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Ciprian D Jauca - One of the best experts on this subject based on the ideXlab platform.
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Blood pressure-lowering efficacy of Loop Diuretics for primary hypertension.
The Cochrane database of systematic reviews, 2015Co-Authors: Vijaya M Musini, Pouria Rezapour, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used to treat hypertension, but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial (RCT) evidence has not been conducted. To determine the dose-related decrease in systolic or diastolic blood pressure, or both, as well as adverse events leading to participant withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of people with primary hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 9), MEDLINE, MEDLINE In-Process, EMBASE, and ClinicalTrials.gov to 27 October 2014. We included double-blind randomized placebo-controlled trials of at least three weeks duration comparing Loop diuretic with a placebo in people with primary hypertension defined as blood pressure greater than 140/90 mmHg at baseline. Two review authors independently assessed the risk of bias and extracted data. We used weighted mean difference and a fixed effects model to combine continuous outcome data. We analysed the drop outs due to adverse effects using relative risk ratio. Nine trials evaluated the dose-related blood pressure-lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg, piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure-lowering efficacy of Loop Diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4 (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.We performed additional searches in 2012 and 2014, which found no additional trials meeting the minimum inclusion criteria. Based on the limited number of published RCTs, the systolic/diastolic blood pressure-lowering effect of Loop Diuretics is -8/-4 mmHg, which is likely an overestimate. We graded the quality of evidence for both systolic and diastolic blood pressure estimates as "low" due to the high risk of bias of included studies and the high likelihood of publication bias. We found no clinically meaningful blood pressure-lowering differences between different drugs within the Loop diuretic class. The dose-ranging effects of Loop Diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with Loop Diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
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blood pressure lowering efficacy of Loop Diuretics for primary hypertension
Cochrane Database of Systematic Reviews, 2015Co-Authors: Vijaya M Musini, Pouria Rezapour, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:BACKGROUND Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used to treat hypertension, but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial (RCT) evidence has not been conducted. OBJECTIVES To determine the dose-related decrease in systolic or diastolic blood pressure, or both, as well as adverse events leading to participant withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of people with primary hypertension. SEARCH METHODS We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 9), MEDLINE, MEDLINE In-Process, EMBASE, and ClinicalTrials.gov to 27 October 2014. SELECTION CRITERIA We included double-blind randomized placebo-controlled trials of at least three weeks duration comparing Loop diuretic with a placebo in people with primary hypertension defined as blood pressure greater than 140/90 mmHg at baseline. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the risk of bias and extracted data. We used weighted mean difference and a fixed effects model to combine continuous outcome data. We analysed the drop outs due to adverse effects using relative risk ratio. MAIN RESULTS Nine trials evaluated the dose-related blood pressure-lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg, piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure-lowering efficacy of Loop Diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4 (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.We performed additional searches in 2012 and 2014, which found no additional trials meeting the minimum inclusion criteria. AUTHORS' CONCLUSIONS Based on the limited number of published RCTs, the systolic/diastolic blood pressure-lowering effect of Loop Diuretics is -8/-4 mmHg, which is likely an overestimate. We graded the quality of evidence for both systolic and diastolic blood pressure estimates as "low" due to the high risk of bias of included studies and the high likelihood of publication bias. We found no clinically meaningful blood pressure-lowering differences between different drugs within the Loop diuretic class. The dose-ranging effects of Loop Diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with Loop Diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
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Blood pressure lowering efficacy of Loop Diuretics for primary hypertension.
The Cochrane database of systematic reviews, 2012Co-Authors: Vijaya M Musini, Pouria Rezapour, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used as antihypertensive drugs but a systematic review of their blood pressure lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial evidence has not been conducted. To determine the dose related decrease in systolic and/or diastolic blood pressure as well as adverse events leading to patient withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of patients with primary hypertension. Medline (1946-February 2012), EMBASE (1974-February 2012), CENTRAL (issue 2, 2012) and bibliographic citations were searched. Double blind randomized placebo controlled trials of at least 3 weeks duration comparing Loop diuretic with a placebo in patients with primary hypertension defined as BP >140/90 mmHg at baseline were included. Two authors independently assessed the risk of bias and extracted data. Weighted mean difference and a fixed effects model were used to combine continuous outcome data. The drop outs due to adverse effects was analysed using relative risk ratio. Nine trials evaluated the dose-related blood pressure lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 to 60mg, cicletanine 100 to 150 mg, piretanide 3 to 6 mg, indacrinone enantiomer -2.5 to -10.0/+80 mg and etozolin 200 mg) in 460 patients with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure lowering efficacy of Loop Diuretics was -7.9 (-10.5, -5.4) mmHg/ -4.4 (-5.6, -2.8) mmHg . Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.The 2012 updated search resulted in no additional new trials meeting the minimum inclusion criteria. Based on the limited number of published RCTs, the systolic/diastolic blood pressure lowering effect of Loop Diuretics is modest (-8/-4 mmHg) and is likely an overestimate due to the high risk of bias in the included studies. There are no clinically meaningful BP lowering differences between different drugs within the Loop diuretic class. The dose ranging effects of Loop Diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with Loop Diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
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Blood pressure lowering efficacy of Loop Diuretics for primary hypertension.
The Cochrane database of systematic reviews, 2009Co-Authors: Vijaya M Musini, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used as antihypertensive drugs but a systematic review of their blood pressure lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial evidence has not been conducted. To determine the dose related decrease in systolic and/or diastolic blood pressure as well as adverse events leading to patient withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of patients with primary hypertension. Medline (Jan.1966-March-2009), EMBASE (Jan.1988-March-2009), CENTRAL (issue 1, 2009) and bibliographic citations were searched. Double blind randomized placebo controlled trials of at least 3 weeks duration comparing Loop diuretic with a placebo or no treatment in patients with primary hypertension defined as BP >140/90 mmHg at baseline were included. Two authors independently assessed the risk of bias and extracted data. Weighted mean difference and a fixed effects model were used to combine continuous outcome data. The drop outs due to adverse effects was analysed using relative risk ratio. Nine trials evaluated the dose-related blood pressure lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 to 60mg, cicletanine 100 to 150 mg, piretanide 3 to 6 mg, indacrinone enantiomer -2.5 to -10.0/+80 mg and etozolin 200 mg) in 460 patients with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of SBP/DBP lowering efficacy of Loop Diuretics was -7.9 (-10.5, -5.4) mmHg/ -4.4 (-5.6, -2.8) mmHg . Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference. Based on the limited number of published RCTs, the SBP/DBP lowering effect of Loop Diuretics is modest -8/-4 mmHg and is likely an overestimate due to the high risk of bias in the included studies. There is no clinically meaningful BP lowering differences between different drugs within the Loop diuretic class. The dose ranging effects of Loop Diuretics could not be evaluated.The review did not provide a good estimate of the incidence of harms associated because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
Vijaya M Musini - One of the best experts on this subject based on the ideXlab platform.
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Blood pressure-lowering efficacy of Loop Diuretics for primary hypertension.
The Cochrane database of systematic reviews, 2015Co-Authors: Vijaya M Musini, Pouria Rezapour, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used to treat hypertension, but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial (RCT) evidence has not been conducted. To determine the dose-related decrease in systolic or diastolic blood pressure, or both, as well as adverse events leading to participant withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of people with primary hypertension. We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 9), MEDLINE, MEDLINE In-Process, EMBASE, and ClinicalTrials.gov to 27 October 2014. We included double-blind randomized placebo-controlled trials of at least three weeks duration comparing Loop diuretic with a placebo in people with primary hypertension defined as blood pressure greater than 140/90 mmHg at baseline. Two review authors independently assessed the risk of bias and extracted data. We used weighted mean difference and a fixed effects model to combine continuous outcome data. We analysed the drop outs due to adverse effects using relative risk ratio. Nine trials evaluated the dose-related blood pressure-lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg, piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure-lowering efficacy of Loop Diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4 (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.We performed additional searches in 2012 and 2014, which found no additional trials meeting the minimum inclusion criteria. Based on the limited number of published RCTs, the systolic/diastolic blood pressure-lowering effect of Loop Diuretics is -8/-4 mmHg, which is likely an overestimate. We graded the quality of evidence for both systolic and diastolic blood pressure estimates as "low" due to the high risk of bias of included studies and the high likelihood of publication bias. We found no clinically meaningful blood pressure-lowering differences between different drugs within the Loop diuretic class. The dose-ranging effects of Loop Diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with Loop Diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
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blood pressure lowering efficacy of Loop Diuretics for primary hypertension
Cochrane Database of Systematic Reviews, 2015Co-Authors: Vijaya M Musini, Pouria Rezapour, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:BACKGROUND Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used to treat hypertension, but a systematic review of their blood pressure-lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial (RCT) evidence has not been conducted. OBJECTIVES To determine the dose-related decrease in systolic or diastolic blood pressure, or both, as well as adverse events leading to participant withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of people with primary hypertension. SEARCH METHODS We searched the Cochrane Hypertension Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL, 2014, Issue 9), MEDLINE, MEDLINE In-Process, EMBASE, and ClinicalTrials.gov to 27 October 2014. SELECTION CRITERIA We included double-blind randomized placebo-controlled trials of at least three weeks duration comparing Loop diuretic with a placebo in people with primary hypertension defined as blood pressure greater than 140/90 mmHg at baseline. DATA COLLECTION AND ANALYSIS Two review authors independently assessed the risk of bias and extracted data. We used weighted mean difference and a fixed effects model to combine continuous outcome data. We analysed the drop outs due to adverse effects using relative risk ratio. MAIN RESULTS Nine trials evaluated the dose-related blood pressure-lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 mg to 60 mg, cicletanine 100 mg to 150 mg, piretanide 3 mg to 6 mg, indacrinone enantiomer -2.5 mg to -10.0/+80 mg, and etozolin 200 mg) in 460 people with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure-lowering efficacy of Loop Diuretics was -7.9 (-10.4 to -5.4) mmHg/ -4.4 (-5.9 to -2.8) mmHg. Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.We performed additional searches in 2012 and 2014, which found no additional trials meeting the minimum inclusion criteria. AUTHORS' CONCLUSIONS Based on the limited number of published RCTs, the systolic/diastolic blood pressure-lowering effect of Loop Diuretics is -8/-4 mmHg, which is likely an overestimate. We graded the quality of evidence for both systolic and diastolic blood pressure estimates as "low" due to the high risk of bias of included studies and the high likelihood of publication bias. We found no clinically meaningful blood pressure-lowering differences between different drugs within the Loop diuretic class. The dose-ranging effects of Loop Diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with Loop Diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
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Blood pressure lowering efficacy of Loop Diuretics for primary hypertension.
The Cochrane database of systematic reviews, 2012Co-Authors: Vijaya M Musini, Pouria Rezapour, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used as antihypertensive drugs but a systematic review of their blood pressure lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial evidence has not been conducted. To determine the dose related decrease in systolic and/or diastolic blood pressure as well as adverse events leading to patient withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of patients with primary hypertension. Medline (1946-February 2012), EMBASE (1974-February 2012), CENTRAL (issue 2, 2012) and bibliographic citations were searched. Double blind randomized placebo controlled trials of at least 3 weeks duration comparing Loop diuretic with a placebo in patients with primary hypertension defined as BP >140/90 mmHg at baseline were included. Two authors independently assessed the risk of bias and extracted data. Weighted mean difference and a fixed effects model were used to combine continuous outcome data. The drop outs due to adverse effects was analysed using relative risk ratio. Nine trials evaluated the dose-related blood pressure lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 to 60mg, cicletanine 100 to 150 mg, piretanide 3 to 6 mg, indacrinone enantiomer -2.5 to -10.0/+80 mg and etozolin 200 mg) in 460 patients with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of systolic/diastolic blood pressure lowering efficacy of Loop Diuretics was -7.9 (-10.5, -5.4) mmHg/ -4.4 (-5.6, -2.8) mmHg . Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference.The 2012 updated search resulted in no additional new trials meeting the minimum inclusion criteria. Based on the limited number of published RCTs, the systolic/diastolic blood pressure lowering effect of Loop Diuretics is modest (-8/-4 mmHg) and is likely an overestimate due to the high risk of bias in the included studies. There are no clinically meaningful BP lowering differences between different drugs within the Loop diuretic class. The dose ranging effects of Loop Diuretics could not be evaluated. The review did not provide a good estimate of the incidence of harms associated with Loop Diuretics because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
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Blood pressure lowering efficacy of Loop Diuretics for primary hypertension.
The Cochrane database of systematic reviews, 2009Co-Authors: Vijaya M Musini, James M Wright, Ken Bassett, Ciprian D JaucaAbstract:Antihypertensive drugs from the thiazide diuretic drug class have been shown to reduce mortality and cardiovascular morbidity. Loop Diuretics are indicated and used as antihypertensive drugs but a systematic review of their blood pressure lowering efficacy or effectiveness in terms of reducing cardiovascular mortality or morbidity from randomized controlled trial evidence has not been conducted. To determine the dose related decrease in systolic and/or diastolic blood pressure as well as adverse events leading to patient withdrawal and adverse biochemical effects (serum potassium, uric acid, creatinine, glucose and lipids profile) due to Loop Diuretics versus placebo control in the treatment of patients with primary hypertension. Medline (Jan.1966-March-2009), EMBASE (Jan.1988-March-2009), CENTRAL (issue 1, 2009) and bibliographic citations were searched. Double blind randomized placebo controlled trials of at least 3 weeks duration comparing Loop diuretic with a placebo or no treatment in patients with primary hypertension defined as BP >140/90 mmHg at baseline were included. Two authors independently assessed the risk of bias and extracted data. Weighted mean difference and a fixed effects model were used to combine continuous outcome data. The drop outs due to adverse effects was analysed using relative risk ratio. Nine trials evaluated the dose-related blood pressure lowering efficacy of five drugs within the Loop Diuretics class (furosemide 40 to 60mg, cicletanine 100 to 150 mg, piretanide 3 to 6 mg, indacrinone enantiomer -2.5 to -10.0/+80 mg and etozolin 200 mg) in 460 patients with baseline blood pressure of 162/103 mmHg for a mean duration of 8.8 weeks. The best estimate of SBP/DBP lowering efficacy of Loop Diuretics was -7.9 (-10.5, -5.4) mmHg/ -4.4 (-5.6, -2.8) mmHg . Withdrawals due to adverse effects and serum biochemical changes did not show a significant difference. Based on the limited number of published RCTs, the SBP/DBP lowering effect of Loop Diuretics is modest -8/-4 mmHg and is likely an overestimate due to the high risk of bias in the included studies. There is no clinically meaningful BP lowering differences between different drugs within the Loop diuretic class. The dose ranging effects of Loop Diuretics could not be evaluated.The review did not provide a good estimate of the incidence of harms associated because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.
Masahito Shimizu - One of the best experts on this subject based on the ideXlab platform.
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effect of Loop Diuretics on skeletal muscle depletion in patients with liver cirrhosis
Hepatology Research, 2019Co-Authors: Tatsunori Hanai, Makoto Shiraki, Takao Miwa, Satoshi Watanabe, Kenji Imai, Atsushi Suetsugu, Koji Takai, Hisataka Moriwaki, Masahito ShimizuAbstract:AIM Sarcopenia, the loss of skeletal muscle mass, impairs prognosis of patients with liver cirrhosis. The aim of this study was to investigate the effect of Loop Diuretics, which are frequently used to treat hepatic edema/ascites, on skeletal muscle depletion and the prognosis in patients with liver cirrhosis. METHODS This retrospective study evaluated 226 patients with liver cirrhosis. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured using computed tomography. The relative change in skeletal muscle area per year (ΔSMA) was calculated, and the association between ΔSMA and therapeutic dosage of Loop Diuretics was examined. RESULTS The therapeutic dosage of Loop Diuretics was inversely correlated with ΔSMA by simple (r = -0.27, P 20 mg than in those who received ≤20 mg (median, 66 vs. 97 months; P = 0.002). Multivariate analysis revealed that Loop Diuretics of >20 mg (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.03-3.24; P = 0.039) and ΔSMA of ≤-3.1% (HR, 3.87; 95% CI, 2.32-6.60; P < 0.0001) were independently associated with mortality. CONCLUSIONS A higher dose of Loop diuretic use was associated with more rapid skeletal muscle depletion and poor survival in patients with liver cirrhosis, independent of the severity of liver disease.
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Effect of Loop Diuretics on skeletal muscle depletion in patients with liver cirrhosis
Hepatology research : the official journal of the Japan Society of Hepatology, 2018Co-Authors: Tatsunori Hanai, Makoto Shiraki, Takao Miwa, Satoshi Watanabe, Kenji Imai, Atsushi Suetsugu, Koji Takai, Hisataka Moriwaki, Masahito ShimizuAbstract:AIM Sarcopenia, the loss of skeletal muscle mass, impairs prognosis of patients with liver cirrhosis. The aim of this study was to investigate the effect of Loop Diuretics, which are frequently used to treat hepatic edema/ascites, on skeletal muscle depletion and the prognosis in patients with liver cirrhosis. METHODS This retrospective study evaluated 226 patients with liver cirrhosis. The skeletal muscle cross-sectional area at the level of the third lumbar vertebra was measured using computed tomography. The relative change in skeletal muscle area per year (ΔSMA) was calculated, and the association between ΔSMA and therapeutic dosage of Loop Diuretics was examined. RESULTS The therapeutic dosage of Loop Diuretics was inversely correlated with ΔSMA by simple (r = -0.27, P 20 mg than in those who received ≤20 mg (median, 66 vs. 97 months; P = 0.002). Multivariate analysis revealed that Loop Diuretics of >20 mg (hazard ratio [HR], 1.86; 95% confidence interval [CI], 1.03-3.24; P = 0.039) and ΔSMA of ≤-3.1% (HR, 3.87; 95% CI, 2.32-6.60; P
Paul Smits - One of the best experts on this subject based on the ideXlab platform.
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Vascular effects of Loop Diuretics
Cardiovascular research, 1996Co-Authors: Tom P. J. Dormans, Peter Pickkers, Frans G. M. Russel, Paul SmitsAbstract:Although it is generally believed that the beneficial effect of Loop Diuretics is the result of a rapid increase in diuresis, substantial evidence, from a large number of in vitro and in vivo experiments, has accumulated showing that administration of furosemide causes direct vascular effects, which probably contribute to its acute clinical effects. Several mechanisms are involved in the vascular response to Loop Diuretics. The role of the renin-angiotensin-adolsterone axis, prostaglandins and the direct vascular effects of Loop Diuretics on both the arterial and venous parts of the vasculature are discussed.
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Review Vascular effects of Loop Diuretics
1996Co-Authors: Peter Pickkers, Paul SmitsAbstract:Although it is generally believed that the beneficial effect of Loop Diuretics is the result of a rapid increase in diuresis, substantial evidence, from a large number of in vitro and in vivo experiments, has accumulated showing that administration of furosemide causes direct vascular effects, which probably contribute to its acute clinical effects, Several mechanisms are involved in the vascular response to Loop Diuretics. The role of the renin-angiotensin-aldosterone axis, prostaglandins and the direct vascular effects of Loop Diuretics on both the arterial and venous parts of the vasculature are discussed. Diuretic therapy has proved to be effective in the treatment of acute and chronic heart failure. The potent Loop Diuretics, furosemide and bumetanide, are frequently used in the treatment of disease states characterized by fluid and sodium retention. After intravenous administra tion of furosemide, clinical relief of symptoms often pre cedes the increase in diuresis in patients with acute heart failure, suggesting the presence of an extrarenal effect. Although it is generally believed that the beneficial effect of Loop Diuretics is the result of a rapid increase in diuresis, substantial evidence, from a large number of in vivo and in vitro experiments, has accumulated showing that adminis tration of furosemide causes vascular effects, which proba bly contribute to its acute clinical effects. At first sight the reports on the vascular non-diuretic effects of furosemide seem conflicting. However, a great deal of the disparity in the results seems to be due to differences in the vascular bed studied (arterial or venous, renal or pulmonary, etc.), the species studied, the timing (acute vs. chronic effects), systemic vs. local effects, direct vs, indirect effects and differences in disease states. In this paper the literature on vascular effects of Loop Diuretics t (with emphasis on furosemide) is reviewed with reference to the differences in experimental protocols. Finally, some general conclusions are drawn, and suggestions for future investigations are given.
David N Sheppard - One of the best experts on this subject based on the ideXlab platform.
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Loop Diuretics are open channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics
British Journal of Pharmacology, 2014Co-Authors: Toby S Scottward, Pissared Khuituan, Stephen M Husbands, Jia Liu, Zhiwei Cai, David N SheppardAbstract:Background and Purpose Loop Diuretics are widely used to inhibit the Na+, K+, 2Cl− co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl− channel. Here, we investigated the mechanism of CFTR inhibition by Loop Diuretics and explored the effects of chemical structure on channel blockade. Experimental Approach Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR. Key Results When added to the intracellular solution, Loop Diuretics inhibited CFTR Cl− currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to Loop Diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl− channels with ‘very fast’ speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with ‘intermediate’ speed and drug-induced blocking events were distinct from channel closures. Conclusions and Implications Structure–activity analysis of the Loop Diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking Loop Diuretics within the intracellular vestibule of the CFTR pore. We conclude that Loop Diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity.
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Loop Diuretics are open‐channel blockers of the cystic fibrosis transmembrane conductance regulator with distinct kinetics
British Journal of Pharmacology, 2013Co-Authors: Min Ju, Toby S. Scott-ward, Pissared Khuituan, Stephen M Husbands, Hongyu Li, David N SheppardAbstract:BACKGROUND AND PURPOSE: Loop Diuretics are widely used to inhibit the Na(+), K(+), 2Cl(-) co-transporter, but they also inhibit the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel. Here, we investigated the mechanism of CFTR inhibition by Loop Diuretics and explored the effects of chemical structure on channel blockade. EXPERIMENTAL APPROACH: Using the patch-clamp technique, we tested the effects of bumetanide, furosemide, piretanide and xipamide on recombinant wild-type human CFTR. KEY RESULTS: When added to the intracellular solution, Loop Diuretics inhibited CFTR Cl(-) currents with potency approaching that of glibenclamide, a widely used CFTR blocker with some structural similarity to Loop Diuretics. To begin to study the kinetics of channel blockade, we examined the time dependence of macroscopic current inhibition following a hyperpolarizing voltage step. Like glibenclamide, piretanide blockade of CFTR was time and voltage dependent. By contrast, furosemide blockade was voltage dependent, but time independent. Consistent with these data, furosemide blocked individual CFTR Cl(-) channels with 'very fast' speed and drug-induced blocking events overlapped brief channel closures, whereas piretanide inhibited individual channels with 'intermediate' speed and drug-induced blocking events were distinct from channel closures. CONCLUSIONS AND IMPLICATIONS: Structure-activity analysis of the Loop Diuretics suggests that the phenoxy group present in bumetanide and piretanide, but absent in furosemide and xipamide, might account for the different kinetics of channel block by locking Loop Diuretics within the intracellular vestibule of the CFTR pore. We conclude that Loop Diuretics are open-channel blockers of CFTR with distinct kinetics, affected by molecular dimensions and lipophilicity.
