Our library of drug research abstracts drawn from the medical literature is updated on a regular schedule, and you can be assured that new hydrodiuril research articles will be listed here shortly after becoming available to us.
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Carbonic anhydrase inhibitors. Sulfonamide diuretics revisited-old leads for new applications?
Org Biomol Chem. 2008 Jul 21; 6(14): 2499-2506
Temperini C, Cecchi A, Scozzafava A, Supuran CT
Sulfonamide diuretics such as hydrochlorothiazide, hydroflumethiazide, quinethazone, metolazone, chlorthalidone, indapamide, furosemide and bumetanide were tested as inhibitors of the zinc enzyme carbonic anhydrases (CAs, EC 4.2.1.1). These drugs were discovered in a period when only isoform CA II was known and considered physiologically/pharmacologically relevant. We prove here that although acting as moderate to weak inhibitors of CA II, all these drugs considerably inhibit other isozymes known nowadays to be involved in critical physiologic processes, among the 16 CAs present in vertebrates. Some low nanomolar/subnanomolar inhibitors against such isoforms were detected, such as among others metolazone against CA VII, XII and XIII, chlorthalidone against CA VB, VII, IX, XII and XIII, indapamide against CA VII, IX, XII and XIII, furosemide against CA I, II and XIV, and bumethanide against CA IX and XII. The X-ray crystal structure of the CA II-indapamide adduct was also resolved at high resolution, and the binding of this sulfonamide to the enzyme was compared to that of dichlorophenamide, sulpiride and a pyridinium containing sulfonamide. Indapamide binds to CA II in a manner not seen earlier for any other CA inhibitor, which might be important for the design of compounds with a different inhibition profile.
Effect of irbesartan on erectile function in patients with hypertension and metabolic syndrome.
Int J Impot Res. 2008 Jul 3;
Baumhäkel M, Schlimmer N, Böhm M
Pathogenesis of erectile dysfunction (ED) is related to endothelial dysfunction and therefore associated with cardiovascular risk factors. Patients with a combination of risk factors, as in metabolic syndrome, are thus likely to have an increased risk of developing endothelial and ED. The angiotensin receptor antagonist irbesartan has been shown to improve endothelial function in cardiovascular high-risk patients, which suggests a beneficial effect of treatment with irbesartan on ED. The aim of the present study was to determine the influence of irbesartan on ED in patients with a metabolic syndrome. A total of 1069 consecutive hypertensive patients with a metabolic syndrome from the Documentation of hypertension and metabolic syndrome in patients with Irbesartan Treatment survey were included. Patients were treated with irbesartan or the combination of irbesartan/hydrochlorothiazide for 6 months. ED was assessed using the international index of erectile function. The Cologne Evaluation Questionnaire of Erectile Dysfunction served as a control. Erectile function increased significantly (P
Am J Health Syst Pharm. 2008 Jul 15; 65(14): 1323-32
Daugherty KK
PURPOSE: The pharmacology, bioavailability and pharmacokinetics, clinical efficacy, adverse effects and toxicity, drug interactions, and dosage and administration of aliskiren as well as safety and economic issues related to its use are reviewed. SUMMARY: Aliskiren is the first of a new class of antihypertensive agents, direct renin inhibitors, that act by blocking the rate- limiting step of the renin-angiotensin- aldosterone system (RAAS). It was approved by the Food and Drug Administration in 2007 for use as monotherapy or in combination with other antihypertensives. Clinical studies comparing aliskiren monotherapy with placebo indicated a dose-dependent reduction in both systolic and diastolic blood pressure (BP). Greater reductions in BP have been achieved when aliskiren was used in combination with hydrochlorothiazide or an angiotensin-receptor blocker. The most common adverse effects reported in clinical trials were headache, fatigue, dizziness, diarrhea, and nasopharyngitis. Aliskiren has not been studied in patients with moderate renal dysfunction; as a RAAS-acting drug, it should be prescribed for such patients only with caution. CONCLUSION: Aliskiren at a dosage of 150 or 300 mg daily may be a good option for control of mild-to-moderate hypertension in patients with or without diabetes in whom first-line antihypertensives have failed to adequately control BP; comparative studies with other antihypertensives are needed to determine which patients can most benefit from aliskiren therapy.
Curr Med Res Opin. 2008 Jun 28;
Calhoun DA, Glazer RD, Pettyjohn FS, Coenen PD, Zhao Y, Grosso A
OBJECTIVE: Most patients with severe hypertension are at high risk for cardiovascular events and require prompt blood pressure (BP)-lowering and combination therapy to achieve BP goals. This study evaluated the therapeutic efficacy and tolerability of initial treatment with the combination of valsartan and hydrochlorothiazide (HCTZ) compared with valsartan monotherapy in patients with severe hypertension.RESEARCH DESIGN AND METHODS: This was a 6-week, randomized, double-blind, multicenter, forced titration study that compared initial therapy with the combination of valsartan/HCTZ 160/12.5 mg (force titrated to 160/25 mg after 2 weeks and to 320/25 mg after 4 weeks) to monotherapy with valsartan 160 mg (force titrated to 320 mg after 2 weeks and sham-titrated to 320 mg after 4 weeks). Eligible patients were 18-80 years old with severe essential hypertension (mean sitting diastolic BP >/= 110 mmHg and /= 140 mmHg and
Intern Med. 2008; 47(13): 1163-4
Miura S, Saku K
Hypertension. 2008 Jun 30;
Turner ST, Bailey KR, Fridley BL, Chapman AB, Schwartz GL, Chai HS, Sicotte H, Kocher JP, Rodin AS, Boerwinkle E
We conducted a genome-wide association study to identify novel genes influencing diastolic blood pressure (BP) response to hydrochlorothiazide, a commonly prescribed thiazide diuretic preferred for the treatment of high BP. Affymetrix GeneChip Human Mapping 100K Arrays were used to measure single nucleotide polymorphisms across the 22 autosomes in 194 non-Hispanic black subjects and 195 non-Hispanic white subjects with essential hypertension selected from opposite tertiles of the race- and sex-specific distributions of age-adjusted diastolic BP response to hydrochlorothiazide (25 mg daily, PO, for 4 weeks). The black sample consisted of 97 "good" responders (diastolic BP response [mean+/-SD]=-18.3+/-4.2 mm Hg; age=47.1+/-6.1 years; 51.5% women) and 97 "poor" responders (diastolic BP response=-0.18+/-4.3; age=47.4+/-6.5 years; 51.5% women). Haplotype trend regression identified a region of chromosome 12q15 in which haplotypes constructed from 3 successive single nucleotide polymorphisms (rs317689, rs315135, and rs7297610) in proximity to lysozyme (LYZ), YEATS domain containing 4 (YEATS4), and fibroblast growth receptor substrate 2 (FRS2) were significantly associated with diastolic BP response (nominal P=2.39x10(-7); Bonferroni corrected P=0.024; simulated experiment-wise P=0.040). Genotyping of 35 additional single nucleotide polymorphisms selected to "tag" linkage disequilibrium blocks in these genes provided corroboration that variation in LYZ and YEATS4 was associated with diastolic BP response in a statistically independent data set of 291 black subjects and in the sample of 294 white subjects. These results support the use of genome-wide association analyses to identify novel genes influencing antihypertensive drug responses.
Hypertension. 2008 Jun 30;
Manunta P, Lavery G, Lanzani C, Braund PS, Simonini M, Bodycote C, Zagato L, Carpini SD, Tantardini C, Brioni E, Bianchi G, Samani NJ
The kidney plays an important role in salt and blood pressure (BP) homeostasis. In previous studies, variants in the genes for alpha-adducin (ADD1), WNK1, and NEDD4L, which all regulate renal sodium absorption, have been associated with increased BP. However, findings have been inconsistent. We tested whether this is because of physiological interactions between the effects of variants in these genes. We assessed the single and combined effects of the ADD1 (Gly460Trp), WNK1 (rs880054 A/G), and NEDD4L (rs4149601 G/A) polymorphisms on renal and BP response to an acute Na load (n=344 subjects), BP decrease after 1 month of treatment with 12.5 mg of hydrochlorothiazide (n=193), and ambulatory 24-hour BP (n=690). Individually, the variants showed modest effects on some of the studied phenotypes. We found the ADD1 Trp allele to be permissive for the effects of variants of the other genes. In combination, the same variants (ADD1 Trp/WNK1 GG/Nedd4L GA+AA) showed a consistent effect on renal Na handling (P=0.009) and acute BP response to a saline infusion (P=0.021), BP lowering after thiazide treatment (P=0.008), and nocturnal systolic BP (P=0.044). Physiological interaction between the ADD1 and WNK1-NEDD4L pathways influences the effects of variants in these genes on sodium-related BP regulation. Relatively common alleles in the ADD1, WNK1, and NEDD4L genes when present in combination may have significant effects on renal sodium handling, BP, and antihypertensive response to thiazides.
Talanta. 2008 Jun 30; 76(1): 15-20
Zheng X, Lu M, Zhang L, Chi Y, Zheng L, Chen G
A simple and sensitive online field-amplification sample stacking (FASS) pre-enrichment method following by capillary electrophoresis with amperometric detection has been developed for the determination of diuretics, such as indapamide (IDP), hydrochlorothiazide (HCT) and bumetanide (BMTN) in urine. Under the optimum conditions, it was found that the low concentration buffer solution could be used as the diluents for simultaneous field-amplification injection of three diuretics after electrokinetically injecting a short water plug (15 kV, 3 s). Three analytes could be well separated within 10 min in an uncoated fused-silica capillary with H(3)BO(3)-Na(2)B(4)O(7) (BB) buffer solution (pH 8.98). The detection limits (S/N=3) were 9.0 ng/mL for IDP, 20 ng/mL for HCT and 1.5 ng/mL for BMTN, respectively. The detection limits of three diuretics were much lower by FASS than that by conventional sample injection, of which the detection limits were 340, 890 and 330 ng/mL for IDP, HCT and BMTN, respectively. Especially, for bumetanide the detection limit was 220-time lower by FASS. The linear ranges of three diuretics were all over three orders of magnitude. The proposed method has been successfully applied to analyze the diuretics in human urine samples without off-column sample pre-concentration.
J Pharm Biomed Anal. 2008 May 21;
Obando MA, Estela JM, Cerdà V
In this paper, a combination of multi-syringe chromatography analysis technique with extraction disks sorbents for the pre-concentration and determination of hydrochlorothiazide and losartan potassium in superficial water, groundwater and wastewater outlet samples has been developed. The system developed was proved for the determination of hydrochlorothiazide and losartan potassium in spiked water samples with recoveries ranging from 95 to 118%. The method involves the on-line enrichment of the targeted analytes from spiked water samples onto a Cation-SR sorbent material. The analytes are subsequently eluted and transported to the monolithic column, Chromolith Flash RP-18e column (25mmx4.6mm i.d.). The mobile phase used was 10mM potassium dihydrogen phosphate (pH 3.0):acetonitrile:methanol (60:30:10 v/v/v), flow-rate 0.8mLmin(-1). UV detection is carried out at 226nm. Under the optimized chemical and physical variables, the detection limit for hydrochlorothiazide and losartan potassium calculated as 3Syx/b was 0.07 and 0.09mgL(-1), respectively, for a sample loading volume of 1.0mL.
Treating Hispanic patients for type 2 diabetes mellitus: special considerations.
J Am Osteopath Assoc. 2008 May; 108(5 Suppl 3): S5-13
Freeman JS
The number of Hispanic people in the United States with diagnosed diabetes mellitus is projected to increase by 107% by 2020. The author presents the case of a 62-year-old obese Hispanic man, with newly diagnosed type 2 diabetes mellitus (T2DM), diabetic peripheral neuropathy, background retinopathy, and diabetic nephropathy. The patient also had diagnosed hypertension, peripheral vascular disease, and hyperlipidemia. The treatment plan for this patient included the following medications: pioglitazone hydrochloride (a thiazolidinedione, 30 mg/d); irbesartan (an angiotensin receptor blocker, 150 mg/d titrated to 300 mg/d); hydrochlorothiazide (an antikaliuretic agent, 12.5 mg/d); and aspirin (325 mg/d). Sitagliptin phosphate (a dipeptidyl peptidase IV inhibitor, 50 mg/d) was added to the treatment regimen to improve glycemic control. Simvastatin (20 mg/d) and niacin (1 g/d) were used for lipid management. Therapy also included a low-protein diet and walking program. At 6-month follow-up, the patient showed substantial improvement in his glycosylated hemoglobin level, lipid profile, blood pressure, creatinine clearance rate, and urine albumin level. There were also improvements in his peripheral vascular disease and diabetic peripheral neuropathy. Furthermore, the patient demonstrated encouraging progress in diet and lifestyle modification and in mental attitude.