Diuretics alter renal sodium handling to reduce extracellular volume.

Because water follows sodium, altering sodium reabsorption alters:

• Blood volume
• Preload
• Blood pressure
• Edema

Diuretics are foundational in:

• Hypertension
• Heart Failure
• Edema states

Understanding diuretics requires understanding where sodium is reabsorbed.

Proximal Tubule:

• ~65% Na⁺ reabsorption

Thick Ascending Limb:

• ~25% Na⁺ reabsorption

Distal Convoluted Tubule:

• ~5% Na⁺ reabsorption

Collecting Duct:

• ~3% Na⁺ reabsorption (aldosterone-sensitive)

Each diuretic class blocks a specific transporter.

Site: Thick Ascending Limb Target: NKCC2 transporter

Block:

• Na⁺
• K⁺
• 2Cl⁻ reabsorption

Agents:

• Furosemide
• Torsemide
• Bumetanide

Clinical use:

• Acute pulmonary edema
• Volume overload
• HFrEF
• Advanced CKD

Strongest natriuresis.

Site: Distal Convoluted Tubule Target: NCC transporter

Block:

• Na⁺/Cl⁻ reabsorption

Agents:

• Hydrochlorothiazide
• Chlorthalidone
• Indapamide

Primary use:

• First-line Hypertension

Moderate natriuresis. Long-term vascular remodeling effects.

Site: Collecting Duct

Two mechanisms:

Mineralocorticoid Receptor Antagonists (MRAs):

• Spironolactone
• Eplerenone

Block aldosterone receptor.

Direct ENaC Blockers:

• Amiloride
• Triamterene

Block epithelial sodium channel.

Clinical use:

• Resistant hypertension
• Heart failure (mortality benefit for MRAs)
• Prevent hypokalemia

Site: Proximal Tubule

Target:

• Carbonic anhydrase

Agent:

• Acetazolamide

Cause:

• Bicarbonate loss
• Mild natriuresis
• Metabolic acidosis

Clinical use:

• Glaucoma
• Altitude sickness
• Metabolic alkalosis

Weak diuretic effect.

Site: Proximal Tubule & Loop

Agent:

• Mannitol

Mechanism:

• Increases tubular osmotic pressure
• Pulls water into tubular lumen

Use:

• Cerebral edema
• Increased intracranial pressure

Loops:

• ↓ K⁺
• ↓ Mg²⁺
• ↓ Ca²⁺

Thiazides:

• ↓ K⁺
• ↑ Ca²⁺

MRAs:

• ↑ K⁺

Carbonic Anhydrase Inhibitors:

• ↓ HCO₃⁻

Electrolyte monitoring is essential.

Hypertension:

• Chlorthalidone preferred

Heart Failure:

• Loop Diuretics for congestion
• Spironolactone for mortality benefit

Resistant Hypertension:

• Add Spironolactone

• Sodium drives water
• Loops are strongest
• Thiazides best for chronic HTN
• MRAs reduce mortality in HFrEF
• Always monitor potassium
• Electrolyte shifts define each class

• Hypertension
• Heart Failure
• Cardiovascular Pharmacology