A Review of Critical Differences among Loop, Thiazide, and Thiazide-Like Diuretics

Abstract

Diuretics are a drug class with heterogeneous assortments. This article reviews general pharmacologic mechanisms and clinical implications of loop, thiazide, and thiazide-like diuretics. Loop diuretics act in the loop of Henle by blocking the sodium-potassium-chloride (Na+-K+-2Cl-) symport. They are effective in relieving congestive symptoms and edematous signs of heart failure. Activation of the neurohormonal system and subsequent pathologic myocardial remodeling limit the use of loop diuretics unless fluid balance is not met to relieve patients' symptoms with life-saving pharmacologic modalities. Adverse effects on electrolyte balance may cause life-threatening consequences. The combination of K+-sparing diuretics or angiotensin-converting enzyme inhibitors with loop diuretics may not only prevent life-threatening complications caused by electrolyte imbalance, but also may delay progression of the disease with proven mortality benefit. Recent findings of worsening renal function and higher mortality rate with the use of oral and intravenous loop diuretics further demands appropriate use of these drugs. Thiazide diuretics and thiazide-like diuretics act in the distal convoluted tubule by blocking Na+-Cl- symport. Thiazide diuretics reduce cardiovascular mortality by achieving target blood pressure in patients with hypertension. Compared with other antihypertensive drugs, thiazide diuretics have less desirable metabolic effects. However, it has not yet been shown that the negative metabolic effects of these drugs are associated with negative mortality and morbidity. Based on the need for a multidrug regimen to reach target blood pressure in most patients with hypertension, thiazide diuretics may be used in addition to a drug or drugs without metabolic complications.