European Heart Journal (1992) 13 {Supplement G), 15-21
Effects of diuretics on renal excretory function A. J. REYES
Institute of Cardiovascular Theory, Montevideo, Uruguay KEY WORDS: Diuretics, furosemide, hydrochlorothiazide, torasemide, urinary potassium excretion, urinary sodium excretion.
% change in mean 24-h natriuresis
Introduction
The diuretics considered in this review include those whose main site of renal action lies in the ascending limb of the loop of Henle (loop diuretics), those whose main site of renal action lies in the early portion of the distal convoluted tubule (early distal tubular diuretics), and those that interfere with the exchange of sodium for potassium and hydrogen ions, which takes place in the late portion of the distal convoluted tubule, the connecting tubule and the early portion of the collecting duct (potassium-retaining diuretics). Furosemide is the prototype loop diuretic; this class also includes azosemide, bumetanide, diapamide, ethacrynic acid, etozoline, muzolimine, ozolinone, piretanide and torasemide. Hydrochlorothiazide is the prototype early distal tubular diuretic; this class includes all the benzothiadiazines (thiazides), chlorthalidone, cicletanine, clorexolone, clopamide, frenquizone, indapamide, metolazone, tienilic acid, tizolemide and xipamide. The anti-aldosterone drugs spironolactone and potassium canrenoate and the substances amiloride and triamterene are potassium-retaining diuretics. Renal excretory potency of diuretics: definition
Criteria for the evaluation of the urinary excretory potency (i.e. the intensity of the urinary excretory action) of diuretics in clinical pharmacology have recently been propounded'1'. Diuretic potency should refer to excretion of sodium ion and should be defined in healthy adults who are in steady-state habitual external sodium balance. Patients with oedema and healthy subjects who are not in steady external sodium balance respond to diuretics with widely scattered urinary sodium outputs. The urinary excretory potency of diuretics should be evaluated after single doses of oral diuretics. During Correspondence: A. J Reyes, MD, I.C.T., Sotelo 3908, 11700 Montevideo, Uruguay. 0195-668X/92 '0G0015 + 07 $08.00/0
Study D E F M/a M/a M/b E N 0 D 0 0 0 N
n Diuretic 14 16 14 10 10 10 16 14 16 14 16 14 16 16
40
mg
Furosemide Furosemide Furosemide Muzolimine Muzolimine Muzolimine Piretanide Torasemide . Torasemide Torasemide Torosemide Torasemide Torasemide Torasemide
40 80 80 20 30 40 12 2-5 2-5 5
5 10 10 20
80
Post-ptocebo
mmol 147 148 147 186 186 225 148 180 180 147 180 147 180 180
c b c ns b a a ns ns ns b ns c c
Figure I Effects of single or once-daily administration of various oral loop diuretics on mean 24-h urinary sodium output in healthy subjects (for explanation see text). Two sided P. a < 0-05; b < 005; c < 0001; ns >0.05. See the references in Table 1 for the sources of data. Study n Diuretic
mg
% change fri mean 24-h natriuresis post40
B B B C G D F H I J K L E P P P P
14 14 14 9 13 14 14 II 12 19 10 7 16 13 13 13 13
Cicletonre Cicletanine Cicletanme Clopamide HCTZ HCTZ HCTZ HCTZ HCTZ HCTZ HCTZ Indapamide Tizolemide Xipamide Xipamide Xipamide Xipamide
50 100 150 5 25 25 25 25 25 50 50 2-5 100 5 10 20 40
80
-PLA
120 - mmol
156 156 156 154 151 147 147 124 185 177 133 • 112 148 151 151 151 151
PLA a c c c c c c c c c c c c b c c c
Figure 2 Effects of single or once-daily administration of various oral early distal tubular diuretics on mean 24-h urinary sodium output in healthy subjects (for explanation see text). Two-sided P: a < 0 0 5 ; b
Effects of diuretics on renal excretory function A. J. REYES
Institute of Cardiovascular Theory, Montevideo, Uruguay KEY WORDS: Diuretics, furosemide, hydrochlorothiazide, torasemide, urinary potassium excretion, urinary sodium excretion.
% change in mean 24-h natriuresis
Introduction
The diuretics considered in this review include those whose main site of renal action lies in the ascending limb of the loop of Henle (loop diuretics), those whose main site of renal action lies in the early portion of the distal convoluted tubule (early distal tubular diuretics), and those that interfere with the exchange of sodium for potassium and hydrogen ions, which takes place in the late portion of the distal convoluted tubule, the connecting tubule and the early portion of the collecting duct (potassium-retaining diuretics). Furosemide is the prototype loop diuretic; this class also includes azosemide, bumetanide, diapamide, ethacrynic acid, etozoline, muzolimine, ozolinone, piretanide and torasemide. Hydrochlorothiazide is the prototype early distal tubular diuretic; this class includes all the benzothiadiazines (thiazides), chlorthalidone, cicletanine, clorexolone, clopamide, frenquizone, indapamide, metolazone, tienilic acid, tizolemide and xipamide. The anti-aldosterone drugs spironolactone and potassium canrenoate and the substances amiloride and triamterene are potassium-retaining diuretics. Renal excretory potency of diuretics: definition
Criteria for the evaluation of the urinary excretory potency (i.e. the intensity of the urinary excretory action) of diuretics in clinical pharmacology have recently been propounded'1'. Diuretic potency should refer to excretion of sodium ion and should be defined in healthy adults who are in steady-state habitual external sodium balance. Patients with oedema and healthy subjects who are not in steady external sodium balance respond to diuretics with widely scattered urinary sodium outputs. The urinary excretory potency of diuretics should be evaluated after single doses of oral diuretics. During Correspondence: A. J Reyes, MD, I.C.T., Sotelo 3908, 11700 Montevideo, Uruguay. 0195-668X/92 '0G0015 + 07 $08.00/0
Study D E F M/a M/a M/b E N 0 D 0 0 0 N
n Diuretic 14 16 14 10 10 10 16 14 16 14 16 14 16 16
40
mg
Furosemide Furosemide Furosemide Muzolimine Muzolimine Muzolimine Piretanide Torasemide . Torasemide Torasemide Torosemide Torasemide Torasemide Torasemide
40 80 80 20 30 40 12 2-5 2-5 5
5 10 10 20
80
Post-ptocebo
mmol 147 148 147 186 186 225 148 180 180 147 180 147 180 180
c b c ns b a a ns ns ns b ns c c
Figure I Effects of single or once-daily administration of various oral loop diuretics on mean 24-h urinary sodium output in healthy subjects (for explanation see text). Two sided P. a < 0-05; b < 005; c < 0001; ns >0.05. See the references in Table 1 for the sources of data. Study n Diuretic
mg
% change fri mean 24-h natriuresis post40
B B B C G D F H I J K L E P P P P
14 14 14 9 13 14 14 II 12 19 10 7 16 13 13 13 13
Cicletonre Cicletanine Cicletanme Clopamide HCTZ HCTZ HCTZ HCTZ HCTZ HCTZ HCTZ Indapamide Tizolemide Xipamide Xipamide Xipamide Xipamide
50 100 150 5 25 25 25 25 25 50 50 2-5 100 5 10 20 40
80
-PLA
120 - mmol
156 156 156 154 151 147 147 124 185 177 133 • 112 148 151 151 151 151
PLA a c c c c c c c c c c c c b c c c
Figure 2 Effects of single or once-daily administration of various oral early distal tubular diuretics on mean 24-h urinary sodium output in healthy subjects (for explanation see text). Two-sided P: a < 0 0 5 ; b
