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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 -
Current Cardiology Reviews 2022Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These... (Review)
Review
Cardiovascular diseases are the most common cause of death worldwide, with cardiovascular medications being amongst the most common medications prescribed. These medications have diverse effects on the heart, vascular system, as well as other tissues and organ systems. The extra cardiovascular effects have been found to be of use in the treatment of non-cardiovascular diseases and pathologies. Minoxidil is used to manage systemic hypertension with its well-known side effect of hirsutism used to treat alopecia and baldness. Sildenafil was originally investigated as a treatment option for systemic hypertension; however, its side effect of penile erection led to it being widely used for erectile dysfunction. Alpha-1 blockers such as terazosin are indicated to treat systemic hypertension but are more commonly used for benign prostatic hyperplasia and post-traumatic stress disorder. Beta blockers are the mainstay treatment for congestive heart failure and systemic hypertension but have been found useful to help in patients with intention tremors as well as prophylaxis of migraines. Similarly, calcium channel blockers are indicated in medical expulsion therapy for ureteric calculi in addition to their cardiovascular indications. Thiazides are commonly used for treating systemic hypertension and as diuretics. Thiazides can cause hypocalciuria and hypercalcemia. This side effect has led to thiazides being used to treat idiopathic hypercalciuria and associated nephrolithiasis. Spironolactone is commonly utilized in treating heart failure and as a diuretic for edema. It's well described anti-androgen side effects have been used for acne vulgaris and hirsutism in polycystic ovarian syndrome. This review article discusses how the various extracardiovascular effects of commonly used cardiovascular medications are put to use in managing non-cardiovascular conditions.
Topics: Adrenergic beta-Antagonists; Cardiovascular Diseases; Diuretics; Heart Failure; Hirsutism; Humans; Hypertension; Male; Thiazides
PubMed: 34779371
DOI: 10.2174/1573403X17666211015145132 -
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 -
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 -
Nutrients Jan 2023The objectives of this paper are to first present physiological and ecological aspects of the unique motivational state of sodium appetite, then to focus on systemic... (Review)
Review
The objectives of this paper are to first present physiological and ecological aspects of the unique motivational state of sodium appetite, then to focus on systemic physiology and brain mechanisms. I describe how laboratory protocols have been developed to allow the study of sodium appetite under controlled conditions, and focus on two such conditions specifically. The first of these is the presentation a sodium-deficient diet (SDD) for at least one week, and the second is accelerated sodium loss using SDD for 1-2 days coupled with the diuretic furosemide. The modality of consumption is also considered, ranging from a free intake of high concentration of sodium solution, to sodium-rich food or gels, and to operant protocols. I describe the pivotal role of angiotensin and aldosterone in these appetites and discuss whether the intakes or appetite are matched to the physiological need state. Several brain systems have been identified, most recently and microscopically using molecular biological methods. These include clusters in both the hindbrain and the forebrain. Satiation of sodium appetite is often studied using concentrated sodium solutions, but these can be consumed in apparent excess, and I suggest that future studies of satiation might emulate natural conditions in which excess consumption does not occur, using either SDD only as a stimulus, offering a sodium-rich food for the assessment of appetite, or a simple operant task.
Topics: Appetite; Sodium; Diuretics; Furosemide; Satiation; Sodium, Dietary
PubMed: 36771327
DOI: 10.3390/nu15030620 -
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 -
Cardiorenal Medicine 2023Fluid overload is a risk factor for increased morbidity and mortality, especially in patients with heart disease. The treatment options are limited to diuretics and... (Review)
Review
Fluid overload is a risk factor for increased morbidity and mortality, especially in patients with heart disease. The treatment options are limited to diuretics and mechanical fluid removal using ultrafiltration or renal replacement therapy. This paper provides an overview of the challenges of managing fluid overload, outlines the risks and benefits of different pharmacological options and extracorporeal techniques, and provides guidance for clinical practice.
Topics: Humans; Diuretics; Ultrafiltration; Heart Failure; Renal Replacement Therapy; Risk Factors
PubMed: 36630939
DOI: 10.1159/000529068 -
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 -
American Journal of Nephrology 2021Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration. (Review)
Review
BACKGROUND
Although diuretics are one of the most widely used drugs by nephrologists, their antiproteinuric properties are not generally taken into consideration.
SUMMARY
Thiazide diuretics have been shown to reduce proteinuria by >35% in several prospective controlled studies, and these values are markedly increased when combined with a low-salt diet. Thiazide-like diuretics (indapamide and chlorthalidone) have shown similar effectiveness. The antiproteinuric effect of mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) has been clearly established through prospective and controlled studies, and treatment with finerenone reduces the risk of chronic kidney disease progression in type-2 diabetic patients. The efficacy of other diuretics such as amiloride, triamterene, acetazolamide, or loop diuretics has been less explored, but different investigations suggest that they might share the same antiproteinuric properties of other diuretics that should be evaluated through controlled studies. Although the inclusion of sodium-glucose cotransporter-2 inhibitors (SGLT2i) among diuretics is a controversial issue, their renoprotective and cardioprotective properties, confirmed in various landmark trials, constitute a true revolution in the treatment of patients with kidney disease. Recent subanalyses of these trials have shown that the early antiproteinuric effect induced by SGLT2i predicts long-term preservation of kidney function. Key Message: Whether the early reduction in proteinuria induced by diuretics other than finerenone and SGLT2i, as summarized in this review, also translates into long-term renoprotection requires further prospective and observational studies. In any case, it is important for the clinician to be aware of the antiproteinuric properties of drugs so often used in daily clinical practice.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Chlorthalidone; Combined Modality Therapy; Diet, Sodium-Restricted; Diuresis; Diuretics; Humans; Hypertension; Indapamide; Mineralocorticoid Receptor Antagonists; Natriuresis; Proteinuria; Sodium Chloride Symporters; Sodium Potassium Chloride Symporter Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Thiazides
PubMed: 34233330
DOI: 10.1159/000517020 -
Clinical and Experimental Nephrology Apr 2021Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated... (Observational Study)
Observational Study
BACKGROUND
Patients with COVID-19 experience multiple clinical conditions that may cause electrolyte imbalances. Hypokalemia is a concerning electrolyte disorder closely associated with severe complications. This study aimed to estimate prevalence, risk factors and outcome of hypokalemia in a cohort of patients with confirmed COVID-19.
METHODS
A retrospective analysis was conducted on 290 non-ICU admitted patients with COVID-19 at the tertiary teaching hospital of Modena, Italy, from February 16 to April 14, 2020.
RESULTS
Hypokalemia was detected in 119 out of 290 patients (41%) during hospitalization. Mean serum potassium was 3.1 ± 0.1 meq/L. The majority of patients (90.7%) patients experienced only a mild decrease in serum potassium level (3-3.4 mEq/L). Hypokalemia was associated with hypocalcemia, which was detected in 50% of subjects. Urine potassium-to-creatinine ratio, measured in a small number of patients (n = 45; 36.1%), revealed an increase of urinary potassium excretion in most cases (95.5%). Risk factors for hypokalemia were female sex (odds ratio (OR) 2.44; 95% CI 1.36-4.37; P 0.003) and diuretic therapy (OR 1.94, 95% CI 1.08-3.48; P 0.027). Hypokalemia, adjusted for sex, age and SOFA score, was not associated with ICU transfer (OR 0.52; 95% CI 0.228-1.212; P = 0.131), in-hospital mortality (OR, 0.47; 95% CI 0.170-1.324; P = 0.154) and composite outcome of ICU transfer or in-hospital mortality (OR 0.48; 95% CI 0.222-1.047; P = 0.065) in our cohort of patients.
CONCLUSIONS
Hypokalemia was a frequent disorder in subjects with COVID-19. Female sex and diuretic therapy were identified as risk factors for low serum potassium levels. Hypokalemia was unrelated to ICU transfer and death in this cohort of patients.
Topics: Aged; Aged, 80 and over; COVID-19; Diuretics; Female; Hospital Mortality; Humans; Hypokalemia; Male; Middle Aged; Potassium; Prevalence; Retrospective Studies; Risk Factors; SARS-CoV-2
PubMed: 33398605
DOI: 10.1007/s10157-020-01996-4