Skip to main content
PMC home page
British Journal of Clinical Pharmacology logoLink to British Journal of Clinical Pharmacology
. 1993 Apr;35(4):373–378. doi: 10.1111/j.1365-2125.1993.tb04153.x

A comparison of the potassium and magnesium-sparing properties of amiloride and spironolactone in diuretic-treated normal subjects.

D L Murdoch 1, G Forrest 1, D L Davies 1, G T McInnes 1
PMCID: PMC1381547  PMID: 8485017

Abstract

1. The relative potencies of amiloride (5 and 20 mg) and spironolactone (25 and 100 mg) for plasma and erythrocyte electrolytes were investigated in a double-blind, randomised, balanced, crossover study in 12 normal men treated concomitantly with hydrochlorothiazide 100 mg daily for 1 week. 2. Participants satisfied an a priori requirement for a fall in plasma potassium concentration of at least 0.5 mmol l-1 after 7 days of treatment with hydrochlorothiazide alone. 3. After hydrochlorothiazide alone, plasma potassium and sodium concentrations fell (P < 0.001). There were associated reductions in erythrocyte sodium (P < 0.01). Plasma magnesium concentration did not change, although erythrocyte magnesium decreased (P < 0.001). 4. Both amiloride and spironolactone attenuated the thiazide-induced fall in plasma potassium (relative potency, amiloride:spironolactone 10:1, 95% confidence interval 6.3-16.2:1). Amiloride but not spironolactone was associated with a dose-related increase in plasma magnesium; a relative potency estimation was precluded. There was little evidence of influences of amiloride or spironolactone on erythrocyte electrolytes. 5. On a weight basis, amiloride is ten times more potent than spironolactone as a potassium-sparing agent in diuretic-treated subjects but neither agent had major effects on erythrocyte potassium. The drugs may have divergent actions on magnesium handling; hydrochlorothiazide alone had no influence on plasma magnesium.

Full text

PDF
375

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlstrand C., Tiselius H. G., Larsson L., Hellgren E. Clinical experience with long-term bendroflumethiazide treatment in calcium oxalate stone formers. Br J Urol. 1984 Jun;56(3):255–262. doi: 10.1111/j.1464-410x.1984.tb05383.x. [DOI] [PubMed] [Google Scholar]
  2. Beermann B., Groschinsky-Grind M. Pharmacokinetics of hydrochlorothiazide in man. Eur J Clin Pharmacol. 1977 Dec 2;12(4):297–303. doi: 10.1007/BF00607430. [DOI] [PubMed] [Google Scholar]
  3. Bergström J. Plasma and muscle electrolytes in patients receiving diuretics. Methodological and clinical considerations. Acta Cardiol. 1973;(Suppl):15–24. [PubMed] [Google Scholar]
  4. Bull M. B., Laragh J. H. Amiloride. A potassium-sparing natriuretic agent. Circulation. 1968 Jan;37(1):45–53. doi: 10.1161/01.cir.37.1.45. [DOI] [PubMed] [Google Scholar]
  5. Cocco G., Iselin H. U., Strozzi C., Cesana B., Baumeler H. R. Magnesium depletion in patients on long-term chlorthalidone therapy for essential hypertension. Eur J Clin Pharmacol. 1987;32(4):335–338. doi: 10.1007/BF00543964. [DOI] [PubMed] [Google Scholar]
  6. Dahlöf C. G., Lundborg P., Persson B. A., Regårdh C. G. Re-evaluation of the antimineralocorticoid effect of the spironolactone metabolite, canrenone, from plasma concentrations determined by a new high-pressure liquid-chromatographic method. Drug Metab Dispos. 1979 Mar-Apr;7(2):103–107. [PubMed] [Google Scholar]
  7. Dyckner T., Wester P. O. Intracellular magnesium loss after diuretic administration. Drugs. 1984 Oct;28 (Suppl 1):161–166. doi: 10.2165/00003495-198400281-00016. [DOI] [PubMed] [Google Scholar]
  8. Dyckner T., Wester P. O. The relation between extra- and intracellular electrolytes in patients with hypokalemia and/or diuretic treatment. Acta Med Scand. 1978;204(4):269–282. doi: 10.1111/j.0954-6820.1978.tb08438.x. [DOI] [PubMed] [Google Scholar]
  9. Dyckner T., Wester P. O. Ventricular extrasystoles and intracellular electrolytes before and after potassium and magnesium infusions in patients on diuretic treatment. Am Heart J. 1979 Jan;97(1):12–18. doi: 10.1016/0002-8703(79)90108-x. [DOI] [PubMed] [Google Scholar]
  10. Dyckner T., Wester P. O., Widman L. Amiloride prevents thiazide-induced intracellular potassium and magnesium losses. Acta Med Scand. 1988;224(1):25–30. doi: 10.1111/j.0954-6820.1988.tb16734.x. [DOI] [PubMed] [Google Scholar]
  11. Dyckner T., Wester P. O., Widman L. Effects of spironolactone on serum and muscle electrolytes in patients on long-term diuretic therapy for congestive heart failure and/or arterial hypertension. Eur J Clin Pharmacol. 1986;30(5):535–540. doi: 10.1007/BF00542411. [DOI] [PubMed] [Google Scholar]
  12. Forrest G., McInnes G. T., Fairhead A. P., Thompson G. G., Brodie M. J. Simple high-performance liquid chromatographic method for the measurement of amiloride in body fluids. J Chromatogr. 1988 Jun 24;428(1):123–130. doi: 10.1016/s0378-4347(00)83896-7. [DOI] [PubMed] [Google Scholar]
  13. Fraser R., Guest S., Young J. A comparison of double-isotope derivative and radioimmunological estimation of plasma aldosterone concentration in man. Clin Sci Mol Med. 1973 Sep;45(3):411–415. doi: 10.1042/cs0450411. [DOI] [PubMed] [Google Scholar]
  14. George C. F., Breckenridge A. M., Dollery C. T. Comparison of the potassium- retaining effects of amiloride and spironolactone in hypertensive patients with thiazide-induced hypokalaemia. Lancet. 1973 Dec 8;2(7841):1288–1291. doi: 10.1016/s0140-6736(73)92869-9. [DOI] [PubMed] [Google Scholar]
  15. Hollifield J. W. Potassium and magnesium abnormalities: diuretics and arrhythmias in hypertension. Am J Med. 1984 Nov 5;77(5A):28–32. doi: 10.1016/s0002-9343(84)80005-4. [DOI] [PubMed] [Google Scholar]
  16. Hollifield J. W. Thiazide treatment of systemic hypertension: effects on serum magnesium and ventricular ectopic activity. Am J Cardiol. 1989 Apr 18;63(14):22G–25G. doi: 10.1016/0002-9149(89)90214-2. [DOI] [PubMed] [Google Scholar]
  17. Kohvakka A., Eisalo A., Manninen V. Maintenance of potassium balance during diuretic therapy. Acta Med Scand. 1979;205(4):319–324. doi: 10.1111/j.0954-6820.1979.tb06056.x. [DOI] [PubMed] [Google Scholar]
  18. Laerum E. Metabolic effects of thiazide versus placebo in patients under long-term treatment for recurrent urolithiasis. Scand J Urol Nephrol. 1984;18(2):143–149. doi: 10.3109/00365598409182182. [DOI] [PubMed] [Google Scholar]
  19. Lim P., Jacob E. Magnesium deficiency in patients on long-term diuretic therapy for heart failure. Br Med J. 1972 Sep 9;3(5827):620–622. doi: 10.1136/bmj.3.5827.620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. McInnes G. T. Relative potency of amiloride and spironolactone in healthy man. Clin Pharmacol Ther. 1982 Apr;31(4):472–477. doi: 10.1038/clpt.1982.62. [DOI] [PubMed] [Google Scholar]
  21. Morgan D. B., Davidson C. Hypokalaemia and diuretics: an analysis of publications. Br Med J. 1980 Mar 29;280(6218):905–908. doi: 10.1136/bmj.280.6218.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mountokalakis T., Merikas G., Skipelitis P., Vardakis M., Sevastos N., Alivisatos J. Changes of fractional renal clearance of magnesium after spironolactone administration in normal subjects. Klin Wochenschr. 1975 Jul 1;53(13):633–635. doi: 10.1007/BF01469684. [DOI] [PubMed] [Google Scholar]
  23. Parfitt A. M. The acute effects of mersalyl, chlorothiazide and mannitol on the renal excretion of calcium and other ions in man. Clin Sci. 1969 Apr;36(2):267–282. [PubMed] [Google Scholar]
  24. Ramsay L. E., Hettiarachchi J., Fraser R., Morton J. J. Amiloride, spironolactone, and potassium chloride in thiazide-treated hypertensive patients. Clin Pharmacol Ther. 1980 Apr;27(4):533–543. doi: 10.1038/clpt.1980.75. [DOI] [PubMed] [Google Scholar]
  25. Ryan M. P., Ryan M. F., Counihan T. B. The effect of diuretics on lymphocyte magnesium and potassium. Acta Med Scand Suppl. 1981;647:153–161. doi: 10.1111/j.0954-6820.1981.tb02651.x. [DOI] [PubMed] [Google Scholar]
  26. SELLER R. H., RAMIREZ-MUXO O., BREST A. N., MOYER J. H. MAGNESIUM METABOLISM IN HYPERTENSION. JAMA. 1965 Feb 22;191:654–656. doi: 10.1001/jama.1965.03080080044012. [DOI] [PubMed] [Google Scholar]
  27. Swales J. D. Magnesium deficiency and diuretics. Br Med J (Clin Res Ed) 1982 Nov 13;285(6352):1377–1378. doi: 10.1136/bmj.285.6352.1377. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Toner J. M., Brawn L. A., Yeo W. W., Ramsay L. E. Adequacy of twice daily dosing with potassium chloride and spironolactone in thiazide treated hypertensive patients. Br J Clin Pharmacol. 1991 Apr;31(4):457–461. doi: 10.1111/j.1365-2125.1991.tb05562.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. WHANG R., WELT L. G. Observations in experimental magnesium depletion. J Clin Invest. 1963 Mar;42:305–313. doi: 10.1172/JCI104717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Whang R. Some aspects of the interrlationship of magnesium and potassium. J Chronic Dis. 1968 Jul;21(4):207–210. doi: 10.1016/0021-9681(68)90057-x. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Clinical Pharmacology are provided here courtesy of British Pharmacological Society

RESOURCES