Drugs that Regulate Extracellular Fluid Volume

About ⅔ of total body water is intracellular and ⅓ is extracellular. Nearly ¾ of the extracellular fluid (ECF) resides in the interstitial space. The remaining ¼ of the ECF, a determinant of tissue perfusion, i.e., the distribution of O₂ and nutrients, is in plasma. Depletion of plasma volume (1) activates the renin-angiotensin-aldosterone system (RAAS), (2) promotes antidiuretic hormone release, and (3) increases renal sympathetic activity; volume overload promotes the release of natriuretic peptides.⁴

Excessive Na⁺ and H₂O retention, primarily a result of renal abnormalities, is responsible for volume-based hypertension.⁴ Pathological Na⁺ and H₂O retention can also lead to transudative edema associated with heart failure, cirrhosis of the liver, and nephrotic syndrome⁴ Drugs in the top 300 that regulate extracellular fluid volume (Table 2) can be divided into two broad classes: (1) agents that act directly on the nephron to increase renal Na⁺ excretion and (2) drugs that modulate the RAAS.^2,^4,¹⁰.

Table 2. Drugs that Regulate Volume.^2,^4,¹⁰

Drugs	Mechanisms of Action	Common Indications
Thiazide diuretics Hydrochlorothiazide Hydrochlorothiazide w/lisinopril Hydrochlorothiazide w/losartan Hydrochlorothiazide w/ triamterene Hydrochlorothiazide w/valsartan Chlorthalidone	Inhibit Na+ reabsorption by cells of the distal convoluted tubule	Hypertension Adjuncts in chronic edema states associated with Congestive heart failure Hepatic cirrhosis Renal dysfunction Pulmonary edema Corticosteroid and estrogen therapy
Loop diuretics Furosemide Torsemide	Inhibit Na⁺ reabsorption by cells of the Loop of Henle
Collecting duct (potassium-sparing) diuretics Spironolactone Triamterene w/hydrochlorothiazide	Spironolactone inhibits Na⁺ reabsorption by inhibiting aldosterone action Triamterene inhibits Na⁺ reabsorption by principal cells of the collecting duct
Angiotensin converting enzyme (ACE) inhibitors Lisinopril Enalapril Benzapril Ramipril Quinapril	Inhibit the conversion of angiotensin (AT) I to AT II thereby decreasing Arteriolar vasoconstriction Aldosterone synthesis Na⁺ reabsorption by cells of renal proximal tubule ADH release Inhibit the degradation of bradykinin and thereby increasing vasodilation	Hypertension Adjuncts in the prevention and treatment of Myocardial infarction Heart failure Diabetic nephropathy
Angiotensin II receptor antagonists Losartan Valsartan Irbesartan Olmesartan	Antagonize the action of AT II at AT₁ receptors May indirectly increase AT₂-receptor-related vasodilation

0/16Next