Ocorrência de carcinoma espinocelular labial não melanocítico em usuários crônicos de hidroclorotiazida / Occurrence of non-melanoma labial squamous cell carcinoma in chronic users of hydrochlorothiazide

Diversos autores desenvolveram estudos acerca da potencial associação entre a etiocarcinogênese do carcinoma espinocelular não melanocítico (CECNM) labial e o uso crônico da hidroclorotiazida (HCTZ). Objetivo: A atual revisão objetivou investigar a relação do diurético HCTZ e o risco de CECNM labial. Métodos: Realizou-se uma revisão de literatura nas bases de dados LILACS, PUBMED/MEDLINE e Periódico CAPES, em que foram incluídos artigos em inglês, português e francês, publicados no período de 2017 a 2022. Foram propostos 60 documentos e, dentre esses, 30 foram selecionados para compor a amostra no estudo. Resultados: Foi evidenciada uma relação entre o uso da HCTZ e a ocorrência de CENM com relação dose cumulativa devido às alterações provocadas pelo fármaco, no entanto, em virtude da heterogeneidade de desenhos metodológicos e concentração dos estudos em populações semelhantes, existem limitações quanto à confiabilidade dessas informações. Conclusão: Identificou-se uma desproporção entre a ocorrência e relevância do CENM e a produção científica vigente, demonstrando a necessidade de estudos com metodologias padronizadas que abranjam diferentes especificidades socioeconômicas e demográficas.(AU)

Several authors have developed studies about a potential association between the etiocarcinogenesis of non-melanocytic lip squamous cell carcinoma (NMSCC) and the chronic use of hydrochlorothiazide (HCTZ). Objective: The current study aimed to investigate the relation between the diuretic HCTZ and the risk of lip NMSCC. Methods: A literature review was carried out in the LILACS, PUBMED/MEDLINE and CAPES Periodical databases, which included articles in English, Portuguese and French, published between 2017 and 2022. Sixty documents were collected and, among these, 30 were selected to compose the sample in the study. Results: There was evidence of a relationship between the use of HCTZ and the occurrence of MSCC with a cumulative dose relationship due to changes caused by the drug, however, because of the heterogeneity of methodological designs and concentration of studies in similar populations, there are limitations regarding the reliability of this information. Conclusion: A disproportion between the occurrence and relevance of the NMSCC and the current scientific production was identified, demonstrating the need for studies with standardized methodologies that cover different demographic socioeconomic specificities.(AU)

Thiazide and thiazide-like diuretics in nephrolithiasis / Diuréticos tiazídicos e tiazídicos-like na nefrolitíase

Abstract Thiazide and thiazide-like diuretics are widely used for the management of hypercalciuria among stone-forming patients. Although the effects of different thiazides should be relatively similar in terms of prevention of stone recurrence, their potency and side effects may differ. However, there is scarce data concerning the metabolic and bone effects of these agents among recurrent nephrolithiasis patients with hypercalciuria. The aim of this update article was to compare our experience in the use of thiazide and thiazide- like diuretics with that of the current literature, concerning their anticalciuric properties and consequent reduction of recurrent stone formation. Their impact on bone mass and potential side effects were also discussed.

Resumo Diuréticos tiazídicos e tiazídicos-like são amplamente usados para o tratamento da hipercalciúria em pacientes com formação de cálculos. Embora os efeitos dos diferentes tiazídicos devam ser relativamente semelhantes em termos de prevenção da recorrência do cálculo, sua potência e efeitos colaterais podem ser diferentes. No entanto, há poucos dados sobre os efeitos metabólicos e ósseos desses agentes em pacientes com nefrolitíase recorrente com hipercalciúria. O objetivo deste artigo de atualização foi comparar nossa experiência quanto ao uso de tiazídicos e tiazídicos-like com a publicada na literatura atual, no que diz respeito às suas propriedades anticalciúricas e consequente redução da formação de cálculos recorrentes. Discutimos também seu impacto na massa óssea e potenciais efeitos colaterais.

EXISTEM DIFERENÇAS ENTRE OS DIURÉTICOS TIAZÍDICOS? / ARE THERE ANY DIFFERENCES BETWEEN THIAZIDE DIURETICS?

Desenvolvidos em 1950, os diuréticos estão entre as drogas mais utilizadas no arsenal terapêutico clínico, principalmente na hipertensão arterial e nos quadros edematosos. O mecanismo de ação envolve a excreção renal de água, eletrólitos e diminuição da reabsorção de sódio em diferentes locais do néfron, com consequente aumento do sódio urinário e da água. Os diuréticos tiazídicos mais usados na prática clínica em pacientes hipertensos são: hidroclorotiazida (HCTZ), clortalidona (CTD) e indapamida (IDP). Em relação à potência anti-hipertensiva, a CTD é uma vez e meia a duas vezes mais potente que a hidroclorotiazida. HCTZ é menos potente do que qualquer outro anti-hipertensivo, incluindo inibidores da enzima de conversão da angiotensina, bloqueadores do receptor da angiotensina e antagonistas dos canais de cálcio. O IDP tem ação anti-hipertensiva devido aos seus efeitos no túbulo distal, inibindo a reabsorção do cloreto de sódio e tem efeitos mais intensos e sustentados na redução da pressão arterial. Os diuréticos tiazídicos são muito diferentes, tanto em níveis variados de redução da pressão arterial quanto em efeitos adversos, de modo que sua proteção contra danos em órgãos-alvo está relacionada ao efeito de classe

Developed in 1950, diuretics are among the most used drugs in the clinician's therapeutic arsenal, especially in arterial hypertension and edematous conditions. The mechanism of action involves the renal excretion of water, electrolytes, and decreasing the reabsorption of sodium in different locations of the nephron, with consequently an increase in urinary sodium and water. The most used thiazide diuretics in clinical practice in hypertensive patients are: hydrochlorothiazide (HCTZ), chlortalidone (CTD) and indapamide (IDP). Regarding the antihypertensive potency, CTD is one and a half to two times more potent than hydrochlorothiazide. HCTZ is less potent than any other antihypertensives including angiotensin converting enzyme inhibitors, angiotensin receptor blockers, and calcium channel antagonists. IDP has an antihypertensive action due to its effects on the distal contoured tubule, inhibiting sodium chloride reabsorption and has more intense and sustained effects in reducing blood pressure. Thiazide diuretics are very different, both in varying levels of blood pressure reduction and adverse effects, so their protection from target organ damage is related to the class effect

Comparación de la equivalencia terapéutica de dos productos de bisoprolol - hidroclorotiazida en pacientes con hipertensión arterial / Comparison of two products containing bisoprolol - hydrochlorothiazide therapeutic equivalence in patients with arterial hypertension

Resumen Objetivo: Evaluar la equivalencia terapéutica de dos marcas comerciales de bisoprolol -hidroclorotiazida como terapia antihipertensiva. Método: Estudio prospectivo, doble ciego, doble falso, aleatorizado, de grupos paralelos, en el que se evaluó el efecto antihipertensivo de la combinación de bisoprolol-hidroclorotiazida 2,5-6,25 y 5-6,25 mg (comprimidos BHL, formulación test) y bisoprolol-hidroclorotiazida 2,5-6,25 y 5-6,25 mg tabletas (BHM, formulación de referencia), administrados en pacientes con hipertensión arterial. Variables de efectividad: Presiones arteriales medidas mediante mediante esfigmomanómetro de mercurio al inicio y después del período placebo, a las 4 y 8 semanas del inicio del tratamiento; cambios horarios de la presión arterial durante 24 horas, mediante monitorización ambulatoria de la presión arterial. Resultados: El control de los valores de presión arterial se logró en ambas formulaciones, principalmente a partir de la cuarta semana de tratamiento. Los pacientes del grupo test ingresaron con presiones arteriales sistólicas más elevadas. Después del tratamiento no hubo diferencias entre los grupos, a ninguno de los tiempos. La relación V/P del grupo test fue 0,5-1. Los índices de suavidad de ambos fueron mayores a 1,75. Conclusiones: La formulación test de la combinación de bisoprolol-hidroclotiazida demostró acción antihipertensiva similar al compararla con la formulación de referencia.

Abstract Objective: To evaluate the therapeutic equivalence of two commercial brands of bisoprolol -hydrochlorothiazide as antihypertensive therapy. Method: A prospective, double blind, double placebo, randomised, parallel group study was conducted, in which the antihypertensive effect of the bisoprolol -hydrochlorothiazide 2.5 - 6.25 mg and 5 - 6.25 mg (tablets BHL, test formula) and bisoprolol -hydrochlorothiazide 2.5 - 6.25 mg and 5 - 6.25 mg tablets (BHM, reference formula), was compared by administering it to patients with arterial hypertension given to patients with arterial hypertension. Effectivity variables: blood pressures measured using a mercury sphygmomanometer at the beginning and after the placebo period, at 4 weeks and 8 weeks from the start of the treatment; blood pressure hours change during 24 hours using an ambulatory blood pressure monitoring device. Results: Control of the blood pressure values was achieved with both formulas, mainly from the fourth week of treatment. The patients of the test group were admitted with higher systolic blood pressures. After the treatment, there were no differences between the groups at any of the times. The V/P ratio of the test group was 0.5 - 1. The smoothness index in both groups was greater than 1.75 of fit of both was greater than 1.75. Conclusions: The test formula of the bisoprolol-hydrochlorothiazide demonstrated an antihypertensive action similar to that achieved with the reference formula.

Simultaneous Determination of Four Related Substances in Olmesartan Medoxomil Hydrochlorothiazide Tablets by HPLC-Principal Component Self-Control with Correct Factor / 中国药房

OBJECTIVE： To establish the method for simultaneous determination of four known related substances （olmesartan，olmesartan ester dimer ，olmesartan ester alkene ，benzothiadiazine impurity ，called impurity A ，B，C，D for short ）in Olmesartan medoxomil hydrochlorothiazide tablets. METHODS ：HPLC-principal component self-control with correction factor were adopted. The determination was performed on YMC-Triart C 8 column with mobile phase A consisted of acetonitrile- 0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（70 ∶ 30，V/V），mobile phase B consisted of acetonitrile-0.015 mol/L potassium dihydrogen phosphate solution （pH adjusted to 2.8 with phosphoric acid ）（15 ∶ 85，V/V）at the flow rate of 0.8 mL/min（gradient elution ）. The detection wavelength was set at 265 nm，and column temperature was 25 ℃. The temperature of injector was 4 ℃；the injection volume was 10 μL. RESULTS：The correction factors of impurity A ，B，C，D were 1.42，1.17，0.89，0.92，respectively. The linear range of olmesartan medoxomil ，hydrochlorothiazide and impurity A ，B，C，D were 0.252 7-7.580 0，1.152 1-4.562 9，0.244 0-18.299 0，0.244 7-3.670 8，0.265 2-3.978 3 and 0.149 9-4.497 3 μg/mL（r≥ 0.999 7），respectively. The limits of detection were 0.084 2，0.050 7，0.081 3，0.081 6，0.088 4，0.050 0 μg/mL，respectively. The quantitative limits were 0.252 7，0.152 1，0.244 0，0.244 7，0.265 2 and 0.149 9 μg/mL，respectively. The results of intermediate precision ，stability（24 h）and repeatability tests all met the relevant requirements. The average recovery rates were 104.00％-108.04％，102.00％-104.94％，100.99％-106.89％，92.00％-95.18％，102.00％-105.06％，103.90％-107.00％（n＝3）， respectively. The contents of impurity A ，B and D in 3 batches of Olmesartan medoxomil hydrochlorothiazide tablets were 0.90％ -1.00％ ，0-0.11％ ，0.16％ -0.24％ ，respectively. The impurity C and other impurities were not detected. There is no significant difference between the results measured by the established method and by the external standard method. CONCLUSIONS：The method has been proved to be highly sensitive and reproducible. It can be used to simultaneously determine four known substances in Olmesartan medoxomil hydrochlorothiazide tablets.

Circulating microparticles and central blood pressure according to antihypertensive strategy

OBJECTIVES: This prospective, randomized, open-label study aimed to compare the effects of antihypertensive treatment based on amlodipine or hydrochlorothiazide on the circulating microparticles and central blood pressure values of hypertensive patients. METHODS: The effects of treatments on circulating microparticles were assessed during monotherapy and after the consecutive addition of valsartan and rosuvastatin followed by the withdrawal of rosuvastatin. Each treatment period lasted for 30 days. Central blood pressure and pulse wave velocity were measured at the end of each period. Endothelial, monocyte, and platelet circulating microparticles were determined by flow cytometry. Central blood pressure values and pulse wave velocity were recorded at the end of each treatment period. RESULTS: No differences in brachial blood pressure were observed between the treatment groups throughout the study. Although similar central blood pressure values were observed during monotherapy, lower systolic and diastolic central blood pressure values and early and late blood pressure peaks were observed in the amlodipine arm after the addition of valsartan alone or combined with rosuvastatin. Hydrochlorothiazide-based therapy was associated with a lower number of endothelial microparticles throughout the study, whereas a higher number of platelet microparticles was observed after rosuvastatin withdrawal in the amlodipine arm. CONCLUSIONS: Despite similar brachial blood pressure values between groups throughout the study, exposure to amlodipine was associated with lower central blood pressure values after combination with valsartan, indicating a beneficial interaction. Differences between circulating microparticles were modest and were mainly influenced by rosuvastatin withdrawal in the amlodipine arm.

Combinação dose fixa de hidroclorotiazida (12, 5 mg) e valsartana (160 mg): Desenvolvimento de metodologia de dissolução in vitro e in silico para avaliar os perfis de dissolução dos produtos comercializados no Brasil e Peru / Fixed dose combination of hydrochlorothiazide (12. 5 mg) and valsartan (160 mg): Development of in vitro and in silico dissolution methodology to evaluate the dissolution profiles of products marketed in Brazil and Peru

Hidroclorothiazida (HTZ) e valsartana (VAL) são fármacos pouco solúveis em meio aquoso e pertencem às classes IV e II do Sistema de Classificação Biofarmacêutica (SCB), respectivamente. O objetivo deste trabalho foi desenvolver um método para avaliar o perfil de dissolução de formas farmacêuticas sólidas de dose fixa combinada contendo HTZ (12,5 mg) e VAL (160 mg) usando ferramentas in silico para avaliar os perfis de dissolução de produtos comercializados no Brasil e Peru. O presente trabalho foi dividido em 4 capítulos. No Capítulo I, foi determinada a solubilidade da HTZ e VAL pelo método shake-flask e potenciométrico, no qual foi possível demonstrar que existe correlação entre ambos os métodos e que HTZ e VAL são solúveis em tampão fosfato pH 6,8. No Capítulo II, um método cromatográfico em HPLC foi desenvolvido com base em Quality by Design (QbD), com auxílio do software Fusion®, no qual foi estabelecido uma zona de confiança dos parâmetros, que garantiu a robustez do método. O Capítulo III descreve o desenvolvimento de um método de dissolução utilizando ferramenta in silico (DDDplus®) na qual foi definido um delineamento experimental do tipo fatorial completo 33 usando como fatores a formulação, utilização de âncora e velocidade de agitação. Para os ensaios de dissolução in vitro, foi proposto um outro delineamento fatorial 3(3-1) com o intuito de obter as constantes de calibração das simulações in silico. Através de uma análise estatística das eficiências de dissolução obtidas nas simulações, foram avaliados os efeitos e as interações entre os fatores. Assim, as condições finais do método de dissolução estabelecidas foram: 900 mL de tampão fosfato pH 6,8 como meio de dissolução, 75 rpm de velocidade de agitação, e utilização de âncora para evitar a flutuação das formulações. O método desenvolvido foi empregado, no contexto do Capítulo IV, para avaliar o perfil de dissolução dos produtos contendo HTZ e VAL comercializados no Brasil e no Peru. Por análise multivariada, a eficiência de dissolução (ED), tempo médio de dissolução (MDT) e as porcentagens de dissolução de 5 até 60 minutos foram utilizadas para agrupar as formulações em grupos distintos. Embora os perfis de dissolução mostrem similaridade entre todas as formulações avaliadas, o produto referência se destacou por apresentar uma maior ED comparado com as outras formulações, devido à maior liberação nos primeiros 5 minutos de ensaio. Concluiu-se que o método proposto, além de garantir a liberação total de HTZ e VAL a partir das formulações, possui adequado poder discriminativo

Hydrochlorothiazide (HTZ) and valsartan (VAL) are poorly soluble drugs in aqueous medium and belong to classes IV and II of the Biopharmaceutical Classification System (BCS), respectively. The objective of this study was to develop a dissolution method to evaluate the dissolution profile of solid pharmaceutical forms of combined dose containing HTZ (12.5 mg) and VAL (160 mg) using in silico tools to evaluate the dissolution profiles of products sold in Brazil and Peru. The present study was divided into four chapters. In Chapter I, the HTZ and VAL solubility were determined by the shake-flask and potentiometric methods, in which it was possible to demonstrate that there is a correlation between both methods and that HTZ and VAL are soluble in pH 6.8 phosphate buffer. In Chapter II, a chromatographic method in HPLC was developed based on Quality by Design (QbD), using the Fusion® software, in which a zone of confidence of the parameters was established, which ensured the robustness of the method. Chapter III presents the development of a dissolution method using in silico (DDDplusTM) as a tool, in which an experimental design of the complete factorial type 33 was defined using as factors: the formulation, use of sinker and agitation speed. For in vitro dissolution assays, another factor design 3(3-1) was proposed to obtain the calibration constants of the in silico simulations. Through a statistical analysis of the dissolution efficiencies obtained in the simulations, the effects and interactions between the factors were evaluated. Thus, the final conditions of the dissolution method established were: 900 mL of pH 6.8 phosphate buffer as a dissolution medium, 75 rpm of stirring speed, and use of sinker to avoid the fluctuation of the formulations. The method developed was used, in the context of Chapter IV, to evaluate the dissolution profile of HTZ and VAL products marketed in Brazil and Peru. By multivariate analysis, the dissolution efficiency (ED), mean dissolution time (MDT) and the dissolution percentages from 5 to 60 minutes were used to group the formulations in different groups. Although the dissolution profiles show a similarity between all the evaluated formulations, the reference product stood out for presenting a higher ED compared to the other formulations, due to the higher release in the first 5 minutes of the test. It was concluded that the proposed method, besides guaranteeing the total release of HTZ and VAL from the formulations, has adequate discriminatory capacity

Influence of valsartan combined hydrochlorothiazide on 24hDBP ,24hSBP and blood pressure variabili— ty in patients with hypertension / 心血管康复医学杂志

Objective :To study influence of valsartan combined hydrochlorothiazide on 24h diastolic blood pressure (DBP) ,24h systolic blood pressure (SBP) and blood pressure variability (BPV) in patients with hypertension .Meth—ods : A total of 94 hypertensive patients treated in our hospital were randomly and equally divided into valsartan group and combined treatment group (received valsartan combined hydrochlorothiazide ) ,both groups were treated for one month .The 24hDBP ,24hSBP ,BPV ,levels of nitric oxide (NO ) and endothelin (ET ) before and after treatment and incidence of adverse reactions were compared between two groups .Results : Compared with valsartan group after treatment ,there were significant reductions in 24hSBP [ (130. 64 ± 10.01) mmHg vs .(121.53 ± 9.35) mmHg] ,24h DBP variability (24hDBPV) [ (12.47 ± 3.32)% vs.(10.82 ± 2.71)%] ,24hSBPV [ (10. 42 ± 2. 00)%vs.(8.51 ± 1. 64)%] and daytime SBPV [ (10.87 ± 2. 05)% vs.(8. 66 ± 1.65)%] , P＜0. 05 or ＜0.01 ;significant rise in NO level [ (42.92 ± 6.84) μmol／L vs.(53.43 ± 7. 16) μmol／L] and significant reduction in ET level [ (38. 62 ± 5.52) ng／L vs .(31. 01 ± 5. 01) ng／L] in combined treatment group , P＝0.001 both .There were no significant difference in incidence of adverse reactions between two groups , P＞ 0.05 all.Conclusion : Valsartan combined hydrochlorothiazide can effectively improve levels of 24hDBP ,24hSBP and blood pressure variability ,and contrib— ute to regulating NO and ET levels in patients with hypertension .

Advancing USP compendial methods for fixed dose combinations: A case study of metoprolol tartrate and hydrochlorothiazide tablets / 药物分析学报

The current United States Pharmacopeia–National Formulary (USP–NF) includes more than 250 mono-graphs of fixed dose combinations (FDCs), and some of them need to be updated due to incompleteness of impurity profiles and obsolescence of analytical methodologies. A case study of metoprolol tartrate and hydrochlorothiazide tablets is presented to summarize challenges encountered during the USP monograph modernization initiative of FDCs and to highlight an "adoption and adaptation" approach employed for method development. To this end, a single stability-indicating HPLC method was devel-oped to separate the two drug substances and eight related compounds with resolution 2.0 or higher between all critical pairs. Chromatographic separations were achieved on a Symmetry column (C18, 100 mm × 4.6 mm, 3.5 μm) using sodium phosphate buffer (pH 3.0; 34 mM) and acetonitrile as mobile phase in a gradient elution mode. The stability-indicating capability of this method has been demon-strated by analyzing stressed samples of the two drug substances. The developed HPLC method was validated for simultaneous determination of metoprolol tartrate and hydrochlorothiazide and relevant impurities in the tablets. Moreover, the developed method was successfully applied to the analysis of commercial tablet dosage forms and proved to be suitable for routine quality control use. The case study could be used to streamline USP's monograph modernization process of FDCs and strengthen compendial procedures.

Efficacy of triple diuretic treatment in continuous ambulatory peritoneal dialysis patients: A randomized controlled trial

BACKGROUND: The efficacy of combined diuretic treatment in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known. METHODS: In a single-center, double-blinded, randomized controlled trial, we randomly assigned 51 adult CAPD patients to receive furosemide 1,000 mg/day, hydrochlorothiazide 100 mg/day, and spironolactone 50 mg/day (triple diuretics [TD] group) or furosemide 1,000 mg/day plus placebo (single diuretic [SD] group) for 6 months. The primary outcome was the difference in daily urine output at the 3rd and 6th month of the study compared to baseline (ΔUO) between the SD and TD group. Secondary outcomes were urinary sodium (UNa) and potassium (UK) excretion and overhydration (OH) measured by bioimpedance at 3 and 6 months compared to baseline (ΔUNa, ΔUK, and ΔOH, respectively) and daily glucose exposure (g/day). RESULTS: Forty-three of 51 patients completed the 6-month trial. The ΔUO at 3 and 6 months was significantly higher in the TD group compared to the SD group (386.32 ± 733.92 mL/day vs. −136.25 ± 629.08 mL/day, P < 0.001, at 3 months; 311.58 ± 640.31 mL/day vs. 120.00 ± 624.07 mL/day, P < 0.001, at 6 months) but there was no significant difference in ΔUNa and ΔUK excretion. Hydration status was significantly better in the TD group (ΔOH 1.84 ± 2.27 L vs. 0.44 ± 1.62 L, P = 0.03, at 3 months; 1.49 ± 2.82 L vs. −0.48 ± 2.61 L, P = 0.02, at 6 months). There was no serious adverse event in this study. CONCLUSION: For end-stage renal disease patients on CAPD, the combination of furosemide, hydrochlorothiazide, and spironolactone results in higher urine output and better volume control compared to furosemide alone.

Efficacy and safety of Irbesartan Hydrochlorothiazide combined with Metoprolol as initial therapy in the treatment of heart failure in the elderly / 中华老年医学杂志

Objective To investigate the efficacy and safety of Irbesartan Hydrochlorothiazide combined with Metoprolol as initial therapy in the treatment of heart failure in the elderly.Methods A total of 128 elderly patients with heart failure admitted into our hospital from September 2017 to August 2018 were randomly divided into Group A(n=64)and Group B(n=64).Group A was treated with oral Irbesartan Hydrochlorothiazide tablets.Group B was treated with sustained-release oral Metoprolol tablets in addition to what was given in Group A.Therapeutic effects were compared between the groups.Results Compared with Group A,the effectiveness rate of group B was significantly improved(93.8％ vs.81.3％,x2 =4.571,P=0.033).There was no significant difference in brain natriuretic peptide (BNP),interleukin (IL)-12,left ventricular ejection fraction (LVEF),left ventricular end-systolic diameter(LVESD),or left ventricular end-diastolic diameter(LVEDD)between the two groups before treatment (P＞0.05).Compared with Group B,BNP,IL-12,LVEF,LVESD and LVEDD had significantly better profiles in Group A after treatment (P ＜ 0.05).The time-domain measurements of heart rate variability such as sequential five-minute R-R interval means(SDANN),standard deviation of the N-N interval(SDNN),percent of differences between adjacent RR intervals ＞50ms(PNN50)and root mean square of the successive differences(RMSSD)were higher in Group B than in Group A after treatment.No serious adverse reactions were observed in either group,and there was no significant difference in the incidence of adverse reactions between the two groups(4.7％ vs.7.8 ％,x2 =0.533,P =0.465).Conclusions Irbesartan Hydrochlorothiazide combined with Metoprolol as initial therapy has good clinical effects in treating elderly heart failure.It can not only improve the clinical symptoms of patients,but also ensure clinical medication safety.

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.

Simultaneous determination of candesartan and hydrochlorothiazide in human plasma by LC-MS/MS

Abstract A simple, sensitive, rapid and highly efficient LC-MS/MS method was developed for the determination of Candesartan and Hydrochlorothiazide simultaneously in human plasma. The method employed Zorbax eclipse C18 (150 X 4.6 mm, 5µ) column using acetate buffer: acetonitrile (25:75%, v/v) as the mobile phase. The mobile phase flow rate is 1 mL/min which was delivered into the mass spectrometer electron spray ionization chamber. The Liquid/liquid extraction procedure was used in the method for the extraction of analytes. The chromatograph was attached to a negative ion mode tandem mass spectrometer and the method was validated for all the parameters as per the guidelines of US-FDA. The ions were detected in multiple reaction monitoring mode and the transitions are m/z 439.00®309.10 and 295.80®268.80 for candesartan and hydrochlorothiazide respectively. Isotopic standards were used as internal standards for effective recovery of the analytes. The drugs were analyzed over a calibration range of 1.027-302.047 ng/mL for candesartan and 1.044-306.945 ng/mL for hydrochlorothiazide respectively with regression coefficient greater than 0.99. The mean extraction recoveries are 96.95±5.61 and 100.55±4.82 for candesartan and hydrochlorothiazide respectively. The precision and accuracy values for all the studies were within the range of ≤15% and 85-115%. The performed stability studies indicate that the developed method is stable in plasma for 15 h at room temperature (bench top); 52 h (in injector); for 112 days at -70 ºC for long term stability; five successive freeze and thaw cycles. The developed method could be successfully employed for the determination of selected drugs in biological samples.

Similarity Evaluation of Dissolution Curves of Self-made and Original Telmisartan /Hydrochlorothiazide Tablets by the f2 Factor Method / 中国药学杂志

OBJECTIVE: To explore the similarity of the dissolution curves of self-made and original telmisartan /hydrochlorothiazide tablets and provide basis for the prescription and process screening of self-made preparation and the quality similarity evaluation with original preparation. METHODS: The dissolution curves of telmisartan and hydrochlorothiazide from self-made and original preparations in four different dissolution media were determined using HPLC. The HPLC method was performed on Welch Ultimate XB-C8 column (4.6 mm × 250 mm, 5 μm) with mobile phase A consisting of ammonium dihydrogen phosphate solution (2.0 g ammonium dihydrogen phosphate was dissolved in 1 L water then adjusted to pH 3.0 with phosphoric acid) and mobile phase B consisting of acetonitrile- methanol (50:50) at a flow rate of 1.2 mL•min-1. The detection wavelength was set at 270 nm. The injection volume was 20 μL. Then f2 factor method was used to evaluate the similarity. RESULTS: The dissolution curves of self-made and original preparations of telmisartan /hydrochlorothiazide tablets in different dissolution media showed similarity, with the f2 factor ≥50 or the dissolution rate within 15 min≥85%. CONCLUSION: The dissolution behaviors of self-made and original telmisartan /hydrochlorothiazide tablets are basically similar, which indicates that the prescription and technology of self-made preparation are reasonable and feasible.

Therapeutic effect and safety of irbesartan hydrochlorothiazide combined amlodipine besylate on young and middle-aged patients with hypertension / 心血管康复医学杂志

Objective :To explore therapeutic effect and safety of irbesartan hydrochlorothiazide (I+H) tablet combined am-lodipine besylate on young and middle-aged patients with hypertension .Methods : A total of 138 young and middle-aged pa-tients with hypertension ,who were treated in our hospital from Jan 2015 to Feb 2017 ,were selected .Patients were ran-domly and equally divided into group A (received I+ H therapy) ,group B (received amlodipine treatment ) and group C (received I+ H+ amlodipine treatment ) ,all groups were continuously treated for three months .Systolic blood pressure (SBP) ,diastolic blood pressure (DBP) and heart rate (HR) before and after treatment ,total effective rate and incidence rate of adverse reactions were measured and compared among three groups .Results :Compared with before treatment ,after treatment ,there were significant reductions in SBP ,DBP and HR in three groups , P＜0.05 or ＜0.01. Compared with group A after treatment ,there was significant reduction in SBP [ (133.1 ± 6.2) mmHgvs.(128.9 ± 6.0) mmHg vs. (122.0 ± 3.8) mmHg] in group B and C ,and that of group C was significantly lower than that of group B ,P＜0.01 all ;compared with group B after treatment ,there was significant reduction in DBP [ (91.7 ± 6.7) mmHg vs.(87.5 ± 4.8) mmHg vs.(79.3 ± 3.0) mmHg] in group A and C ,and that of group C was significantly lower than that of group A ,P＜0.01 all.Compared with group A and B ,there was significant rise in total effective rate (78.3% vs.73.9% vs.97.8%) in group C , P＜0.01 all.There was no significant difference in incidence rate of adverse reactions among three groups , P＝0.876 .Conclusion : Irbesartan hydrochlorothiazide tablet combined amlodipine besylate tablet can significantly improve blood pressure in young and middle-aged patients with hypertension , Its effect is better than that of two drugs alone use . Which is safe and reliable ,and is worth extending .

Precise dosage of commercial warfarin sodium tablets and hydrochlorothiazide tablets by 3D printing / 药学学报

The aim of this study is to apply 3D printing technology to hospital drug dosing operations, and explore its feasibility and scalability. Drugs often dosed in hospitals are selected as models. The commercially available drug was ground into powder, diluted with medicinal excipients and then mixed with 75% ethanol and binder to prepare a paste for 3D printing. The dose and physicochemical properties of divided tablets were controlled by setting print parameters and printing models in computer software. Different 3D printers were employed to evaluate the impact of the device on the dosing tablet. Two drugs were dosed in this study to explore the scalability of 3D printing technology between different drugs. The drug content of the three divided dose tablets (warfarin sodium 1 mg, 2 mg, hydrochlorothiazide 5 mg) was 1.02±0.03, 1.96±0.01, 5.19±0.06 mg. The content uniformity was 1.0, 5.3, 2.6, respectively. The drug dissolution rate was (99.3±1.2)%, (101.5±0.3)%, (98.1±0.8)% in 45, 45 and 30 min. The mechanical properties of the three sub-doses and the stability within 30 days were in line with the Chinese Pharmacopoeia (2015) requirements. At the same time, it was found that the printing parameters and prescriptions can affect the properties of the divided dose tablets. By controlling the dilution ratio of commercial drug and printing parameters, the drug release rate can be customized to achieve individualized treatment. Both different modes of 3D printers can produce qualified sub-doses, and 3D print dispensing technology was also versatile between the two drugs. 3D printing can prepare small-volume, high-precision, high-repetition dosing tablets, with all properties in compliance with pharmacopoeia regulations. Thus, this method can be used as a new and scalable sub-dosing method.

Edema pulmonar agudo no cardiogénico secundario a hidroclorotiazida: reporte de un caso y revisión de la literatura / Hydrochlorothiazide induced non-cardiogenic acute pulmonary edema: a case report

Las tiazidas son fármacos frecuentemente usados en la terapia de la hipertensión arterial. Las reacciones adversas de riesgo vital como shock y edema pulmonar agudo son raros. Comunicamos el caso de una mujer de 55 años de edad atendida en Hospital de Puerto Montt, quien tras dos horas de ingerir hidroclorotiazida presentó disnea. Los exámenes de laboratorio generales e imágenes muestran cuadro concordante con edema pulmonar agudo no cardiogénico. Además de la suspensión del fármaco, se realizó soporte hemodinámico y ventilatorio no invasivo, evidenciándose resolución del cuadro a las 48 h. La paciente fue dada de alta 3 días después de su ingreso sin sintomatología.

Thiazides are drugs often used in management of high arterial blood pressure. Shock and acute pulmonary edema are rarely described as adverse reactions related to this drug. We report the case of a 55 years-old woman admitted at Hospital de Puerto Montt, Chile. Two hours after having her first dose of hydrochlorothiazide she presented dyspnea. Laboratory tests and images support the diagnosis of non-cardiogenic pulmonary edema. Resolution of her clinical picture was observed 48 hours after hydrochlorothiazide administration was discontinued and hemodynamic and non invasive ventilation support were supplied. The patient was discharged without symptoms, 3 days after entering to hospital.

Continuous wavelet transform methods for the simultaneous determinations and dissolution profiles of valsartan and hydrochlorothiazide in tablets

ABSTRACT Continuous wavelet transform (CWT) was proposed for the simultaneous determination and dissolution profiles of valsartan (VAL) and hydrochlorothiazide (HCT) in tablets, without the use of a chemical separation procedure. The CWT approach was applied to the original UV spectra and their ratio spectra in the optimal wavelength ranges. After testing several wavelet families, Mexican hat function-CWT and Daubechies7-CWT (mexh-CWT and db7-CWT, respectively) were found to be suitable for the transformation of the original UV spectra. In the following procedure, mexh-CWT and Coiflets3-CWT (coif3-CWT) were found to be appropriate for the signal analysis of ratio spectra (RS) of VAL/HCT and HCT/VAL. Calibration graphs for VAL and HCT were obtained by measuring db7-CWT and mexh-CWT amplitudes in the transformation of the original absorption spectra and RS-coif-CWT and RS-mexh-CWT amplitudes in the transformation of the ratio spectra. The validity and applicability of the proposed CWT methods were evaluated through the analysis of an independent set of synthetic binary mixtures consisting of VAL and HCT. The proposed signal processing methods were then successfully applied to the simultaneous quantitative evaluation and simultaneous dissolution profiles of the related drugs in commercial tablets, with good agreement reported for the experimental results.

Clinical Observation of Valsartan Combined with Hydrochlorothiazide in the Treatment of Chronic Renal Disease Complicated with Hypertension / 中国药房

OBJECTIVE:To observe clinical efficacy and safety of valsartan combined with hydrochlorothiazide in the treat-ment of chronic renal disease complicated with hypertension. METHODS:A total of 156 chronic kidney disease patients with renal hypertensive were randomly divided into control group and observation group with 78 cases in each group. Control group was given hydrochlorothiazide tablets 25 mg orally,once a day. Observation group was additionally given valsartan capsule 80 mg orally,once a day,on the basis of control group. Treatment course of 2 groups lasted for 4 weeks. Clinical efficacies of 2 groups were observed and compared,and the levels of SBP,DBP,GFR,24 h urine protein quantification,Scr and BUN were observed before and after treatment. The occurrence of ADR was recorded. RESULTS:After treatment,total response rate of observation group was signifi-cantly higher than that of control group,with statistical significance (85.90% vs. 64.10%,P<0.05). Before treatment,there was no statistical significance in SBP,DBP,GFR,24 h urine protein quantification,Scr and BUN between 2 groups(P>0.05). After treatment,SBP,DBP,24 h urine protein quantification,Scr and BUN of 2 groups were significantly lower than before treatment,the observation group was significantly lower than the control group,GFR was significantly higher than before treatment,the observa-tion group was significantly higher than that of control group,with statistical significance(P<0.05). There was no statistical signif-icance in the incidence of ADR between 2 groups(P>0.05). CONCLUSIONS:Valsartan combined with hydrochlorothiazide show good therapeutic efficacy for chronic renal disease complicated with hypertension,and can significantly improve blood pressure and renal function with good safety.

Simultaneous quantification of amiloride and hydrochlorothiazide in human plasma by liquid chromatography–tandem mass spectrometry / 药物分析学报

A selective, sensitive and precise assay based on solid phase extraction and liquid chromatography–tandem mass spectrometry (LC–MS/MS) was developed for the simultaneous determination of amiloride (AMI) and hydrochlorothiazide (HCTZ) in human plasma. Sample clean-up with 250 μL of plasma was done on Phenomenex Strata?-X extraction cartridges using their labeled internal standards (AMI-15N3 and HCTZ- 13C,d2). Chromatography was performed on Hypersil Gold C18 (50 mm×3.0 mm, 5 μm) column using acetonitrile with 4.0 mM ammonium formate (pH 4.0, adjusted with 0.1% formic acid) (80:20, v/v) as the mobile phase. Detection was carried out on a triple quadrupole API 5500 mass spectrometer utilizing an electrospray ionization interface and operating in the positive ionization mode for AMI and negative ionization mode for HCTZ. Multiple reaction monitoring was used following the transitions at m/z 230.6/116.0, m/z 233.6/116.0, m/z 296.0/204.9 and m/z 299.0/205.9 for AMI, AMI-15N3, HCTZ and HCTZ-13C,d2, respectively. Calibration curves were linear (r2≥0.9997) over the concentration range of 0.050–50.0 and 0.50–500 ng/mL for AMI and HCTZ, respectively, with acceptable accuracy and precision. The signal-to-noise ratio at the limit of quantitation was ≥14 for both the analytes. The mean recovery of AMI and HCTZ from plasma was 89.0% and 98.7%, respectively. The IS-normalized matrix factors determined for matrix effect ranged from 0.971 to 1.024 for both the analytes. The validated LC–MS/MS method was successfully applied to a bioequivalence study using 5 mg AMI and 50 mg HCTZ fixed dose tablet formulation in 18 healthy Indian volunteers with good reproducibility.