Avaliação da qualidade de medicamentos contendo clortalidona / Quality Assessment of medication containing chlorthalidone

Os diuréticos são a classe de fármacos mais utilizados no tratamento da hipertensão devido a sua eficácia terapêutica e ao baixo custo. Isto faz com que uma grande variedade de medicamentos esteja disponível no comercio e atrelado a este fator muitas empresas tem seus lotes de medicamentos suspensos devido a desvios de qualidade e das modificações realizadas nas formulações após o seu registro. A clortalidona é um diurético tiazídico indicada para o tratamento de hipertensão arterial leve ou moderada e com normalidade das funções cardíacas e renal. Este trabalho teve como objetivo verificar a qualidade de comprimidos de clortalidona comercializados no município de Sinop/ MT. O controle de qualidade foi realizado como estabelecido na Farmacopeia Brasileira quinta edição (ensaios de identificação, pureza, doseamento, ensaios referentes a forma farmacêutica de comprimidos e perfil de dissolução), de cinco produtos contendo clortalidona 25 mg sendo um produto de medicamento referência, dois de medicamentos genéricos e dois de medicamentos similares. Verificou-se que todos os produtos foram aprovados, cumprindo com todos os requisitos exigidos nos ensaios de qualidade e que estudos referentes ao perfil de dissolução nos lotes de produção de medicamentos são importantes para prever a absorção adequada do princípio ativo

Diuretics are the most used class of drugs that are used to treat hypertension because of their therapeutic efficiency and low cost. This makes a wide variety of medicines commercially available and, linked to this factor, many companies have their batches of medicines suspended due to deviations of quality and modifications made in the formulas after their registration. Chlorthalidone, is a thiazide diuretic drug indicated for treatment of hypertension of patients with mild or moderate hypertension, and with normal cardiac and renal function. This work aimed to assess and compare the quality of medicines containing chlorthalidone commercialized in Sinop-MT. The quality control was performed as established in the fifth edition of the Brazilian Pharmacopoeia (identification, purity and dosage assays, tests referring to the pharmaceutical form of the tablets and their dissolution profile). Among five products containing 25 mg of chlortalidone, one was a reference drug product, two were generic and two were similar drugs. It was found that all products were approved, meeting all the requirements required in the quality tests, and that studies concerning the dissolution profile in batches of drug production are important to predict adequate absorption of the active principle

Serious adverse events during clinical trial for pharmacokinetic interaction between telmisartan and chlorthalidone in healthy Korean subjects: A case report

Telmisartan is an angiotensin II receptor antagonist and chlorthalidone is a thiazide-like diuretics. In this study, we report serious adverse events (SAEs) during clinical trial for pharmacokinetic interaction between telmisartan and chlorthalidone in healthy Korean subjects. Two separate, randomized, multiple-dose, two-period, one-sequence studies were conducted at Kyungpook National University Hospital. In part A, 43 volunteers received telmisartan for 7 days, and then chlorthalidone for 14 days (days 8-21). Telmisartan was co-administered during day 15-21 to evaluate the effects of chlorthalidone on the pharmacokinetics of telmisartan at steady state. A healthy 36-year-old male in part A was referred to the emergency room due to severe nausea and vomiting developed about 3 h after administration of chlorthalidone on day 9. Hypokalemia and QT prolongation were observed during his initial laboratory examination and electrocardiogram (ECG) monitoring in the emergency unit. Nausea and vomiting improved after conservative management with hospitalization for 9 days. We consider that the episodes of excessive nausea and vomiting resulted in hypokalemic state which was potentiated by chlorthalidone. And the hypokalemic state caused the lengthening of the QT interval on ECG.

Existem diferenças entre os diversos diuréticos? / Are there differences among the several diuretics?

Esse artigo faz uma breve revisão sobre as principais classes dos diuréticos e suas indicações. Aborda com detalhes os diuréticos tiazídicos, principal classe utilizada no tratamento da hipertensão arterial, abordando as diferenças entre eles em relação à estrutura, farmacodinâmica e farmacocinética. Posteriormente, avalia criteriosamente os principais trials clínicos, discutindo os efeitos dos tiazídicos na redução da pressão arterial, nos eventos cardiovasculares, incluindo acidente vascular encefálico, insuficiência cardíaca congestiva e doença arterial coronariana; além de abordar os efeitos sobre a glicemia. Finalmente, compara os principais diuréticos tiazídicos em relação à potência e efetividade na redução da pressão arterial.

This article is a brief review on the main classes of diuretics and indications. It discusses in detail the thiazide diuretics, the principal class used in the treatment of hypertension, addressing the differences between them in relation to structure, pharmacokinetics and pharmacodynamics. Afterwards, carefully assesses the key clinical trials, discussing the effects of thiazides in reducing blood pressure, cardiovascular events, including stroke, heart failure and coronary artery disease; in addition to addressing the effects on blood glucose. Finally, it compares the main thiazide diuretics in relation to the potency and effectiveness in lowering blood pressure.

Avaliação comparativa em longo prazo da eficácia, tolerabilidade e efeitos metabólicos de combinações de atenolol com anlodipino ou clortalidona no tratamento da hipertensão arterial ? subanálise do estudo ATENAS / Comparative evaluation in the long range of the efficacy, tolerability and metabolic effects of combinations of atenolol with amlodipine or chlorthalidone in the treatment of hypertension ? sub-analysis of ATENAS study

Em estudo multicêntrico, aberto, randomizado e comparativo (estudo ATENAS) foi avaliado no período de extensão (da 12ª a 48ª semanas) a eficácia anti-hipertensiva, a tolerabilidade, a segurança e o impacto sobre a sensibilidade à insulina da combinação galênica única de atenolol 25 a 50 mg e anlodipino 5 mg comparada à combinação livre de atenolol 50 a 100 mg com clortalidona 12,5 a 25 mg em hipertensos primários estágios 1 e 2. Observamos que a combinação de atenolol e anlodipino é segura, bem tolerada e proporciona em longo prazo maiores reduções da pressão arterial que o tratamento com a combinação de atenolol e clortalidona. A maior redução da pressão arterial permitiu que maior percentual de pacientes tivesse a pressão arterial controlada tanto para o critério de PAD < 90 mmHg (87,7% a 95,9%) quanto para PAD £ 85 mmHg (69,9% a 90,2%). Menor incidência de bradicardia, cefaleia, alterações lipídicas e glicêmicas foram relatadas nos pacientes tratados com a combinação de atenolol e anlodipino. A incidência de edema de membros inferiores neste grupo (6,1%) foi menor que a relatada na literatura para mesma dose de anlodipino em monoterapia. O tratamento com atenolol combinado com o anlodipino não alterou a sensibilidade à insulina. Concluindo, a combinação em formulação galênica única de atenolol e anlodipino em doses baixas a medianas constitui boa opção terapêutica da hipertensão arterial primária estágio 1 e 2 em longo prazo, é superior à combinação de atenolol e clortalidona, sendo opção preferencial para pacientes hipertensos com doença arterial coronariana.

Direct Vascular Actions of Indapamide in Aorta from Renal Hypertensive Rats / 대한신장학회지

PURPOSE: Thiazide diuretics exert their hypotensive efficacy through a combined vasodilator and diuretic effect. The present study was conducted to assess the inhibitory effect of thiazide diuretic, hydrochlorothiazide, and the thiazide-like diuretics, indapamide and chlorthalidone on contractile responses to norepinephrine and arginine vasopressin in aortic rings from 2K1C renal hypertensive and sham-clipped normotensive rats. METHODS: 2K1C hypertension was made by clipping the left renal artery and age-matched control rats received a sham treatment. Changes in the tension of aortic ring preparations were measured isometrically. RESULTS: Indapamide inhibits the contractile responses to norepinephrine and vasopressin in aortic rings from 2K1C rats, while it did not modify in control rats. The inhibitory effect of indapamide was abolished by endothelium removal. Hydrochlorothiazide or chlorthalidone did not affect the vasoconstriction induced by norepinephrine and vasopressin either in sham or in 2K1C hypertensive rats. CONCLUSION: These results suggest that indapamide inhibits the contractile responses to norepinephrine and vasopressin via an endothelium-dependent mechanism in 2K1C renal hypertension.

Simple and rapid HPLC method for simultaneous determination of atenolol and chlorthalidone in spiked human plasma

A simple, sensitive and rapid chromatographic method was developed and validated for the simultaneous quantification of atenolol and chlorthalidone in human plasma using hydrochlorothiazide as internal standard [IS]. The method utilized proteins precipitation with acetonitril as the only sample preparation involved prior to reverse phase-HPLC. The analytes were chromatographed on Shim-pack cyanopropyl column with isocratic elution with 10 mM KH2PO4 [pH 6.0] - methanol [70:30, v/v] at ambient temperature with flow rate of 1 mL min-1 and UV detection at 225 nm. The chromatographic run time was less than 10 min for the mixture. The calibration curves were linear over the range of 0.1-10 mg mL-1. The method was validated in terms of accuracy, precision, absolute recovery, freeze-thaw stability, bench-top stability and re-injection reproducibility. The within- and between-day accuracy and precision were found to be within acceptable limits <15%. The analytes were stable after three freeze-thaw cycles [deviation <15%]. The proposed method was specific for the simultaneous determination of atenolol and chlorthalidone in human plasma where there was no interference from endogenous biological substances

Improvement of diastolic function after regression of left ventricular hypertrophy / Mejora de la función diastólica tras regresión de la hipertrofia ventricular izquierda

OBJECTIVE: To evaluate the diastolic function after regression of left ventricular hypertrophy, in mild to moderate hypertension treated with angiotensin converting enzyme(ACE) inhibitor and, if necessary, with a diuretic. METHODS: Ninety-eight hypertensive patients with left ventricular hypertrophy (LVH) and abnormal left ventricle diastolic function indexes received captopril (Capotena) 50 to 200 mg/day plus chlortalidone during 12 months to reach blood pressure control, defined as a diastolic blood pressure < or =90 and systolic blood pressure < or =140 mm Hg. Left ventricular (LV) mass index was calculated by M mode and two-dimensional echocardiography, and left ventricular diastolic function was assessed by transmitral pulsed Doppler ultrasound every 3 months. RESULTS: Sixty-three patients were women and 35 were men, mean age was 53.4 +/- 8.4 years (range 34-70). Thirty-six patients had mild (36.7%) and 62 (63.3%) moderate hypertension. Treatment reduced significantly both systolic pressure from 165 +/- 13 to 137 +/- 12.9 mm Hg (p<0.05) and diastolic pressure from 99 +/- 8.6 to 86 +/- 6.37 mm Hg (p<0.05). LV mass index decreased from 155.4 +/- 32.9 to 121.7 +/- 29.14 g/m2 (p<0.05). Late diastolic filling velocity (A wave) and the ratio of E/A waves improved (p<0.05), but early diastolic filling velocity (E wave) and isovolumetric relaxation time did not change with treatment. CONCLUSIONS: Some indexes of diastolic function improved after regression of left ventricular hypertrophy and good blood pressure control with captopril and chlortalidone.

Serum uric acid prevalence and changes post various antihypertensive agents in patients with essential hypertension / 中华心血管病杂志

<p><b>OBJECTIVE</b>To survey the prevalence of hyperuricacidemia and serum uric acid (SUA) changes and electrolyte changes after 6 weeks antihypertensive treatment with thiazide diuretics, losartan or losartan+hydrochlorothiazide (Hyzaar) in patients with essential hypertension (EH).</p><p><b>METHODS</b>A total of 1080 consecutive EH patients [662 males, mean age (60.9 +/- 12.3) years] who seeked for medical consultation in study hospitals in Fuzhou city during October 2004 and October 2006 were included in this study. The blood pressure before and after antihypertensive treatments were obtained in 1000 patients, and the renal function and electrolyte before and after antihypertensive treatments were obtained in 600 patients. Patients with SBP > 140 and/or DBP > 90 mm Hg 2 weeks after initial antihypertensive agents were cotreated with felodipine, patients with SBP > 140 and/or DBP > 90 mm Hg 4 weeks after initial antihypertensive agents were cotreated with beta and/or alpha blockers.</p><p><b>RESULTS</b>The prevalence of hyperuricacidemia in EH patients was 25.83% (279/1080). Body mass index (BMI) and creatinine were significantly higher while creatinine clearance rate (Ccr) calculated by Cockcroft-Gault equation was significantly lower in EH patients with hyperuricacidemia than EH patients without hyperuricacidemia (all P < 0.05). Similar antihypertensive effects were observed in EH patients treated with thiazide diuretics (n = 200), losartan (n = 324) or losartan + hydrochlorothiazide (Hyzaar, n = 476) and SBP was lower than 140 mm Hg in 69.40% and DBP was less than 90 mmHg in 85.30% EH patients 6 weeks after antihypertensive treatments. SUA was significantly increased (43.81 micromol/L +/- 71.79 micromol/L) low dose diuretics group (P < 0.01 vs. pretreatment), significantly reduced (44.96 micromol/L +/- 90.63 micromol/L) in losartan group (P < 0.0001 vs. pretreatment) and remained unchanged in Hyzaar group (7.46 +/- 84.72 micromol/L, P > 0.05 vs. pretreatment). Serum potassium was significantly decreased (0.30 +/- 0.44 mmol/L) in diuretic group (P < 0.01 vs. pretreatment) and remained unchanged in losartan group (+0.06 +/- 0.43 mmol/L) and Hyzaar group (-0.04 +/- 0.44 mmol/L, all P > 0.05 vs. pretreatment).</p><p><b>CONCLUSION</b>Hyperuricacidemia prevalence was 25.83% and associated with higher BMI and abnormal renal function in examined EH patients. The low dose thiazide diuretics could further aggravate hyperuricacidemia and induce hypopotassemia while losartan could reduce hyperuricacidemia in EH patients.</p>

Drug-induced acute myopia following chlorthalidone treatment.

We report a case of sudden loss of vision due to the development of acute myopia after the intake of chlorthalidone used for treating systemic hypertension. Clinically this was associated with ciliary spasm, shallow peripheral choroidal effusion and retinal striae at the macula with increase in macular thickness seen on optical coherence tomography. All these findings were reversed completely once the drug was discontinued. Development of acute myopia should be kept in mind as an adverse effect of a commonly used antihypertensive drug, namely chlorthalidone.

Estudo multicêntrico da eficácia, tolerabilidade e efeito sobre a calemia da combinação fixa de clortalidona e amilorida no tratamento da hipertensão arterial primária / Multicenter trial on efficacy, tolerability and effect upon kalemia of the fixed combination of chlorthalidone and amiloride in the treatment of primary hypertension n

Em estudo multicêntrico e randomizado, avaliamos a eficácia anti-hipertensiva, tolerabilidade e efeito sobre a calemia da combinação fixa de clortalidona e amilorida comparada à clortalidona isolada no tratamento de pacientes com hipertensão arterial primária estágios 1 e 2. Após três semanas de descontinuidade da medicação anti-hipertensiva prévia, 201 pacientes de ambos os sexos foram randomizados para tratamento com a combinação fixa na dose de 25/5 mg (102 pacientes) ou com a clortalidona isolada na dose de 25 mg (99 pacientes), durante 12 semanas consecutivas. Resultados: observamos que a combinação fixa apresentou alta eficácia anti-hipertensiva (ΔPA = 21,7/12,6 mmHg, percentual de respondedores igual a 80,4 e 67,4

Estudo aberto, randomizado de avaliação de eficácia e tolerabilidade da combinação fixa de anlodipino e enalapril em uma única formulação galênica comparado a clortalidona e atenolol, no tratamento da hipertensão arterial primária estágios 1 e 2 - subestudo do estudo EMBATES / An open-label, randomized, comparative study of the efficacy and tolerability of the fixed combination on amlodipine and enalapril versus chlortalidone and atenolol in the treatmente of stages 1 and 2 essential hypertension - sub-study of EMBATES trial

O objetivo deste estudo aberto, comparativo, multicêntrico, de 20 semanas foi avaliar a eficácia e tolerabilidade da combinação fixa de anlodipino e enalapril em uma única formulação galênica, uma vez ao dia, comparada ao atenolol e clortalidona, em pacientes com hipertensão arterial primária estágios 1 e 2. A eficácia anti-hipertensiva da combinação fixa foi avaliada considerando-se dois critérios diferentes de normalidade da pressão arterial: PAD aproximadamente 90 mmHg (critério clássico) e PAD aproximadamente 85 mmHg (novo critério).Métodos: Trinta e seis pacientes foram avaliados no grupo anlodipino + enalapril (Grupo AE), 18 pacientes no grupo clortalidàna (Grupo C) e 19 no grupo atenolol (Grupo A). Após quatro semanas de washout, os pacientes receberam a combinação fixa de AE, A ou C em doses iniciais de 2,5 e 10 mg, 50 mg e 12,5 mg, respectivamente, administrados em uma única tomada diária. Pacientes com níveis de pressão arterial diastólica igualou inferior a 90 mmHg eram mantidos nesta dose ao longo do estudo ou tinham as doses dos medicamentos do estudo aumentadas para 5 e 10 mg ao dia ou 5 e 20 mg ao dia, 100 mg ao dia, e 25 mg ao dia, a cada quatro semanas, quando fosse detectado valor para a pressão arterial diastólica acima de 90 mmHg. A duração total do tratamento ativo foi de 16 semanas. Resultados: 80,6 por cento dos pacientes no grupo AE, 52,6 por cento no grupo A e 72,2 por cento no grupo C atingiram a meta de normalidade da pressão arterial pelo critério clássico (PAD aproximadamente 90mmHg) e 44,5 por cento, 26,3 por cento e 38,9 por cento, respectivamente, AE, A e C pelo novo critério (PAD aproximadamente 85mmHg). As reduções pressóricas foram de 23,2 x 15,2 mmHg no grupo AE (p < 0,000001), 13,3 x 10,1 no grupo A (p < 0,001), e 15,1 x 11,4 mmHg no grupo C (p < 0,00001). As reduções na PAS foram estatisticamente diferentes no grupo A versus C e AE. Os eventos adversos mais freqüentes foram tosse no grupo AE e cefaléia nos outros dois grupos.Conclusão: Os resultados mostraram que os três agentes estudados reduziram a PAS e a PAD de forma significativa. A eficácia anti-hipertensiva da combinação fixa de anlodipino e enalapril foi maior que a da clortalidona e, especialmente, que do propranolol. Os tratamentos não diferiram quanto à tolerabilidade

Comparaçäo entre os efeitos da clortalidona e do diltiazem sobre a isquemia miocárdica em idosos hipertensos portadores de doença arterial coronariana / Effects of chlorthalidone and diltiazem on myocardial ischemia in elderly patients with hypertension and coronary artery disease

OBJECTIVE: Antihypertensive therapy with thiazides decreases coronary events in elderly patients. However, the influence of diuretics on myocardial ischemia has not been fully investigated. The aim of this study was to compare the effect of chlorthalidone and diltiazem on myocardial ischemia. METHODS: Following a randomized, double-blind, crossover protocol, we studied 15 elderly hypertensive patients aged 73.6 + or - 4.6 years with myocardial ischemia. All patients had angiographically documented coronary artery disease. We measured patients using 48- hour ambulatory electrocardiogram monitoring and exercise testing. After a 2-week period using placebo, patients received chlorthalidone or diltiazem for 4 weeks. RESULTS: Both treatments lowered systolic and diastolic blood pressures...

Evaluation of protein and peptide hydrolases in DOCA-salt hypertensive rats treated with chlorthalidone

We have reported that chlorthalidone (Chlor) prevents the development of heart hypertrophy in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. The present study was carried out to determine whether Chlor (8 mg/day per animal, added to the food, for 20 days) affects kidney and heart hypertrophy in DOCA-salt (8 mg/kg, sc, twice a week) rats by causing alterations in protein and peptide hydrolysis Heart (left ventricle) and kidney enzyme activities were measured i tissue homogenates from normal-control, salt-control, DOCA-sa salt and DOCA-salt-Chlor male Wistar rats (N = 6 for each group), using azocasein as the substrate for proteolytic enzymes and specific peptides for prolylendopeptidase (PEP) and multicatalytic proteinase (MCP). The tissue weight/body weight ratio increased in parallel to elevation of blood pressure. The left ventricular muscle hypertrophy (26 per cent, P<0.05) present in the DOCA-salt hypertensive group was completely prevented by simultaneous Chlor treatment. Chlor treatment did not change the kidney hypertrophy (+79 per cent, P<0.05) observe in the salt-control (+57 per cent, P<0.05) and DOCA-salt (+74 per cent, P<0.05) groups. The hydrolysis of peptides by PEP and MCP was similar in the normal and salt-control groups. The heart PEP activity was 24 per cent higher (P<0.01) in DOCA-salt rats, whereas MCP activity was not different when compared to control groups. DOCA-salt treatment increased MCP activity in the kidney by 44 per cent while PEP activity did not differ from that of control groups. The hydrolysis of proteins by heart enzymes was increased by salt by 47 per cent. Chlor treatment restored the reduction in protein hydrolysis induced by DOCA-salt (a 21 per cent decrease, P<0.05) to a level similar to that of the normal-control group. Similarly, Chlor coadministration prevented the 30 per cent reduction in renal proteolytic activity elicited by DOCA-salt treatment. Although Chlor treatment prevented the DOCA-salt-induced reduction in protein hydrolysis, this response did not interfere with kidney hypertrophy. The mechanism by which hypertension produces hypertrophy is unclear, but our results suggest that this structural modification is not related to the activities of some peptidases, e.g. protein and peptide hydrolases.

Comparação entre os efeitos de captopril e da clortalidona sobre a tolerância á glicose e os níveis séricos de insulina em hipertensos essenciais / Comparative Effects of Captopril and Chlortalidone on Glucose Tolerance and Insulin Levels in Essential Hypertensives

OBJETIVO- Comparar efeitos da clotalidona (CL) e do captopril (Cp) sobre o metabolismo de glicose e níveisséricos de insulina em portadores de hipertensäo arterial.MÉTODOS- Pacientes hipertensos essenciais, näo obesos, sem intolerância á glicose e com níveis da pessäo arterial diastólica (PAD) na posiçäo sentada >90mmHg e _<115mmHg receberam Cp ou CL durante 16 semanas,após outras 16 semanas de uso de placebo. O teste oral de sobrecarga à glicose (OGTT) foi realizado antes e após o tratamento com droga ativa, com dosagens de insulina sérica antes e 120min após a sobrecarga de glicose.RESULTADOS - Concluíram o estudo 24 pacientes do grupo CL e 19 do grupo Cp.Em nove pacientes do CL (CL-H) ocorreu hipocalemia (potássio sérico<3,8mEq/L ou reduçöesnos níveis séricos de potássio_>0,9mEq/L).Neste grupo a Cl provocou aumentos da área sob curva da glicemia durante a OGTT (582vs 610mg/h/dL;p<0,05)que näo foram detectadas no grupo CL sem hipocalemia (CL N;n=15)ou no grupo Cp.Os níveis de insulina na OGTT näo monstraram alteraçöes significantes com o tratamento.O índice de sencibilidade à insulina, entretanto, mostrou reduçöes nos grupos CLH(1,9vs 1,4;p<0,05) e CLN (10,1 vs 4,3, p<0,05), permanecendo inalterado no grupo Cp (3,1 vs 2,5;NS).O índice de resposta da insulina à sobrecarga de glicose, por outro lado,näo monstrou alteraçöes significantes nos grupos CLH(0,25 vs 0,42;) e CLN(0,07 vs 0,024;NS) mas elevou-se no Cp (0,28 vs 0,40;p<0,005).CONCLUSAO- O tratamento de pacientes hipertensos essenciais com LC resulta em reduçöes na sensibilidade à insulina que podem se acompanhar de elevaçöes nos níveis de glicemia após sobrecarga de glicose, particularmente naqueles pacientes que desenvolvem hipocalemia, sugerindo que o Cp aumentaa secreçäo de insulina em respósta às elevaçöes de glicemia, sem alterar a sensibilidade à insulina.

Efeito do tratamento com clortalidona na redução da massa ventricular esquerda de pacientes com hipertensão arterial sistêmica / Effect of Treatment with Chlorthalidone on Reduction of Left Ventricular Mass of Patients with Systemic Arterial Hypertension

PURPOSE--To evaluate the effects of the use of chlorthalidone on left ventricular mass of patients with mild and moderate systemic arterial hypertension (SAH). METHODS--Twenty-nine patients with mild and moderate SAH were studied with mean age of 48.4 years and 16 men. Clinical evaluation, systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR), in supine and standing positions, were obtained before and every 3 weeks, after 2 with placebo, during 12 weeks of treatment with 50mg of chlorthalidone each 48 hours. Laboratory data (hemogram, sodium, potassium, urea creatinine, glucose, hepatic aminotransferases and urinalysis) were done before and at end of study. Echocardiographic study was performed by M-mode before and after 6 and 12 weeks of treatment, and obtained the following data: diastolic diameter (DdLV), diastolic septum (DSTLV) and posterior wall thickness (PWTLV) of left ventricle. The left ventricular mass (LVM) was calculated by the formula: LVM = (DSTLV+PWTLV+DdLVE)3 - (DdLV)3 x 1.05/body surface, in g/m2. RESULTS--A significant reduction of SBP (p < 0.0001), DBP (p < 0.001) in supine and standing positions. HR did not show statistical difference. At echocardiographic study, M-mode, was observed a significant reduction of LVM after 12 weeks of treatment (181 +/- 67 to 156 +/- 34 g/m2, p < 0.01). CONCLUSION--Chlorthalidone was effective to control blood pressure and to reduce LVM of patients with SAH.

Efeitos hemodinâmicos de baixas doses de clortalidona em pacientes com hipertensäo arterial sistêmica leve / Hemodynamic effects of low dosis of chlorthalidone in patients with light systemic arterial hypertension

Objetivo - Avaliar os efeitos hemodinâmicos de baixas doses de clortalidona em pacientes com hipertensäo arterial sistêmica leve. Métodos - Oito pacientes com hipertensäo arterial sistêmica (HAS) leve, com idade de 52 ñ 8.9 anos, sendo 7 do sexo masculino. Avaliaçäo clínica, medidas da pressäo arterial sistólica (PAS), diastólica (PAD) e da freqüência cardíaca, em posiçöes supina e ortostática, foram obtidas no início e, posteriormente, a cada 2 semanas, durante 12 semanas, sendo as 2 primeiras em uso de placebo. Os exames laboratoriais hemograma, sódio, potássio, uréia, creatinina, glicemia, transaminases hepáticas e urina I, foram realizados no início e no final do estudo. A monitorizaçäo hemodinâmica foi realizada com cateter de Swan-Ganz em artéria pulmonar obtendo-se as pressöes médias de átrio direito, artéria pulmonar e capilar pulmonar, em mmHg. O débito cardíaco (DC) foi obtido pela técnica da termodiluiçäo. Como parâmetro derivado obteve-se a resistência vascular sistêmica (RVS). As medidas foram realizadas nas 2ª (pré) e 12ª (pós) semanas de tratamento com 50mg de clortalidona em dias alternados. Resultados - Observou-se reduçäo significante, nas posiçöes supina e ortostática, da PAS (p = 0,005 e p = 0,003) e PAD (p < 0,001 em ambas as posiçöes). A FC manteve-se inalterada. A monitorizaçäo hemodinâmica observou-se reduçäo estatisticamente significativa da RVS (p < 0,02) e o DC manteve-se inalterado. Conclusäo - A clortalidona em baixas doses mostrou-se eficaz no tratamento da HAS e o mecanismo básico deve-se a reduçäo da RVS

Purpose - To evaluate the hemodynamic effects of low dosis of chlortalidone (CHT) in patients with systemic arterial hypertension (SAH). Methods - Eight patients with mild SAH, mean age of 52± 8.9 years, 7 men, were studied. Clinical evaluation, systolic (SBP) and diastolic (DBP) blood pressure and heart rate (HR), in supine and standing positions, were obtuined before and every two weeks, first two in placebo, during 12 weeks. Laboratory data, hemogram, sodium, potassium, urea, creatinine, glucose, hepatic aminotransferases and urinalysis, were done and at end of study. Hemodynamic monitorization was periormed by Swan-Gans catheter in pulmonary artery to obtain RAP and PAWP, in mmHg. Cardiac output (CO) was obtained by thermodilution method. Systemic vascular resistence (SVR) arised from variables above. Hemodynamic variables were measured at 2nd and 12th weeks during treatment with 50mg of chlorthalidone each 48 h. Results - A significant reduction of SBP (p = 0.005 and p = 0.003), DBP (p < 0.0001 and p < 0.0001), respectively in supine and standing positions. HR did not show statistical diference. At hemodynamic monitoring was observed a signifcative reduction of SVR (p < 0.02), but not with CO. Conclusion - Chlorthalidone in low dosis was effective to treat mild SAH, basically by lowering SVR

Estudo aberto comparativo captopril + hidroclorotiazida versus clortalidona para tratamento da hipertensäo primária leve e moderada / An open comparative study of captopril + hydrochlorothiazide versus chlorthalidone for the treatment of mild and moderate primary hypertension

Objetivo - Comparar o efeito anti-hipertensivo e alterações metabólicas da associação captopril + hidroclorotiazida (C+HCTZ) contra clortalidona (CT) para tratamento de hipertensão arterial primária leve e moderada. Métodos - cinqüenta e cinco pacientes que tiveram a sua medicação anti-hipertensiva suspensa por 15 dias ou sem tratamento prévio, foram randomizados para tratamentos com a associação captopril 50mg + hidroclorotiazida 25mg (n=29) ou clortalidona 50mg (n=26). A avaliação clínica foi realizada previamente à medicação e mensalmente durante 3 meses e os exames laboratoriais foram feitos no início e ao final do estudo. Resultados - A pressão arterial (PA) no período placebo não foi diferente entre os grupos (C+CHTZ: 161 ± 25/102 ± 6 - CT: 155 ± 18/101 ± 6 mmHg), porém a diminuição da pressão diastólica já no 1° mês foi estatisticamente significante no grupo C+HCTZ (89±8 mmHg) comparado ao grupo CT (94±8 mmHg, p<0,05). O perceptual de queda da PA diastólica em média, de 12% no grupo C+HCTZ e no grupo CT variou de 7 (1° e 2° mês) a 11% (3° mês). Embora sem diferença estatística, obteve-se normalização pressórica em 69% dos pacientes com captopril associado ao diurético e, em 50%, com clortalidona. Observou-se uma redução significativa da potassemia com clortalidona (4,2±0,7 para 3,7±0,4 mEq/L, p<0,01) e manutenção dos níveis de potássio com associação captopril e tiazídico. Este último tratamento também reduziu significativamente os níveis de colesterol (219±39 mg/dl para 202±39 mg/dl, p<0,04). Conclusão - Os resultados mostraram que a associação de captopril com dose baixa de tiazídico normaliza a PA em 69% de pacientes portadores de hipertensão arterial primária leve e moderada e age mais rapidamente que a clortalidona no controle pressórico, apresentando efeito metabólico benéfico de reduzir os níveis de colesterol sem alterar a potassemia

Purpose - To compara the antihypertensive and metabolic effects of captopril combined with hydrochlorothiazide (C+HCTZ) versus chlorthalidone (CT) in mild and moderate primary hypertensive patients. Methods - Fifty five patients, whithout treatment or treated with 15 days placebo were randomized for treatment with the combination of captopril 50mg and hydrochlorothiazide 25mg (n=29) against chlorthalidone (n=26). The clinical evaluation was done during placebo and monthly throughout three months, and the laboratory tests were done before and at the end of the study. Results - The blood pressure were similar between groups during placebo period (C+HCTZ: 161±25/102±6 - CT: 155±18/101±6 mmHg); the diastolic blood pressure decreases significantly at first month already in the group C+HCTZ (89±8 mmHg) comparad to group CT (94±8 mmHg, p<0,05). The percentile diastolic and mean blood pressure dropped, in average, 12% in C+HCTZ group and in CT varied between 7 (1st and 2nd month) to 11% (3rd month). Without statistical difference, the blood pressure normalization was obtained in 69% of the patients with the association captopril and diuretic and in 50% of the patients in the chlorthalidone group. It was observed a significant reduction of potassium in patients treated with chlorthalidone (4,2±0,7 to 3,7±0,4 mEq/L, p<0,01) that was not observed with the captopril and the thyazide associated. The last treatment also significantly reduced the cholesterol levels (219±39mg/dl to 202±39mg/dl, p<0,04). Conclusion - Our results indicate that captopril combined with low diuretic dose normalize the blood pressure in 69% mild to moderate primary hypertensive patients, and acts faster than chlorthalidone in this control. In addition has metabolic benefits reducing cholesterol levels with no alteration in potassium levels