Premium
Standard oral water load to determine the site of action of diuretics in man With data on metolazone, a new diuretic
Author(s) -
Michelis Michael F.,
DeRubertis Frederick,
Beck Nama P.,
McDonald Robert H.,
Davis Bernard B.
Publication year - 1970
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1970116821
Subject(s) - diuretic , chemistry , nephron , clearance , free water clearance , hydrochlorothiazide , diuresis , excretion , sodium , urine flow rate , endocrinology , urine , medicine , renal function , urology , biochemistry , blood pressure , organic chemistry
Two male volunteers were given metolazone, a new diuretic, intravenously during a stable protracted water diuresis. The drug caused a mean decrease in CH 2 O of 2.8 c.c. per minute, a mean increase in sodium excretion of 419.5 μEq. per minute and no Significant change in urine flow rate or clearance of either inulin or PAH. The data suggested that metolazone affects the diluting segment of the nephron reducing the ability to clear free water. Five volunteers were given a standard water load with and without metolazone 10 mg. orally. The data revealed that total free water cleared in the 4 hours following the administration of water decreased (387.6 C.c. S.E. ± 73.9, P < 0.02), while osmols cleared increased (546.6 C.c., S.E. ± 106.7, P < 0.01) and sodium excretion increased (60.6 mEq., S.E. ± 10.5, P < 0.01). Urine volumes and potassium excretion were unchanged. Similar studies with oral water loads given to 4 volunteers who were also given 50 mg. of hydrochlorothiazide, which acts on the diluting segment of the nephron, produced changes such as those seen with metolazone. The data suggest, therefore, that metolazone, like hydrochlorothiazide, acts on the diluting segment of the nephron and that the standard oral water load is an accurate and convenient means of determining the site of action of diuretics.