Combination Of Hydrochlorothiazide Research Articles

EXPLORING THE POTENTIAL OF ORODISPERSIBLE TABLET OF ENALAPRIL MALEATE AND HYDROCHLOROTHIAZIDE DRUG COMBINATION

The objective of the present work was to formulate and evaluate orodispersible tablets of enalapril maleate and hydrochlorothiazide combination to overcome the shortcomings of conventional dosage forms and improve patient compliance. Eleven formulations were prepared by wet granulation method using sodium starch glycolate as superdisintegrant and microcrystalline cellulose and Pearlitol 200 SD as diluents. The process variables were optimized to get desired characteristics. Various pre-compression and post-compression quality control parameters were evaluated. The wetting and disintegration times of formulation F10 were found to be 11 ± 4 and 15 ± 2 seconds, respectively. The in vitro dissolution study showed 97.2 % release of enalapril maleate and 96.94 % release of hydrochlorothiazide within 10 min. The optimized formulation was found to be stable during stability study. The study concludes that orodispersible tablet of enalapril maleate and hydrochlorothiazide could be a better approach for the treatment of hypertension.

SO001BOTH HYDROCHLOROTHIAZIDE AND METFORMIN AMELIORATE AQUARETIC SIDE-EFFECTS IN ADPKD PATIENTS THAT ARE TREATED WITH TOLVAPTAN

Abstract Background and Aims The vasopressin V2 receptor antagonist tolvaptan is the first drug that was proven to ameliorate kidney function decline in ADPKD. Blockade of the vasopressin V2 receptor, however, also results in nephrogenic diabetes insipidus (NDI), with an associated polyuria of on average 6 to 8 L/24h, limiting its clinical use. Hydrochlorothiazide (HCT) is an established treatment in NDI of other origins, but is unclear whether it is also efficacious in tolvaptan-caused NDI. Importantly, the combination of HCT and tolvaptan could cause electrolyte disturbances, and HCT treatment could theoretically increase vasopressin, which might accelerate ADPKD disease progression. Recently, metformin has been shown to ameliorate aquaresis in an animal model of NDI, but has never been investigated for this indication in humans. We aimed to investigate efficacy and safety of hydrochlorothiazide and metformin treatment to ameliorate the aquaretic side-effects of tolvaptan. Method This is an investigator driven, double-blind, randomized, controlled cross-over trial. ADPKD patients (Ravine criteria) were eligible for inclusion if they were 18-55 years of age, had an eGFR ≥ 30 mL/min/1.73m2 and were treated with a stable dose of tolvaptan. Patients were treated for three 2 week-periods with hydrochlorothiazide (HCT) 25 mg (12.5 mg in the first week), metformin 2000 mg (1000 mg in the first week) or placebo (half dose in the first week), in random order. Primary outcome was change in 24-hour urine volume (average of 2 collections) compared to baseline. Key secondary outcomes were measured GFR (mGFR), plasma copeptin (the stable precursor of vasopressin), quality of life and electrolytes. Results All 13 patients that were included were able to complete every treatment period in the trial. Their mean age was 45±8 years, 54% was female and mGFR was 55±11 mL/min/1.73m2 (Table). 85% of participants used the maximum tolvaptan dose (90/30 mg). At baseline urine volume was 6.9±1.4 L/24h. On HCT treatment urine volume decreased with -25±13% (p<0.001) and on metformin with -22±10% (p<0.001). Metformin treatment induced no change in mGFR and copeptin compared to baseline. During HCT treatment however, both mGFR and copeptin were lower (p=0.002 and p=0.001, respectively). There were no adverse events that required dose reductions. Quality of life was found to be equal on metformin and borderline better (p=0.06) on HCT treatment when compared to tolvaptan only. Plasma sodium was similar during all three treatment periods. Plasma potassium was significantly lower during HCT treatment (p=0.01), but in only three cases mild hypokalemia was noted (plasma potassium 3.0-3.5 mmol/L). Conclusion This is the first study to show that metformin can ameliorate aquaresis in NDI, and that HCT improves tolvaptan-caused NDI. Both treatments were well tolerated and safe during short-term use. The fact that copeptin is not increased by metformin, and even decreased by HCT suggests that these treatments will not negatively impact renoprotection by tolvaptan. These data provide an evidence base to test metformin and especially HCT in a real life setting to improve aquaresis and tolerability in patients with tolvaptan induced NDI. BaselineHCTPlaceboMetforminAbsolute urine volume (L/24h)6.95.1**6.35.4**Change in urine volume (%)0-25**-8-22**Creatinine excretion (mmol/24h)15.815.416.115.7Osmolar excretion (mOsm/24h)104410201013947*mGFR (mL/min/1.73m2)5551**5554SBP (mmHg)125117**122120Plasma copeptin (pmol/L)2520**2628Plasma sodium (mmol/L)141139141140Plasma potassium (mmol/L)3.83.6*3.94.0Plasma urea (mmol/L)7.08.6**6.97.2QoL ImprovedN/A7 (58%)2 (17%)1 (8%)Results in n=13 ADPKD patients on highest tolerated tolvaptan dose*P<0.05 compared to placebo ** p<0.01 compared to placeboFigure:

MON-627 Number of Antihypertensives Required for Achieving BP Goals in Individuals with Diabetes and Hypertension-A Cross-Sectional Observational Study

BACKGROUND: The 2019 ADA Standards of Medical Care in Diabetes, recommends blood pressure (BP) target of <130/80 mmHg for individuals with diabetes and hypertension at higher cardiovascular (CV) risk and a BP target of <140/90 mmHg for individuals at lower risk for CV disease.1 Monotherapy can attain goal BP in some patients with diabetes and hypertension. This is most likely to occur in those with BP that are only modestly above goal. However, combination therapy is eventually required in most patients.2 AIM: To assess the number of antihypertensives that are required for optimal control of BP in Indian patients with type 2 diabetes mellitus (T2DM) and hypertension. METHODS: Data was retrieved from the electronic database of a tertiary super-speciality hospital in Kolkata over a period of four weeks in July to August 2018. The inclusion criteria- T2DM patients with hypertension between 35 to 55 years of age. Patients with recent weight gain, recent use of SGLT 2 inhibitors and those with prior cardiac events were excluded from the study.The study included 2000 adult patients with T2DM with normal renal function. Of these, 58% were male patients. The mean age was 48 years. The mean HbA1c was 7.4% during the period of observation. Patients were being treated with oral hypoglycaemic agents (OHA) (except SGLT 2 inhibitors which might affect BP) or insulin. All patients were receiving statins. The antihypertensives that were considered were analysis were telmisartan, amlodipine, and hydrochlorothiazide. RESULTS: The number of T2DM Hypertensive patients requiring 3 or more drugs were 640 (32 %). Out of the 640 patients, 300 patients (15 %) required higher dose of telmisartan 80 mg.A total 980 patients (49%) required a combination of two drugs (telmisartan and amlodipine) for optimal BP control. Out of these 980 patients, 360 patients (18%) required higher dose of telmisartan i.e. 80 mg. One hundred and eighty patients (9%) required a combination of telmisartan and hydrochlorothiazide. Out of these 180 patients, 80 patients (4%) required higher dose of Telmisartan i.e. 80mg. Two hundred patients (10 %) required only one drug i.e. telmisartan for achieving optimal BP. Out of these 200 patients, 110 patients (5.5 %) required the higher dose of telmisartan i.e. 80 mg CONCLUSION: The optimal control of BP is mandatory in T2DM patients in order to reduce cardiovascular events as well as microvascular complications. As evident from our study majority of patients required more than one antihypertensive, 32% required triple drug therapy and 49 % required dual therapy for optimal BP control. Regular monitoring of BP and timely up-titration of antihypertensives are of utmost importance to prevent future micro- and macro- vascular complications in young diabetic hypertensives.

The Effects of Telmisartan and Its Combinations on Office Blood Pressure: Results of Prospective Observational Study TAINA

Aim. To evaluate the effectiveness and safety of telmisartan, used in monotherapy or in combination with hydrochlorothiazide or amlodipine, in real clinical practice in patients with diagnosed arterial hypertension who have not reached the target levels of blood pressure (BP).Material and methods. The study was a non-intervention, prospective, multicenter, comparative, observational, epidemiological program, which was carried out in Russian medical institutions. The total patient population in which the prescribed therapy was administered included 1933 people (758 men and 1175 women, mean age 57.0-59.3 years). Participants were followed-up for 12 weeks. The change in office BP was evaluated on the 4th and 12th week.Results. Significant (p&lt;0.001 in all cases) change in office BP compared with the initial data were recorded in all study groups of therapy already at 4 weeks of treatment and became even more pronounced at 12 weeks. In the telmisartan monotherapy group, BP decreased from 155.7±10.7/92.2±7.6 mm Hg to 131.4±12.1/80.8±7.3 mm Hg at the end of the 4th week and to 125.3±7.6/78.2±6.1 mm Hg – at the end of the 12th week. Similarly, after treatment with the combination of telmisartan and hydrochlorothiazide, BP decreased from 162.7±12.6/94.3±7.9 mm Hg to 133.2±12.5/81.6±8.4 mmHg at the end of the 4th week and to 126.0±7.8/78.4±6.7 mm Hg – at the end of the 12th week. In telmisartan/amlodipine group, a decrease in BP also occurred, from 162.5±13.2/94.6±8.6 mm Hg to 132.8±14.5/81.3±7.5 mm Hg on the 4th week and to 125.4±8.7/78.4±5.6 mm Hg at the end of follow up (12 weeks). The proportion of patients who reached the target BP (&lt;140/90 mm Hg) after treatment with telmisartan as monotherapy was 91.7%, after treatment with telmisartan+hydrochlorothiazide – 89.6%, after treatment with telmisartan+amlodipine – 92.8%. Throughout the program, prescribed therapy was well tolerated by patients. During the study, 47 adverse events (AEs) were recorded in 36 patients: 31 AEs with telmisartan monotherapy, 5 AEs with telmisartan/hydrochlorothiazide combination, and 11 AEs with telmisartan/amlodipine combination. Most of the AEs registered during the trial resolved by the end of the study, in four cases the date of AEs resolve is unknown, in two cases, at the time of completion of the study, AEs continued.Conclusion. In the TAINA study a high antihypertensive efficacy and a comparable favorable safety and tolerability profile of telmisartan, used as monotherapy and in combination with hydrochlorothiazide or amlodipine was determined.

Dissolution and Permeability Properties of Co-Amorphous Formulations of Hydrochlorothiazide

A biopharmaceutics classification system class IV drug, hydrochlorothiazide (HCT), was combined with co-formers of L-and d-arginine (ARG) and sodium lauryl sulphate (SLS) by cryomilling in 1:1 molar ratio. Co-amorphization was observed with L- and D-ARG. These mixtures showed a single glass transition, evidence of possible salt formation and improved physical stability at elevated temperatures and/or humidity when compared with amorphous HCT. The co-amorphous formulations, along with the combinations of HCT and HCT:L-ARG with polyvinylpyrrolidone (PVP) in 1:1 mass ratio, were investigated with a simultaneous dissolution/permeation setup using parallel artificial membrane permeability assay (PAMPA) or Madine Darby kidney cells (MDCKII) as the permeation barrier. It was observed that co-amorphization with L-ARG and D-ARG was able to induce a supersaturated state for HCT, possibly through intermolecular interactions, but there was virtually no difference between the dissolution properties of the mixtures formed with the 2 optical isomers of ARG. The permeability of HCT was found to be dependent on the dissolution properties of the formulations in both PAMPA and cellular barrier experiments. Thus, co-amorphization of HCT with L- and D-ARG demonstrated the possibility to enhance the dissolution and thereby the permeation potential of a BCS class IV drug.

Sequential liquid-liquid extraction coupled to LC-MS/MS for simultaneous determination of amlodipine, olmesartan and hydrochlorothiazide in plasma samples: Application to pharmacokinetic studies

A recent fixed combination of amlodipine (AML) besylate, olmesartan (OLM) medoxomil and hydrochlorothiazide (HCT) has been marketed for the treatment of hypertension. The bioanalysis of this mixture is a challenge due to the diverse physicochemical properties. The aim of this study is to develop a method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous bioanalysis of the mixture in human plasma.A mobile phase of 10 mM ammonium formate containing 0.1% formic acid: methanol: acetonitrile (35:50:15, v/v/v) was recruited for the chromatographic separation of the mixture on a Zorbax SB-Aq (150×4.6 mm, 5 µm) column. The deutrated analogues of AML, OLM and HCT were used as the internal standards (IS). Polarity switching SRM transitions in positive-mode for AML, OLM, and negative-mode for HCT were applied for detection. Sequential double liquid-liquid extraction (SdLLE) was adopted for sample preparation. The developed method was fully validated and applied for the determination of AML, OLM and HCT following a single oral administration of 5/20/12.5 mg of AML, OLM and HCT, respectively tablets to healthy volunteers (n = 30).The developed method was linear (r2> 0.99), accurate (105 - 90%), precise (CV% <11.92) and specific for the determination of AML, OLM and HCT over the concentration range of 0.1–15, 5–1200 and 2–150 ng/mL. The adopted SdLLE resulted into reproducible extraction recoveries of 75%, 63% and 83% for AML, OLM and HCT, respectively. The pharmacokinetic analysis revealed uniform profile in the subjects which were comparable to previously reported results in other populations.

Simultaneous Determination of Hydrochlorothiazide in Combination with Some Antihypertensive Drugs in The Presence of Its Main Impurities in Pure Form and Pharmaceutical Formulations

Background:Hydrochlorothiazide (HCTZ) is potent diuretic that is used alone or in combination with other drugs such as labetalol (Lab) (mixtures Ι) or nebivolol (Neb) (mixtures ΙΙ) to control moderate to sever hypertension.Introduction:This paper demonstrates the establishment of different validated spectrophotometric and chemometric methods for simultaneous estimation of these mixtures in pure form and pharmaceutical formulations in the presence of HCTZ related impurities in quality control laboratories.Methods:(A) Derivative method (D3) of Lab and HCTZ and its related impurities at 245.3nm and 278.5nm respectively, (D1) of Neb and HCTZ at 294.2nm and 282.2nm, respectively. (B) First derivative of ratio spectra method (DD 1) of Lab at 244.3nm, HCTZ at 261.2nm and 275.4nm, while at 294nm for Neb and 269.4nm for HCTZ. (C) Ratio difference method which depends on measuring the distinction between the amplitudes of ratio spectra at 240nm and 288.3nm for Lab and at 270.1nm and 277.4nm for HCTZ for mixture Ι while at 290.4nm and 299.2nm for Neb and at 232.2nm and 254nm for HCTZ for mixture ΙΙ. (D) Mean centering of ratio spectra (MC) and (E) partial least squares regression (PLS) and principal component regression (PCR).Results:These methods were applied over concentration ranges of 10-100 µg/ml, 10-75 µg/ml and 2.5- 25 µg/ml of Lab, Neb and HCTZ, respectively. Methods were validated according to ICH guidelines and statistical comparison of results of reported and proposed methods revealed no difference.Conclusion:The methods were successfully used for the frequent analysis of selected mixtures in quality control laboratories.

Efficacy of chlorthalidone and hydrochlorothiazide in combination with amiloride in multiple doses on blood pressure in patients with primary hypertension: a protocol for a factorial randomized controlled trial

BackgroundThiazide diuretics have demonstrated favorable blood pressure lowering efficacy, but the equivalent doses of their more common agents, chlorthalidone and hydrochlorothiazide, are still unclear. Further, concerns exist regarding adverse metabolic effects, which may be attenuated with the concomitant administration of a potassium-sparing diuretic, such as amiloride. This trial aims to investigate the efficacy of chlorthalidone and hydrochlorothiazide, in combination with amiloride at different doses, for initial management of patients with primary hypertension.Methods/designThis is a factorial (2 × 2) randomized double-blinded clinical trial comparing the association of a thiazide diuretic (chlorthalidone 25 mg/day or hydrochlorothiazide 50 mg/day) with a potassium-sparing diuretic (amiloride 10 mg/day or amiloride 20 mg/day) in patients with primary hypertension. The primary outcome will be the mean change from baseline in 24-h systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring. The secondary outcomes will be the mean change from baseline in daytime and nighttime systolic and diastolic blood pressure measured by ambulatory blood pressure monitoring, mean change from baseline in systolic and diastolic blood pressure measured by office blood pressure, incidence of adverse events, variation of laboratory parameters, and proportion of patients who achieved blood pressure control. The follow-up will last 12 weeks. For a P alpha of 0.05, power of 80%, standard deviation of 9 mmHg, and absolute difference of 6 mmHg on systolic blood pressure on 24-h ambulatory blood pressure monitoring, it will be necessary to study a total of 76 patients. The sample size will be increased by 10% to compensate for losses, resulting in 84 patients being randomized.DiscussionDiuretics are pivotal drugs for the treatment of hypertension. Chlorthalidone and hydrochlorothiazide, in combination with amiloride in multiple doses, will be tested in terms of blood pressure lowering efficacy and safety. Since the intensity of blood pressure reduction is the major determinant of reduction in cardiovascular risk in hypertensive patients, this study will help to determine which combination of diuretics represents the most appropriate treatment for this population.Trial registrationClinicalTrials.gov, NCT03928145. Registered on 25 April 2019. Last update on 29 April 2019.

Highlights of the December issue.

Highlights of the December issue.

A VALIDATED HIGH PERFORMANCE THIN LAYER CHROMATOGRAPHIC METHOD FOR LOSARTAN POTASSIUM AND HYDROCHLOROTHIAZIDE IN COMBINATION

A high performance thin layer chromatographic method has been reported for estimation of losartan potassium with hydrochlorothiazide in combination. The analytes were resolved on precoated silica gel 60 F254 TLC plates prewashed with methanol using solvent system composition of chloroform: Methanol : Ethyl acetate (4:2:2 v/v/v) with 15 min time of saturation. The analytes were tracked down at 255 nm. The components were resolved with retention factor of losartan potassium (0.59 ± 1.98) and hydrochlorothiazide (0.83 ± 1.95). The method assured linearity in the concentration range of 600-1000 ng/spot for losartan potassium and 300-500 ng/spot for hydrochlorothiazide, respectively. Accuracy of method was assessed and found upto 100 % ± &lt;2. The method assured high degree of precision. The robustness was confirmed by deliberately varying the parameters like composition of mobile phase, mobile phase volume, detection wavelength, chamber saturation time.

The effectiveness of therapy with valsartan and hydrochlorothiazide and its effect on the left atrial myocardium condition in women with arterial hypertension in postmenopause

Purpose - to evaluate the effectiveness of the combination of valsartan and hydrochlorothiazide and its effect on the structural and functional parameters of the left atrial myocardium in postmenopausal women with arterial hypertension.Materials and methods. An open prospective controlled study included 100 postmenopausal women with uncomplicated arterial hypertension. Transthoracic and speckle tracking echocardiography was performed on a Vivid E9 XDClear Console 4D Expert 100 ultrasound scanner (General Electric, USA) with ECG-synchronization. Ambulatory blood pressure monitoring was performed using the device ABPM-04 (Meditech, Hungary). After 6 months of treatment with the antihypertensive combination of valsartan and hydrochlorothiazide, all women were re-examined in full. Statistical analysis of the results was performed using the Statistica 13.0 software package. All tests were two-way, statistically significant considered differences at P < 0.05.Results. As a result of our study, office systolic and office diastolic blood pressure in postmenopausal women with arterial hypertension significantly decreased (P < 0.001) due to a 6-month treatment with valsartan and hydrochlorothiazide. The target level of blood pressure, according to office measurements, was reached by 64 % of patients. A significant decrease of the SBP time index in the daytime in 1.6 times (P = 0.012), morning rise of SBP (P = 0.021) and the average pulse blood pressure (P = 0.012) was observed. Analysis of the LA deformation dynamics under the 6-month antihypertensive therapy did not reveal significant changes in the longitudinal strain of the LA in postmenopausal women with AH, unlike left ventricular strain.Conclusions. Combined antihypertensive therapy with valsartan and hydrochlorothiazide in postmenopausal women is effective, safe and well-tolerated. The use of this therapy for 6 months does not significantly affect the size and deformation properties of the left atrium, in contrast to the positive structural and functional remodeling of the left ventricle.

Adverse effects of interactions between antidepressants and medications used in treatment of cardiovascular disorders.

To evaluate harmful interactions between antidepressants and medications used in treatment of cardiovascular disorders. The analysis of 66 cases of adverse reactions with a clinical picture indicating, to a degree that is probable or certain, that they were the result of the combination of antidepressant with cardiovascular medication. The most common side effect (n = 25, 37.9%) was bradycardia (and other side effects of beta blockers) as a consequence of addition of metoprolol or propranolol to SSRI or bupropion. In one case combination of fluoxetine with propranolol resulted in cardiac arrest. We observed 8 cases of intensified side effects of amlodipine (swelling of lower limbs, headaches) after its combination with: fluoxetine, sertraline and paroxetine, and occurrence of myalgia, elevated aminotransferase levels, polyuria and hypotension after combination of lercanidipine with some of the SSRIs. We also found i.a. worsening of propafenone tolerance in combination with venlafaxine or bupropion, 2 cases of granulopenia associated with duloxetine-propafenone combination, 2 cases of hemorrhagic complications associated with the combination of vortioxetine-warfarin, 1 case of hyponatremia associated with the combination of vortioxetine and hydrochlorothiazide, as well as antagonizing clonidine's hypotensive effect by mirtazapine, and peripheral thrombosis following the combination of warfarin with trazodone. Because of ahigh risk of interactions and related adverse effects, especially in older patients, each decision regarding combination of a particular antidepressant with a medication used in treatment of cardiovascular disorders should be preceded by a detailed analysis of safety and risk-benefit ratio, and also be associated with the search for the safest, alternative combinations of the above-mentioned medications.

DYNAMICS OF LEFT VENTRICULAR DEFORMATION INDICATORS AND MARKERS OF CARDIAC REMODELING ST-2 AND CARDIOTROPHIN-1 IN POSTMENOPAUSAL WOMEN WITH ARTERIAL HYPERTENSION UNDER THE INFLUENCE OF COMBINED ANTIHYPERTENSIVE THERAPY

Objective - to determine the effect of the combination of valsartan and hydrochlorothiazide on the parameters of the left ventricular deformation and the dynamics ofbiochemical markers of cardiac remodeling (cardiotrophin-1 and soluble ST-2) inpostmenopausal women with arterial hypertension.Material and methods. An open, prospective, controlled study included 100 postmenopausal women with stage I - II of arterial hypertension. Transthoracic and speckletracking echocardiography were performed on a Vivid E9 XDClear Console 4D Expert100 ultrasound scanner (General Electric, USA) with ECG synchronization. Ambulatorymonitoring of blood pressure was performed using the device ABPM-04 (Meditech, Hungary). The concentrations of cardiotrophin-1 and ST-2 were determined by the method ofenzyme-linked immunosorbent assay. After 6 months of treatment with a combination ofvalsartan and hydrochlorothiazide, all women were re-examined. Statistical analysis wasperformed using the Statistica 13.0 software package. All tests were two-sided;statistically significant differences were considered at p &lt;0.05.Results. As a result of a 6-month treatment of patients with a combination of valsartan andhydrochlorothiazide, a significant decreasing of the interventricular septum thickness andLV myocardial mass index, increasing of the LV global longitudinal strain and a decreasing of the mechanical dispersion of segmental strain curves were recorded. Thepositive effect of combination therapy with valsartan and hydrochlorothiazide on thedynamics of cardiac remodeling markers has been established. The median of decreasingof cardiotrophin-1 was -37.93% (p &lt;0.000001), and of soluble ST-2 was -19.74% (p =0.000046).Conclusions. Therapy with a combination of valsartan and hydrochlorothiazide during 6months helps to reduce the severity of left ventricular hypertrophy and improves thedeformation properties of the myocardium. For the first time it was found that thiscombination significantly reduced the concentration of cardiac remodeling and fibrosismarkers - cardiotrophin-1 and soluble ST-2.

Evaluation of losartan plus hydrochlorothiazide combination therapy against amlodipine monotherapy in patients of hypertension

Background: Microalbuminuria has been shown to predict cardiovascular disease (CVD) in patients with hypertension. Recently the FDC of losartan and hydrochlorothiazide (HCTZ) has been reported to be effective for achieving a target BP level and also improvement in cardiovascular prognosis. The present study was conducted to compare effect of losartan plus hydrochlorothiazide combination therapy and high dose amlodipine monotherapy on blood pressure and microalbuminuria.Methods: Total 184 patients with hypertension were randomly allocated to two groups. The patients in group 1 received Amlodipine 5 mg orally for first 4 weeks. The patients from group 2 received losartan 50 mg orally for first 4 weeks. Patients in group 1 were titrated to amlodipine 10 mg orally for next 4 weeks. The patients in group 2 were titrated to FDC of losartan (50 mg) plus HCTZ (12.5 mg) for next 4 weeks. Follow–up visits were scheduled at 4 weeks and 8 weeks. Pulse rate, sSBP and sDBP were estimated at each follow–up. Microalbuminuria was estimated at 8 weeks.Results: There was no significant difference in mean change in sSBP, sDBP and pulse rate between two treatment groups (p&gt;0.05). There was greater reduction in microalbuminuria in group 2 patients (p&lt;0.0001). The adverse effects such as flushing and lower extremity oedema were significantly more in amlodipine group (p&lt;0.05).Conclusions: Losartan plus HCTZ has similar effect on BP, better safety profile and superior effect on microalbuminuria level reduction.

To analyse the efficacy and safety of valsartan along with combination of valsartan and hydrochlorothiazide in mild to moderate arterial hypertension patients

To analyse the efficacy and safety of valsartan along with combination of valsartan and hydrochlorothiazide in mild to moderate arterial hypertension patients

Comparison efficacy and side effects of combined cystone and hydrochlorothiazide with cystone monotherapy in treatment and passage of upper urinary stones; a randomized clinical trial

Introduction: Urinary stones are one of the most common and painful diseases of humans after urinary tract infections and prostate diseases. Objectives: The aim of this study was comparing the efficacy and complications of combined cystone and hydrochlorothiazide with cystone monotherapy in the treatment of upper urinary stones. Patients and Methods: In this randomized clinical trial 80 patients older than 15 years old with renal and ureteral stones less than 10 mm after taking informed consent form were allocated randomly in one of two groups. Patients with azotemia, hydronephrosis, bothersome pain and pregnant women were excluded. In the first group, combinations of cystone and hydrochlorothiazide tablets (every 12 hours, two 100 mg cystone and 25 mg hydrochlorothiazide) were prescribed. In the second group, cystone were prescribed as the first group. One month later, patients were followed by kidney, ureter, and bladder x-ray (KUB) and ultrasonography and the success of treatment was determined by changing the size of stones and report of stone passage by the patients. All data were collected and analyzed by SPSS software version 23 and statistical tests. Results: The mean age of the patients in combined and single groups were 48.02±13.72 and 44.15 ± 14.86(P = 0.24) years respectively. The mean size of stone after treatment in two groups was 1.72±0.98 and 1.85±0.78 mm respectively (P=0.53). Regarding efficacy of combined and single group, more than 90% of the patients reported stones passage after the intervention (P=0.06). There were no significant differences in mean blood urea (P=0.38) and serum creatinine (P=0.53) after treatment in two groups. Conclusion: The results of this study showed that combination of cystone and hydrochlorothiazide do not increase the efficacy of cystone in treatment and passage of urinary stones, although in both groups stone passage significantly increased.

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

BackgroundThe efficacy of combined diuretic treatment in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) is not known.MethodsIn 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).ResultsForty-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.ConclusionFor 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.

Stability-indicating methods for determination of hydrochlorothiazide in combination with some antihypertensive drugs in the presence of its main impurities

Hydrochlorothiazide (HCTZ) is potent diuretic that used alone or in combination with other antihypertensive drugs such as labetalol hydrochloride (Lab) or nebivolol hydrochloride (Neb) to control moderate to severe hypertension. As there is no published method for simultaneous determination of HCTZ and Lab (mixture Ι) or Neb (mixture ΙΙ) in pharmaceutical formulations in presence of HCTZ-related impurities, it was important to develop validated stability-indicating HPLC methods for analysis of these mixtures in quality control laboratories. These methods based on gradient RP-HPLC separation of mixture Ι at 215 nm using acetonitrile:0.1% triethylamine pH = 2 (12:88 v/v) as mobile phase at flow rate 1.0 mL/min using Promosil C18 (150 mm × 4.6 mm i.d.; 5 µm) column. While mixture ΙΙ separation was performed at 220 nm using BDS Hypersil C18 (250 mm × 4.6 mm i.d.; 5 µm) column with mobile phase of acetonitrile:phosphate buffer pH = 3 (15:85 v/v) at flow rate 1.0 mL/min. The responses were linear over concentration ranges 2.0–100 µg/mL (r = 0.9997) and 1.0–100 µg/mL (r = 0.9998) with mean recoveries 100.16% and 100.43% of Lab and HCTZ, respectively meanwhile 5.0–100 µg/mL (r = 0.9997) and 2.0–100 µg/mL (r = 0.9996) with mean recoveries 99.99% and 100.63% of Neb and HCTZ, respectively. Methods were validated according to ICH guidelines; the results were statistically compared with the company methods and there was no significant difference. The proposed methods have the advantages of being stability-indicating and time saving with low solvent consumption which favors their usage in quality control routine analysis of selected mixtures in their pharmaceutical formulations.

Development of Validated Q-absorbance Ratio, Derivative Spectrophotometric and Stability indicating RP-HPLC methods for the simultaneous estimation of Losartan Potassium &amp; Hydrochlorothiazide in Pharmaceutical Dosage Form and comparison of the results by ANOVA

Hypertension is estimated to cause 7.5 million deaths, leading to 12.8 % of the total of all deaths worldwide. In the recent years, the combination of Losartan Potassium and Hydrochlorothiazide has attained significant popularity in reducing the risk of heart diseases particularly in the patients with hypertension and ventricular hypertrophy. The literature survey revealed that there were several chromatographic and spectroscopic methods for the simultaneous estimation of the selected drugs but it was noted that there were no reported comparative studies of the developed methods. Hence the authors attempted to develop new validated Q- absorbance ratio, Derivative spectrophotometric and Stability indicating RP-HPLC methods for the simultaneous estimation of Losartan Potassium and Hydrochlorothiazide in pharmaceutical dosage form. The authors also propose to compare the results obtained by ANOVA. The two Spectrophotometric methods were carried out using an Agilent Cary 60 UV-Visible double beam Spectrophotometer. In Q-absorbance ratio method, samples were measured at two wavelengths, 230 nm (isoabsorptive point) and 225.5 nm (?max of Hydrochlorothiazide). In Derivative spectroscopy, analysis was performed by derivatizing the zero order spectrum to the corresponding second order spectrum. Stability indicating RP-HPLC method was performed using Eclipse XDB C18 column where the samples were analyzed using a mixture of Acetonitrile and Water in the ratio of 70:30 % v/v as mobile phase at a flow rate of 1 ml/min. The drugs were monitored at 230 nm. The retention times for Losartan Potassium and Hydrochlorothiazide were found to be 1.010 minutes and 1.387 minutes respectively. The proposed methods were validated as per ICH guidelines. The results obtained from the three developed methods were then compared by ANOVA which indicated that the proposed methods can successfully be used for the analysis of Losartan Potassium and Hydrochlorothiazide in bulk or in combined dosage forms.

Association Between the Use of Thiazide Diuretics and the Risk of Skin Cancers: A Meta-Analysis of Observational Studies.

BackgroundThiazide diuretics are among the most widely prescribed antihypertensive agents. Given their photosensitizing effects, however, there are concerns that they may increase the risk of skin cancers. In this meta-analysis, we investigated an association between the use of thiazide diuretics and the risk of skin cancers.MethodsWe identified studies by searching three electronic databases (PubMed, EMBASE, and the Cochrane Library) from their inception to October 30, 2017. Nine relevant observational studies (seven case-control and two cohort studies) were included in this study. Since included studies were unlikely to be functionally equal, pooled estimates were calculated using random-effects meta-analysis.ResultsThe use of thiazide diuretics was associated with an increased risk of squamous cell carcinoma (adjusted odds ratio (aOR), 1.86; 95% confidence interval (CI), 1.23 - 2.80) and marginally increased risk of basal cell carcinoma (aOR, 1.19; 95% CI, 1.02 - 1.38) and malignant melanoma (aOR, 1.14; 95% CI, 1.01 - 1.29). In the subgroup analysis, hydrochlorothiazide or hydrochlorothiazide combination medications were significantly associated with squamous cell carcinoma without significant heterogeneity among studies (aOR, 2.04; 95% CI, 1.79 - 2.33; Higgin’s I2 value = 0.0 %; Q-statistics = 2.7, P value = 0.445).ConclusionsOur results suggested that the use of thiazide diuretics may be associated with an increased risk of skin cancers. This association was most prominent between the use of hydrochlorothiazide or hydrochlorothiazide combination medications and the risk of squamous cell carcinoma. Further studies are needed to confirm these findings.