Electrolyte Blood Press.  2013 Dec;11(2):56-59. 10.5049/EBP.2013.11.2.56.

Severe Hyponatremia Associated with the Use of Angiotensin II Receptor Blocker/thiazide Combinations

Affiliations
  • 1Department of Nephrology, KyungHee University School of Medicine, Seoul, Korea. cgihm@naver.com

Abstract

There are several widely used combinations of angiotensin II receptor blocker (ARB)/thiazide. The complimentary mechanism of action for such anti-hypertensive therapies is that, while ARB inhibits the vasoconstricting and aldosterone-secreting effects of angiotensin II, hydrochlorothiazide affects the renal tubular mechanisms of electrolyte reabsorption and increases excretion of sodium and chloride in the distal tubule, consequently promoting water excretion. In addition, hypokalemia, which may be triggered by a hydrochlorothiazide-induced increase in urinary potassium loss, is resisted by the use of ARB. Hence, the ARB/thiazide combination is safe in terms of potassium imbalance. For these reasons, fixed-dose ARB/thiazide combination anti-hypertensive drugs have been widely used for the treatment of hypertension. However, there have not been many studies done regarding cases where patients under such regimens showed severe hyponatremia, even when the amount of thiazide included was low. Here we report two cases in which severe hyponatremia occurred following treatment with the ARB/thiazide combinations. Upon discontinuation of the regimen, both patients showed recovery from hyponatremia.

Keyword

Angiotensin II type 1 receptor blockers; Hydrochlorothiazide; Hyponatremia

MeSH Terms

Angiotensin II Type 1 Receptor Blockers
Angiotensin II*
Angiotensins*
Antihypertensive Agents
Humans
Hydrochlorothiazide
Hypertension
Hypokalemia
Hyponatremia*
Potassium
Receptors, Angiotensin*
Sodium
Water
Angiotensin II
Angiotensin II Type 1 Receptor Blockers
Angiotensins
Antihypertensive Agents
Hydrochlorothiazide
Potassium
Receptors, Angiotensin
Sodium
Water

Reference

1. Chobanian AV, Bakris GL, Black HR, et al. Seventh report of the Joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure. Hypertension. 2003; 42:1206–1252. PMID: 14656957.
Article
2. Cifkova R, Erdine S, Fagard R, et al. Practice guidelines for primary care physicians: 2003 ESH/ESC hypertension guidelines. J Hypertens. 2003; 21:1779–1786. PMID: 14508180.
3. Burnier M. Angiotensin II type 1 receptor blockers. Circulation. 2001; 103:904–912. PMID: 11171802.
Article
4. Mizuno M, Sada T, Ikeda M, et al. Pharmacology of CS-866, a novel nonpeptide angiotensin II receptor antagonist. Eur J Pharmacol. 1995; 285:181–188. PMID: 8566137.
Article
5. Koike H, Sada T, Mizuno M. In vitro and in vivo pharmacology of olmesartan medoxomil, an angiotensin II type AT1 receptor antagonist. J Hypertens Suppl. 2001; 19:S3–S14. PMID: 11451212.
Article
6. Giles TD, Oparil S, Silfani TN, Wang A, Walker JF. Comparison of increasing doses of olmesartan medoxomil, losartan potassium, and valsartan in patients with essential hypertension. J Clin Hypertens (Greenwich). 2007; 9:187–195. PMID: 17341994.
Article
7. Meredith PA. Angiotensin II receptor antagonists alone and combined with hydrochlorothiazide: potential benefits beyond the antihypertensive effect. Am J Cardiovasc Drugs. 2005; 5:171–183. PMID: 15901205.
8. Kjeldsen SE, Os I, Høieggen A, Beckey K, Gleim GW, Oparil S. Fixed-dose combinations in the management of hypertension: defining the place of angiotensin receptor antagonists and hydrochlorothiazide. Am J Cardiovasc Drugs. 2005; 5:17–22. PMID: 15631534.
9. Manolis AJ, Grossman E, Jelakovic B, et al. Losartan Trial Investigators. Effects of losartan and candesartan monotherapy and losartan/hydrochlorothiazide combination therapy in patients with mild to moderate hypertension. Clin Ther. 2000; 22:1186–1203. PMID: 11110230.
Article
10. Chrysant SG, Weber MA, Wang AC, Hinman DJ. Evaluation of antihypertensive therapy with the combination of olmesartanmedoxomil and hydrochlorothiazide. Am J Hypertens. 2004; 17:252–259. PMID: 15001200.
11. Neutel JM. Clinical studies of CS-866, the newest angiotensin II receptor antagonist. Am J Cardiol. 2001; 87:37C–43C.
Article
12. Norwood D, Branch E, Smith B, Honeywell M. Olmesartanmedoxomil for hypertension: a clinical review. Drug Forecast. 2002; 27:611–618.
13. Sharabi Y, Illan R, Kamari Y, et al. Diuretic induced hyponatraemia in elderly hypertensive women. J Hum Hypertens. 2002; 16:631–635. PMID: 12214259.
Article
14. Messerli FH, Grossman E, Goldbourt U. Are beta blockers efficacious as first-line therapy for hypertension in the elderly? A systematic review. JAMA. 1998; 279:1903–1907. PMID: 9634263.
15. Kostis JB, et al. The effect of chlorthalidone on ventricular ectopic activity in patients with isolated systolic hypertension. The SHEP Study Group. Am J Cardiol. 1994; 74:464–467. PMID: 7520210.
16. Siegel D, Hulley SB, Black DM, et al. Diuretics, serum and intracellular electrolyte levels, and ventricular arrhythmias in hypertensive men. JAMA. 1992; 267:1083–1089. PMID: 1735925.
Article
17. Friedman E, Shadel M, Halkin H, Farfel Z. Thiazide induced hyponatremia. reproducibility by single dose rechallenge and an analysis of pathogenesis. Ann Intern Med. 1989; 110:24–30. PMID: 2491733.
18. Fichman MP, Vorherr H, Kleeman CR, Telfer N. Diuretic-induced hyponatremia. Ann Intern Med. 1971; 75:853–863. PMID: 4944156.
Article
19. Kinoshita H, Kobayashi K, Yaguramaki T, et al. Losartan potassium/hydrochlorothiazide (Preminent®) and hyponatremia: case series of 40 patients. Hum Exp Toxicol. 2011; 30:1409–1414. PMID: 20974655.
Article
20. Cakir M. Significant hyperkalemia and hyponatremia secondary to telmisartan/hydrochlorothiazide treatment. Blood Press. 2010; 19:380–382. PMID: 20486869.
Article
Full Text Links
  • EBP
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2023 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr