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1.
Ann Pharm Fr ; 82(1): 53-63, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37541616

RESUMO

OBJECTIVES: A simple, accurate, and reliable high-performance thin-layer chromatographic technique has been developed and validated for the simultaneous quantitation of azelnidipine and chlorthalidone in bulk and synthetic mixtures. MATERIAL AND METHODS: The procedure was carried out using a precoated silica gel 60 F254 TLC plate with a mobile phase of chloroform, ethyl acetate, and methanol in the ratio of 6.5:3.5:0.6 (by volume). Thin-layer chromatographic densitometry at 240nm was used to quantify medicines chromatographically. RESULTS: Over concentration ranges of 250.0 to 1000.0ng/band for chlorthalidone and 160.0 to 640.0ng/band for azelnidipine, the high-performance thin-layer chromatography technique was quantitated. This technique produced a tight and well-resolved band at retention factors of 0.67±0.02 and 0.24±0.02 for azelnidipine and chlorthalidone, respectively. Data from a linear regression study calibrating this method revealed a strong linear correlation between the two approaches, with regression coefficients of r2>0.99 for both. According to The International Conference for Harmonization of Technical Requirements for Pharmaceuticals for Human Use requirements, the procedures were validated for precision, robustness, accuracy, and specificity. CONCLUSION: The developed method was also used to simultaneously estimate azelnidipine and chlorthalidone in a synthetic mixture. The results were found to be in exemplary % assay with label claims.


Assuntos
Clortalidona , Di-Hidropiridinas , Humanos , Reprodutibilidade dos Testes , Cromatografia em Camada Fina/métodos
2.
Curr Atheroscler Rep ; 25(1): 31-41, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36602752

RESUMO

PURPOSE OF REVIEW: Summarize selected late-breaking science on cardiovascular (CV) disease prevention presented at the 2022 scientific session of the American Heart Association (AHA). RECENT FINDINGS: The PROMINENT trial compared pemafibrate to a placebo in patients with type 2 diabetes mellitus (DM) and mild-to-moderate hypertriglyceridemia and high-density lipoprotein cholesterol (HDL-C)<40 mg/dL who were already on guideline-directed statin therapy. The RESPECT-EPA trial compared purified eicosapentaenoic acid (EPA) and statin therapy to statin therapy alone for secondary prevention of atherosclerotic CV disease (ASCVD). SPORT compared the efficacy of low-dose statin therapy with a placebo and six commonly used dietary supplements on lipid and inflammatory markers. Data from long-term follow-up of the FOURIER-OLE study was presented to evaluate the efficacy of very low low-density lipoprotein cholesterol (LDL-C) levels with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Patient-level meta-analyses evaluated the association of statin therapy with new-onset DM and worse glycemic control. PROMPT-LIPID evaluated if automated electronic alerts to physicians with guideline-based recommendations improved the management of hyperlipidemia in patients at very high risk. NOTIFY-1 trial evaluated if notifying physicians and patients about coronary artery calcium (CAC) scores in non-ECG gated computed tomography scans led to increased prescription of statin therapy for primary ASCVD prevention. The DCP trial compared hydrochlorothiazide and chlorthalidone for blood pressure control and CV outcomes in hypertension. The CRHCP study compared the effectiveness of a village doctor for hypertension management and CV outcomes in rural areas of China. The QUARTET USA trial compared the effectiveness and safety of 4 antihypertensive medications in ultra-low doses with angiotensin-receptor blocker monotherapy. The late-breaking science presented at the 2022 scientific session of the AHA paves the way for future pragmatic trials and provides meaningful information to guide management strategies in cardiovascular disease prevention.


Assuntos
Anticolesterolemiantes , Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Inibidores de Hidroximetilglutaril-CoA Redutases , Hiperlipidemias , Hipertensão , Estados Unidos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Pró-Proteína Convertase 9 , Anticolesterolemiantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , American Heart Association , Hiperlipidemias/tratamento farmacológico , HDL-Colesterol , Hipertensão/tratamento farmacológico
3.
Nephrol Dial Transplant ; 38(12): 2694-2703, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-37355779

RESUMO

Hypertension is very common and remains often poorly controlled in patients with chronic kidney disease (CKD). Accurate blood pressure (BP) measurement is the essential first step in the diagnosis and management of hypertension. Dietary sodium restriction is often overlooked, but can improve BP control, especially among patients treated with an agent to block the renin-angiotensin system. In the presence of very high albuminuria, international guidelines consistently and strongly recommend the use of an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker as the antihypertensive agent of first choice. Long-acting dihydropyridine calcium channel blockers and diuretics are reasonable second- and third-line therapeutic options. For patients with treatment-resistant hypertension, guidelines recommend the addition of spironolactone to the baseline antihypertensive regimen. However, the associated risk of hyperkalemia restricts the broad utilization of spironolactone in patients with moderate-to-advanced CKD. Evidence from the CLICK (Chlorthalidone in Chronic Kidney Disease) trial indicates that the thiazide-like diuretic chlorthalidone is effective and serves as an alternative therapeutic opportunity for patients with stage 4 CKD and uncontrolled hypertension, including those with treatment-resistant hypertension. Chlorthalidone can also mitigate the risk of hyperkalemia to enable the concomitant use of spironolactone, but this combination requires careful monitoring of BP and kidney function for the prevention of adverse events. Emerging agents, such as the non-steroidal mineralocorticoid receptor antagonist ocedurenone, dual endothelin receptor antagonist aprocitentan and the aldosterone synthase inhibitor baxdrostat offer novel targets and strategies to control BP better. Larger and longer term clinical trials are needed to demonstrate the safety and efficacy of these novel therapies in the future. In this article, we review the current standards of treatment and discuss novel developments in pathophysiology, diagnosis, outcome prediction and management of hypertension in patients with CKD.


Assuntos
Hiperpotassemia , Hipertensão , Insuficiência Renal Crônica , Humanos , Espironolactona/efeitos adversos , Hiperpotassemia/induzido quimicamente , Clortalidona/uso terapêutico , Hipertensão/tratamento farmacológico , Hipertensão/etiologia , Hipertensão/diagnóstico , Anti-Hipertensivos/efeitos adversos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Pressão Sanguínea
4.
Nutr Metab Cardiovasc Dis ; 32(11): 2451-2458, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36064690

RESUMO

AIMS: Chronic kidney disease is a common cardiovascular risk indicator and strongly associated with increased morbidity and mortality. The heart and kidneys are pathophysiologically closely connected, which becomes particularly obvious in patients with cardiorenal syndrome. This review summarizes clinically relevant studies on the cardio-renal interaction published in 2021 and 2022. DATA SYNTHESIS: Selected trials published in high-impact journals were chosen from the database Pubmed and included in this review. New evidence about the selective mineralocorticoid receptor antagonist finerenone and the renoprotective sodium-glucose co-transporter-2-inhibitors (SGLT2-Inhibitors) are discussed and we update on novel insights about the treatment of arterial hypertension in patients with severe chronic kidney disease with the thiazide-like diuretic chlorthalidone. Finally, data on infective endocarditis in patients on chronic hemodialysis and the treatment of secondary hyperparathyroidism with the calcimimetic drug etelcalcetide in patients with end stage kidney disease are critically reviewed. CONCLUSION: Several important studies investigating cardio-renal interactions were recently published may affect clinical practice. The graphical abstract (Fig. 1) depicts the most relevant clinical studies investigating cardio-renal interactions.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Renal Crônica , Inibidores do Transportador 2 de Sódio-Glicose , Clortalidona/uso terapêutico , Ensaios Clínicos como Assunto , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucose , Humanos , Rim , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Sódio , Transportador 2 de Glucose-Sódio , Tiazidas/uso terapêutico
5.
BMC Nephrol ; 23(1): 316, 2022 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-36127661

RESUMO

BACKGROUND: The co-administration of loop diuretics with thiazide diuretics is a therapeutic strategy in patients with hypertension and volume overload. The aim of this study was to assess the efficacy and safety of treatment with bumetanide plus chlorthalidone in patients with chronic kidney disease (CKD) stage 4-5 KDIGO. METHODS: A double-blind randomized study was conducted. Patients were randomized into two groups: bumetanide plus chlorthalidone group (intervention) and the bumetanide plus placebo group (control) to evaluate differences in TBW, ECW and ECW/TBW between baseline and 30 Days of follow-up. Volume overload was defined as 'bioelectrical impedance analysis as fluid volume above the 90th percentile of a presumed healthy reference population. The study's registration number was NCT03923933. RESULTS: Thirty-two patients with a mean age of 57.2 ± 9.34 years and a median estimated glomerular filtration rate (eGFR) of 16.7 ml/min/1.73 m2 (2.2-29) were included. There was decreased volume overload in the liters of total body water (TBW) on Day 7 (intervention: -2.5 vs. control: -0.59, p = 0.003) and Day 30 (intervention: -5.3 vs. control: -0.07, p = 0.016); and in liters of extracellular water (ECW) on Day 7 (intervention: -1.58 vs. control: -0.43, p < 0.001) and Day 30 (intervention: -3.05 vs. control: -0.15, p < 0.000). There was also a decrease in systolic blood pressure on Day 7 (intervention: -18 vs. control: -7.5, p = 0.073) and Day 30 (intervention: -26.1 vs. control: -10, p = 0.028) and in diastolic blood pressure on Day 7 (intervention: -8.5 vs. control: -2.25, p = 0.059) and Day 30 (intervention: -13.5 vs. control: -3.4, p = 0.018). CONCLUSION: In CKD stage 4-5 KDIGO without renal replacement therapy, bumetanide in combination with chlorthalidone is more effective in treating volume overload and hypertension than bumetanide with placebo.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Desequilíbrio Hidroeletrolítico , Idoso , Bumetanida/uso terapêutico , Clortalidona/uso terapêutico , Humanos , Hipertensão/tratamento farmacológico , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Terapia de Substituição Renal , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio e Potássio/uso terapêutico , Água
6.
Curr Cardiol Rep ; 24(12): 2131-2137, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36301404

RESUMO

PURPOSE OF REVIEW: Hypertension is often difficult to control in patients with CKD as manifested by suboptimal control rates in this population. Use of thiazides in CKD patients has been limited as these agents are thought to be ineffective in reducing blood pressure in people with advanced CKD. This review summarizes recent studies impacting indications and safety of use of thiazide in patients with CKD and discusses the mechanism of how thiazides reduce blood pressure. RECENT FINDINGS: Chlorthalidone reduces blood pressure compared to placebo in patients with advanced CKD, challenging the belief that thiazide diuretics lose efficacy at lower levels of GFR. Recent clinical trial data indicate that thiazides are effective in patients with advanced kidney disease for blood pressure lowering. However, monitoring of electrolytes and kidney function is important to ensure patient safety when prescribing these agents in patients with CKD.


Assuntos
Hipertensão , Insuficiência Renal Crônica , Humanos , Tiazidas/uso terapêutico , Anti-Hipertensivos/efeitos adversos , Hipertensão/tratamento farmacológico , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Diuréticos/uso terapêutico
7.
Kidney Int ; 99(5): 1118-1126, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33417997

RESUMO

To study human idiopathic hypercalciuria we developed an animal model, genetic hypercalciuric stone-forming rats, whose pathophysiology parallels that of human idiopathic hypercalciuria. Fed the oxalate precursor, hydroxyproline, every rat in this model develops calcium oxalate stones. Using this rat model, we tested whether chlorthalidone and potassium citrate combined would reduce calcium oxalate stone formation and improve bone quality more than either agent alone. These rats (113 generation) were fed a normal calcium and phosphorus diet with hydroxyproline and divided into four groups: diets plus potassium chloride as control, potassium citrate, chlorthalidone plus potassium chloride, or potassium citrate plus chlorthalidone. Urine was collected at six, 12, and 18 weeks and kidney stone formation and bone parameters were determined. Compared to potassium chloride, potassium citrate reduced urinary calcium, chlorthalidone reduced it further and potassium citrate plus chlorthalidone even further. Potassium citrate plus chlorthalidone decreased urine oxalate compared to all other groups. There were no significant differences in calcium oxalate supersaturation in any group. Neither potassium citrate nor chlorthalidone altered stone formation. However, potassium citrate plus chlorthalidone significantly reduced stone formation. Vertebral trabecular bone increased with chlorthalidone and potassium citrate plus chlorthalidone. Cortical bone area increased with chlorthalidone but not potassium citrate or potassium citrate plus chlorthalidone. Mechanical properties of trabecular bone improved with chlorthalidone, but not with potassium citrate plus chlorthalidone. Thus in genetic hypercalciuric stone-forming rats fed a diet resulting in calcium oxalate stone formation, potassium citrate plus chlorthalidone prevented stone formation better than either agent alone. Chlorthalidone alone improved bone quality, but adding potassium citrate provided no additional benefit.


Assuntos
Cálculos Renais , Citrato de Potássio , Animais , Cálcio , Oxalato de Cálcio , Clortalidona , Hipercalciúria , Cálculos Renais/genética , Cálculos Renais/prevenção & controle , Ratos
8.
Circ Res ; 124(7): 1061-1070, 2019 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-30920924

RESUMO

Resistant hypertension (RHTN) is defined as uncontrolled blood pressure despite the use of ≥3 antihypertensive agents of different classes, including a diuretic, usually thiazide-like, a long-acting calcium channel blocker, and a blocker of the renin- angiotensin system, either an ACE (angiotensin-converting enzyme) inhibitor or an ARB (angiotensin receptor blocker), at maximal or maximally tolerated doses. Antihypertensive medication nonadherence and the white coat effect, defined as elevated blood pressure when measured in clinic but controlled when measured outside of clinic, must be excluded to make the diagnosis. RHTN is a high-risk phenotype, leading to increased all-cause mortality and cardiovascular disease outcomes. Healthy lifestyle habits are associated with reduced cardiovascular risk in patients with RHTN. Aldosterone excess is common in patients with RHTN, and addition of spironolactone or amiloride to the standard 3-drug antihypertensive regimen is effective at getting the blood pressure to goal in most of these patients. Refractory hypertension is defined as uncontrolled blood pressure despite use of ≥5 antihypertensive agents of different classes, including a long-acting thiazide-like diuretic and an MR (mineralocorticoid receptor) antagonist, at maximal or maximally tolerated doses. Fluid retention, mediated largely by aldosterone excess, is the predominant mechanism underlying RHTN, while patients with refractory hypertension typically exhibit increased sympathetic nervous system activity.


Assuntos
Anti-Hipertensivos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Resistência a Medicamentos , Hiperaldosteronismo/tratamento farmacológico , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Aldosterona/metabolismo , Animais , Anti-Hipertensivos/efeitos adversos , Quimioterapia Combinada , Humanos , Hiperaldosteronismo/epidemiologia , Hiperaldosteronismo/metabolismo , Hiperaldosteronismo/fisiopatologia , Hipertensão/epidemiologia , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Antagonistas de Receptores de Mineralocorticoides/efeitos adversos , Fatores de Risco , Inibidores de Simportadores de Cloreto de Sódio/efeitos adversos , Sistema Nervoso Simpático/efeitos dos fármacos , Sistema Nervoso Simpático/fisiopatologia , Simpatolíticos/uso terapêutico , Resultado do Tratamento , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
9.
J Fluoresc ; 31(1): 97-106, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33089428

RESUMO

This study is the first to develop and optimize a method for the simultaneous determination of chlorthalidone (CLT) and telmisartan (TEL) in, human plasma samples as well as in their newly released pharmaceutical tablet form, (Telmikind-CT 40®). The method is based on measuring fluorescence intensity, employing synchronous fluorescence mode coupled to third-order derivative signal processing, 0.5% w/v cetyl trimethyl ammonium bromide was used as cationic surfactant to enhance the fluorescence signal intensity and improve method sensitivity. The third-order derivative synchronous spectra of CLT and TEL are well separated with two zero-crossing points which allowed for the determination of CLT and TEL at 362 nm and 351 nm, respectively. Different experimental parameters were carefully investigated and optimized, calibration curves were constructed over concentration ranges of 20-1200 ng.mL-1 and 5-800 ng.mL-1 for CLT and TEL respectively. The developed method is simple and rapid, analytical parameters were validated according to ICH guidelines and high sensitivity was achieved as represented by limits of detection (LOD) of 4.69 and 1.58 ng.mL-1 for CLT and TEL respectively.


Assuntos
Análise Química do Sangue/métodos , Clortalidona/sangue , Telmisartan/sangue , Combinação de Medicamentos , Humanos , Limite de Detecção , Espectrometria de Fluorescência
10.
Biomed Chromatogr ; 35(11): e5203, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34145610

RESUMO

An accurate and sensitive UPLC-MS/MS method was developed and validated for the simultaneous estimation of the newly developed combination of sacubitril and valsartan and the co-administered drugs nebivolol, chlorthalidone and esomeprazole in human plasma. Solid-phase extraction was conducted for the purification and extraction of the drugs from human plasma. Chromatographic separation was carried out on an Agilent SB-C18 (1.8 µm, 2.1 × 50 mm) column using losartan as internal standard. Isocratic elution was applied using acetonitrile-0.1% formic acid in water (85: 15, v/v) as mobile phase. Detection was carried out using a triple-quadrupole tandem mass spectrometer using multiple reaction monitoring, at positive mode at m/z 412.23 → 266.19 for sacubitril, m/z 436.29 → 235.19 for valsartan, m/z 405.8 → 150.98 for nebivolol, m/z 346.09 → 198 for esomeprazole and a selected combination of two fragments m/z 423.19 → 207.14 and 423.19 → 192.2 for losartan (internal standard), and in negative ionization mode at m/z 337.02 → 190.12 for chlorthalidone. The method was linear over the concentration ranges 30-2,000 ng/ml for sacubitril, 70-2,000 ng/ml for valsartan, esomeprazole and chlorthalidone and 70-5,000 pg/ml for nebivolol. The developed method is sensitive and selective and could be applied for dose adjustment, bioavailability and drug-drug interaction studies.


Assuntos
Aminobutiratos/sangue , Compostos de Bifenilo/sangue , Cromatografia Líquida de Alta Pressão/métodos , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Valsartana/sangue , Aminobutiratos/administração & dosagem , Aminobutiratos/isolamento & purificação , Compostos de Bifenilo/administração & dosagem , Compostos de Bifenilo/isolamento & purificação , Clortalidona/administração & dosagem , Clortalidona/sangue , Clortalidona/isolamento & purificação , Combinação de Medicamentos , Estabilidade de Medicamentos , Esomeprazol/administração & dosagem , Esomeprazol/sangue , Esomeprazol/isolamento & purificação , Humanos , Limite de Detecção , Modelos Lineares , Nebivolol/administração & dosagem , Nebivolol/sangue , Nebivolol/isolamento & purificação , Reprodutibilidade dos Testes , Valsartana/administração & dosagem , Valsartana/isolamento & purificação
11.
Am J Kidney Dis ; 75(2): 256-264, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31606239

RESUMO

Hyponatremia can complicate thiazide use in a minority of susceptible individuals and can result in significant morbidity and even mortality. Risk factors for thiazide-associated hyponatremia include age, female sex, and possibly low body mass. A genetic susceptibility has recently been uncovered. Although frequently developing early after thiazide treatment initiation, many cases of hyponatremia present after months or years of use. Many cases are asymptomatic or have mild symptoms, but seizures and/or coma may develop, especially in those with acute onset. The pathophysiology is incompletely understood and includes some combination of excessive fluid intake, cation (sodium and potassium) depletion, osmotic inactivation of sodium, and reduced ability to excrete free water. Reduced distal delivery of filtrate, reduced solute load (urea), direct inhibition of the sodium-chloride cotransporter, and increased collecting duct permeability to water mediated by some combination of antidiuretic hormone, prostaglandins, and thiazides themselves may contribute to this diluting defect. The predominant pathophysiologic mechanism(s) varies from patient to patient. The cornerstone of therapy is cessation of thiazide use, cation repletion, and oral fluid restriction. If severely symptomatic, 3% saline solution may be indicated. Overly rapid correction of chronic hyponatremia must be avoided in all cases.


Assuntos
Hiponatremia/induzido quimicamente , Sódio/sangue , Tiazidas/efeitos adversos , Biomarcadores/sangue , Humanos , Hipertensão/tratamento farmacológico , Hiponatremia/sangue , Hiponatremia/diagnóstico
13.
Rev Med Liege ; 73(4): 176-182, 2018 Apr.
Artigo em Francês | MEDLINE | ID: mdl-29676870

RESUMO

The use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. However, these metabolic disturbances are less marked with low-dose of hydrochlorothiazide and with thiazide-like diuretics such as chlorthalidone and indapamide. In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazide(-like) diuretics resulted in a significant reduction in cardiovascular events, all-cause mortality and hospitalization for heart failure compared to placebo. Furthermore, they were shown to be non-inferior to other antihypertensive agents, including blockers of the renin-angiotensin system in diabetic patients without albuminuria. Benefits attributed to thiazide(-like) diuretics (especially at low dose) in terms of cardiovascular protection outweigh the risk of worsening glucose control and inducing other metabolic disorders in patients with type 2 diabetes. Thus low dose thiazide(-like) drugs still play a major role in the treatment of hypertension in patients with type 2 diabetes.


L'utilisation des diurétiques de type thiazide a été controversée en raison des divers troubles métaboliques qu'ils sont susceptibles d'induire comme manifestations indésirables, notamment les effets diabétogènes. Ces manifestations sont, cependant, moins marquées pour de faibles doses d'hydrochlorothiazide et pour les thiazidiques apparentés comme la chlorthalidone et l'indapamide. Dans des analyses post hoc de sous-groupes de patients avec un diabète de type 2 et une hypertension artérielle, les diurétiques thiazidiques ont montré une réduction significative des événements cardiovasculaires, de la mortalité toutes causes et des hospitalisations pour insuffisance cardiaque par rapport à un placebo. De plus, ils se sont révélés non inférieurs à d'autres antihypertenseurs, en ce compris les inhibiteurs du système rénine-angiotensine chez les patients sans albuminurie. Les bénéfices attribués aux diurétiques thiazidiques, surtout à faible posologie, en termes de protection cardiovasculaire chez le patient diabétique de type 2 hypertendu dépassent largement les éventuels effets secondaires de détérioration de certains paramètres métaboliques. Ainsi, les diurétiques thiazidiques et apparentés, à faible posologie, gardent une place de choix dans le traitement de l'hypertension artérielle chez les patients avec diabète de type 2.


Assuntos
Diabetes Mellitus Tipo 2/complicações , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Tiazidas/uso terapêutico , Humanos , Hipertensão/complicações
14.
Am J Kidney Dis ; 69(6): 796-804, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28259499

RESUMO

BACKGROUND: Chlorthalidone is a very effective antihypertensive drug, but it has not been studied prospectively in kidney transplant recipients with hypertension. Recent data indicate that calcineurin inhibitors activate the thiazide-sensitive sodium chloride cotransporter, providing further rationale to test thiazides in this population. STUDY DESIGN: Randomized noninferiority crossover trial (noninferiority margin, -2.8mmHg). SETTING & PARTICIPANTS: Hypertensive kidney transplant recipients using tacrolimus (median duration, 2.4 years after transplantation; mean estimated glomerular filtration rate, 63±27 [SD] mL/min/1.73m2; mean systolic blood pressure [SBP], 151±12mmHg). INTERVENTION: Amlodipine (5-10mg) and chlorthalidone (12.5-25mg) for 8 weeks (separated by 2-week washout). OUTCOMES: Average daytime (9 am to 9 pm) ambulatory SBP. MEASUREMENTS: Blood pressure and laboratory parameters. RESULTS: 88 patients underwent ambulatory blood pressure monitoring, of whom 49 (56%) with average daytime SBP>140mmHg were enrolled. 41 patients completed the study. Amlodipine and chlorthalidone both reduced ambulatory SBP after 8 weeks (mean changes of 150±12 to 137±12 [SD] vs 151±12 to 141±13mmHg; effect size, -4.2 [95% CI, -7.3 to 1.1] mmHg). Despite these similar blood pressure responses, chlorthalidone reduced proteinuria by 30% (effect size, -65 [95% CI, -108 to -35] mg/g) and also reduced physician-assessed peripheral edema (22% to 10%; P<0.05 for both). In contrast, chlorthalidone temporarily reduced kidney function and increased both serum uric acid and glycated hemoglobin levels. LIMITATIONS: Open-label design, short follow-up, per-protocol analysis. CONCLUSIONS: Chlorthalidone is an antihypertensive drug equally effective as amlodipine after kidney transplantation.


Assuntos
Anlodipino/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Clortalidona/uso terapêutico , Hipertensão/tratamento farmacológico , Falência Renal Crônica/cirurgia , Transplante de Rim , Idoso , Monitorização Ambulatorial da Pressão Arterial , Estudos Cross-Over , Edema , Feminino , Taxa de Filtração Glomerular , Rejeição de Enxerto/prevenção & controle , Humanos , Hipertensão/complicações , Imunossupressores/uso terapêutico , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Proteinúria , Tacrolimo/uso terapêutico , Resultado do Tratamento
15.
Biomed Chromatogr ; 31(9)2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28178366

RESUMO

A novel, precise, sensitive and accurate ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of a novel drug combination, candesartan (CAN) and chlorthalidone (CHL), in human plasma. Chromatographic separation was achieved on Waters Acquity UPLC BEH C18 (50 × 2.1 mm, 1.7 µm). Mobile phase consisting of 1 mm ammonium acetate in water-acetonitrile (20:80 v/v) was used. The total chromatographic runtime was 1.9 min with retention times for CAN and CHL at 0.7 and 1.1 min respectively. Ionization and detection of analytes and internal standards was performed on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring and negative ionization mode. Quantitation was done to monitor protonated precursor → product ion transition of m/z 439.2 → 309.0 for CAN, 337.0 → 189.8 for CHL and 443.2 → 312.1 for candesartan D4 and 341.0 → 189.8 for chlorthalidone D4. The method was validated over a wide dynamic concentration range of 2.0-540.0 ng/mL for candesartan and 1.0-180.0 ng/mL for chlorthalidone. The validated method was successfully applied for the assay of CAN and CHL in healthy volunteers.


Assuntos
Benzimidazóis/sangue , Clortalidona/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Tetrazóis/sangue , Adolescente , Adulto , Benzimidazóis/química , Benzimidazóis/farmacocinética , Compostos de Bifenilo , Clortalidona/química , Clortalidona/farmacocinética , Combinação de Medicamentos , Estabilidade de Medicamentos , Humanos , Limite de Detecção , Modelos Lineares , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tetrazóis/química , Tetrazóis/farmacocinética , Adulto Jovem
16.
Kardiologiia ; 57(11): 12-18, 2017 Nov.
Artigo em Russo | MEDLINE | ID: mdl-29276912

RESUMO

AIM: To study effects of a fixed azilsartan medoxomil/chlorthalidone combination (Edarbi Clo) on clinical, ambulatory and central blood pressure (BP) in patients with uncontrolled arterial hypertension (AH)). MATERIALS AND METHODS: Patients (n=25) with uncontrolled AH were given fixed azilsartan medoxomil/chlorthalidone combination (40 / 12.5 mg / day) for 4 weeks. After 4 weeks, in patients who did not achieve target BP levels the dose was increased up to 40 / 25 mg / day. Duration of the study was 12 weeks. RESULTS: After 12 weeks of treatment 88 % of patients achieved target clinical BP (.


Assuntos
Anti-Hipertensivos/uso terapêutico , Benzimidazóis/uso terapêutico , Clortalidona/uso terapêutico , Hipertensão , Oxidiazóis/uso terapêutico , Pressão Sanguínea , Quimioterapia Combinada , Humanos , Hipertensão/tratamento farmacológico , Tetrazóis , Resultado do Tratamento
17.
Pediatr Nephrol ; 31(12): 2223-2233, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-26983630

RESUMO

Diuretics have long been used for the treatment of hypertension. Thiazide diuretics are the most commonly prescribed diuretics for hypertension, but other classes of diuretics may be useful in alternative circumstances. Although diuretics are no longer considered the preferred agent for treatment of hypertension in adults and children, they remain acceptable first-line options. Diuretics effectively decrease blood pressure in hypertensive patients, and in adults with hypertension reduce the risk of adverse cardiovascular outcomes. Because of varied pharmacokinetic and pharmacodynamic differences, chlorthalidone may be the preferred thiazide diuretic in the treatment of primary hypertension. Other types of diuretics (e.g., loop, potassium sparing) may be useful for the treatment of hypertension related to chronic kidney disease (CKD) and other varied conditions. Common side effects of thiazides are mostly dose-related and involve electrolyte and metabolic abnormalities.


Assuntos
Anti-Hipertensivos/uso terapêutico , Diuréticos/uso terapêutico , Hipertensão/tratamento farmacológico , Adolescente , Anti-Hipertensivos/efeitos adversos , Anti-Hipertensivos/farmacologia , Criança , Pré-Escolar , Diuréticos/efeitos adversos , Diuréticos/farmacologia , Guias como Assunto , Humanos , Hipertensão/fisiopatologia , Lactente , Recém-Nascido , Tiazidas/uso terapêutico
18.
Clin Exp Hypertens ; 38(2): 180-8, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26817604

RESUMO

This 56-week phase 3, open-label, treat-to-target study, involving 2 consecutive, non-randomized cohorts, evaluated the safety and tolerability of azilsartan medoxomil (AZL-M) in essential hypertension (mean baseline blood pressure [BP] 152/100 mmHg). All subjects (n = 669) initiated AZL-M 40 mg QD, force-titrated to 80 mg QD at week 4, if tolerated. From week 8, subjects could receive additional medications, starting with chlorthalidone (CLD) 25 mg QD (Cohort 1) or hydrochlorothiazide (HCTZ) 12.5-25 mg QD (Cohort 2), if required, to reach BP targets. Adverse events (AEs) were reported in 75.9% of subjects overall in the two cohorts (73.8% Cohort 1, 78.5% Cohort 2). The most common AEs were dizziness (14.3%), headache (9.9%) and fatigue (7.2%). Transient serum creatinine elevations were more frequent with add-on CLD. Clinic systolic/diastolic BP (observed cases at week 56) decreased by 25.2/18.4 mmHg (Cohort 1) and 24.2/17.9 mmHg (Cohort 2). These results demonstrate that AZL-M is well tolerated over the long term and provides stable BP improvements when used in a treat-to-target BP approach with thiazide-type diuretics.


Assuntos
Benzimidazóis/uso terapêutico , Tontura/induzido quimicamente , Fadiga/induzido quimicamente , Cefaleia/induzido quimicamente , Hipertensão/tratamento farmacológico , Oxidiazóis/uso terapêutico , Adulto , Idoso , Clortalidona/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Hipertensão Essencial , Feminino , Humanos , Hidroclorotiazida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Inibidores de Simportadores de Cloreto de Sódio/uso terapêutico , Resultado do Tratamento
19.
Biomed Chromatogr ; 30(2): 208-16, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26096961

RESUMO

A simple, sensitive and reproducible ultra-performance liquid chromatography-tandem mass spectrometry method has been developed for the simultaneous determination of atenolol, a ß-adrenergic receptor-blocker and chlorthalidone, a monosulfonamyl diuretic in human plasma, using atenolol-d7 and chlorthalidone-d4 as the internal standards (ISs). Following solid-phase extraction on Phenomenex Strata-X cartridges using 100 µL human plasma sample, the analytes and ISs were separated on an Acquity UPLC BEH C18 (50 mm × 2.1 mm, 1.7 µm) column using a mobile phase consisting of 0.1% formic acid-acetonitrile (25:75, v/v). A tandem mass spectrometer equipped with electrospray ionization was used as a detector in the positive ionization mode for both analytes. The linear concentration range was established as 0.50-500 ng/mL for atenolol and 0.25-150 ng/mL for chlorthalidone. Extraction recoveries were within 95-103% and ion suppression/enhancement, expressed as IS-normalized matrix factors, ranged from 0.95 to 1.06 for both the analytes. Intra-batch and inter-batch precision (CV) and accuracy values were 2.37-5.91 and 96.1-103.2%, respectively. Stability of analytes in plasma was evaluated under different conditions, such as bench-top, freeze-thaw, dry and wet extract and long-term. The developed method was superior to the existing methods for the simultaneous determination of atenolol and chlorthalidone in human plasma with respect to the sensitivity, chromatographic analysis time and plasma volume for processing. Further, it was successfully applied to support a bioequivalence study of 50 mg atenolol + 12.5 mg chlorthalidone in 28 healthy Indian subjects.


Assuntos
Atenolol/sangue , Clortalidona/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas em Tandem/métodos , Atenolol/química , Atenolol/farmacocinética , Clortalidona/química , Clortalidona/farmacocinética , Estabilidade de Medicamentos , Humanos , Modelos Lineares , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
20.
Sleep Med ; 119: 417-423, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38781664

RESUMO

BACKGROUND: Obstructive sleep apnea (OSA) and hypertension are common conditions that may be linked through sympathetic activation and water retention. We hypothesized that diuretics, which reduce the body water content, may be more effective than amlodipine, a blood pressure (BP)-lowering agent implicated with edema, in controlling OSA in patients with hypertension. We also aimed to compare the effects of these treatments on ambulatory blood pressure monitoring (ABPM). METHODS: In a randomized, double-blind clinical trial, we compared the effects of chlorthalidone/amiloride 25/5 mg with amlodipine 10 mg on OSA measured by portable sleep monitor and BP measured by ABPM. The study included participants older than 40 who had moderate OSA (10-40 apneas/hour of sleep) and BP within the systolic range of 140-159 mmHg or diastolic range of 90-99 mmHg. RESULTS: The individuals in the experimental groups were comparable in age, gender, and other relevant characteristics. Neither the combination of diuretics nor amlodipine alone reduced the AHI after 8 weeks of treatment (AHI 26.3 with diuretics and 25.0 with amlodipine. P = 0.713). Both treatments significantly lowered office, 24-h, and nighttime ABP, but the two groups had no significant difference. CONCLUSION: Chlorthalidone associated with amiloride and amlodipine are ineffective in decreasing the frequency of sleep apnea episodes in patients with moderate OSA and hypertension. Both treatments have comparable effects in lowering both office and ambulatory blood pressure. The notion that treatments could offer benefits for both OSA and hypertension remains to be demonstrated. TRIAL REGISTRATION CLINICALTRIALS. GOV IDENTIFIER: NCT01896661.


Assuntos
Amilorida , Anlodipino , Anti-Hipertensivos , Monitorização Ambulatorial da Pressão Arterial , Clortalidona , Hipertensão , Apneia Obstrutiva do Sono , Humanos , Masculino , Feminino , Método Duplo-Cego , Hipertensão/tratamento farmacológico , Hipertensão/complicações , Pessoa de Meia-Idade , Anti-Hipertensivos/uso terapêutico , Clortalidona/uso terapêutico , Anlodipino/uso terapêutico , Apneia Obstrutiva do Sono/tratamento farmacológico , Apneia Obstrutiva do Sono/complicações , Amilorida/uso terapêutico , Diuréticos/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Polissonografia/efeitos dos fármacos , Idoso
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