... insipidus and certain electrolyte disturbances and to prevent kidney stones in patients with high levels of calcium in ... doctor prescribes a low-salt or low-sodium diet, or to eat or drink increased amounts of ...
The present study was carried out to determine factors that influence caesium metabolism in normal human subjects with particular interest in finding a therapeutic regimen for reducing the body burden of caesium. Since caesium and potassium are chemically similar, and are both localized in the intracellular compartment of the body, principally in muscle, it seemed possible that chlorothiazide, which has a marked potassium diuretic effect, might also increase caesium excretion. Four normal subjects were given a single dose of 0.1 μc of caesium-137 by mouth. Two subjects were given chlorothiazide 2.0 g/d for a total of three consecutive days starting 1 h after the caesium intake. The chlorothiazide dose was repeated at two weeks. The other two subjects were used as controls. The body burden of caesium-137 was measured by a whole-body counter at intervals up to 320 d. Daily urine collections were made for three control days and 20 d following caesium intake. The samples were analysed for electrolytes and caesium activity. Although chlorothiazide increased K excretion to 1. 5 times the control values, it had no significant effect on caesium excretion or in reducing the body burden of caesium. In all subjects a small fraction of caesium (10-20%) was excreted rapidly with a biological half-life (T),) of less than 1 d. The remainder was excreted at a constant rate with Tb of 90 to 155 d. More than 70% of the caesium eliminated from the body per day was excreted by the kidney. Tb of K was also calculated by the formula TbK = Total body K/Urine K x 0,693 x 0,8 assuming 80% of the total potassium excreted is by kidney. Tb of K was 35 to 42 d. The discrimination ratio TbCs/TbK was 2.1 to 3.8. These results demonstrate that caesium and potassium are not utilized interchangeably. Caesium is retained preferentially over potassium and changes in potassium turnover have no effect on caesium turnover. Studies are being carried out at the present time to determine the effect of
... (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS ORAL DOSAGE FORM NEW ANIMAL DRUGS § 520.420...) Limitations. (a) Dosage must be adjusted to meet the changing needs of the individual animal. In mild and... higher doses. Certain animals may respond adequately to intermittent therapy; in these cases, the...
R. A. Mhaske et al.
Full Text Available A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of anti-hypertensive drugs Irbesartan, Losartan, diuretics Hydrochlorothiazide and Chlorthalidone. The separation was achieved on Hypersil BDS (Length 250 mm × Diameter 4.6 mm Particle size 5 μm column with gradient flow. The mobile phase at a flow rate of 1.0 mL min−1 consisted of 0.05 M sodium dihydrogen phosphate buffer and acetonitrile (Gradient ratio. The UV detection was carried out at 220 nm. The method was successfully validated in accordance to ICH guidelines. Further, the validated method was applied for commercially available pharmaceutical dosage form.
Paluch, Krzysztof J; Tajber, Lidia; Corrigan, Owen I; Healy, Anne Marie
In order to investigate the effect of using different solid state forms and specific surface area (TBET) of active pharmaceutical ingredients on tabletability and dissolution performance, the mono- and dihydrated crystalline forms of chlorothiazide sodium and chlorothiazide potassium (CTZK) salts were compared to alternative anhydrous and amorphous forms, as well as to amorphous microparticles of chlorothiazide sodium and potassium which were produced by spray drying and had a large specific surface area. The tablet hardness and tensile strength, porosity, and specific surface area of single-component, convex tablets prepared at different compression pressures were characterized. Results confirmed the complexity of the compressibility mechanisms. In general it may be concluded that factors such as solid-state form (crystalline vs amorphous), type of hydration (presence of interstitial molecules of water, dehydrates), or specific surface area of the material have a direct impact on the tabletability of the powder. It was observed that, for powders of the same solid state form, those with a larger specific surface area compacted well, and better than powders of a lower surface area, even at relatively low compression pressures. Compacts prepared at lower compression pressures from high surface area porous microparticles presented the shortest times to dissolve, when compared with compacts made of equivalent materials, which had to be compressed at higher compression pressures in order to obtain satisfactory compacts. Therefore, materials composed of nanoparticulate microparticles (NPMPs) may be considered as suitable for direct compaction and possibly for inclusion in tablet formulations as bulking agents, APIs, carriers, or binders due to their good compactibility performance. PMID:23961942
Greene, Jeremy A
This article narrates the development and promotion in the 1950s and 1960s of Merck, Sharp & Dohme's Diuril (chlorothiazide), an antihypertensive drug, which played a significant role in the redefinition of high blood pressure as a widespread target for chronic pharmaceutical consumption. The joined careers of Diuril and hypertension in the late twentieth century demonstrate the connections between the clinical research, clinical practice, and marketing practices through which pharmaceuticals and disease categories come to define one another. By examining a series of internal documents preserved in the Merck Archives alongside a careful reading of the clinical literature and industry journals of the time, this article explores how the ambitions of marketers, physicians, and public health advocates found convergence in the expanding pharmaceutical prevention of chronic diseases. PMID:16327086
Xundou Li; Mindi Zhao; Menglin Li; Lulu Jia; Youhe Gao
Biomarker is the measurable change associated with a physiological or pathophysiolog-ical process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F;hydro-chlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were col-lected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on the criteria of P 6 0.05, a fold change P2, a spectral count P5, and false positive rate (FDR) 61%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.
Borowska, Ewa; Bourgin, Marc; Hollender, Juliane; Kienle, Cornelia; McArdell, Christa S; von Gunten, Urs
The efficiency of wastewater ozonation for the abatement of three nitrogen-containing pharmaceuticals, two antihistamine drugs, cetirizine (CTR) and fexofenadine (FXF), and the diuretic drug, hydrochlorothiazide (HCTZ), was investigated. Species-specific second-order rate constants for the reactions of the molecular, protonated (CTR, FXF) or deprotonated (HCTZ) forms of these compounds with ozone were determined. All three compounds are very reactive with ozone (apparent second order rate constants at pH 7: kO3,pH7 = 1.7·10(5) M(-1)s(-1), 8.5·10(4) M(-1)s(-1) and 9.0·10(3) M(-1)s(-1) for CTR, HCTZ and FXF, respectively). Transformation product (TP) structures were elucidated using liquid chromatography coupled with high-resolution tandem mass spectrometry, including isotope-labeled standards. For cetirizine and hydrochlorothiazide 8 TPs each and for fexofenadine 7 TPs were identified. The main TPs of cetirizine and fexofenadine are their respective N-oxides, whereas chlorothiazide forms to almost 100% from hydrochlorothiazide. In the bacteria bioluminescence assay the toxicity was slightly increased only during the ozonation of cetirizine at very high cetirizine concentrations. The main TPs detected in bench-scale experiments were also detected in full-scale ozonation of a municipal wastewater, for >90% elimination of the parent compounds. PMID:26971810
Milošević, Danko; Batinić, Danica; Turudić, Daniel; Batinić, Danko; Topalović-Grković, Marija; Gradiški, Ivan Pavao
The aim of this study was to assess demographic data, clinical presentation, metabolic features, and treatment in 76 children with urolithiasis presented from 2002 to 2011. Urolithiasis is responsible for 2.5/1,000 pediatric hospitalizations, with new cases diagnosed in 1.1/1,000 admissions. From the observed period, two-fold rise of incidence rate was observed. Compiling the data from other pediatric institutions in our country, we estimated present overall incidence rate in Croatia as 6.5/100,000 children under 18 years. There were 41 boys and 35 girls (ratio 1.17:1). The mean age at diagnosis was 9.7 (range 0.8-16) years and follow-up duration was 5.3 (range 1.8-10) years. Renal colic (75.0 %) and hematuria (57.89 %) were the main symptoms. In 65.78 % of children, stones were unilateral. Stones were located in kidney in 52.63 %, in the ureter in 26.32 %, and in bladder in 6.58 % cases. Stone analysis showed calcium oxalate in 75.0 % of the cases. Associated urinary tract abnormalities were found in 19.73 % children. Most common metabolic disturbances were hypercalciuria (47.37 %) and idiopathic or mild hyperoxaluria (18.42 %). Urine saturation (EQUIL2) was elevated in 61.84 % cases. Spontaneous stone evacuation occurred in 51.21 % children. Extracorporeal shock wave lithotripsy, surgical evacuation, and endoscopic removal of calculi were performed in 21.0, 6.58, and 5.26 % of cases, respectively. Follow-up conservative therapy, consisting of fluid/diet recommendations and additional potassium citrate and/or chlorothiazide in children with increased risk, was sufficient for stone recurrence prevention in 92.1 % of children. In conclusion, the study gave insight in epidemiology and metabolic disturbances of urinary stone disease in Croatian children. PMID:24096520
J. Keerthi Sagar*, S. Narendranath, H.S. Somashekar, S.R. Reshma, Susheela Somappa Halemani and Prabhakar Adake
Full Text Available Objective: Analysis of prescribing pattern of antihypertensives in patients with hypertension alone and with coexisting diabetes mellitus. Materials and Methods: A cross sectional study was conducted in an outpatient and inpatient department of general medicine at JJM Medical College hospital for a period of 3 months (July 2011 to September 2011. Prescriptions of the patients were collected and relevant data was entered in the preformed proforma and analyzed.Results: A total of 210 prescriptions were analyzed using chi square test. Out of which 126 prescriptions were of patients with hypertension alone which contain calcium channel blockers (30%, beta blockers (26%, angiotensin receptor blockers (15%, angiotensin converting enzyme inhibitors (4% and fixed dose combinations of angiotensin receptor blockers with hydrochlorothiazide (11% and combination of amlodipine with hydro-chlorothiazide (2.5%.84 Prescriptions of hypertension with coexisting diabetes mellitus had calcium channel blockers (24%, angiotensin converting enzyme inhibitors (19%, angiotensin receptor blockers (13%, beta blockers (13%, and fixed dose combinations of angiotensin receptor blockers with hydrochlorothiazide (18% and combination of amlodipine with hydrochlorothiazide (6%.[χ2=17.01, p=o.oo4] Conclusion- The present study shows that angiotensin converting enzyme inhibitors because of its beneficial effects which are well known are more commonly prescribed drugs in individuals with hypertension with coexisting diabetes mellitus. Calcium channel blockers and newly introduced angiotensin receptor blockers alone or in combination with hydrochlorothiazide are preferred drugs in both the study groups. Beta blockers are less preferred in patients of hypertension with coexisting diabetes mellitus for obvious reasons.
Savio G Barreto
Full Text Available Context Acute pancreatitis is associated with risk of morbidity and even mortality. Routine prescription drugs have been linked to the causation of acute pancreatitis. Objective To determine the incidence, presentation, course and outcome of drug-induced acute pancreatitis amongst patients admitted to a public hospital. Design/setting A retrospective analysis of patients presenting with acute pancreatitis to the Modbury Hospital, South Australia from January 2006 to April 2011. Main outcome measure Each admission was reviewed within the electronic database for patient details as well as to determine the aetiological factor. In patients with druginduced acute pancreatitis, the WHO Probability Scale was used to evaluate causality relationship. Results Three-hundreds and 28 patients were treated for acute pancreatitis during the study period. Biliary and alcohol-induced acute pancreatitis accounted for 80.8% of cases. Eleven patients (2 male and 9 female patients; median age: 59 years were diagnosed with drug-induced acute pancreatitis. These included 5 cases of codeine-, 2 cases of azathioprine-, and 1 case each of chlorothiazide-, valproic acid-, oestradiol- and rosuvastatin-induced acute pancreatitis. Nine patients had a mild disease while 2 patients had severe acute pancreatitis with a median hospital stay of 4 days. Withdrawal of the drug resulted in cessation of the attacks in all patients over a median follow-up of 24 months. Conclusions Routine prescription drugs, as an aetiological factor, accounted for 3.4% of cases of acute pancreatitis. The disease appeared to be more common in middle-aged women. It is likely that the overall incidence of this entity is under-reported owing to the stringent criteria needed to conclusively determine a causal relationship.