sodium chloride symporter inhibitors


Summary: Agents that inhibit SODIUM CHLORIDE SYMPORTERS. They act as DIURETICS. Excess use is associated with HYPOKALEMIA.

Top Publications

  1. Belge H, Gailly P, Schwaller B, Loffing J, Debaix H, Riveira Munoz E, et al. Renal expression of parvalbumin is critical for NaCl handling and response to diuretics. Proc Natl Acad Sci U S A. 2007;104:14849-54 pubmed
    ..They also provide insights into the Ca(2+)-sparing action of thiazides and the pathophysiology of distal tubulopathies. ..
  2. Lee C, Shang S, Lai L, Yong K, Lien Y. Effect of thiazide on renal gene expression of apical calcium channels and calbindins. Am J Physiol Renal Physiol. 2004;287:F1164-70 pubmed
  3. Fretheim A, Oxman A, Håvelsrud K, Treweek S, Kristoffersen D, Bjørndal A. Rational prescribing in primary care (RaPP): a cluster randomized trial of a tailored intervention. PLoS Med. 2006;3:e134 pubmed
    ..Our tailored intervention had a significant impact on prescribing of antihypertensive drugs, but was ineffective in improving the quality of other aspects of managing hypertension and hypercholesterolemia in primary care. ..
  4. Dahlof B, Sever P, Poulter N, Wedel H, Beevers D, Caulfield M, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (AS. Lancet. 2005;366:895-906 pubmed
    ..Nevertheless, the results have implications with respect to optimum combinations of antihypertensive agents. ..
  5. Nijenhuis T, Vallon V, Van Der Kemp A, Loffing J, Hoenderop J, Bindels R. Enhanced passive Ca2+ reabsorption and reduced Mg2+ channel abundance explains thiazide-induced hypocalciuria and hypomagnesemia. J Clin Invest. 2005;115:1651-8 pubmed
    ..Thus, Trpm6 downregulation may represent a general mechanism involved in the pathogenesis of hypomagnesemia accompanying NCC inhibition or inactivation...
  6. Schrader J, Lüders S, Kulschewski A, Hammersen F, Plate K, Berger J, et al. Morbidity and Mortality After Stroke, Eprosartan Compared with Nitrendipine for Secondary Prevention: principal results of a prospective randomized controlled study (MOSES). Stroke. 2005;36:1218-26 pubmed
    ..In hypertensive stroke patients, for the same level of blood pressure control, eprosartan will be more effective than nitrendipine in reducing cerebrovascular and cardiovascular morbidity and mortality...
  7. Herbert C, Wright J, Maclure M, Wakefield J, Dormuth C, Brett MacLean P, et al. Better Prescribing Project: a randomized controlled trial of the impact of case-based educational modules and personal prescribing feedback on prescribing for hypertension in primary care. Fam Pract. 2004;21:575-81 pubmed
    ..Clear messages, proper trial design and sensitive outcomes are necessary to demonstrate these changes. ..
  8. Fretheim A, Oxman A, Flottorp S. Improving prescribing of antihypertensive and cholesterol-lowering drugs: a method for identifying and addressing barriers to change. BMC Health Serv Res. 2004;4:23 pubmed
    ..The effectiveness of our multifaceted intervention is under evaluation in a randomised controlled trial. ..
  9. Julius S, Kjeldsen S, Weber M, Brunner H, Ekman S, Hansson L, et al. Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial. Lancet. 2004;363:2022-31 pubmed
    ..The findings emphasise the importance of prompt blood-pressure control in hypertensive patients at high cardiovascular risk. ..

More Information


  1. Chrysant S, Weber M, Wang A, Hinman D. Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide. Am J Hypertens. 2004;17:252-9 pubmed
    ..5 mg, and olmesartan medoxomil/HCTZ 40/25 mg, respectively. All treatments were well tolerated. Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and was well tolerated. ..
  2. Fretheim A, Aaserud M, Oxman A. Rational prescribing in primary care (RaPP): economic evaluation of an intervention to improve professional practice. PLoS Med. 2006;3:e216 pubmed
    ..The cost of the intervention was more than twice the savings within the time frame of our study. However, we predict modest savings over a 2-y period. ..
  3. Maclure M, Dormuth C, Naumann T, McCormack J, Rangno R, Whiteside C, et al. Influences of educational interventions and adverse news about calcium-channel blockers on first-line prescribing of antihypertensive drugs to elderly people in British Columbia. Lancet. 1998;352:943-8 pubmed
    ..Changes in prescribing practices occur gradually with the accumulation of small impacts from educational interventions and lay media attention. ..
  4. Monroy A, Plata C, Hebert S, Gamba G. Characterization of the thiazide-sensitive Na(+)-Cl(-) cotransporter: a new model for ions and diuretics interaction. Am J Physiol Renal Physiol. 2000;279:F161-9 pubmed
    ..Both ion binding sites alter thiazide-mediated inhibition of transport, indicating that the thiazide-binding site is either shared or modified by both Na(+) and Cl(-). ..
  5. Na K, Oh Y, Han J, Joo K, Lee J, Earm J, et al. Upregulation of Na+ transporter abundances in response to chronic thiazide or loop diuretic treatment in rats. Am J Physiol Renal Physiol. 2003;284:F133-43 pubmed
    ..These increases in the abundance of Na(+) transporters in response to chronic diuretic treatment may account for the generation of diuretic tolerance associated with long-term diuretic use. ..
  6. Pepine C, Handberg E, Cooper Dehoff R, Marks R, Kowey P, Messerli F, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease. The International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA. 2003;290:2805-16 pubmed
    ..The verapamil-trandolapril-based strategy was as clinically effective as the atenolol-hydrochlorothiazide-based strategy in hypertensive CAD patients. ..
  7. Nijenhuis T, Hoenderop J, Loffing J, Van Der Kemp A, Van Os C, Bindels R. Thiazide-induced hypocalciuria is accompanied by a decreased expression of Ca2+ transport proteins in kidney. Kidney Int. 2003;64:555-64 pubmed
    ..These data suggest that ECV contraction is a critical determinant of the thiazide-induced hypocalciuria, which is accompanied by a decreased expression of Ca2+ transport proteins. ..
  8. Fretheim A, Oxman A, Treweek S, Bjørndal A. Rational Prescribing in Primary Care (RaPP-trial). A randomised trial of a tailored intervention to improve prescribing of antihypertensive and cholesterol-lowering drugs in general practice [ISRCTN48751230]. BMC Health Serv Res. 2003;3:5 pubmed
  9. Fretheim A, Aaserud M, Oxman A. The potential savings of using thiazides as the first choice antihypertensive drug: cost-minimisation analysis. BMC Health Serv Res. 2003;3:18 pubmed
    ..8 million dollars, US37.4 million dollars, US72.2 million dollars, US10.7 million dollars, US119.7 million dollars and US433.6 million dollars, respectively. ..
  10. Siegel D, Lopez J, Meier J, Cunningham F. Changes in the phamacologic treatment of hypertension in the Department of Veterans Affairs 1997-1999: decreased use of calcium antagonists and increased use of beta-blockers and thiazide diuretics. Am J Hypertens. 2001;14:957-62 pubmed
    ..These changes were consistent with improved compliance with VA national guidelines. The cost implications of these changes in practice patterns were considerable. ..
  11. Wright J. Choosing a first-line drug in the management of elevated blood pressure: what is the evidence? 2: Beta-blockers. CMAJ. 2000;163:188-92 pubmed
    ..The evidence indicates that beta-blockers are probably not as effective in reducing morbidity and mortality as low-dose thiazide diuretics and that there may be significant differences in effectiveness among various beta-blockers. ..
  12. Wright J. Choosing a first-line drug in the management of elevated blood pressure: what is the evidence? 1: Thiazide diuretics. CMAJ. 2000;163:57-60 pubmed
    ..The evidence indicates that low-dose thiazides are preferable to high-dose thiazides and that low-dose thiazides are better than or equivalent to other antihypertensive drugs for each of the goals of therapy. ..
  13. Kadlec A, Turk T. Update on the evaluation of repeated stone formers. Curr Urol Rep. 2013;14:549-56 pubmed publisher
    ..Future studies on preventive therapy of urolithiasis are likely to focus on strategies to increase compliance, cost-effectiveness, and systems-based implementation. ..
  14. Alberti L, Torlasco C, Lauretta L, Loffi M, Maranta F, Salonia A, et al. Erectile dysfunction in heart failure patients: a critical reappraisal. Andrology. 2013;1:177-91 pubmed publisher
    ..Physicians should be aware of the close relation between HF and ED and of the related clinical and therapeutic implications, in order to improve patients quality of life and clinical outcome. ..
  15. Cooper Dehoff R, Pacanowski M, Pepine C. Cardiovascular therapies and associated glucose homeostasis: implications across the dysglycemia continuum. J Am Coll Cardiol. 2009;53:S28-34 pubmed publisher
    ..These considerations have particular importance in younger patients who may also have pre-diabetes or the metabolic syndrome and who are likely to require therapy over the course of decades. ..
  16. Hix J, Silver S, Sterns R. Diuretic-associated hyponatremia. Semin Nephrol. 2011;31:553-66 pubmed publisher
    ..Hypokalemia, which often is present, increases the susceptibility to osmotic demyelination syndrome and replacement of potassium deficits contributes to the increase in serum sodium concentration. ..
  17. Dresser G, Feldman R. New trends in hypertension management: of salt, going solo and single pill combos. Curr Opin Cardiol. 2010;25:342-9 pubmed publisher
  18. Fogari R, Mugellini A, Zoppi A, Lazzari P, Destro M, Rinaldi A, et al. Effect of telmisartan/hydrochlorothiazide vs lisinopril/hydrochlorothiazide combination on ambulatory blood pressure and cognitive function in elderly hypertensive patients. J Hum Hypertens. 2006;20:177-85 pubmed
  19. Yamanari H, Nakamura K, Miura D, Yamanari S, Ohe T. Spironolactone and chlorthalidone in uncontrolled elderly hypertensive patients treated with calcium antagonists and angiotensin II receptor-blocker: effects on endothelial function, inflammation, and oxidative stress. Clin Exp Hypertens. 2009;31:585-94 pubmed publisher
  20. Calhoun D. Low-dose aldosterone blockade as a new treatment paradigm for controlling resistant hypertension. J Clin Hypertens (Greenwich). 2007;9:19-24 pubmed
    ..Risk of hyperkalemia is increased in patients with chronic kidney disease or diabetes, elderly patients, and patients already receiving an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. ..
  21. Moes A, van der Lubbe N, Zietse R, Loffing J, Hoorn E. The sodium chloride cotransporter SLC12A3: new roles in sodium, potassium, and blood pressure regulation. Pflugers Arch. 2014;466:107-18 pubmed publisher
    ..This review aims to summarize these new insights in an integrated manner while identifying unanswered questions. ..
  22. Moe O. Kidney stones: pathophysiology and medical management. Lancet. 2006;367:333-44 pubmed
    ..Manipulation of inhibitors and epithelial factors is important and needs further investigation. Advances in the management of nephrolithiasis depend on combined efforts of clinicians and scientists to understand the pathophysiology. ..
  23. Flottorp S, Fretheim A. [Thiazides (only) and hard endpoints]. Tidsskr Nor Laegeforen. 2004;124:2277; author reply 2277-8 pubmed
  24. Waeber B. Position of fixed-dose combinations containing an AT(1)-receptor blocker and a thiazide diuretic. Blood Press. 2005;14:324-36 pubmed
  25. Eladari D, Hübner C. Novel mechanisms for NaCl reabsorption in the collecting duct. Curr Opin Nephrol Hypertens. 2011;20:506-11 pubmed publisher
  26. Wróblewski T, Wystrychowski A. [Hypercalciuria]. Przegl Lek. 2011;68:107-13 pubmed
    ..In addition, a low-calcium diet may lead to negative calcium balance in subjects with hypercalciuria, and therefore increases the risk of osteopenia. ..
  27. Shapiro D, Sonnenblick M, Galperin I, Melkonyan L, Munter G. Severe hyponatraemia in elderly hospitalized patients: prevalence, aetiology and outcome. Intern Med J. 2010;40:574-80 pubmed publisher
    ..Severe hyponatraemia in elderly hospitalized medical patients is more frequent in women and of multifactorial aetiology in 50% of cases. It is most commonly caused by SIADH; CSWS is an unlikely cause. ..
  28. Walsh J, Newman C, Eastell R. Heart drugs that affect bone. Trends Endocrinol Metab. 2012;23:163-8 pubmed publisher
    ..These observations point towards opportunities for new drug development for bone diseases, and possibly the development of treatments that will benefit more than one disease. ..
  29. Fomin V, Eliseev O. [Combination of ACE inhibitor with thiazide-like diuretic as an independent strategy of improved prognosis in type 2 diabetes mellitus. ADVANCE trial]. Ter Arkh. 2008;80:82-5 pubmed
  30. Carter B, Sica D. Strategies to improve the cardiovascular risk profile of thiazide-type diuretics as used in the management of hypertension. Expert Opin Drug Saf. 2007;6:583-94 pubmed
    ..When these strategies are employed, the adverse effects seen with diuretics can be minimized or negated, and in so doing cardiovascular benefits can be optimized. ..
  31. Unwin R, Capasso G. Bartter's and Gitelman's syndromes: their relationship to the actions of loop and thiazide diuretics. Curr Opin Pharmacol. 2006;6:208-13 pubmed
    ..This is a good example of one form of 'translational research', the message being the importance of our ability to link (in this instance) basic renal physiology and pharmacology, with clinical nephrology and genetics...
  32. Weintraub H, Duprez D, Cushman W, Zappe D, Purkayastha D, Samuel R, et al. Antihypertensive response to thiazide diuretic or angiotensin receptor blocker in elderly hypertensives is not influenced by pretreatment plasma renin activity. Cardiovasc Drugs Ther. 2012;26:145-55 pubmed publisher
    ..Higher baseline PRA was associated with a greater reactive rise in PRA. Baseline PRA is not a useful guide to the BP responses of initial combination V/HCTZ in elderly individuals with systolic hypertension. ..
  33. Braun L, Rosenfeldt F. Pharmaco-nutrient interactions - a systematic review of zinc and antihypertensive therapy. Int J Clin Pract. 2013;67:717-25 pubmed publisher
    ..Additional research using larger participant numbers and accounting for dietary zinc intakes are required. ..
  34. Diken A, Yalcinkaya A, Erçen Diken O, Aksoy E, Dogan I, Yılmaz S, et al. Hyponatremia Due to Escitalopram and Thiazide Use After Cardiac Surgery. J Card Surg. 2016;31:96-7 pubmed publisher
    ..We report the development of severe hyponatremia leading to adverse clinical effects due to escitalopram and thiazide diuretic use concomitantly in a patient with depression after emergency coronary artery bypass grafting. ..
  35. Leung A, Wright A, Pazo V, Karson A, Bates D. Risk of thiazide-induced hyponatremia in patients with hypertension. Am J Med. 2011;124:1064-72 pubmed publisher
    ..12-1.42). The number needed to harm (to result in one excess case of incident hyponatremia in 5 years) was 15.02 (95% CI, 7.88-160.30). Approximately 3 in 10 patients exposed to thiazides who continue to take them develop hyponatremia. ..
  36. Khan M, Khan R, Islam F, Laghari J, Jamali S. To study the efficacy of Losartan on urinary uric acid excretion in Thiazide induced hyperuricemic and hypertensive patients. Pak J Pharm Sci. 2011;24:583-7 pubmed
    ..Ultimately Losartan decrease serum uric acid level and uricosuric effect of Losartan might be particularly useful in Hyperuricemic patients those on Thiazide diuretic (for hypertension and heart failure). ..
  37. Menon M, Garcha A, Khanna A. The management of hyponatremia in HIV disease. J Nephrol. 2013;26:61-72 pubmed publisher
    ..Using an illustrative case as an example, in the following review, we discuss the varied etiologies, pathogenetic mechanisms , clinical features, diagnosis, and outline the management of hyponatremia in HIV patients. ..
  38. Nesbitt S, Shojaee A, Maa J, Weir M. Efficacy of an amlodipine/olmesartan treatment algorithm in patients with or without type 2 diabetes and hypertension (a secondary analysis of the BP-CRUSH study). J Hum Hypertens. 2013;27:445-52 pubmed publisher
    ..Treatment was well tolerated, with low rates of peripheral edema. In summary, switching to a treatment algorithm based on AML/OM±HCTZ after failed monotherapy was safe and improved BP control in patients with hypertension and T2DM. ..
  39. Sakhaee K, Maalouf N, Kumar R, Pasch A, Moe O. Nephrolithiasis-associated bone disease: pathogenesis and treatment options. Kidney Int. 2011;79:393-403 pubmed publisher
    ..This manuscript reviews the epidemiology, pathophysiology, and potential treatments of bone disease in patients with nephrolithiasis. ..
  40. Rump L, Sellin L. Combination therapy for hypertension: focus on high-dose olmesartan medoxomil (40 mg) plus hydrochlorothiazide. Expert Opin Pharmacother. 2010;11:2231-42 pubmed publisher
  41. Mukamal K, Ghimire S, Pandey R, O Meara E, Gautam S. Antihypertensive medications and risk of community-acquired pneumonia. J Hypertens. 2010;28:401-5 pubmed publisher
    ..These results are consistent with possible differences in noncardiovascular outcomes among users of antihypertensives and other commonly used cardiovascular drugs but require confirmation in other populations. ..
  42. Bandi G, Nakada S, Penniston K. Practical approach to metabolic evaluation and treatment of the recurrent stone patient. WMJ. 2008;107:91-100 pubmed
    ..The recommendations are based on the latest available information regarding the pathogenesis, medical treatment options, and decision-making rationale when managing these challenging patients. ..
  43. Makolkin V. [Is the role of thiazine-like diuretics verified in therapy of arterial hypertension?]. Ter Arkh. 2006;78:85-8 pubmed
  44. Schlienger R, Kraenzlin M, Jick S, Meier C. Use of beta-blockers and risk of fractures. JAMA. 2004;292:1326-32 pubmed
    ..Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with beta-blockers and thiazides. ..
  45. Wu Y, Li Y, Bejan Angoulvant T, Gueyffier F. [Modeling of systolic blood pressure reaction to antihypertensive agents in people with hypertension]. Zhonghua Xin Xue Guan Bing Za Zhi. 2011;39:309-14 pubmed publisher
  46. Niang A. [Arterial hypertension and the kidney]. Dakar Med. 2008;53:1-6 pubmed
    ..Their association with ACE inhibitors or angiotensin receptor antagonists seem to give the best effectiveness in term of cardioprotection and nephroprotection. ..
  47. Parks J, Coe F, Evan A, Worcester E. Urine pH in renal calcium stone formers who do and do not increase stone phosphate content with time. Nephrol Dial Transplant. 2009;24:130-6 pubmed publisher
    ..We conclude that high pH may not be acquired as a result of stones or their treatments but may precede transformation from CaOx to CaP stones and arise from diet or possibly heredity. ..
  48. Volpe M, Tocci G. Rationale for triple fixed-dose combination therapy with an angiotensin II receptor blocker, a calcium channel blocker, and a thiazide diuretic. Vasc Health Risk Manag. 2012;8:371-80 pubmed publisher
    ..The availability of these fixed-dose combinations should lead to improvement in blood pressure control and aid compliance with long-term therapy, optimizing the management of this chronic condition. ..
  49. Petitti D, Xie F, Barzilay J. Prescribing patterns for thiazide diuretics in a large health maintenance organization: relationship to participation as an ALLHAT clinical center. Contemp Clin Trials. 2006;27:397-403 pubmed
    ..8% to 13.0% in the two regions without an ALLHAT clinical site (p > 0.05). Participation in a clinical hypertension study does not appear to accelerate adoption of study recommendations. ..
  50. Suissa S, Hutchinson T, Brophy J, Kezouh A. ACE-inhibitor use and the long-term risk of renal failure in diabetes. Kidney Int. 2006;69:913-9 pubmed
    ..Our data suggest instead that ACE inhibitors might actually increase this risk, which may possibly contribute to the continued increasing incidence of ESRD owing to diabetes. ..
  51. Mimran A, Weir M. Angiotensin-receptor blockers and diuretics--advantages of combination. Blood Press. 2005;14:6-11 pubmed
    ..The combination of an ARB and a thiazide diuretic may be of particular value in patient populations who tend to have poor BP control on monotherapy, or have additional cardiovascular or renal risk factors. ..
  52. Zendelovska D, Stafilov T, Milosevski P. Development of solid-phase extraction method and its application for determination of hydrochlorothiazide in human plasma using HPLC. Biomed Chromatogr. 2004;18:71-6 pubmed
    ..Limit of quantification was 10 ng mL(-1). The method has been implemented to monitor hydrochlorothiazide levels in patient samples. ..
  53. Ogata S, Sharyo S, Hinman D, Manabe S. Renal effects of 26-week administration of olmesartan medoxomil/hydrochlorothiazide in rats. J Toxicol Sci. 2004;29:37-46 pubmed
    ..These results suggest that OM/HCTZ may have renoprotective effects in clinical treatment of hypertensive patients. ..