Uses
Hypertension
Used alone or in combination with other antihypertensive agents for all stages of hypertension.
Thiazides have well-established benefits, can be useful in achieving goal BP alone or combined with other antihypertensive drugs, enhance the antihypertensive efficacy of multidrug regimens, and are more affordable than other agents.
JNC 7 recommends that thiazides be used as initial therapy for the treatment of uncomplicated hypertension in most patients, either alone or combined with other classes of antihypertensive drugs with demonstrated benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, β-blockers, calcium-channel blockers).
Most hypertension outcome studies have involved thiazides, which generally have been unsurpassed in preventing cardiovascular complications of hypertension and are relatively inexpensive and well tolerated.
The principal goal of preventing and treating hypertension is to reduce the risk of cardiovascular and renal morbidity and mortality, including target organ damage. The higher the baseline BP, the more likely the development of MI, heart failure, stroke, and renal disease.
Effective antihypertensive therapy reduces the risk of stroke by about 34–40%, MI by about 20–25%, and heart failure by more than 50%.
Antihypertensive drug therapy is recommended for all patients with SBP/DBP ≥140/90 mm Hg who fail to respond to lifestyle/behavioral modifications.
Initial antihypertensive therapy with drugs generally is recommended for anyone with diabetes mellitus, chronic renal impairment, or heart failure having SBP ≥130 mm Hg or DBP≥80 mm Hg.
Black hypertensive patients generally tend to respond better to monotherapy with diuretics or calcium-channel blockers than to monotherapy with ACE inhibitors, angiotensin II receptor antagonists, or β-blockers.
Thiazides are preferred in hypertensive patients with osteoporosis. Secondary beneficial effect in hypertensive geriatric patients of reducing the risk of osteoporosis secondary to effect on calcium homeostasis and bone mineralization.
Thiazide diuretics (unlike potassium-sparing diuretics) may be used in patients who are at an increased risk for developing hyperkalemia (e.g., those receiving an ACE inhibitor).
Although hypertension during pregnancy responds well to thiazides, and the drugs had been used widely in the past for preeclampsia and eclampsia, such use no longer is recommended and other antihypertensives (e.g., methyldopa, hydralazine, labetalol) currently are preferred.
Although rarely induces acute gout, generally avoid or use with caution in hypertensive patients with a history of gout or elevated uric acid concentrations.
Edema (General)
Management of edema resulting from various causes; diagnose etiology before use.
Edema caused by renal disease or by corticosteroids or estrogens may be relatively resistant to treatment.
Ineffective in patients with Scr or BUN concentrations greater than twice normal.
May be ineffective in patients with a GFR of <15–25 mL/minute; even when GFR is 25–50 mL/minute, more potent (e.g., loop) diuretics may be indicated.
No substantial difference in clinical effects or toxicity of comparable thiazide or thiazide-like diuretics, except metolazone may be more effective in edema with renal impairment.
Edema in CHF
Management of edema associated with CHF.
Used in conjunction with moderate sodium restriction (≤3 g of sodium daily), an ACE inhibitor, and usually a β-adrenergic blocking agent, with or without a cardiac glycoside.
Beneficial effects are additive with those of cardiac glycosides and/or ACE inhibitors.
Unless contraindicated or not tolerated, all patients with mild to severe CHF secondary to left ventricular systolic dysfunction (ejection fraction less than 35–40%) generally should receive therapy with a diuretic in conjunction with an ACE inhibitor with or without a cardiac glycoside or a β-adrenergic blocking agent.
Diuretic therapy and sodium restriction are not routinely necessary in patients with left ventricular systolic dysfunction and no or minimal overt signs or symptoms of heart failure (NYHA functional class I heart failure); diuretics should be added to ACE inhibitor therapy if volume overload develops or if symptoms of heart failure continue.
Concomitant diuretic therapy usually is indicated in patients with symptomatic heart failure (NYHA class II or greater) because of the likelihood of sodium and fluid retention.
Do not use diuretics as monotherapy in CHF even if symptoms (e.g., peripheral edema, pulmonary congestion) are well controlled; diuretics alone do not prevent progression of heart failure.
Diuretics produce rapid symptomatic benefits, relieving pulmonary and peripheral edema more rapidly (within hours or days) than cardiac glycosides, ACE inhibitors, or β-blockers (in weeks or months).
Once fluid retention has resolved in CHF, diuretic therapy should be maintained to prevent recurrence of fluid retention. Ideally, diuretic therapy should be adjusted according to changes in body weight (as an indicator of fluid retention) rather than maintained at a fixed dosage.
Diuretics should be continued in CHF and comorbid conditions (e.g., hypertension) where ongoing therapy with the drugs is indicated.
Edema Secondary to Nephrotic Syndrome
May be useful if the patient fails to respond to corticosteroid therapy.
More likely to become refractory to thiazides than edema associated with CHF, and more potent diuretics may be required.
Edema in Pregnancy
Generally responds well to thiazides except when caused by renal disease.
Thiazides should not be used for routine therapy in pregnant women with mild edema who are otherwise healthy.
Diabetes Insipidus
Has been used widely in the treatment of diabetes insipidus†.
Effective in both the neurohypophyseal and nephrogenic forms of the disease, decreasing urine volume by up to 50%.
Particularly useful in nephrogenic diabetes insipidus, since this form of the disease is unresponsive to vasopressin or lypressin and chlorpropamide.
Useful in patients who are allergic or refractory to vasopressin or lypressin and has been used in combination with one of these hormones and a low-salt diet in patients who excrete an exceptionally large volume of urine.
Renal Tubular Acidosis
Has been used with success in the treatment of electrolyte disturbances associated with renal tubular acidosis†.
Renal Calculus Formation
Has been used with success in the prophylaxis of renal calculus formation associated with hypercalciuria†.
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