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 syndrome.4 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