Loop Diuretics

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

Site of Action

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

Agents

All inhibit NKCC2.

Hemodynamic Effects

Immediate:

Venodilation (before diuresis)
↓ Preload

Later:

↓ Plasma volume
↓ Cardiac filling pressures

Primary cardiovascular effect:

Volume reduction

Electrolyte Effects

↓ Potassium
↓ Magnesium
↓ Calcium
↓ Sodium

Metabolic Effects:

Metabolic alkalosis (contraction alkalosis)

Monitor:

Potassium
Magnesium
Renal function

Clinical Use

Acute Pulmonary Edema:

Rapid IV administration

Decompensated HFrEF:

First-line for congestion
Combine with:

Advanced CKD:

Effective even when eGFR < 30

Hypercalcemia:

Increase calcium excretion (with fluids)

Loop Diuretics vs Thiazides

Compared to Thiazide Diuretics:

Much stronger natriuresis
Effective in advanced CKD
Cause calcium loss

Thiazides:

Better chronic BP control
Increase calcium retention

Adverse Effects

Hypokalemia
Hypomagnesemia
Ototoxicity (high doses)
Hypovolemia
Renal dysfunction

Risk increased with:

Aminoglycosides
Rapid IV administration

Pharmacologic Differences

Furosemide:

Most commonly used
Variable oral bioavailability

Torsemide:

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

Bumetanide:

Potent
Good bioavailability

Clinical Pearls

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)