Loop diuretics are the most potent natriuretic agents.

They inhibit sodium reabsorption in the thick ascending limb of the loop of Henle.

Primary use:

• Acute decompensated Heart Failure
• Pulmonary edema
• Advanced CKD with volume overload
• Severe edema

→ Diuretics

Thick Ascending Limb

Target transporter:

• Na⁺-K⁺-2Cl⁻ cotransporter (NKCC2)

Normal physiology:

• Reabsorbs ~25% of filtered sodium
• Generates medullary concentration gradient
• Reabsorbs calcium and magnesium (paracellular)

Blocking NKCC2 results in:

• Massive natriuresis
• ↓ Medullary gradient
• ↓ Water reabsorption downstream
• ↑ Calcium and magnesium excretion

• Furosemide
• Torsemide
• Bumetanide

All inhibit NKCC2.

Immediate:

• Venodilation (before diuresis)
• ↓ Preload

Later:

• ↓ Plasma volume
• ↓ Cardiac filling pressures

Primary cardiovascular effect:

• Volume reduction

• ↓ Potassium
• ↓ Magnesium
• ↓ Calcium
• ↓ Sodium

Metabolic Effects:

• Metabolic alkalosis (contraction alkalosis)

Monitor:

• Potassium
• Magnesium
• Renal function

Acute Pulmonary Edema:

• Rapid IV administration

Decompensated HFrEF:

• First-line for congestion
• Combine with:
  • Spironolactone
  • ACE Inhibitors
  • Beta-Blockers
  • SGLT2 Inhibitors

Advanced CKD:

• Effective even when eGFR < 30

Hypercalcemia:

• Increase calcium excretion (with fluids)

Compared to Thiazide Diuretics:

• Much stronger natriuresis
• Effective in advanced CKD
• Cause calcium loss

Thiazides:

• Better chronic BP control
• Increase calcium retention

• Hypokalemia
• Hypomagnesemia
• Ototoxicity (high doses)
• Hypovolemia
• Renal dysfunction

Risk increased with:

• Aminoglycosides
• Rapid IV administration

Furosemide:

• Most commonly used
• Variable oral bioavailability

Torsemide:

• More reliable bioavailability
• Longer half-life
• Possible improved HF outcomes (data evolving)

Bumetanide:

• Potent
• Good bioavailability

• Most potent diuretics
• Work in thick ascending limb
• Cause calcium loss
• Cause metabolic alkalosis
• Essential for acute HF management
• Not mortality-reducing agents (symptom relief only)

• Heart Failure
• Hypertension
• Thiazide Diuretics
• Potassium-Sparing Diuretics