Comments on hydrochlorothiazide
Hydrochlorothiazide is a thiazide diuretic
used to treat edema due to cardiac, liver, and renal disease. It is also useful alone or
as part of combinations with other antihypertensives for treatment of hypertension. When
used with furosemide, hydrochlorothiazide exhibits a synergistic effect that can cause
a significant loss of fluids and electrolytes. Following oral administration, about
65% of the drug is absorbed (this can be increased to 75% if given with food). Thiazide
diuretics probably act on the proximal portion of the distal tubule. The drug acts upon
the cells to prevent 5 to 8% of the filter sodium from being reabsorbed (Chemtob, Pediatr
Clin N A 1989; 36:1231). Since much of the filtered chloride has been reabsorbed prior
to this point, the thiazides are not as effective as the "loop" diuretics such
as furosemide (Green, "The Pharmacologic Basis of Diuretic Therapy in the
Newborn," Clin Perinatol 1987; 14:951). Since more sodium remains within the
lumen, it is exchanged for potassium in the distal tubule which results in increased
potassium losses. The peak effect in achieved within 2 to 6 hours. Unlike furosemide,
there is not an increase in calcium excretion. However, with chronic use, a magnesium
deficiency can develop. In adults this is associated with a refractory potassium
deficiency, i.e., the hypokalemia cannot be corrected without the addition of magnesium
(Rude, American Journal of Cardiology 1989; 63:31G). In addition, some adults are
thought to have developed ectopic ventricular beats due to magnesium deficiency
(Hollifield, American Journal of Cardiology 1989; 63:22G). The thiazides also have
a direct vasoconstricting effect upon the renal arteries. This will produce a decrease in
GFR (more pronounced with iv administration). This could potentially be a problem in
infants with decreased renal blood flow due to congestive heart failure (Roberts. Drug
Therapy in Infants. Philadelphia: W. B. Saunders, 1984:244). See diuretic for comparisons
of the effects and complications of the different diuretics.
When used with furosemide, hydrochlorothiazide
exhibits a synergistic effect that can cause a significant loss of fluids and electrolytes
that have lead to deaths in situations where these losses were not anticipated (Roberts. Drug
Therapy in Infants. Philadelphia: W. B. Saunders, 1984:246). In treating hypertension,
doses as high as 9 mg/kg/day have been recommended (Adelman, "The Hypertensive
Neonate," Clin Perinatol 1988 15:567). There does not appear to be any benefit
in giving the dose more frequently. Although thiazide diuretics are associated with
decreased calcium excretion, this depends upon intact parathyroid function and appropriate
supplementation with vitamin D. Calcium loss has been reported to occur in very low birth
weight infants who were treated with thiazide diuretics. This is thought to occur
secondary to inadequate intakes of sodium, calcium, phosphorous, magnesium, and vitamin D
as well as due to problems with parathyroid function (Chemtob, Pediatr Clin N A,
36:1231, 1989).