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BMC Veterinary Research Sep 2021Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in...
Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs.
BACKGROUND
Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design.
RESULTS
The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF).
CONCLUSIONS
These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.
Topics: Administration, Intravenous; Administration, Oral; Alginates; Animals; Cross-Over Studies; Diuretics; Dogs; Drug Delivery Systems; Female; Furosemide; Male; Tablets
PubMed: 34488750
DOI: 10.1186/s12917-021-02998-4 -
Blood Purification 2017The negative prognostic impact of congestion and worsening renal function in patients with decompensated heart failure (HF) has been widely recognized. As diuretics are... (Review)
Review
The negative prognostic impact of congestion and worsening renal function in patients with decompensated heart failure (HF) has been widely recognized. As diuretics are thought to provide suboptimal results and are associated with a number of adverse effects, a number of diuretic-sparing therapeutic strategies have been explored. Extracorporeal ultrafiltration (UF) represents an intriguing option that presumably lacks many of the untoward effects of diuretic-based regimens while portending several advantages. However, conflicting data have recently emerged in relation to some of its previously proposed beneficial effects possibly due to counterbalance of the underexplored mechanisms. Herein, the existing literature on the role of UF therapy for management of acute decompensated HF is briefly reviewed with special emphasis on its impact on surrogates of efficacy and safety such as excess fluid removal and renal function. A number of topics relevant to cardiorenal syndrome such as congestion and sodium removal are also discussed.
Topics: Acute Disease; Cardio-Renal Syndrome; Diuretics; Heart Failure; Humans; Ultrafiltration
PubMed: 27846622
DOI: 10.1159/000451054 -
Congestive Heart Failure (Greenwich,... 2006Hyponatremia as it occurs in the heart failure patient is a multifactorial process. The presence of hyponatremia in the heart failure patient correlates with both the... (Review)
Review
Hyponatremia as it occurs in the heart failure patient is a multifactorial process. The presence of hyponatremia in the heart failure patient correlates with both the severity of the disease and its ultimate outcome. The therapeutic approach to the treatment of hyponatremia in heart failure has traditionally relied on attempts to improve cardiac function while at the same time limiting fluid intake. In more select circumstances, hypertonic saline, loop diuretics, and/or lithium or demeclocycline have been used. The latter two compounds act by retarding the antidiuretic effect of vasopressin but carry with their use the risk of serious renal and/or cardiovascular side effects. Alternatively, agents that selectively block the type 2 vasopressin receptor increase free water excretion without any of the adverse consequences of other therapies. Conivaptan, lixivaptan, and tolvaptan are three such aquaretic drugs. Vasopressin receptor antagonists will redefine the treatment of heart failure-related hyponatremia and may possibly evolve as adjunct therapies to loop diuretics in diuretic-resistant patients.
Topics: Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Diuretics; Heart Failure; Humans; Hyponatremia
PubMed: 16470095
DOI: 10.1111/j.1527-5299.2006.04844.x -
Cleveland Clinic Journal of Medicine Aug 2015Thiazide diuretics are the cornerstone of treatment of hypertension in most patients. Hydrochlorothiazide is the most commonly used thiazide diuretic in the United... (Review)
Review
Thiazide diuretics are the cornerstone of treatment of hypertension in most patients. Hydrochlorothiazide is the most commonly used thiazide diuretic in the United States, but interest in chlorthalidone is increasing. The authors summarize the literature comparing these two agents.
Topics: Antihypertensive Agents; Chlorthalidone; Diuretics; Humans; Hydrochlorothiazide; Hypertension
PubMed: 26270432
DOI: 10.3949/ccjm.82a.14091 -
Molecules (Basel, Switzerland) Apr 2022Urea transporter (UT) inhibitors are a class of promising novel diuretics that do not cause the imbalance of Na, K, Cl, and other electrolytes. In our previous studies,...
Urea transporter (UT) inhibitors are a class of promising novel diuretics that do not cause the imbalance of Na, K, Cl, and other electrolytes. In our previous studies, , a promising diuretic candidate inhibiting UT, was discovered and showed potent diuretic activities in rodents. Here, a sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of in rat plasma, urine, feces, bile, and tissue homogenates was developed and validated to support the preclinical pharmacokinetic studies. The tissue distribution, excretion, and plasma protein binding were investigated in rats. After a single oral dose of at 25, 50, and 100 mg/kg, the drug exposure increased linearly with the dose. The drug accumulation was observed after multiple oral doses compared to a single dose. In the distribution study, exhibited a wide distribution to tissues with high blood perfusion, such as kidney, heart, lung, and spleen, and the lowest distribution in the brain and testis. The accumulative excretion rate of was 0.14%, 3.16%, and 0.018% in urine, feces, and bile, respectively. The plasma protein binding of was approximately 60% in rats and 40% in humans. This is the first study on the preclinical pharmacokinetic profiles of .
Topics: Animals; Chromatography, Liquid; Diuretics; Male; Membrane Transport Proteins; Rats; Rats, Sprague-Dawley; Urea; Urea Transporters
PubMed: 35458649
DOI: 10.3390/molecules27082451 -
European Journal of Heart Failure Oct 2022
Topics: Humans; Diuretics; Sodium; Heart Failure; Sodium Potassium Chloride Symporter Inhibitors; Furosemide
PubMed: 36164941
DOI: 10.1002/ejhf.2704 -
Expert Review of Cardiovascular Therapy Jan 2022Torsemide is a loop diuretic that inhibits the Na+/K+/2Cl- cotransporter type 2 in the thick ascending loop of Henle, leading to increased excretion of urinary sodium... (Review)
Review
INTRODUCTION
Torsemide is a loop diuretic that inhibits the Na+/K+/2Cl- cotransporter type 2 in the thick ascending loop of Henle, leading to increased excretion of urinary sodium and chloride and associated diuresis. While furosemide remains the dominant diuretic utilized in current practice, increasing evidence supports potential advantages of torsemide in heart failure (HF) and/or renal disease.
AREAS COVERED
This narrative review covers the evidence for use of torsemide in HF and renal disease. Comparative effectiveness with regards to clinical outcomes is reviewed, as well as the ongoing multicenter trial, TRANSFORM-HF, comparing the effect of torsemide versus furosemide among patients with HF.
EXPERT OPINION
Compared with furosemide, torsemide has favorable pharmacodynamics/pharmacokinetics including higher bioavailability, longer duration of effect, minor renal excretion, decreased kaliuresis, and enhanced natriuresis/diuresis. These properties may be further supported by differential effects on RAAS regulation and fibrosis modulation as compared with other diuretics. The limited current body of evidence indicates that torsemide may be superior to furosemide with respect to improving HF functional status and reducing HF hospitalization, and there are mixed data regarding effect on reducing overall cardiovascular hospitalizations/mortality. Further, randomized data are necessary to definitively determine if torsemide can reduce risk of mortality and hospitalization among patients with HF.
Topics: Diuretics; Furosemide; Heart Failure; Humans; Multicenter Studies as Topic; Sodium Potassium Chloride Symporter Inhibitors; Torsemide
PubMed: 34936522
DOI: 10.1080/14779072.2022.2022474 -
European Review For Medical and... Apr 2021Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a... (Comparative Study)
Comparative Study Meta-Analysis
OBJECTIVE
Up to 50% of patients hospitalized for acute heart failure (AHF) show resistance to diuretics. This condition contributes to a prolonged hospital length of stay and a higher risk of death. This review aimed to investigate whether a diuretic therapeutic approach more effective than furosemide alone exists for patients with diuretic-resistant AHF.
MATERIALS AND METHODS
We identified all randomized controlled trials (RCTs) evaluating diuretic therapy in patients with diuretic-resistant AHF. We searched Pubmed, BioMed Central, and Cochrane CENTRAL databases.
RESULTS
Six RCTs were identified, involving a total of 845 patients. The P-score ranges from 0.6663 for furosemide to 0.2294 for the tolvaptan-furosemide. We found no significant differences in efficacy for any drug comparison.
CONCLUSIONS
None of the diuretics considered in RCTs performed to date (tolvaptan, metolazone, hydrochlorothiazide, indapamide) appear to be more effective than furosemide therapy alone for the treatment of patients with diuretic-resistant AHF.
Topics: Acute Disease; Carbonic Anhydrase Inhibitors; Diuretics; Drug Resistance; Heart Failure; Humans; Randomized Controlled Trials as Topic
PubMed: 33877660
DOI: 10.26355/eurrev_202104_25550 -
PloS One 2019To inform future outcomes research on diuretics, we sought to describe modern patterns of diuretic use in the intensive care unit (ICU), including diuretic type,...
PURPOSE
To inform future outcomes research on diuretics, we sought to describe modern patterns of diuretic use in the intensive care unit (ICU), including diuretic type, combination, and dosing. We also investigated two possible quality improvement targets: furosemide dosing in renal impairment and inclusion of an initial bolus with continuous furosemide infusions.
MATERIALS AND METHODS
In this descriptive study, we retrospectively studied 46,037 adult ICU admissions from a publicly available database of patients in an urban, academic medical center.
RESULTS
Diuretics were employed in nearly half (49%, 22,569/46,037) of ICU admissions. Mechanical ventilation, a history of heart failure, and admission to the post-cardiac surgery unit were associated with a higher frequency of diuretic use. Combination use of different diuretic classes was uncommon. Patients with severely impaired kidney function were less likely to receive diuretics. Furosemide was by far the most common diuretic given and the initial intravenous dose was only 20 mg in more than half of ICU admissions. Among patients treated with a continuous infusion, 30% did not receive a bolus on the day of infusion initiation.
CONCLUSIONS
Patterns of diuretic use varied by patient-specific factors and by ICU type. Diuretic dosing strategies may be suboptimal.
Topics: Aged; Diuretics; Dose-Response Relationship, Drug; Female; Furosemide; Heart Failure; Hospital Administration; Humans; Hypertension; Intensive Care Units; Male; Middle Aged
PubMed: 31150512
DOI: 10.1371/journal.pone.0217911 -
Journal of Clinical Hypertension... Mar 2013Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple... (Meta-Analysis)
Meta-Analysis Review
Many hypertensive patients require ≥2 drugs to achieve blood pressure targets. This study aims to review and analyze the clinical studies conducted with dual or triple combination of angiotensin II receptor blockers (ARBs), calcium channel blockers (CCBs), and diuretics. Medical literature between January 1990 and April 2012 was reviewed systematically and data from eligible studies were abstracted. Data were analyzed using random-effects models. Of the 224 studies screened, 7563 eligible patients from 11 studies were included. Triple combinations of ARBs (olmesartan or valsartan), CCBs (amlodipine), and diuretics (hydrochlorothiazide) at any dose provided more blood pressure reduction in office and 24-hour ambulatory measurements than any dual combination of these molecules (P<.0001 for both). Significantly more patients achieved blood pressure targets with triple combinations (odds ratio, 2.16; P<.0001). Triple combinations did not increase adverse event risk (odds ratio, 0.96; P=.426). Triple combinations at any dose seem to decrease blood pressure more effectively than dual combination of the same molecules without any remarkable risk elevation for adverse events. Further prospective studies evaluating the efficacy and safety of triple combinations, especially in the form of single pills, are required.
Topics: Angiotensin Receptor Antagonists; Antihypertensive Agents; Blood Pressure; Calcium Channel Blockers; Diuretics; Drug Therapy, Combination; Humans; Hypertension; Treatment Outcome
PubMed: 23458592
DOI: 10.1111/jch.12040