Thiazide and thiazide-like diuretics
Derived from sulfonamides, thiazide and
thiazide-like diuretics are used to treat edema and to prevent the development
and recur-rence of renal calculi. They’re also used for such cardiovascular
diseases as hypertension and heart failure.
Thiazide diuretics include:
Thiazide-like diuretics include:
Thiazide diuretics are absorbed rapidly but
incompletely from the GI tract after oral administration. They cross the
placenta and are secreted in breast milk. These drugs differ in how well
they’re me-tabolized, but all are excreted primarily in urine.
Thiazide-like diuretics are absorbed from the GI
tract. Chlor-thalidone is 90% bound to erythrocytes; little is known about its
metabolism. Indapamide is distributed widely into body tissues and metabolized
in the liver. Little is also known about the metab-olism of metolazone. All of
these drugs are primarily excreted in urine.
Thiazide and thiazide-like diuretics promote the
excretion of wa-ter by preventing the reabsorption of sodium in the kidneys. As
the kidneys excrete the excess sodium, they excrete water along with it. These
drugs also increase the excretion of chloride, potas-sium, and bicarbonate,
which can result in electrolyte imbalances. With long-term use, thiazide
diuretics also lower blood pressure by causing arteriolar vasodilation.
Initially, diuretic drugs decrease circulating
blood volume, leading to reduced cardiac output. However, if therapy is
maintained, car-diac output stabilizes but plasma fluid volume decreases.
Thiazides are used for the long-term treatment of
hypertension; they’re also used to treat edema caused by kidney or liver
disease, mild or moderate heart failure, and corticosteroid and estrogen
therapy. Because these drugs decrease the level of calcium in urine, they may
be used alone or with other drugs to prevent the development and recurrence of
In patients with diabetes insipidus (a disorder
characterized by excessive urine production and excessive thirst resulting from
re-duced secretion of antidiuretic hormone), thiazides paradoxically decrease
urine volume, possibly through sodium depletion and plasma volume reduction.
Drug interactions related to thiazide and
thiazide-like diuretics re-sult in altered fluid volume, blood pressure, and
serum electrolyte levels:
§ These drugs may decrease excretion of
lithium, causing lithium toxicity.
§ Nonsteroidal anti-inflammatory drugs,
including cyclooxyge-nase-2 (COX-2) inhibitors, may reduce the antihypertensive
effect of these diuretics.
§ Use of these drugs with other
potassium-depleting drugs and digoxin may cause an additive effect, increasing
the risk of digox-in toxicity.
§ These diuretics may increase the response to
§ Use of these drugs may increase blood glucose
levels, re-quiring higher doses of insulin or oral antidiabetic drugs.
§ These drugs may produce additive hypotension
when used with antihypertensives. (See Adverse
reactions to thi-azide and thiazide-like diuretics.)