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November 4, 1974, Vol 230, No. 5 >
ARTICLE | November 4, 1974

Management of Potassium Problems During Long-Term Diuretic Therapy FREE

Mary Ellen Kosman, PhD
[+] Author Affiliations

Reprint requests to AMA Department of Drugs, 535 N Dearborn St, Chicago, IL 60610.


JAMA. 1974;230(5):743-748. doi:10.1001/jama.1974.03240050065033
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References

MOST diuretics increase the renal excretion of potassium as part of their pharmacologic action. The thiazides and the loop diuretics (furosemide and ethacrynic acid) have a more pronounced potassium-wasting effect than the mercurials, primarily because they remain effective during continuous long-term therapy, and also because of differences in site and mechanism of action. There is a wide diversity of opinion and there are many unsettled questions regarding the implications of potassium loss during long-term diuretic therapy, the indications for correction, and the best method for offsetting the loss. This commentary will examine the current state of the art.

POTASSIUM BALANCE AND DIURETIC THERAPY  To maintain potassium homeostasis, the amount of potassium ingested must equal the amount excreted, and under normal conditions, most of the potassium that is lost from the body is excreted in the urine. The regulation of potassium balance by the kidney is closely related to the renal

REFERENCES

1 +
Frazier HS, Yager H:  Clinical use of diuretics . N Engl J Med 288:246-249, 455-457, 1973;.
2 +
Cannon PJ:  Physiology of diuretics: How they work, how to pick best one . Res Staff Physi cian 18:31-83, 1972;.
3 +
Kleit S, et al: Diuretic therapy:  Current status . Am Heart J 79:700-712, 1970;.
4 +
Schultze RG:  Recent advances in physiology and pathophysiology of potassium excretion . Arch Intern Med 131:885-897, 1973;.
5 +
Morgan TO:  Clinical use of potassium supplements and potassium-sparing diuretics . Drugs 6:222-229, 1973;.
6 +
Soffer A (ed): Potassium Therapy: Seminar . Springfield, Ill, Charles C Thomas Publisher, 1968;.
7 +
Rovner DR:  Use of pharmacologic agents in treatment of hypokalemia and hyperkalemia . Ration Drug Ther 6:1-6, 1972;.
8 +
Lowenstein J:  Hypokalemia and hyperkalemia . Med Clin North Am 57:1435-1439, 1973;.
9 +
Zipes DP:  Electrolyte derangements in genesis of arrhythmias , in Dreifus LS, Likoff W (eds): Cardiac Arrhythmias . New York, Grune & Stratton, 1973;, pp 55-69.
10 +
Graybiel AL, Sode J:  Diuretics, potassium depletion, and carbohydrate intolerance, letter . Lancet 2:265, 1971;.
11 +
 Drug treatment of ambulatory patients with hypertension, Committee on Hypertension . JAMA 225:1647-1653, 1973;.
12 +
Anderson J, et al:  Comparison of effects of hydrochlorothiazide and frusemide in treatment of hypertensive patients . Q J Med 40:541-560, 1971;.
13 +
Healy JT, et al:  Body composition changes in hypertensive subjects on long-term oral diuretic therapy . Br Med J 1:716-719, 1970;.
14 +
Hollander W Jr, Blythe WB:  Nephropathy of potassium depletion , in Strauss MB, Welt LG (eds): Diseases of the Kidney , ed 2. Boston, Little, Brown & Co, 1971;, vol 2.
15 +
Nagant de Deuxchaisnes C, et al:  Exchangeable potassium in wasting, amyotrophy, heart disease, and cirrhosis of liver . Lancet 1:681687, 1961;.
16 +
Gifford RW, et al:  Effect of thiazide diuretics on plasma volume, body electrolytes, and excretion of aldosterone in hypertension . Circulation 24:1197-1205, 1961;.
17 +
Edmonds CJ, Jasani B:  Total body potassium in hypertensive patients during prolonged diuretic therapy . Lancet 2:8-12, 1972;.
18 +
Flear CTG:  Potassium problems in heart disease . Adverse Drug Reaction Bulletin , No. 32, 33, 1972;, pp 96-99, 100-103.
19 +
Novak LP, Harrison CE:  Abnormalities of cellular potassium concentration in uncompensated and compensated congestive heart failure . Mayo Clin Proc 48:107-113, 1973;.
20 +
Knox FG:  Role of proximal tubule in regulation of urinary sodium excretion . Mayo Clin Proc 48:565-573, 1973;.
21 +
Ben-Ishay D, Engelman K:  Bioavailability of potassium from slow-release tablet . Clin Pharmacol Ther 14:250-258, 1973;.
22 +
McKenna TJ, et al:  Potassium-sparing agents during diuretic therapy in hypertension . Br Med J 2:739-741, 1971;.
23 +
Sandoe E, Olesen K:  Hypokalaemia, hypochloraemia, and baseosis in long-term treatment of oedematous heart failure with benzothiadiazine diuretics: II. Prophylactic value of potassium chloride . Acta Med Scand 172:699-702, 1962;.
24 +
Edmondson RPS, et al:  Leucocyte electrolytes in cardiac patients and noncardiac patients receiving diuretics . Lancet 1:12-14, 1974;.
25 +
White RJ:  Effect of potassium supplements on exchangeable potassium in chronic heart disease . Br Med J 3:141-142, 1970;.
26 +
Nagant de Deuxchaisnes C, Mach R-S:  Potassium depletion and potassium supplementation in cardiac failure . Lancet 1:517, 1974;.
27 +
Down PF, et al:  Fate of potassium supplements in six patients receiving long-term diuretics for oedematous disease . Lancet 2:721-724, 1972;.
28 +
Boley SJ, et al:  Potassium-induced lesions of small bowel: I. Clinical aspects . JAMA 193:997-1000, 1965;.
29 +
Jacobs E, Pringot J:  Gastric ulcers due to intake of potassium chloride . Am J Dig Dis 18:289-294, 1973;.
30 +
Gerstein AR, et al:  Potassium losing pyelonephritis: Response to spironolactone . Arch Intern Med 123:55-57, 1969;.
31 +
Warr OS, Nash JP:  Jejunal ulceration: Report of case apparently associated with potassium gluconate . JAMA 199:217-218, 1967;.
32 +
Rosenthal T, et al:  Esophageal ulceration and oral potassium chloride ingestion . Chest 65:463-465, 1974;.
33 +
Burchell HB:  Dilemmas in potassium therapy . Circulation 47:1144-1146, 1973;.
34 +
Reynolds EW:  Use of potassium in treatment of heart disease . Am Heart J 70:1-5, 1965;.
35 +
 Potassium-sparing diuretics: Spironolactone, triamterene, and amiloride . Drug Ther Bull 10:30-32, 1972;.
36 +
George CF, et al:  Comparison of potassium-retaining effects of amiloride and spironolactone in hypertensive patients with thiazideinduced hypokalemia . Lancet 2:1288-1291, 1973;.
37 +
Olesen K, Sandoe E:  Hypokalaemia, hypochloraemia, and baseosis in long-term treatment of oedematous heart failure with benzothiadiazine diuretics: III. Effect of spironolactone . Acta Med Scand 172:703-709, 1962;.
38 +
Winer BM, et al:  Antihypertensive actions of diuretics . JAMA 204:775-779, 1968;.
39 +
Hollander W:  Aldosterone antagonists in arterial hypertension . Heart Bull 12:108-111, 1963;.
40 +
Heath WC, Freis E:  Triamterene and hydrochlorothiazide in treatment of hypertension . JAMA 186:119-122, 1963;.
41 +
Spiekerman RE, et al:  Potassium-sparing effects of triamterene in treatment of hypertension . Circulation 34:524-531, 1966;.
42 +
Cranston WI, et al:  Effects of triamterene on elevated arterial pressure . Am Heart J 70:455-460, 1965;.
43 +
Leth A, et al:  Effect of triamterene on plasma and extracellular fluid volume and blood pressure in ten thiazide-treated hypokalemic patients with essential hypertension . Scand J Clin Lab Invest 30:437-440, 1972;.
44 +
Davidson C, Gillebrand IM:  Use of amiloride as potassium conserving agent in severe cardiac disease . Br Heart J 35:456-461, 1973;.
45 +
Antcliff AC, et al:  Use of amiloride in correction of hypokalemic alkalosis induced by diuretics . Postgrad Med J 47:644-647, 1971;.
46 +
Croxson MS, et al:  Exchangeable potassium in heart disease: Long-term effects of potassium supplements and amiloride . Am Heart J 84:53-60, 1972;.
47 +
Senewiratne B, Sherlock S:  Amiloride (MK-870) in patients with ascites due to cirrhosis of liver . Lancet 1:120-122, 1968;.
48 +
Paterson JW, et al:  Amiloride hydrochloride in hypertensive patients . Br Med J 1:422-423, 1968;.
49 +
Antcliff AC, et al:  Amiloride hydrochloride combined with hydrochlorothiazide in control of hypertension and plasma potassium levels . Br J Clin Pract 26:413-416, 1972;.
50 +
Yamada S, Reynolds TB:  Amiloride (MK-870), a new antikaluretic diuretic . Gastroenterology 59:833-841, 1970;.
51 +
Salako LA, Falase AO:  Clinical evaluation of Moduretic in treatment of arterial hypertension . Nigerian Med J 3:150-155, 1973;.
52 +
Greenblatt DJ, Koch-Weser J:  Adverse reactions to spironolactone . JAMA 225:40-43, 1973;.
53 +
Lieberman FL, Bateman JR:  Megaloblastic anemia possibly induced by triamterene in patients with alcoholic cirrhosis . Ann Intern Med 68:168-173, 1968;.

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1 +
Frazier HS, Yager H:  Clinical use of diuretics . N Engl J Med 288:246-249, 455-457, 1973;.
2 +
Cannon PJ:  Physiology of diuretics: How they work, how to pick best one . Res Staff Physi cian 18:31-83, 1972;.
3 +
Kleit S, et al: Diuretic therapy:  Current status . Am Heart J 79:700-712, 1970;.
4 +
Schultze RG:  Recent advances in physiology and pathophysiology of potassium excretion . Arch Intern Med 131:885-897, 1973;.
5 +
Morgan TO:  Clinical use of potassium supplements and potassium-sparing diuretics . Drugs 6:222-229, 1973;.
6 +
Soffer A (ed): Potassium Therapy: Seminar . Springfield, Ill, Charles C Thomas Publisher, 1968;.
7 +
Rovner DR:  Use of pharmacologic agents in treatment of hypokalemia and hyperkalemia . Ration Drug Ther 6:1-6, 1972;.
8 +
Lowenstein J:  Hypokalemia and hyperkalemia . Med Clin North Am 57:1435-1439, 1973;.
9 +
Zipes DP:  Electrolyte derangements in genesis of arrhythmias , in Dreifus LS, Likoff W (eds): Cardiac Arrhythmias . New York, Grune & Stratton, 1973;, pp 55-69.
10 +
Graybiel AL, Sode J:  Diuretics, potassium depletion, and carbohydrate intolerance, letter . Lancet 2:265, 1971;.
11 +
 Drug treatment of ambulatory patients with hypertension, Committee on Hypertension . JAMA 225:1647-1653, 1973;.
12 +
Anderson J, et al:  Comparison of effects of hydrochlorothiazide and frusemide in treatment of hypertensive patients . Q J Med 40:541-560, 1971;.
13 +
Healy JT, et al:  Body composition changes in hypertensive subjects on long-term oral diuretic therapy . Br Med J 1:716-719, 1970;.
14 +
Hollander W Jr, Blythe WB:  Nephropathy of potassium depletion , in Strauss MB, Welt LG (eds): Diseases of the Kidney , ed 2. Boston, Little, Brown & Co, 1971;, vol 2.
15 +
Nagant de Deuxchaisnes C, et al:  Exchangeable potassium in wasting, amyotrophy, heart disease, and cirrhosis of liver . Lancet 1:681687, 1961;.
16 +
Gifford RW, et al:  Effect of thiazide diuretics on plasma volume, body electrolytes, and excretion of aldosterone in hypertension . Circulation 24:1197-1205, 1961;.
17 +
Edmonds CJ, Jasani B:  Total body potassium in hypertensive patients during prolonged diuretic therapy . Lancet 2:8-12, 1972;.
18 +
Flear CTG:  Potassium problems in heart disease . Adverse Drug Reaction Bulletin , No. 32, 33, 1972;, pp 96-99, 100-103.
19 +
Novak LP, Harrison CE:  Abnormalities of cellular potassium concentration in uncompensated and compensated congestive heart failure . Mayo Clin Proc 48:107-113, 1973;.
20 +
Knox FG:  Role of proximal tubule in regulation of urinary sodium excretion . Mayo Clin Proc 48:565-573, 1973;.
21 +
Ben-Ishay D, Engelman K:  Bioavailability of potassium from slow-release tablet . Clin Pharmacol Ther 14:250-258, 1973;.
22 +
McKenna TJ, et al:  Potassium-sparing agents during diuretic therapy in hypertension . Br Med J 2:739-741, 1971;.
23 +
Sandoe E, Olesen K:  Hypokalaemia, hypochloraemia, and baseosis in long-term treatment of oedematous heart failure with benzothiadiazine diuretics: II. Prophylactic value of potassium chloride . Acta Med Scand 172:699-702, 1962;.
24 +
Edmondson RPS, et al:  Leucocyte electrolytes in cardiac patients and noncardiac patients receiving diuretics . Lancet 1:12-14, 1974;.
25 +
White RJ:  Effect of potassium supplements on exchangeable potassium in chronic heart disease . Br Med J 3:141-142, 1970;.
26 +
Nagant de Deuxchaisnes C, Mach R-S:  Potassium depletion and potassium supplementation in cardiac failure . Lancet 1:517, 1974;.
27 +
Down PF, et al:  Fate of potassium supplements in six patients receiving long-term diuretics for oedematous disease . Lancet 2:721-724, 1972;.
28 +
Boley SJ, et al:  Potassium-induced lesions of small bowel: I. Clinical aspects . JAMA 193:997-1000, 1965;.
29 +
Jacobs E, Pringot J:  Gastric ulcers due to intake of potassium chloride . Am J Dig Dis 18:289-294, 1973;.
30 +
Gerstein AR, et al:  Potassium losing pyelonephritis: Response to spironolactone . Arch Intern Med 123:55-57, 1969;.
31 +
Warr OS, Nash JP:  Jejunal ulceration: Report of case apparently associated with potassium gluconate . JAMA 199:217-218, 1967;.
32 +
Rosenthal T, et al:  Esophageal ulceration and oral potassium chloride ingestion . Chest 65:463-465, 1974;.
33 +
Burchell HB:  Dilemmas in potassium therapy . Circulation 47:1144-1146, 1973;.
34 +
Reynolds EW:  Use of potassium in treatment of heart disease . Am Heart J 70:1-5, 1965;.
35 +
 Potassium-sparing diuretics: Spironolactone, triamterene, and amiloride . Drug Ther Bull 10:30-32, 1972;.
36 +
George CF, et al:  Comparison of potassium-retaining effects of amiloride and spironolactone in hypertensive patients with thiazideinduced hypokalemia . Lancet 2:1288-1291, 1973;.
37 +
Olesen K, Sandoe E:  Hypokalaemia, hypochloraemia, and baseosis in long-term treatment of oedematous heart failure with benzothiadiazine diuretics: III. Effect of spironolactone . Acta Med Scand 172:703-709, 1962;.
38 +
Winer BM, et al:  Antihypertensive actions of diuretics . JAMA 204:775-779, 1968;.
39 +
Hollander W:  Aldosterone antagonists in arterial hypertension . Heart Bull 12:108-111, 1963;.
40 +
Heath WC, Freis E:  Triamterene and hydrochlorothiazide in treatment of hypertension . JAMA 186:119-122, 1963;.
41 +
Spiekerman RE, et al:  Potassium-sparing effects of triamterene in treatment of hypertension . Circulation 34:524-531, 1966;.
42 +
Cranston WI, et al:  Effects of triamterene on elevated arterial pressure . Am Heart J 70:455-460, 1965;.
43 +
Leth A, et al:  Effect of triamterene on plasma and extracellular fluid volume and blood pressure in ten thiazide-treated hypokalemic patients with essential hypertension . Scand J Clin Lab Invest 30:437-440, 1972;.
44 +
Davidson C, Gillebrand IM:  Use of amiloride as potassium conserving agent in severe cardiac disease . Br Heart J 35:456-461, 1973;.
45 +
Antcliff AC, et al:  Use of amiloride in correction of hypokalemic alkalosis induced by diuretics . Postgrad Med J 47:644-647, 1971;.
46 +
Croxson MS, et al:  Exchangeable potassium in heart disease: Long-term effects of potassium supplements and amiloride . Am Heart J 84:53-60, 1972;.
47 +
Senewiratne B, Sherlock S:  Amiloride (MK-870) in patients with ascites due to cirrhosis of liver . Lancet 1:120-122, 1968;.
48 +
Paterson JW, et al:  Amiloride hydrochloride in hypertensive patients . Br Med J 1:422-423, 1968;.
49 +
Antcliff AC, et al:  Amiloride hydrochloride combined with hydrochlorothiazide in control of hypertension and plasma potassium levels . Br J Clin Pract 26:413-416, 1972;.
50 +
Yamada S, Reynolds TB:  Amiloride (MK-870), a new antikaluretic diuretic . Gastroenterology 59:833-841, 1970;.
51 +
Salako LA, Falase AO:  Clinical evaluation of Moduretic in treatment of arterial hypertension . Nigerian Med J 3:150-155, 1973;.
52 +
Greenblatt DJ, Koch-Weser J:  Adverse reactions to spironolactone . JAMA 225:40-43, 1973;.
53 +
Lieberman FL, Bateman JR:  Megaloblastic anemia possibly induced by triamterene in patients with alcoholic cirrhosis . Ann Intern Med 68:168-173, 1968;.

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