DOI: http://dx.doi.org/10.18203/2319-2003.ijbcp20181638

A comparative analysis of hydrochlorothiazide and chlorthalidone induced hyponatremia at the dose commonly prescribed in clinical practice

Sura Kishore Mishra, Abinash Panda

Abstract


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.


Keywords


Anti-hypertensive, Chlorthalidone, Hydrochlorothiazide, Hyponatremia

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References


The Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Arch Intern Med. 1997;157:2413-46.

Messerli FH, Grossman E, Goldbourt U. Are beta-blockers efficacious as first-line therapy for hypertensionin the elderly? A systematic review. JAMA. 1998;279:1903-7.

Messerli FH, Makani H, Benjo A, Romero J, Alviar C, Bangalore S. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring: a meta-analysis of randomized trials. Journal of the American College of Cardiology. 2011;57(5):590-600.

Lund BC, Ernst ME. The Comparative Effectiveness of Hydrochlorothiazide and Chlorthalidone in an Observational Cohort of Veterans. The Journal of Clinical Hypertension. 2012;14(9):623-9.

Sonnenblick M, Friedlander Y, Rosin AJ. Diuretic-induced severehyponatremia. Review and analysis of 129 reported patients. Chest. 1993;103:601-6.

Kostis JB, Lacy CR, Hall WD, Wilson AC, Borhani NO, Krieger SD, et al. SHEP Study Group. The effect of chlorthalidone on ventricular ectopic activity in patients with isolated systolic hypertension. The American journal of cardiology. 1994 Sep 1;74(5):464-7.

Siegel D, Hulley SB, Black DM. Diuretics, serum and intracellular electrolyte levels, and arrhythmias in hypertensive men. JAMA. 1992;267:1083-9.

Siscovick DS, Raghunathan TE, Psaty BM. Diuretic therapy for hypertension and the risk of primary cardiac arrest. NEngl J Med. 1994,330:1852-7.

Chobanian AV, Bakris GL, Black HR. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA. 2003;289:2560-72.

Van Blijderveen JC, Sabine M. Straus SM, Eline M, Rodenburg EM, Zietse R, et al. Hyponatremia: Chlorthalidone versus Hydrochlorothiazide The American Journal of Medicine. 2014;127:763-71.

Byatt CM, Millard PH, Levin GE. Diuretics and electrolyte disturbances in 1000 consecutive geriatric admissions. J R Soc Med. 1990;83:704-8.

Mount DB. Fluid and electrolyte disturbances. In: Dennis L. Kasper, editor. Harrison’s principles of internal medicine, 19th Edition. New York: McGrew-Hill Education; 2015:298.

SHEP Cooperative Research Group Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA. 1991;265:3255-64.

Sunderam SG, Mankikar GD. Hyponatraemia in the elderly.Age Ageing. 1983;12:77-80.

Gantait K, Ghosh TP, Gantait I, Patra S, Bhunia P. Journal of Medical Science and Clinical Research. 2017;5(1):15286-92.

Hwang KS, Kim Gheun-Ho. Thiazide-Induced Hyponatremia. Electrolyte Blood Press. 2010;8:51-7.

Roush GC, Holford TR, Guddati AK. Chlorthalidone compared with hydrochlorothiazide in reducing cardiovascular events: systematic review and network meta-analyses. Hypertension. 2012;59:1110-17.

Kurtz TW. Chlorthalidone: Don’t call it thiazide-like anymore. Hypertension. 2010 Sep;56(3):335-7.

Beaumont K, Vaughn DA, Fanestil DD. Thiazide diuretic drug receptors in rat kidney: identification with 3H-metolazone. Proceedings of the National Academy of Sciences of the United States of America. 1988;85(7):2311-4.

Dieterle W, Wagner J, Faigle JW. Binding of Chlorthalidone (Hygrotonr) to Blood Components in Man. Eur J Clin Pharmacol. 1976;10(1):37-42.

Schiavi P, Jochemsen R, Guez D. Pharmacokinetics of sustained and immediate release formulations of indapamide after single and repeated oral administration in healthy volunteers. Fundamental and clinical pharmacology. 2000;14(2):139-46.

Matthews KA, Brenner MJ, Brenner AC. Evaluation of the efficacy and safety of a hydrochlorothiazide to chlorthalidone medication change in veterans with hypertension. Clinical therapeutics. 2013;35(9):1423-30.

Mann SJ. The Silent Epidemic of Thiazide-Induced Hyponatremia. The Journal of Clinical Hypertension. 2008;10(6):477-84.

Chow KM, Szeto CC, Wong TY, Leung CB, Li PK. Risk factors for thiazide-induced hyponatraemia. QJM. 2003;96:911-7.

Rodenburg EM, Hoorn EJ, Ruiter R, Lous JJ, Hofman A, Uitterlinden AG, et al. Thiazide-associated hyponatremia: a population-based study. American Journal of Kidney Diseases. 2013 Jul 1;62(1):67-72.