Potassium-Sparing Diuretics

Potassium-sparing diuretics act at the collecting duct.

They reduce sodium reabsorption while preserving potassium.

These agents have weak diuretic effect but important clinical roles.

Used in:

Heart Failure
Resistant Hypertension
Prevention of hypokalemia

Site of Action

Collecting Duct

Normal physiology:

Aldosterone → ↑ ENaC expression
↑ Sodium reabsorption
↑ Potassium secretion

Potassium-sparing agents interfere with this process.

Two Major Subclasses

[[cardio:diuretics:potassium_sparing:mra|Mineralocorticoid Receptor Antagonists (MRAs)]]

Mechanism:

Block aldosterone receptor
↓ ENaC expression
↓ Sodium reabsorption
↑ Potassium retention
↓ Myocardial fibrosis

Agents:

Clinical Importance:

Mortality reduction in HFrEF
Preferred 4th-line agent in resistant hypertension
Treat primary hyperaldosteronism

Key Feature:

Neurohormonal blockade — not just diuresis

[[cardio:diuretics:potassium_sparing:enac|ENaC Inhibitors]]

Mechanism:

Directly block epithelial sodium channel (ENaC)
Reduce sodium reabsorption
Reduce potassium secretion

Agents:

Clinical Use:

Prevent hypokalemia from:
- Loop Diuretics
- Thiazide Diuretics

No mortality benefit in heart failure.

Electrolyte Effects

All potassium-sparing diuretics:

↑ Potassium
Mild natriuresis

Risk:

Hyperkalemia
Worsened by:

MRAs vs ENaC Inhibitors

MRAs:

Block aldosterone receptor
Reduce cardiac remodeling
Reduce mortality in HFrEF
Cause endocrine side effects (spironolactone)

ENaC Inhibitors:

Pure potassium preservation
No cardiac remodeling benefit
Used primarily for electrolyte balance

Clinical Pearls

Weak diuretics
Strong neurohormonal agents (MRAs)
Essential in HFrEF
Spironolactone causes gynecomastia
Monitor potassium closely
Hyperkalemia risk increases with RAAS blockade