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Biomedicine & Pharmacotherapy =... Jul 2023Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide...
Torsemide is commonly used to relieve edema during the treatment of acute promyelocytic leukemia (APL) with arsenic trioxide (ATO). We explored the effect of torsemide on the plasma concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethyarsinic acid (DMA) in APL patients treated with ATO and clarified its molecular mechanism in rats and cells. The study included 146 APL patients treated with ATO. 60(41.1 %) of these 146 patients were co-administered with torsemide. The treatment of torsemide increased plasma concentrations of iAs (P < 0.05) and DMA (P < 0.05) in APL patients. The single co-administration of ATO and torsemide in rats significantly increased the plasma concentrations and AUC of iAs (P < 0.05) and MMA (P < 0.05), decreased the urinary excretion rates and the urine concentrations of iAs (P < 0.05) and DMA (P < 0.05), and enhanced iAs (P < 0.05) and MMA (P < 0.05) concentrations in the kidneys of rats. In addition, torsemide decreased the expression of multidrug resistance protein 4 (MRP4) in rat kidneys after 7 days of continuous co-administration (P < 0.05). We also treated MRP4-overexpressing HEK293T cells with ATO and different concentrations of torsemide. Torsemide markedly increased the concentrations of iAs, MMA and DMA by inhibiting MRP4 compared with ATO alone (P < 0.05). In conclusion, torsemide increased the plasma concentrations of arsenic metabolites in APL patients treated with ATO by inhibiting the transporter MRP4 in a dose-dependent manner.
Topics: Animals; Humans; Rats; Antineoplastic Agents; Arsenic; Arsenic Trioxide; Arsenicals; Drug Resistance, Multiple; HEK293 Cells; Leukemia, Promyelocytic, Acute; Multidrug Resistance-Associated Proteins; Oxides; Torsemide
PubMed: 37172335
DOI: 10.1016/j.biopha.2023.114858 -
Cell Metabolism Nov 2021Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest unmet needs in medicine. In the EMPEROR-Preserved trial, recently reported in the...
Heart failure with preserved ejection fraction (HFpEF) represents one of the greatest unmet needs in medicine. In the EMPEROR-Preserved trial, recently reported in the NEJM, the SGLT2 inhibitor empagliflozin reduced the primary outcome of heart failure hospitalizations and cardiovascular death by 21% in patients with HFpEF. This represents an important breakthrough in the war against heart failure.
Topics: Heart Failure; Humans; Sodium-Glucose Transporter 2 Inhibitors; Stroke Volume
PubMed: 34731652
DOI: 10.1016/j.cmet.2021.10.011 -
Clinical Cardiology Jan 2024
Topics: Humans; Furosemide; Torsemide; Randomized Controlled Trials as Topic; Heart Failure; Sulfonamides; Diuretics
PubMed: 37608566
DOI: 10.1002/clc.24088 -
The Cochrane Database of Systematic... Feb 2015Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusions are associated with significant morbidity and mortality. Prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) is common practice, especially among people who are at risk for circulatory overload, pulmonary oedema or both.
OBJECTIVES
This review aimed to determine if the prophylactic administration of loop diuretics (furosemide, bumetanide, ethacrynic acid, or torsemide) provides a therapeutic advantage (that is, a favourable risk benefit ratio) in adults and children who are recipients of any blood product transfusion versus placebo, no treatment, or general fluid restriction measures.
SEARCH METHODS
We searched the Cochrane Renal Group's Specialised Register to 13 January 2015 through contact with the Trials' Search Co-ordinator using search terms relevant to this review.
SELECTION CRITERIA
All randomised controlled trials (RCTs) and quasi-RCTs assessing a loop diuretic in patients receiving any blood transfusion were considered for inclusion.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed study quality and extracted data. Study authors were contacted for additional information. Results were to be expressed as risk ratios (RR) and their 95% confidence intervals (CI) for dichotomous outcomes, and mean difference (MD) and 95% CI for continuous outcomes. Mean effect sizes were to be calculated using the random-effects models.
MAIN RESULTS
We included four studies that involved 100 participants. Furosemide was the only diuretic investigated in all four studies.None of the included studies assessed the clinically important outcomes noted in our protocol. The studies focused on various markers of respiratory function. An improvement in fraction of inspired oxygen (in favour of furosemide) was noted in one study. An improvement in pulmonary capillary wedge pressure (in favour of furosemide) was noted in two studies.
AUTHORS' CONCLUSIONS
There was insufficient evidence to determine whether premedicating people undergoing blood transfusion with loop diuretics prevents clinically important transfusion-related morbidity. Due to the continued use of prophylactic loop diuretics during transfusions, and because this review highlights the absence of evidence to justify this practice, well-conducted RCTs are needed. Given the high mortality, severe morbidity and increasing incidence of transfusion-associated circulatory overload, determining the therapeutic utility of pre-transfusion loop diuresis is an urgent need.
Topics: Adult; Body Water; Confidence Intervals; Furosemide; Humans; Infant, Newborn; Infant, Premature; Pulmonary Edema; Randomized Controlled Trials as Topic; Sodium Potassium Chloride Symporter Inhibitors; Transfusion Reaction
PubMed: 25685898
DOI: 10.1002/14651858.CD010138.pub2 -
American Journal of Veterinary Research Oct 2007To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs.
OBJECTIVE
To investigate the diuretic effects, tolerability, and adverse effects of furosemide and torsemide after short- and long-term administration in healthy dogs.
ANIMALS
8 mixed-breed dogs.
PROCEDURES
In a crossover study, furosemide (2 mg/kg), torsemide (0.2 mg/kg), or placebo (bifidobacterium [1 mg/kg]) was administered orally to each dog every 12 hours for 14 days. Blood and urine samples were collected before the study (baseline data) and at intervals on the 1st (short-term administration) and 14th day (long-term administration) of treatment for assessment of urine volume and specific gravity and selected clinicopathologic variables including BUN, creatinine, and aldosterone concentrations, and creatinine clearance.
RESULTS
Compared with the baseline value, short-term administration of furosemide or torsemide immediately increased urine volume significantly; after long-term administration of either drug, urine specific gravity decreased significantly. Compared with the effect of placebo, the 24-hour urine volume was significantly increased after short-term administra-tion of furosemide or torsemide. In addition, it was significantly increased after long-term administration of torsemide, compared with that of short-term administration. Long-term administration of furosemide or torsemide increased the BUN and plasma creatinine con-centrations, compared with the baseline value. Compared with the baseline value, plasma aldosterone concentration was significantly increased after long-term administration of either drug and was significantly higher after torsemide treatment than after furosemide treatment.
CONCLUSIONS AND CLINICAL RELEVANCE
In dogs, diuretic resistance developed after 14 days of furosemide, but not torsemide, administration; however, both loop diuretics were associated with increased BUN and plasma creatinine concentrations, compared with values before treatment.
Topics: Administration, Oral; Animals; Blood Proteins; Blood Urea Nitrogen; Body Weight; Creatinine; Diuretics; Dogs; Female; Furosemide; Hematocrit; Male; Placebos; Sulfonamides; Torsemide; Urine
PubMed: 17916010
DOI: 10.2460/ajvr.68.10.1058 -
JACC. Heart Failure May 2021Randomized clinical trials are the foundation of evidence-based medicine and central to practice guidelines and patient care decisions. Nonetheless, randomized trials in... (Review)
Review
Randomized clinical trials are the foundation of evidence-based medicine and central to practice guidelines and patient care decisions. Nonetheless, randomized trials in heart failure (HF) populations have become increasingly difficult to conduct and are frequently associated with slow patient enrollment, highly selected populations, extensive data collection, and high costs. The traditional model for HF trials has become particularly difficult to execute in the United States, where challenges to site-based research have frequently led to modest U.S. representation in global trials. In this context, the TRANSFORM-HF (Torsemide Comparison with Furosemide for Management of Heart Failure) trial aims to overcome traditional trial challenges and compare the effects of torsemide versus furosemide among patients with HF in the United States. Loop diuretic agents are regularly used by most patients with HF and practice guidelines recommend optimal use of diuretic agents as key to a successful treatment strategy. Long-time clinical experience has contributed to dominant use of furosemide for loop diuretic therapy, although preclinical and small clinical studies suggest potential advantages of torsemide. However, due to the lack of appropriately powered clinical outcome studies, there is insufficient evidence to conclude that torsemide should be routinely recommended over furosemide. Given this gap in knowledge and the fundamental role of loop diuretic agents in HF care, the TRANSFORM-HF trial was designed as a prospective, randomized, event-driven, pragmatic, comparative-effectiveness study to definitively compare the effect of a treatment strategy of torsemide versus furosemide on long-term mortality, hospitalization, and patient-reported outcomes among patients with HF. (TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure [TRANSFORM-HF]; NCT03296813).
Topics: Diuretics; Furosemide; Heart Failure; Humans; Prospective Studies; Randomized Controlled Trials as Topic; Torsemide; Treatment Outcome
PubMed: 33714745
DOI: 10.1016/j.jchf.2021.01.013 -
Studies in Health Technology and... 2019Death, as a biological phenomenon, is well understood and a commonly employed endpoint for clinical trials. However, death identification and adjudication may be...
Death, as a biological phenomenon, is well understood and a commonly employed endpoint for clinical trials. However, death identification and adjudication may be difficult for pragmatic clinical trials (PCT) that rely upon electronic health record and patient reported data. We propose a novel death identification and verification approach that is being used in the ToRsemide compArisoN with furoSemide FOR Management of Heart Failure (TRANSFORM-HF) PCT. We describe our hybrid approach that includes gathering information from clinical trial sites, a centralized call center, and National Death Index searches. Our methods detail how a possible death is triggered from each of these components and the types of information we require to verify a triggered death. Our different trigger/verification elements collectively define the TRANSFORM-HF PCT's definition of a death event.
Topics: Clinical Trials as Topic; Data Collection; Diuretics; Endpoint Determination; Furosemide; Heart Failure; Humans; Mortality; Torsemide
PubMed: 30741178
DOI: No ID Found -
Journal of Advanced Research Nov 2015Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME) induced hypertension in...
Comparative study of cardio protective effect of aliskiren, telmisartan, and torsemide was carried out on l-nitro arginine methyl ester (l-NAME) induced hypertension in rats. The three drugs were given daily for 8 weeks simultaneously with l-NAME, with a control group for each drug and l-NAME. The degree of protection was assessed by measurement of systolic blood pressure and heart rate of animals every two weeks. At the end of the experimental period blood sampling was carried out for estimation of the level of NO2 (-)/NO3 (-). After which animals were sacrificed for heart dissection to detect collagen types I and III gene expression. Histopathological study was done to evaluate the extension of collagen deposits. The study revealed that the three drugs decreased blood pressure significantly compared to l-NAME. There was no significant difference between aliskiren and telmisartan in all measurements, but there was significant decrease in measurements of both aliskiren and telmisartan treated groups compared to torsemide starting from 4th week. There were insignificant changes in pulse rate values between the three l-NAME treated groups through the experiment. The three drugs significantly increased NO compared to l-NAME. Collagen I and III gene expression was significantly decreased by the three drugs but the highest percentage of inhibition was with telmisartan compared to l-NAME. Comparing the percentage inhibition of cardiac fibrosis, there was insignificant difference between telmisartan and torsemide treated groups while both were superior to aliskiren. In conclusion, further experimental studies are required to elucidate the potential cardioprotective mechanisms of aliskiren, telmisartan and torsemide, and assess their efficacy in treatment of heart failure.
PubMed: 26644935
DOI: 10.1016/j.jare.2014.11.003 -
The National Medical Journal of India 2018Mild hypokalaemia is a common electrolyte abnormality following therapeutic doses of diuretics such as torsemide. If undiagnosed and untreated, hypokalaemia progresses...
Mild hypokalaemia is a common electrolyte abnormality following therapeutic doses of diuretics such as torsemide. If undiagnosed and untreated, hypokalaemia progresses and smooth muscle, skeletal muscle and the heart are affected. Potassium-sparing diuretics such as spironolactone are commonly added to loop diuretics to prevent symptomatic hypokalaemia. We present a patient with moderate hypokal-aemia associated with the use of torsemide and spironolactone, resulting in quadriparesis, hospitalization and electrophysio-logical abnormalities.
Topics: Diuretics; Drug Therapy, Combination; Edema; End Stage Liver Disease; Humans; Hypokalemia; Male; Middle Aged; Quadriplegia; Spironolactone; Torsemide
PubMed: 31397368
DOI: 10.4103/0970-258X.262913 -
European Journal of Heart Failure Mar 2018
Topics: Furosemide; Heart Failure; Humans; Sulfonamides; Torsemide; Water
PubMed: 29082584
DOI: 10.1002/ejhf.1024