 -
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