Comparative Efficacy of Hydrochlorthiazide and Chlorthalidone, used either alone or in Combination Therapy in Patients with Essential Hypertension in Tertiary Care Hospital of Uttrakhand

Aims : To study the comparative efficacy of Hydrochlorothiazide and Chlorthalidone, either used alone or in combination on Systolic Blood Pressure (SBP), Diastolic Blood Pressure (DBP), Lipid Profile and Anthropometry. Methods : It was a Prospective, Randomised, Longitudinal study, where consecutive patients presenting to medicine Out Patient Department (OPD) and In Patient Department (IPD) were screened for essential hypertension based upon the JNC VII Guidelines. Those subjects who satisfy the inclusion and exclusion criterias were included in the study. These subjects were divided into four subgroups. Each patient was assessed for Blood Pressure (BP), Lipid profile, Anthropometry for a period of 180 days. Results : There was statistically significant reduction in both systolic blood pressure and DBP in both the groups over a period of 180 days. This trend was progressive during the observed period in both the groups till a stable state was reached. There was a greater reduction in the SBP in the chlorthalidone group as compared to the Hydrochlorothiazide group (P value 0.05). However, such trend was not observed on the DBP on the two groups. Over a six months follow up there was no change in the Lipid parameters either on the same group or while comparing the two groups. The body Anthropometry , especially waist Hip ratio and Body Mass Index also did not show any significant difference in the two groups( either used alone or in combination). Conclusion : Chlorthalidone was found to be a relatively more potent Anti-hypertensive on SBP when compared with Hydrochlorothiazide .Both these drugs failed to show any significant difference in the Lipid Profile and Anthropometry in a period of six months.

Related Impurities High-Performance Liquid Chromatography Method Development And Validation For Drug Combinations: Olmesartan Medoxomil, Chlorthalidone And Cilnidipine

The liquid chromatography mass spectrometry (LC-MS) compatible, stability-indicating, specific, linear, accurate, sensitive with less run-time related impurities reversed phase high-performance liquid chromatography (RP-HPLC) related impurities method has been developed for olmesartan medoxomil (OLM), chlorthalidone (CHLR), and cilnidipine (CIL) drug combinations, and the method has been validated according to ICH and US-FDA guidelines. The chromatographic separation was performed by using Hypersil-BDS Thermo-Scientific, C18 (12.5 cm, 4.6 mm, 5 microns particle size) column. Mobile phase-A was prepared by mixing 3.85 gm ammonium acetate in HPLC water and adjust pH 5.0 by using diluted acetic acid. Acetonitrile was taken as mobile phase-B. Initial mobile phase ratio (55:45 v/v) was adjusted for mobile phase-A: mobile phase-B followed by gradient program. Other chromatographic conditions such as column temperature 25 degrees, flow rate 1.0 mL/minutes with the detection wavelength at 260 nm. The retention time for CHLR impurity A, olmesartan (OL), OLM impurity A, were found about 2.7, 3.3, and 7.2 minutes respectively, with a total run time of 18.0 minutes. The linearity calibration plot was performed and found linear relationship over the concentration range of 1.25 limit of quantitation (LoQ)–18.75 μg/mL, 3.6 LoQ–60.0 μg/mL, 3.6 LoQ– 60.0 μg/mL respectively for CHLR impurity A, OL and OLM impurity A respectively. The limit of detection (LoD) and LoQ were found 0.4 ppm (μg/mL) and 1.2 ppm (μg/mL), 1.2 ppm (μg/mL) and 3.5 ppm (μg/mL), 1.1 ppm (μg/mL) and 3.3 ppm (μg/mL) for CHLR impurity A, OL and OLM impurity A respectively. The accuracy was determined by recovery studies and was found between 90.0–110.0%. The developed analytical method has been validated for LoD-LoQ, specificity, linearity, accuracy, precision, robustness, and ruggedness, which were well within the acceptance limit as per ICH guidelines. All the degradation products generated by stress conditions were found to be well separated from one another (all drug components and impurities). The developed method with shorter runtime was successfully implemented for routine quality control and stability analysis to check the quality of OLM, CHLR, and CIL drug combinations.

An observational comparative study of different doses of azilsartan and with chlorthalidone combination in moderate hypertension

Background: High blood pressure (BP) is one of the significant non-communicable diseases that are of high prevalence in our country. Hypertension (HTN) is responsible cause of 57% of stroke and 24% of coronary heart disease deaths in India. Eight classes of medications are currently used in the treatment of hypertension. Azilsartan medoxomil is a newly added FDA approved drug to the ARB class of antihypertensive agents. azilsartan and chlorthalidone combination is also got the FDA approval. There is limited study in between these two groups regarding efficacy especially in rural Bengal.Methods: A prospective observational study was done in medicine OPD of Bankura Sammilani Medical College for twelve weeks with two groups that are azilsartan (80mg) and fixed dose combination of azilsartan (40mg) plus chlorthalidone (12.5mg) in the age group of 18 to 55years of moderate hypertensive patients. Change of heart rate was assessed as safety parameter.Results: It was found that both the group of drugs are very much effective in lowering blood pressure constantly in respect of both systolic and diastolic BP but azilsartan monotherapy in high dose reduce systolic blood pressure slightly high. Significant change of heart rate was not seen with both the groups.Conclusions: Both the group was effective as well as safe in hypertensive patients.

A comparative analysis of hydrochlorothiazide and chlorthalidone induced hyponatremia at the dose commonly prescribed in clinical practice

Background: Despite the differences in cardiovascular outcomes, pharmacokinetics, pharmacodynamics, the diuretics, chlorthalidone (CTD) and hydrochlorothiazide (HCTZ) are often considered as interchangeable. There is an on-going debate whether CTD should be preferred over HCTZ, because it appears to be more effective in the prevention of cardiovascular events. The relative difference in the incidence of hypokalemia and hyponatremia, is also a topic of debate. With this background, the study was carried out to compare the prevalence of hyponatremia between CTD and HCTZ used in the treatment of hypertension at the dose commonly prescribed in clinical practice.Methods: This was a cross sectional study carried out on a convenience sample of 74 adult patients with provisional diagnosis of hyponatremia or with a plasma sodium level of less than 135mmol/L and having a history of anti-hypertensive use of HTCZ or CTD in the dose range of 12.5-25mg/day and 6.25-12.5mg/day respectively. Chi square test and independent samples ‘t’ test were used analyse the results in GraphPad Prism 6.0.Results: HCTZ was found to be the preferred diuretic in hypertension, whereas CTD was preferred in the age group of 65-74 years. The symptoms indicative of hyponatremia as well as a lower plasma sodium level were more common in the HTCZ treated group. Patients of hypertension using CTD were less predisposed to hyponatremia (OR 0.804, 95% CI 0.207-3.12).Conclusions: Chlorthalidone, when used at a lower dose of 6.25-12.5mg/day for the treatment of hypertension cause a lesser risk of hyponatremia than hydrochlorothiazide.

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

A comparative study on curative effect of chlorthalidone and bisoprolol in treatment of hypertension in the elderly man / 中国生化药物杂志

Objective To compare curative effect of chlorthalidone and bisoprolol in treatment of hypertension in the elderly man.Methods 2013 January to 2013 December in our hospital treatment of 60 elderly patients with hypertension were randomly divided into treatment group and control group, each of 30 cases.Treatment group was treated with chlorthalidone tablet, control group was treated with imported bisoprolol tablets.Observed and recorded the two groups before and after treatment the clinical curative effect, blood pressure, fasting blood glucose, uric acid, creatinine, urea nitrogen and adverse reaction.Results The total effective rate of the treatment group ( 90.00%) was significantly higher than that of the control group (73.33%), the difference was statistically significant (P<0.05); compared with before treatment, the treatment group before and after treatment systolic blood pressure and diastolic blood pressure were significantly decreased, the difference was statistically significant (P<0.05);the control group after treatment systolic blood pressure diastolic blood pressure, there was statistical significance between before and after treatment ( P<0.05 );compared with the control group, the treatment group after treatment systolic blood pressure was significantly better than the control group (P<0.05), while the two group of diastolic blood pressure had no significant difference in improving.The two groups before and after treatment, fasting blood glucose, uric acid, creatinine, urea nitrogen were no statistically significant difference.The treatment group and the control group had no obvious adverse reactions.Conclusion The curative effect of chlorthalidone treatment of hypertension in the elderly with good curative effect, few side effects, and beffer than bisoprolol.

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.

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.