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[PMID]:28228057
[Au] Autor:Michaud CJ; Mintus KC
[Ad] Endereço:1 Spectrum Health, Grand Rapids, MI, USA.
[Ti] Título:Intravenous Chlorothiazide Versus Enteral Metolazone to Augment Loop Diuretic Therapy in the Intensive Care Unit.
[So] Source:Ann Pharmacother;51(4):286-292, 2017 Apr.
[Is] ISSN:1542-6270
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In cases of loop diuretic resistance in the intensive care unit (ICU), recommendations for a specific second-line thiazide agent are lacking. OBJECTIVE: To compare the effects of intravenous chlorothiazide (CTZ) and enteral metolazone (MET) on urine output (UOP) when added to furosemide monotherapy therapy in critically ill adults. METHODS: This was a retrospective cohort study conducted in the medical, surgical, and cardiothoracic ICUs of a quaternary medical center. The primary outcome was change in UOP induced by the study interventions compared with furosemide alone. Secondary outcomes included onset of diuresis, eventual need for hemodialysis, and incidence of adverse events. RESULTS: A total of 122 patients (58 in CTZ, 64 in MET) were included. When added to furosemide monotherapy, CTZ induced a greater change in UOP at 24 hours compared with MET (2405 vs 1646 mL, respectively; P = 0.01). CTZ also caused a more rapid dieresis: 1463 mL total UOP in the first 6 hours compared with 796 mL in the MET group ( P < 0.01). There were no differences found regarding ICU length of stay, need for renal replacement therapy, or survival to discharge. The CTZ arm required more potassium supplementation to maintain normokalemia (median 100 vs 57 mEq in MET; P = 0.02) and carried a higher cost (mean $97 vs $8, P < 0.01). CONCLUSION: Both CTZ and MET induced significant increases in UOP. CTZ induced a greater and more rapid change and was associated with higher cost and greater need for potassium replacement. Randomized controlled trials are needed to establish whether a preferable thiazide diuretic exists in this setting.
[Mh] Termos MeSH primário: Clorotiazida/uso terapêutico
Diurese/efeitos dos fármacos
Unidades de Terapia Intensiva
Metolazona/uso terapêutico
Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico
[Mh] Termos MeSH secundário: Administração Intravenosa
Administração Oral
Adulto
Clorotiazida/administração & dosagem
Clorotiazida/efeitos adversos
Estado Terminal
Quimioterapia Combinada
Feminino
Furosemida/administração & dosagem
Furosemida/efeitos adversos
Furosemida/uso terapêutico
Seres Humanos
Masculino
Metolazona/administração & dosagem
Metolazona/efeitos adversos
Estudos Retrospectivos
Inibidores de Simportadores de Cloreto de Sódio e Potássio/administração & dosagem
Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sodium Potassium Chloride Symporter Inhibitors); 77W477J15H (Chlorothiazide); 7LXU5N7ZO5 (Furosemide); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170811
[Lr] Data última revisão:
170811
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170224
[St] Status:MEDLINE
[do] DOI:10.1177/1060028016683971


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[PMID]:27823694
[Au] Autor:Lee DS; Lee JS; Schull MJ; Grimshaw JM; Austin PC; Tu JV
[Ad] Endereço:Institute for Clinical Evaluative Sciences, University of Toronto, Toronto, Canada; Division of Cardiology, Peter Munk Cardiac Centre of the University Health Network and Joint Department of Medical Imaging, University of Toronto, Toronto, Canada; Department of Medicine, University of Toronto, Toron
[Ti] Título:Design and rationale for the Acute Congestive Heart Failure Urgent Care Evaluation: The ACUTE Study.
[So] Source:Am Heart J;181:60-65, 2016 Nov.
[Is] ISSN:1097-6744
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Heart failure (HF) is one of the leading reasons for emergency department (ED) visits and hospitalization. However, externally validated risk algorithms for acute prognostication of heart failure patients are not available. Thus, many low-risk patients are hospitalized and some high-risk patients are discharged home, which, in some cases, may lead to death. OBJECTIVES: The first objective of the ACUTE study is to perform a prospective validation of the Emergency Heart failure Mortality Risk Grade (EHMRG), which is a risk score derived to predict 7-day mortality in the ED setting. The second objective is to independently validate the 30-day model extension of the risk score (EHMRG30-ST) in the same cohort. STUDY DESIGN: Patients with HF presenting to the ED will be recruited with a waiver of informed consent as a minimal risk study. The ED physician will calculate the EHMRG 7-day risk score, but treatment decisions will not be influenced by the predictive models. Follow-up will be obtained using probabilistic linkage with the Registered Persons Database of vital statistics, whereby deaths will be ascertained. We will examine mortality rates according to EHMRG and EHMRG30-ST algorithms. We will also compare physician-judged risk estimates, based on clinical judgment alone, with the EHMRG score. CONCLUSION: The ACUTE study will determine if a retrospectively derived algorithm for simultaneous estimation of 7-day and 30-day mortality risk can accurately identify low- and high-risk patients with acute HF and improve upon physician-judged risk estimation.
[Mh] Termos MeSH primário: Algoritmos
Serviço Hospitalar de Emergência
Insuficiência Cardíaca/mortalidade
Medição de Risco/métodos
[Mh] Termos MeSH secundário: Fatores Etários
Ambulâncias/utilização
Anti-Hipertensivos/uso terapêutico
Pressão Sanguínea
Comorbidade
Creatinina/sangue
Serviços Médicos de Emergência/estatística & dados numéricos
Insuficiência Cardíaca/diagnóstico
Frequência Cardíaca
Hospitalização
Seres Humanos
Metolazona/uso terapêutico
Mortalidade
Neoplasias/epidemiologia
Oximetria
Potássio/sangue
Prognóstico
Estudos Prospectivos
Troponina/sangue
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY; VALIDATION STUDIES
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Troponin); AYI8EX34EU (Creatinine); RWP5GA015D (Potassium); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170525
[Lr] Data última revisão:
170525
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161109
[St] Status:MEDLINE


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[PMID]:27393709
[Au] Autor:Shulenberger CE; Jiang A; Devabhakthuni S; Ivaturi V; Liu T; Reed BN
[Ad] Endereço:PinnacleHealth, Harrisburg, PA.
[Ti] Título:Efficacy and Safety of Intravenous Chlorothiazide versus Oral Metolazone in Patients with Acute Decompensated Heart Failure and Loop Diuretic Resistance.
[So] Source:Pharmacotherapy;36(8):852-60, 2016 Aug.
[Is] ISSN:1875-9114
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:STUDY OBJECTIVE: To assess the efficacy and safety of intravenous (IV) chlorothiazide versus oral metolazone when added to loop diuretics in patients with acute decompensated heart failure (ADHF) and loop diuretic resistance. DESIGN: Retrospective cohort study. SETTING: Large urban academic medical center. PATIENTS: Adults admitted with ADHF between 2005 and 2015 who had loop diuretic resistance, defined as administration of IV furosemide at a dose of 160 mg/day or higher (or an equivalent dose of IV bumetanide), during hospitalization, and who then received at least one dose of IV chlorothiazide (88 patients) or oral metolazone (89 patients) to augment diuresis. MEASUREMENTS AND MAIN RESULTS: The primary efficacy end point was a change in 24-hour net urine output (UOP) from before to after thiazide-type diuretic administration, and the study was designed to test for the noninferiority of metolazone. Safety end points included changes in renal function and electrolyte concentrations. The mean dose of IV loop diuretic therapy (in IV furosemide equivalents) at baseline (before thiazide-type diuretic administration) was higher in the chlorothiazide group (mean ± SD 318.9 ± 127.7 vs 268.4 ± 97.6 mg/day in the metolazone group, p=0.004), but net UOP was similar (mean ± SD 877.0 ± 1189.0 ml in the chlorothiazide group vs 710.6 ± 1145.9 ml in the metolazone group, p=0.344). Mean doses of chlorothiazide and metolazone were 491 ± 282 mg and 5.8 ± 3.5 mg, respectively. Following thiazide-type diuretic administration, net UOP improved to a similar degree (2274.6 ± 1443.0 ml vs 2030.2 ± 1725.0 ml in the chlorothiazide and metolazone groups, respectively, p=0.308). For the primary efficacy end point, metolazone met the threshold for noninferiority by producing a net UOP of 1319.6 ± 1517.4 ml versus 1397.6 ± 1370.7 ml for chlorothiazide (p=0.026 for noninferiority). No significant differences in renal function were observed between the groups. Although hypokalemia was more frequent in the chlorothiazide group (75% with chlorothiazide vs 60.7% with metolazone, p=0.045), no significant differences in the rates of severe hypokalemia or other electrolyte abnormalities were observed between the groups. CONCLUSION: Oral metolazone was noninferior to IV chlorothiazide for enhancing net UOP in patients with ADHF and loop diuretic resistance and was similarly safe with regard to renal function and electrolyte abnormalities. Given the significant cost disparity between the two agents, these findings suggest that oral metolazone may be considered a first-line option in this patient population.
[Mh] Termos MeSH primário: Clorotiazida/uso terapêutico
Diuréticos/uso terapêutico
Insuficiência Cardíaca/tratamento farmacológico
Metolazona/uso terapêutico
[Mh] Termos MeSH secundário: Doença Aguda
Administração Intravenosa
Administração Oral
Adulto
Idoso
Clorotiazida/efeitos adversos
Estudos de Coortes
Resistência a Medicamentos
Feminino
Seres Humanos
Masculino
Metolazona/efeitos adversos
Meia-Idade
Estudos Retrospectivos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 77W477J15H (Chlorothiazide); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160710
[St] Status:MEDLINE
[do] DOI:10.1002/phar.1798


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[PMID]:27321568
[Au] Autor:Cardinale M; Altshuler J; Testani JM
[Ad] Endereço:Pharmacy Department, Saint Peter's University Hospital, New Brunswick, New Jersey.
[Ti] Título:Efficacy of Intravenous Chlorothiazide for Refractory Acute Decompensated Heart Failure Unresponsive to Adjunct Metolazone.
[So] Source:Pharmacotherapy;36(8):843-51, 2016 Aug.
[Is] ISSN:1875-9114
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:STUDY OBJECTIVE: To assess the efficacy of intravenous chlorothiazide in patients with acute decompensated heart failure (ADHF) who were determined to be loop diuretic resistant and refractory to metolazone. DESIGN: Retrospective cohort study with patients serving as their own controls. SETTING: Large, academic, tertiary care hospital. PATIENTS: Forty-five patients with ADHF who had an inadequate response to high-dose loop diuretics and then received at least one dose of oral metolazone 5 mg or greater (metolazone index dose) followed by at least one dose of intravenous chlorothiazide 500 mg (chlorothiazide index dose) if the response to metolazone was considered inadequate, according to the institutional protocol, between February 4, 2013, and February 28, 2015, were included. If multiple doses of metolazone were administered, the last dose given before the chlorothiazide index dose was considered the index dose; the metolazone index dose had to have been administered more than 2 hours before the chlorothiazide index dose. MEASUREMENTS AND MAIN RESULTS: Data for a total of 90 diuretic doses (45 metolazone, 45 chlorothiazide) were included in the analysis. The median dose of loop diuretic in intravenous furosemide equivalents given over the 24-hour period before the metolazone index dose was 400 mg. The average length of stay was 34.7 days, and in-hospital mortality was 35.6% (16/45 patients). The primary end point of a net-negative urine output of 500 ml or greater during the 12 hours after the index dose occurred in 42.2% (19/45 patients) and 35.5% (16/45 patients) for the chlorothiazide and metolazone doses, respectively (p=0.581). The median 12-hour urine output following administration of metolazone was 810 ml (interquartile range [IQR] 866 ml) versus 1075 ml (IQR 940 ml) following administration of chlorothiazide (p=0.363). Compared with metolazone, the chlorothiazide doses did not result in an increase in urine output of at least 500 ml during the 12 hours following the dose relative to the 12 hours before the dose (31.1% vs 22.2%, p=0.754). No significant difference in achievement of net-negative urine output of 500 ml or greater during the 12 hours following the chlorothiazide or metolazone dose was noted (42.2% for chlorothiazide vs 35.5% for metolazone, p=0.581). CONCLUSION: The addition of intravenous chlorothiazide did not result in improved diuresis in patients with ADHF determined to be refractory to loop diuretics and adjunctive oral metolazone.
[Mh] Termos MeSH primário: Clorotiazida/uso terapêutico
Insuficiência Cardíaca/tratamento farmacológico
Metolazona/uso terapêutico
[Mh] Termos MeSH secundário: Doença Aguda
Administração Intravenosa
Adulto
Idoso
Clorotiazida/administração & dosagem
Diuréticos/uso terapêutico
Feminino
Seres Humanos
Masculino
Meia-Idade
Estudos Retrospectivos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 77W477J15H (Chlorothiazide); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170919
[Lr] Data última revisão:
170919
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160621
[St] Status:MEDLINE
[do] DOI:10.1002/phar.1787


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[PMID]:25947361
[Au] Autor:Dubey R; Ghosh M; Sinha BN; Muthukrishnan V
[Ad] Endereço:Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, India.
[Ti] Título:Simultaneous Determination and Pharmacokinetics of Metolazone, Losartan and Losartan Carboxylic Acid in Rat Plasma by HPLC-ESI-MS-MS.
[So] Source:J Chromatogr Sci;53(9):1520-7, 2015 Oct.
[Is] ISSN:1945-239X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:For the first time, we developed and validated a highly sensitive, selective and rapid HPLC-ESI-MS-MS method for simultaneous quantification of metolazone (MET), losartan (LOS) and its metabolite losartan carboxylic acid (LCA) in rat plasma. After solid-phase extraction, the analytes and internal standard (irbesartan) were extracted from 100 µL plasma sample on an Agilent Poroshell 120, EC-C18 (50 × 4.6 mm, i.d., 2.7 µm) column using 5 µL injection volume with a total run time of 3 min. Acidified methanol/water mixture was used as a mobile phase. The parent → product ion transitions for MET (m/z 366.0 → 258.9), LOS (m/z 423.2 → 207.0), LCA (m/z 437.0 → 235.1) and IS (m/z 429.2 → 207.0) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and positive ion mode. The method was found to be linear in the range of 0.05-250 for MET, 2-3,000 for LOS and 4-3,500 ng/mL for LCA. The method was validated with respect to selectivity, linearity, accuracy, precision, recovery and stability according to accepted regulatory guidelines. The described method was successfully applied to preclinical pharmacokinetic studies of analytes after an oral administration of mixture of MET (1 mg/kg) and LOS (10 mg/kg) in rats.
[Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos
Losartan/sangue
Losartan/farmacocinética
Metolazona/sangue
Metolazona/farmacocinética
Espectrometria de Massas em Tandem/métodos
[Mh] Termos MeSH secundário: Animais
Modelos Lineares
Losartan/química
Masculino
Metolazona/química
Ratos
Ratos Wistar
Reprodutibilidade dos Testes
Sensibilidade e Especificidade
Espectrometria de Massas por Ionização por Electrospray/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
JMS50MPO89 (Losartan); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1605
[Cu] Atualização por classe:151013
[Lr] Data última revisão:
151013
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150508
[St] Status:MEDLINE
[do] DOI:10.1093/chromsci/bmv047


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[PMID]:25712736
[Au] Autor:Moranville MP; Choi S; Hogg J; Anderson AS; Rich JD
[Ad] Endereço:Department of Pharmacy, Johns Hopkins Hospital, Baltimore, MD, USA.
[Ti] Título:Comparison of metolazone versus chlorothiazide in acute decompensated heart failure with diuretic resistance.
[So] Source:Cardiovasc Ther;33(2):42-9, 2015 Apr.
[Is] ISSN:1755-5922
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:AIMS: Sequential nephron blockade with thiazide-like diuretics is a strategy used to overcome diuretic resistance in acute decompensated heart failure (ADHF), but head-to-head studies are lacking and equipoise exists regarding the preferred thiazide-like diuretic in this setting. We thus compared the effectiveness of oral metolazone versus intravenous (IV) chlorothiazide as add-on therapy to loop diuretics in hospitalized patients with ADHF and renal dysfunction. METHODS: This retrospective cohort study evaluated the efficacy and safety of oral metolazone versus IV chlorothiazide as add-on therapy to loop diuretics in patients hospitalized with ADHF and renal dysfunction. The primary endpoint was net urine output (UOP) at 72 h after initiation of thiazide-like diuretics. Safety endpoints included worsening renal function, hypotension, and electrolyte abnormalities. RESULTS: Fifty-five patients were enrolled with 33 patients receiving metolazone and 22 patients receiving chlorothiazide. There was no difference in median net UOP at 72 h in those receiving metolazone (4828 mL, interquartile range [IQR] 2800-7209 mL) compared to chlorothiazide (3779 mL, IQR 1885-6535 mL) (P = 0.16). There was no difference in hypotension, worsening renal function, hyponatremia, or hypokalemia (P = NS for all comparisons). Hospital length of stay was shorter in the metolazone cohort (median 7 days) compared to chlorothiazide (median 15 days), suggesting the chlorothiazide cohort was likely sicker. CONCLUSION: Sequential nephron blockade with either metolazone or chlorothiazide appears to be efficacious and safe in ADHF, renal dysfunction, and diuretic resistance. Given the considerable cost difference favoring oral metolazone, larger randomized studies are warranted to confirm our findings and to exclude the possibility of confounding by indication.
[Mh] Termos MeSH primário: Clorotiazida/uso terapêutico
Insuficiência Cardíaca/terapia
Metolazona/uso terapêutico
Néfrons/efeitos dos fármacos
Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico
Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico
[Mh] Termos MeSH secundário: Doença Aguda
Administração Intravenosa
Administração Oral
Idoso
Chicago
Clorotiazida/administração & dosagem
Clorotiazida/efeitos adversos
Resistência a Medicamentos
Quimioterapia Combinada
Feminino
Insuficiência Cardíaca/diagnóstico
Insuficiência Cardíaca/fisiopatologia
Hospitalização
Seres Humanos
Tempo de Internação
Masculino
Metolazona/administração & dosagem
Metolazona/efeitos adversos
Meia-Idade
Néfrons/fisiopatologia
Estudos Retrospectivos
Inibidores de Simportadores de Cloreto de Sódio/administração & dosagem
Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos
Inibidores de Simportadores de Cloreto de Sódio e Potássio/efeitos adversos
Fatores de Tempo
Resultado do Tratamento
Micção/efeitos dos fármacos
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Sodium Chloride Symporter Inhibitors); 0 (Sodium Potassium Chloride Symporter Inhibitors); 77W477J15H (Chlorothiazide); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150330
[Lr] Data última revisão:
150330
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150226
[St] Status:MEDLINE
[do] DOI:10.1111/1755-5922.12109


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[PMID]:24819365
[Au] Autor:Nair DG; Narayanan SP; Chittalakkottu S
[Ad] Endereço:a Department of Biotechnology and Microbiology , Kannur University , Thalassery Campus, Palayad P.O., Kannur , Kerala 670661 , India.
[Ti] Título:Interactions of some commonly used drugs with human α-thrombin.
[So] Source:J Biomol Struct Dyn;33(5):1008-15, 2015.
[Is] ISSN:1538-0254
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Adverse side effects of drugs are often caused by the interaction of drug molecules to targets other than the intended ones. In this study, we investigated the off-target interactions of some commercially available drugs with human α-thrombin. The drugs used in the study were selected from Super Drug Database based on the structural similarity to a known thrombin inhibitor argatroban. Interactions of these drugs with thrombin were initially checked by in silico docking studies and then confirmed by thrombin inhibition assay using a fluorescence microplate-based method. Results show that the three commonly used drugs piperacillin (anti-bacterial), azlocillin (anti-bacterial), and metolazone (anti-hypertensive and diuretic) have thrombin inhibitory activity almost similar to that of argatroban. The Ki values of piperacillin, azlocillin, and metolazone with thrombin are .55, .95, and .62 nM, respectively. The IC50 values of piperacillin, azlocillin, and metolazone with thrombin are 1.7, 2.9, and 1.92 nM, respectively. This thrombin inhibitory activity might be a reason for the observed side effects of these drugs related to blood coagulation and other thrombin activities. Furthermore, these compounds (drugs) may be used as anti-coagulants as such or with structural modifications.
[Mh] Termos MeSH primário: Antitrombinas/química
Simulação de Acoplamento Molecular
Ácidos Pipecólicos/química
Trombina/química
[Mh] Termos MeSH secundário: Antitrombinas/metabolismo
Azlocilina/química
Azlocilina/metabolismo
Seres Humanos
Cinética
Metolazona/química
Metolazona/metabolismo
Estrutura Molecular
Ácidos Pipecólicos/metabolismo
Piperacilina/química
Piperacilina/metabolismo
Ligação Proteica
Estrutura Terciária de Proteína
Trombina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antithrombins); 0 (Pipecolic Acids); EC 3.4.21.5 (Thrombin); HUM6H389W0 (Azlocillin); IY90U61Z3S (argatroban); TZ7V40X7VX (Metolazone); X00B0D5O0E (Piperacillin)
[Em] Mês de entrada:1601
[Cu] Atualização por classe:161125
[Lr] Data última revisão:
161125
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140514
[St] Status:MEDLINE
[do] DOI:10.1080/07391102.2014.923329


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[PMID]:24801161
[Au] Autor:Laughon MM; Chantala K; Aliaga S; Herring AH; Hornik CP; Hughes R; Clark RH; Smith PB
[Ad] Endereço:Division of Neonatal-Perinatal Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.
[Ti] Título:Diuretic exposure in premature infants from 1997 to 2011.
[So] Source:Am J Perinatol;32(1):49-56, 2015 Jan.
[Is] ISSN:1098-8785
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: Diuretics are often prescribed off-label to premature infants, particularly to prevent or treat bronchopulmonary dysplasia. We examined their use and safety in this group. STUDY DESIGN: Retrospective cohort study of infants < 32 weeks gestation and < 1,500 g birth weight exposed to diuretics in 333 neonatal intensive care units from 1997 to 2011. We examined use of acetazolamide, amiloride, bumetanide, chlorothiazide, diazoxide, ethacrynic acid, furosemide, hydrochlorothiazide, mannitol, metolazone, or spironolactone combination. Respiratory support and fraction of inspired oxygen on the first day of each course of diuretic use were identified. RESULTS: About 37% (39,357/107,542) infants were exposed to at least one diuretic; furosemide was the most commonly used (93% with ≥ 1 recorded dose), followed by spironolactone, chlorothiazide, hydrochlorothiazide, bumetanide, and acetazolamide. About 74% patients were exposed to one diuretic at a time, 19% to two diuretics simultaneously, and 6% to three diuretics simultaneously. The most common combination was furosemide/spironolactone, followed by furosemide/chlorothiazide and chlorothiazide/spironolactone. Many infants were not receiving mechanical ventilation on the first day of each new course of furosemide (47%), spironolactone (69%), chlorothiazide (61%), and hydrochlorothiazide (68%). Any adverse event occurred on 42 per 1,000 infant-days for any diuretic and 35 per 1,000 infant-days for furosemide. Any serious adverse event occurred in 3.8 for any diuretic and 3.2 per 1,000 infant-days for furosemide. The most common laboratory abnormality associated with diuretic exposure was thrombocytopenia. CONCLUSION: Despite no Food and Drug Administration (FDA) indication and little safety data, over one-third of premature infants in our population were exposed to a diuretic, many with minimal respiratory support.
[Mh] Termos MeSH primário: Displasia Broncopulmonar/prevenção & controle
Diuréticos/uso terapêutico
Respiração Artificial/estatística & dados numéricos
Trombocitopenia/epidemiologia
[Mh] Termos MeSH secundário: Acetazolamida/uso terapêutico
Amilorida/uso terapêutico
Displasia Broncopulmonar/tratamento farmacológico
Clorotiazida/uso terapêutico
Estudos de Coortes
Diazóxido/uso terapêutico
Quimioterapia Combinada
Ácido Etacrínico/uso terapêutico
Feminino
Furosemida/uso terapêutico
Seres Humanos
Hidroclorotiazida/uso terapêutico
Lactente Extremamente Prematuro
Recém-Nascido
Recém-Nascido Prematuro
Masculino
Manitol/uso terapêutico
Metolazona/uso terapêutico
Uso Off-Label
Estudos Retrospectivos
Espironolactona/uso terapêutico
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Diuretics); 0J48LPH2TH (Hydrochlorothiazide); 27O7W4T232 (Spironolactone); 3OWL53L36A (Mannitol); 77W477J15H (Chlorothiazide); 7DZO8EB0Z3 (Amiloride); 7LXU5N7ZO5 (Furosemide); M5DP350VZV (Ethacrynic Acid); O3FX965V0I (Acetazolamide); O5CB12L4FN (Diazoxide); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1509
[Cu] Atualização por classe:161215
[Lr] Data última revisão:
161215
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140508
[St] Status:MEDLINE
[do] DOI:10.1055/s-0034-1373845


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[PMID]:25181459
[Au] Autor:Banerjee M; Chen T
[Ad] Endereço:Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Mail Stop 1000, 262 Danny Thomas Place, Memphis, TN 38105-3678, USA.
[Ti] Título:Thiazide-like diuretic drug metolazone activates human pregnane X receptor to induce cytochrome 3A4 and multidrug-resistance protein 1.
[So] Source:Biochem Pharmacol;92(2):389-402, 2014 Nov 15.
[Is] ISSN:1873-2968
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Human pregnane X receptor (hPXR) regulates the expression of drug-metabolizing enzyme cytochrome P450 3A4 (CYP3A4) and drug transporters such as multidrug-resistance protein 1 (MDR1). PXR can be modulated by small molecules, including Federal Drug Administration (FDA)-approved drugs, thus altering drug metabolism and causing drug-drug interactions. To determine the role of FDA-approved drugs in PXR-mediated regulation of drug metabolism and clearance, we screened 1481 FDA-approved small-molecule drugs by using a luciferase reporter assay in HEK293T cells and identified the diuretic drug metolazone as an activator of hPXR. Our data showed that metolazone activated hPXR-mediated expression of CYP3A4 and MDR1 in human hepatocytes and intestine cells and increased CYP3A4 promoter activity in various cell lines. Mammalian two-hybrid assays showed that hPXR recruits its co-activator SRC-1 upon metolazone binding in HepG2 cells, explaining the mechanism of hPXR activation. To understand the role of other commonly-used diuretics in hPXR activation and the structure-activity relationship of metolazone, thiazide and non-thiazide diuretics drugs were also tested but only metolazone activates hPXR. To understand the molecular mechanism, docking studies and mutational analysis were carried out and showed that metolazone binds in the ligand-binding pocket and interacts with mostly hydrophobic amino acid residues. This is the first report showing that metolazone activates hPXR. Because activation of hPXR might cause drug-drug interactions, metolazone should be used with caution for drug treatment in patients undergoing combination therapy.
[Mh] Termos MeSH primário: Indutores do Citocromo P-450 CYP3A/farmacologia
Citocromo P-450 CYP3A/biossíntese
Diuréticos/farmacologia
Metolazona/farmacologia
Proteínas Associadas à Resistência a Múltiplos Medicamentos/biossíntese
Receptores de Esteroides/metabolismo
[Mh] Termos MeSH secundário: Sobrevivência Celular/efeitos dos fármacos
Sobrevivência Celular/fisiologia
Relação Dose-Resposta a Droga
Células HEK293
Células Hep G2
Seres Humanos
Ligação Proteica/fisiologia
Tiazidas/farmacologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Cytochrome P-450 CYP3A Inducers); 0 (Diuretics); 0 (Multidrug Resistance-Associated Proteins); 0 (Receptors, Steroid); 0 (Thiazides); 0 (pregnane X receptor); EC 1.14.14.1 (Cytochrome P-450 CYP3A); TZ7V40X7VX (Metolazone); Y49M64GZ4Q (multidrug resistance-associated protein 1)
[Em] Mês de entrada:1503
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140903
[St] Status:MEDLINE


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[PMID]:24824145
[Au] Autor:Cheng HW; Sham MK; Chan KY; Li CW; Au HY; Yip T
[Ad] Endereço:Palliative Medical Unit, Grantham Hospital, 125 Wong Chuk Hang Road, Aberdeen, Hong Kong, China, benchw@hkstar.com.
[Ti] Título:Combination therapy with low-dose metolazone and furosemide: a "needleless" approach in managing refractory fluid overload in elderly renal failure patients under palliative care.
[So] Source:Int Urol Nephrol;46(9):1809-13, 2014 Sep.
[Is] ISSN:1573-2584
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND AND OBJECTIVE: End-stage renal failure (ESRF) patients under palliative care could live for months or even years after deciding not to start dialysis. They could experience significant symptom burden with recurrent fluid overload due to poor renal reserve. This could imply repeated hospital admissions for parenteral diuretics, which may destabilize their community support and limit their precious time spent with family. Diuretic therapy remains the cornerstone of managing fluid overload, but when per-oral administration become ineffective, parenteral diuretics may cause extra discomfort with potential infective complications. Metolazone, since its introduction in 1970s, has been proven effective in managing refractory heart failure, but whether its potential effect could be applied in ESRF patients not receiving dialysis is awaited to be proven. METHOD: In our case series, we recruited elderly renal failure patients under palliative care with refractory fluid overload resistant to oral furosemide (120-160 mg daily dose), which was successfully managed after addition of low-dose metolazone (2.5-5 mg) for short duration (2-5 days). Reasoning behind not to initiate intravenous diuretics was discussed. RESULTS: All patients show good tolerance to combined diuretics without significant blood pressure fluctuation or electrolytes disturbance. Peripheral and pulmonary edema was clinically improved. Body weight reduction of 2.0-5.0 kg was achieved. CONCLUSION: Our case series support the use of above regimen as a potential alternative in ESRF patients under palliative care, without bearing the parenteral route of treatment burden.
[Mh] Termos MeSH primário: Diuréticos/administração & dosagem
Edema/tratamento farmacológico
Edema/etiologia
Furosemida/administração & dosagem
Falência Renal Crônica/complicações
Falência Renal Crônica/terapia
Metolazona/administração & dosagem
Cuidados Paliativos
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Quimioterapia Combinada
Seres Humanos
Masculino
[Pt] Tipo de publicação:CASE REPORTS; EVALUATION STUDIES; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Diuretics); 7LXU5N7ZO5 (Furosemide); TZ7V40X7VX (Metolazone)
[Em] Mês de entrada:1505
[Cu] Atualização por classe:171102
[Lr] Data última revisão:
171102
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:140515
[St] Status:MEDLINE
[do] DOI:10.1007/s11255-014-0724-z



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