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Cardiovascular Drugs Our Patients Take

Course Number: 581

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.4 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 three broad classes: (1) agents that act directly on the nephron to increase renal Na+ excretion, (2) drugs that modulate the RAAS, and (3) drugs that modulate the natriuretic peptide (NP) system.2,4,10,16

Table 2. Drugs that Regulate Volume.2,4,10,16

Drugs (Rank/300) Mechanisms of ActionCommon Indications
Thiazide diuretics
• Hydrochlorothiazide (11)
• Chlorthalidone (133)
Inhibit Na+ reabsorption by cells of the distal convoluted tubule • Edema
 o Congestive heart failure
 o Cirrhosis of the liver
 o Corticosteroid and estrogen therapy
 o Renal disease
• Hypertension
Loop diuretics
• Furosemide (19)
• Torsemide (213)
• Bumetanide (270)
Inhibit Na+ reabsorption by cells of the Loop of Henle • Edema
 o Congestive heart failure
 o Cirrhosis of the liver
 o Renal disease
• Hypertension
Neprilysin inhibitor
• Sacubitril*
Inhibit the degradation of natriuretic peptide thereby increasing vasodilation • Heart failure
Mineralocorticoid receptor antagonist (MRA) diuretics
• Spironolactone (51)
• Triamterene**
Spironolactone inhibits Na+ reabsorption by inhibiting aldosterone action

Triamterene inhibits Na+ reabsorption by principal cells of the collecting duct
• Primary hyperaldosteronism
• Edema
 o Heart failure
 o Cirrhosis of the liver
 o Nephrotic syndrome
• Hypertension
• Hypokalemia
Angiotensin converting enzyme (ACE) inhibitors
• Lisinopril (4)
• Benzapril (141)
• Ramipril (196)
• Quinapril (253)
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
• Heart failure
• Acute myocardial infarction
Angiotensin II receptor blockers
• Losartan (9)
• Valsartan (123)
• Olmesartan (139)
• Irbesartan (148)
• Telmisartan (248)
Antagonize the action of AT II at AT1 receptors

May indirectly increase AT2-receptor-related vasodilation
• Hypertension
• Nephropathy in type 2 diabetic patients
Sodium-glucose cotransporter 2 (SGLT2) inhibitor
• Empagliflozin (102)
• Dapagliflozin (217)
Inhibit Na+ reabsorption by cells of the distal convoluted tubule
• Type 2 diabetes
• Congestive heart failure
*Not available as single agent; see Table 6 Combination Cardiovascular Drugs

**Not a top 300 single agent; see Table 6 Combination Cardiovascular Drugs