Classes Of Diuretics Research Articles

Diuretics and risk of major adverse limb events in patients with type-2 diabetes: An observational retrospective study

AimIn patients with type-2 diabetes mellitus (T2DM), sodium-glucose co-transporter 2 inhibitors are suspected to increase the risk of amputation. “Traditional” diuretics may increase major adverse limb events (MALEs), but the evidence is weak. We studied the association between common diuretics (i.e. thiazides, loop- and potassium-sparing diuretics) and MALEs/amputations in patients with T2DM. MethodsConsecutive T2DM patients without cardiovascular history referred to our center for cardiovascular check-ups were retrospectively studied. Follow-up data on MALEs were collected. We used Cox models to assess the association between diuretics and MALEs, or amputation alone. A propensity score with inverse probability of diuretic treatment weighting (IPTW) analysis was performed. ResultsWe studied 1309 patients, (59.5 ± 10.7 years, 51 % females) with diabetes duration of 9.1 ± 8.5 years, among whom 402 (30 %) were taking diuretics. During a follow-up of 3.8 ± 1.64 years, 121 (9.1 %) had MALEs, including 19 (1.4 %) amputations. Death occurred in 111 patients and the proportion of death was significantly different between groups: patients with diuretics n = 49, 44.1% vs patients without diuretics n = 62, 55.9 %, P = 0.001. Diuretics, in multivariable analysis, were associated with MALEs (aHR[95 %CI] 1.96[1.32;2.91] P = 0.001), even after adjustment on propensity score (aHR 1.66[1.08;2.56] P = 0.02) and IPTW analysis (aHR 1.76[1.67;1.84] P < 0.0001). This risk was particularly increased in case of an abnormal ankle-brachial index (aHR 2.29[1.32;3.96], P = 0.003) at baseline. Looking at diuretic classes separately, the adjusted risk was increased with loop diuretics (aHR 2.56[1.16;5.64] P = 0.020), thiazides (aHR 2.21[1.37;3.57] P = 0.001) or potassium sparing diuretics (aHR 2.56[1.16;5.64] P = 0.020). ConclusionDiuretic treatment weighting may be associated with increased risk of MALEs. We identified several markers of increased risk of limb events where the use of diuretics should be considered with caution.

Diuretic Combination Therapy in Acute Heart Failure: An Updated Review.

Loop diuretics are the cornerstone of decongestive therapy in patients presenting with acute heart failure and have been extensively studied in randomized clinical trials. Therefore, in current guidelines, they are the only drug with a class I recommendation to treat signs and symptoms of congestion when present. However, the percentage of patients achieving successful decongestion is suboptimal, and diuretic resistance frequently develops. Patients with a poor response to loop diuretics and those discharged with residual signs of congestion are characterized by a worse prognosis over time. Recently, a renovated interest in different diuretic classes sprouted among heart failure researchers in order to improve decongestion strategies and ameliorate short- and long-term clinical outcomes. Randomized clinical trials investigating associations among diuretic classes and loop diuretics have been performed but yielded variable results. Therefore, despite initial evidence of a possible benefit from some of these compounds, a definite way to approach diuretic resistance via diuretic combination therapy is still missing. The aim of this review is to summarize current clinical evidence on the use of diuretic combination therapy in patients with acute heart failure and to suggest a possible approach to avoid or counteract diuretic resistance.

Characteristics, Treatment, and Prognosis of Heart Failure Patients with Chronic Obstructive Pulmonary Disease in the Colombian Heart Failure Registry (RECOLFACA).

The impact of chronic obstructive pulmonary disease (COPD) on heart failure (HF) has yet to be well assessed in the Latin American population. This study aimed to analyze the impact of COPD on HF patients from the Colombian Heart Failure Registry (RECOLFACA). The primary outcome was all-cause mortality. A Cox proportional-hazards regression model was used to assess the impact of COPD on mortality. From the total of 2528 patients in the registry, 2514 patients had information regarding COPD diagnosis. COPD diagnosis was associated with a worse functional class and higher use of diuretics than non-COPD patients (p < 0.001). Patients with this comorbidity had a significantly better ejection fraction (median ejection fraction 35% vs. 32% in non-COPD patients; p = 0.004), with a higher occurrence of HF with preserved ejection fraction (HFpEF) in the COPD group (p = 0.000). Finally, patients with COPD had a significantly higher risk of mortality in the multivariate regression model (HR 1.47; 95% CI 1.02, 2.11). COPD is a prevalent comorbidity among patients with HF in Colombia, showing a different clinical profile and a worse functional class than patients without this condition. Patients with COPD and HFpEF have a high mortality risk according to our results.

Bronchopulmonary dysplasia and diuretic use in an outpatient setting.

During Neonatal Intensive Care Unithospitalization, children born preterm with bronchopulmonary dysplasia (BPD) are frequently prescribed diuretics for chronic respiratory symptoms. However, less is known about diuretic use and weaning in an outpatient setting. Thestudy sought to characterize clinical features associated with outpatient diuretic use and timing of diuretic weaning in children with BPD. Data was obtained by chart review from 1224 registry participants born <32 weeks gestation, discharged between 2008 and 2023 and recruited from outpatient BPD clinics at Johns Hopkins Children's Center and the Children's Hospital of Philadelphia (97.4% diagnosed with BPD). Data was analyzed using Chi-square tests, t-tests, and ANOVA tests. Children on diuretics at their first pulmonary visit (n = 737) were more likely to have lower birth weights, earlier gestational age, and severe BPD compared to those not on diuretics (n = 487). Of those prescribed diuretics, most children were on a thiazide alone (46.4%) or a thiazide and a potassium sparing agent (44.8%) with a minority prescribed loop diuretics alone (3.3%) or loop diuretic combinations (4.7%). Most children weaned off diuretics by 2 years of age. Public insurance, early gestational age, technology dependence, home supplemental oxygen use and loop diuretics were associated with slower diuretic weaning. Outpatient diuretic use is common in children with BPD, however variations in diuretic use and diuretic combinations exist across centers. Time to wean off home supplemental oxygen is similar between children on one diuretic compared to none. Timing of outpatient diuretic weaning is influenced by diuretic class, respiratory support, and co-morbidities.

Sympathetic overactivity and nocturnal diuresis in obstructive sleep apnea alter the response to hypertension therapy

BackgroundObstructive sleep apnea (OSA) is associated with high blood pressure that responds poorly to usual antihypertensive therapy.Methods and resultsForty-one subjects with OSA had 25% higher plasma norepinephrine and 42% higher epinephrine measured every 2 h over 24 h than 20 control subjects. They also excreted more sodium during sleep. This suggested that that a sympatholytic would be a more successful antihypertensive than a diuretic. To test this hypothesis we treated a second group of 23 hypertensive apneics with placebo, 6 weeks of the sympatholytic guanfacine and 6 weeks of hydrochlorothiazide in a crossover study. Guanfacine lowered 24-hour blood pressure by 9.6/6.7 mmHg, more than the 5.4/2.9 mmHg effect of hydrochlorothiazide (P < 0.05). Nighttime systolic blood pressure dipping was poor at 6.6 ± 1.8%. Hydrochlorothiazide did not alter blood pressure dipping but guanfacine improved dipping to 9.1 ± 1.2%, a better result (P = 0.03) than from the diuretic. Central aortic pressure by pulse wave analysis was 120/84 mmHg on hydrochlorothiazide and 109/72 on guanfacine, (P < 0.05). Guanfacine, but not hydrochlorothiazide, improved baroreflex sensitivity, heart rate variability and flow mediated vascular dilation, suggesting that decreasing the elevated sympathetic nerve activity of obstructive sleep apnea returned vascular function toward normal.ConclusionsOSA is the most common condition associated with antihypertensive treatment failure. It increased sympathetic nerve activity day and night. Drugs that block sympathetic nerve function are not among the 4 most commonly recommended classes of antihypertensives but diuretics are. Sympatholytic therapy was superior to diuretic treatment for hypertension associated with sleep apnea.Trial registrationNCT, NCT02699125, Registered 26 February 2016 - Retrospectively registered, https://clinicaltrials.gov/study/NCT02699125.

How the kidney regulates magnesium: a modelling study.

The kidneys are crucial for maintaining Mg2+ homeostasis. Along the proximal tubule and thick ascending limb, Mg2+ is reabsorbed paracellularly, while along the distal convoluted tubule (DCT), Mg2+ is reabsorbed transcellularly via transient receptor potential melastatin 6 (TRPM6). TRPM6 and other renal transporter expressions are regulated by sex hormones. To investigate renal Mg2 handling, we have developed sex-specific computational models of electrolyte transport along rat superficial nephron. Model simulations indicated that along the proximal tubule and thick ascending limb, Mg2+ and Na+ transport occur parallelly, but they are dissociated along the DCT. In addition, our models predicted higher paracellular Mg2+ permeability in females to attain similar cortical thick ascending limb fractional Mg2+ reabsorption in both sexes. Furthermore, DCT fractional Mg2+ reabsorption is higher in females than in males, allowing females to better fine-tune Mg2+ excretion. We validated our models by simulating the administration of three classes of diuretics. The model predicted significantly increased, marginally increased and significantly decreased Mg2+ excretions for loop, thiazide and K-sparing diuretics, respectively, aligning with experimental findings. The models can be used to conduct in silico studies on kidney adaptations to Mg2+ homeostasis alterations during conditions such as pregnancy, diabetes and chronic kidney disease.

Role of Conventional and Novel Classes of Diuretics in Various Diseases

Abstract: Diuretics are advised as the initial course of action for hypertension because they are successful in lowering hypervolemia and resolving electrolyte abnormalities. The most popular diuretics are included with their main characteristics in this summary. The primary line of treatment for common cardiovascular and non-cardiovascular diseases is diuretics. Patients with hypertension, oedema, heart failure, as well as a variety of renal disorders are frequently treated with conventional diuretics. The usage of the various types of diuretics that are now licensed for therapeutic use generally has a favourable risk/benefit ratio. Nevertheless, they are not without drawbacks. Pharmaceutical scientists have thus been working to develop new drugs with an enhanced pharmacological profile. SGLT2 inhibitors (sodium-glucose-linked cotransporter 2 inhibitors) have altered how hypoglycaemic medications are thought to affect heart failure. Despite the presence or absence of diabetes, the sodiumglucose-linked cotransporter subtype 2-inhibitor class, which was first developed as a therapy for T2DM (Type 2 Diabetes mellitus), has shown considerable promise in lowering cardiovascular risk, particularly in relation to heart failure (HF) outcomes. The immediate and substantial improvements observed in clinical studies do not appear to be attributable to the drug's fundamental mechanism, which involves inducing glycosuria and diuresis by blocking receptors in the renal nephron. Among patients with chronic heart failure and cirrhosis, hyponatremia is a risk factor for death.

Abstract 15269: Effect of a Systemic Right Ventricle With A Biventricular Circulation on Cardiorespiratory Fitness

Background: The clinical care of adults with a systemic right ventricle with biventricular circulation (sRV-biV) is influenced by cardiorespiratory fitness (CRF) evaluation. However, prognostic markers for CRF are derived from analyses of adults with a systemic left ventricle (sLV). While some studies suggest that CRF is lower in adults with sRV-biV compared to those with a sLV, they have not controlled for key clinical characteristics and ventricular function of the systemic ventricle. Research Question: Is CRF lower in adults with a sRV-biV compared to adults with sLV matched for clinical characteristics and systemic ventricular function? Methods: A retrospective cross-sectional comparison of exercise stress test results was performed comparing 24 adults with sRV-biV to 24 adults with a sLV matched for sex (4 females), age (sRV-biV: 46 ± 9 years, sLV: 46 ± 11 years), body mass index (sRV-biV: 28 ± 4 kg/m 2 , sLV: 27 ± 4 kg/m 2 ), ejection fraction of the systemic ventricle (normal: 2, mild: 4, moderate: 11, severe: 7), NYHA class (I: 6, II: 17, III: 1), and doses of diuretics (spironolactone ≤ 25 mg: 24, furosemide ≤ 80 mg: 24 ). Peak VO 2 was compared between groups with Wilcoxon signed-rank tests. Effect sizes are reported as Cohen’s d . Results: Peak VO 2 did not differ significantly between groups (sRV-biV: 20.3 ± 4.2 vs. sLV: 20.9 ± 6.0 mL/kg/min, p=0.43, d =0.18). When patients were dichotomized according to the Weber criterion for optimal versus suboptimal CRF (sLV peak VO 2 &gt; or ≤ 20 mL/kg/min), peak VO 2 was lower in sRV-biV in those with optimal CRF (sRV-biV: 21.0 ± 4.8 vs sLV: 26.6 ± 5.1 mL/kg/min, p=0.006, d =0.72). In contrast, peak VO 2 was greater in sRV-biV in those with suboptimal CRF (sRV-biV: 19.3 ± 3.5 vs. sLV: 16.9 ± 2.0 mL/kg/min, p=0.12, d =NA). Conclusion: Although peak VO 2 values are similar among patients with a sRV-biV and matched controls with a sLV, differences are observed when stratified according to the Weber criteria for optimal CRF. These results may reflect different pathophysiological adaptive mechanisms of a sRV vs sLV. Further studies are required to establish specific prognostic thresholds for patients with sRV-biV.

Mechanisms of action and clinical application of diuretics in intensive care medicine

The paired kidneys play a significant role in the human body due to the multitude of physiological tasks. Complex biochemical processes keep the sensitive electrolyte and water balance stable and thus ensure the organism's ability to adapt to exogenous and endogenous factors, which is essential for survival. The drug class of diuretics includes substances with very differing pharmacological characteristics. The functioning of the nephron is therefore indispensable for a deeper understanding of the pharmacodynamics, pharmacokinetics and side effect profile of diuretics. In the treatment of acute heart failure with pulmonary congestion, certain diuretics represent an important therapeutic option to counteract hypervolemia and thus an increase in preload. According to current data, diuretics have no proven benefits in the treatment or prevention of acute kidney injury but they can counteract hypervolemia and under certain conditions even reduce the use of renal replacement procedures.

#3508 FUROSEMIDE DECREASES KYNURENIC ACID SYNTHESIS IN RAT KIDNEY IN VITRO

Abstract Background and Aims Loop diuretics are highly potent agents, particularly beneficial in patients with impaired kidney function or heart failure exacerbation. Furosemide, due to fast onset and short time of action, remains the most commonly used drug from this class of diuretics. Inhibition of sodium-potassium-chloride cotransporter (NKCC2) in the thick ascending limb of Henle's loop is the main mechanism of furosemide's action. Other effects of furosemide, like modulation of potassium channels activity or activation of prostaglandin synthesis, were previously described. It was postulated that furosemide may exacerbate kidney injury in a dose dependent manner. Kynurenic acid (KYNA) is a tryptophan derivative synthesized from L-kynurenine (L-KYN) by kynurenine aminotransferases (KATs). KAT I and KAT II are the main KAT isoenzymes. Non-selective antagonism towards ionotropic glutamatergic receptors, as well as activation of aryl hydrocarbon receptors and the α7 nicotinic acetylcholine receptors are known mechanisms of KYNA’s action. KYNA was shown to regulate water and electrolyte balance through natriuretic effect. By some researchers KYNA, together with other tryptophan metabolites, is classified as uremic toxin. We aimed to analyze the influence of furosemide, widely used loop diuretic, on KYNA’s synthesis and the activity of both KATs in rat kidney in vitro. Method The influence of furosemide on KYNA’s production with KAT I and KAT II activity was tested in rat kidney homogenates in vitro after 2 hours incubation in the presence of KYNA precursor L-KYN and furosemide. Diuretic was examined at increasing concentrations: 1 μM, 10 μM, 50 μM, 100 μM, 500 μM and 1 mM. Enzymatic KYNA’s production was measured by high performance liquid chromatography (HPLC) with fluorometric detector. All applicable international, national and institutional guidelines for the care and use of animals were followed. Results Furosemide at 500 μM and 1 mM lowered KYNA formation in kidney homogenates in vitro to 80% (p &amp;lt; 0.05) and 70% (p &amp;lt; 0.05) of control value, respectively. At 1 mM concentration furosemide inhibited kidney KAT I activity in vitro to 38% (p &amp;lt; 0.01) of control value. Similarly, furosemide at 500 μM and 1 mM concentration decreased kidney KAT II activity in vitro to 53% (p &amp;lt; 0.01) and 18% (p &amp;lt; 0.001) of control value, respectively. Conclusion Our study presents a novel mechanism of action of furosemide. Inhibition of KYNA synthesis in the kidney by furosemide may have influence on kidney function.

Worsening of chronic heart failure: definition, epidemiology, management and prevention. A clinical consensus statement by the Heart Failure Association of the European Society of Cardiology.

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline-recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice.

A comparative review on In-vivo and In-vitro screening models for diuretic agents

Diuretics are medications that aid in the elimination of excess urine. Water, electrolytes, and metabolic waste are all found in urine. The anatomy and physiology of the renal excretion system are the topics of the current study. Along with the reasonable diuretic activity it also highlights the kidney's involvement in renal excretion. The mechanism of several diuretic classes is connected to their active target site in this overview. Diuretics have previously demonstrated their clinical efficacy in treating conditions including hypertension, renal failure, nephritic syndrome, and others. Here, several in-vitro and screening models demonstrate their clinical relevance. The logical goal, experimental methods, and assessment criteria of diverse screening models of diuretic action are highlighted in the current study. It also highlights the value and significance of these screening methods for determining the efficacy and safety of various members of various types of diuretic medicines. This review also revealed how some screening model improvements were successful. Studying the diuretic potential of various drugs is therefore absolutely helpful. In the end, the current review establishes a robust framework for dosage modification and fatal impact research of diverse kinds of diuretics. Thus, this study provides some suggestions for choosing cutting-edge methods to check the activity of diuretics. It also exposes the effects of the creation and adjustment of these screening methods, making them more effective in the future for assessing the diuretic potential of various diuretics agents.

Renal Mechanisms of Diuretic Resistance in Congestive Heart Failure

This study reviews the renal aspects of diuretic resistance occurring in diuretic treatment, mostly with loop diuretics of congestive heart failure. A short discussion on the different classes of diuretics, including the recently introduced sodium-glucose transporter 2 inhibitors, and their mechanism of action in the nephron is provided, followed by a summary of recent data discussing the different causes and pathophysiological mechanisms of diuretic resistance. The major cause of diuretic resistance appears to be localized within the distal tubule. Traditionally, the concept of compensatory post-diuretic sodium reabsorption (CPDSR) was considered the major cause of diuretic resistance; however, recent studies have disputed this traditional concept and demonstrated that patients with congestive heart failure are in constant sodium-avid state. Finally, the different options of therapeutic strategies, combining different classes of diuretics are summarized.

Diuretic combinations in critically ill patients with respiratory failure: A systematic review and meta-analysis.

BACKGROUNDIn patients with respiratory failure, loop diuretics remain the cornerstone of the treatment to maintain fluid balance, but resistance is common. AIMTo determine the efficacy and safety of common diuretic combinations in critically ill patients with respiratory failure.METHODSWe searched MEDLINE, Embase, Cochrane Library and PROSPERO for studies reporting the effects of a combination of a loop diuretic with another class of diuretic. A meta-analysis using mean differences (MD) with 95% confidence interval (CI) was performed for the 24-h fluid balance (primary outcome) and the 24-h urine output, while descriptive statistics were used for safety events.RESULTSNine studies totalling 440 patients from a total of 6510 citations were included. When compared to loop diuretics alone, the addition of a second diuretic is associated with an improved negative fluid balance at 24 h [MD: -1.06 L (95%CI: -1.46; -0.65)], driven by the combination of a thiazide plus furosemide [MD: -1.25 L (95%CI: -1.68; -0.82)], while no difference was observed with the combination of a loop-diuretic plus acetazolamide [MD: -0.40 L (95%CI: -0.96; 0.16)] or spironolactone [MD: -0.65 L (95%CI: -1.66; 0.36)]. Heterogeneity was high and the report of clinical and safety endpoints varied across studies.CONCLUSIONBased on limited evidence, the addition of a second diuretic to a loop diuretic may promote diuresis and negative fluid balance in patients with respiratory failure, but only when using a thiazide. Further larger trials to evaluate the safety and efficacy of such interventions in patients with respiratory failure are required.

Most commonly prescribed blood pressure lowering drug linked with increased risk of skin cancer.

To the Editor, Hydrochlorothiazide (HCTZ) is the most commonly prescribed antihypertensive drug that belongs to a diuretic class.1 It mainly works by increasing the removal of excess water and salts from the body into the urine and by this function it is most widely used alone or in combination with other medications to treat patients with uncontrolled blood pressure and edema that results from numerous medical conditions like heart, Liver and kidney diseases. It also helps treat other ailments like diabetes insipidus, renal tubular acidosis and reduce the risk of kidney stones in patients with high calcium levels in urine. Despite its various uses and benefits, HCTZ comes with a heavy price of undesirable side effects like fatigue, lethargy, gastrointestinal discomfort and is known to cause hyperuricemia and hypokalemia associated with increased blood glucose.2 Furthermore, HCTZ increases the skin sensitivity to sunlight. However, recent research has revealed a more worrisome side effect of HCTZ that needs to be highlighted. In 2017, a nationwide study conducted in Denmark involving more than 70,000 patients with Basal cell carcinoma and 8000 patients with squamous cell carcinoma found a considerably increased risk of developing Non melanoma skin cancer, particularly among the users of HCTZ.3 A recent study also substantiated that a total of 135 squamous cell carcinoma events per 100,000 person years were reported in new users of HCTZ.4 These alarming figures raise a question mark on the safety of HCTZ use. Moreover, HCTZ is now classified as a carcinogenic agent for humans by the International Agency for Research on Cancer and the U.S. Food and Drug Administration has also permitted changes to the HCTZ drug label to warn the health care workers and patients of the risk of non-melanoma skin cancer. 5, 6 Unfortunately in Pakistan, HCTZ is still heavily used as a diuretic and people are not much aware of this new fact. In view of these findings and the fact that HCTZ is among the most generally prescribed drugs in Pakistan, its potential indication of causing skin cancer would impose a serious public health concern so the responsibility lies on the cardiologists, nephrologists and other medical physicians to be aware of this possible hazardous outcome of HCTZ use and should be cautious while prescribing it to patients who are at risk of developing skin cancer or who have had a history of skin cancer.

PATTERN OF ANTIHYPERTENSION DRUG ADMINISTRATION IN HYPERTENSION PATIENTS IN OUTPATIENT TUAN RONDA HOSPITAL PEMATANG RAYA, SIMALUNGUN DISTRICT

Until now, hypertension is still a big challenge in Indonesia. In accordance with the 2013 Riskesdas data, the prevalence of hypertension is quite high, namely 25,896. This study aims to determine the pattern of administration of antihypertensive drugs to hypertensive patients at Tuan Rondahaim Hospital, Pematang Raya, Simalungun Regency. This research was conducted using a descriptive research design and data collected retrospectively. The material used is data from hypertension patient prescriptions at Tuan Rondahaim Hospital, Pematang Raya, Simalungun Regency. The number of samples used was obtained as many as 231 patients. The results obtained were that hypertension patients based on sex characteristics were mostly women 54.1196, the most age was 61 — 80 years 65.806. On the profile of antihypertensive drug use by patients, There are 5 classes of antihypertensives used. The most widely used anti-pertensive class Blocker (CCB) was the Calcium Channel amlodipine group of 61.03%, which was used by 141 patients, then the diuretic class of furosemide type was 41.9% used by 97 patients.

Synthesis and characterization of Schiff base derivatives and its effect on urinary parameters of Wistar rats: A comparative analysis with different classes of diuretics

Structural modifications in previously studied substances are one of the strategies commonly used for the discovery of new drugs. In this study, we have reported the synthesis and characterization of a series of Schiff bases (SB) derivatives and the assessment of its effect on urinary parameters of Wistar rats. Different classes of diuretics were included in the study for comparative purposes. The synthesis of the SB 1–6 was carried out by the reaction between ethylenediamine and aldehydes derived from benzaldehyde in ethanol under agitation. Compounds 1–6 were acute orally given to rats (5 mg/kg) to assess its effects on kidney function. SB 1, 3, and 4 increased urinary volume, and showed natriuretic and kaliuretic effects associated with a Ca2+-sparing action; while compound 6 showed only an aquaretic effect. Besides, SB 1, 3, and 4, decreased the number of calcium oxalate crystals in the urine. All the results were similar to those obtained with the thiazide diuretic hydrochlorothiazide (Na+/Cl− cotransporter inhibitor), and do not resemble the characteristics provided by treatment with furosemide (Na+/K+/2Cl− cotransporter inhibitor) or amiloride (epithelial Na+ channel inhibitor). Comparative analysis of 1–6 indicated an inverse correlation between lower pKa values and pharmacological activity. Taking together, this study evaluated a series of SB derivatives for their effect on urine parameters, which the compounds 1, 3 and, 4 showed better activity with pharmacological properties similar to hydrochlorothiazide, even though they do not present similar structures or physical-chemical parameters.

Thiazide and thiazide-like diuretics: how to make the right choice?

Most patients with arterial hypertension (AH) require a combination treatment to achieve the goal blood pressure. According to Russian and international clinical guidelines on the treatment of AH patients, various antihypertensive drugs may be combined; however, not all combinations have similar profiles of safety and clinical efficacy. In this respect, special attention is given to combinations of renin-angiotensin-aldosterone system inhibitors and thiazide (hydrochlorothiazide) or thiazide-like (chlortalidone, indapamide) diuretics. Diuretics also differ in their mechanisms of action, presence of pleiotropic effects and organ-protective properties, effects on the prognosis, and in the evidence base. This review discusses the place of thiazide and thiazide-like diuretics in the treatment of patients with AH and provides an evaluation of major differences in pharmacological and clinical effects of drugs of the diuretic class.

A critical analysis of urea transporter B inhibitors: molecular fingerprints, pharmacophore features for the development of next-generation diuretics.

Urea transporter is a membrane transport protein. It is involved in the transferring of urea across the cell membrane in humans. Along with urea transporter A, urea transporter B (UT-B) is also responsible for the management of urea concentration and blood pressure of human. The inhibitors of urea transporters have already generated a huge attention to be developed as alternate safe class of diuretic. Unlike conventional diuretics, these inhibitors are suitable for long-term therapy without hampering the precious electrolyte imbalance in the human body. In this study, UT-B inhibitors were analysed by using multi-chemometric modelling approaches. The possible pharmacophore features along with favourable and unfavourable sub-structural fingerprints for UT-B inhibition are extracted. This information will guide the medicinal chemist to design potent UT-B inhibitors in future.

Diuretic strategies in patients with resistance to loop-diuretics in the intensive care unit: A retrospective study from the MIMIC-III database.

To investigate various diuretic strategies to alleviate loop-diuretics resistance in critically ill patients. ICU adults requiring more than 1 mg/kg/day of furosemide, from the MIMIC-III database. Four diuretic strategies were investigated: incremental dose of loop diuretics, continuous infusion, combinations with a second class of diuretics and administration of intravenous albumin. A generalized estimating equation was used to investigate the associations between these strategies and endpoints. The primary outcome was the 24-h urine output and secondary endpoints included fluid balance, weight change, electrolyte and acid-base abnormalities, kidney replacement therapy initiation, and mortality. A total of 7645 ICU stays from 6358 patients were included. After adjustment, the use of continuous loop-diuretic infusion was associated with a higher 24-h urine output (β: 732, 95% CI:669-795, p < 0.001), lower 24-h fluid balance (p < 0.001) and greater weight loss at 48-h (p < 0.001). Thiazide- and carbonic anhydrase inhibitor combinations were both associated with higher urine output (p < 0.001) and weight loss at 48-h (p < 0.01), while intravenous albumin was associated with fluid gain (p < 0.001). Risks of electrolyte and metabolic disturbances varied across diuretic strategies. Continuous loop-diuretic infusion and thiazide- or acetazolamide-loop diuretic combinations increased urine output significantly, leading to a negative fluid balance and weight loss.