Comments on chlorothiazide
Chlorothiazide is used as a diuretic
(increased sodium and chloride excretion) and as an antihypertensive (the mechanism of
action is unknown). At maximum doses the effects of the different thiazide diuretics
are essentially equal. Following oral administration, 20% or less of the drug is absorbed.
An IV dose of 1 to 4 mg/kg can be given every 12 hours. 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 Appendix P 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). The optimal therapeutic effect may not
be seen for one to two weeks after therapy has been started. 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).