Thiazide and thiazide-like diuretics

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:

·                 bendroflumethiazide

·                 chlorothiazide

·                 hydrochlorothiazide

·                 hydroflumethiazide

·                 methyclothiazide

·                 polythiazide.

Thiazide-like diuretics include:

·                 chlorthalidone

·                 indapamide

·                 metolazone.

Pharmacokinetics (how drugs circulate)

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.

Pharmacodynamics (how drugs act)

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.

Turning down the volume

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.

Pharmacotherapeutics (how drugs are used)

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 renal calculi.

Pointing out a paradox

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

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 skeletalmuscle relaxants.

§    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.)