Diuretics

Diuretics alter renal sodium handling to reduce extracellular volume.

Because water follows sodium, altering sodium reabsorption changes:

• Blood volume
• Preload
• Blood pressure
• Edema

Diuretics are foundational in:

• Hypertension
• Heart Failure
• Volume overload states

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Sodium reabsorption by segment:

Proximal Tubule:

• ~65%

Thick Ascending Limb:

• ~25%

Distal Convoluted Tubule:

• ~5%

Collecting Duct:

• ~3% (aldosterone-sensitive)

Each diuretic class blocks a specific transporter.

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Carbonic Anhydrase Inhibitors

Weak Diuretic Effect

Agents:

• Acetazolamide
• Methazolamide
• Dichlorphenamide

Effect:

• ↓ HCO₃⁻ reabsorption
• Mild natriuresis
• Metabolic acidosis

Clinical Use:

• Glaucoma
• Altitude sickness
• Metabolic alkalosis
• Periodic paralysis

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Loop Diuretics

Very Strong Diuresis

Agents:

• Furosemide
• Torsemide
• Bumetanide

Clinical Role:

• Acute pulmonary edema
• Decompensated Heart Failure
• Advanced CKD
• Severe volume overload

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Thiazide & Thiazide-Like Diuretics

Long-term vascular remodeling benefits.

Agents:

• Hydrochlorothiazide
• Chlorthalidone
• Indapamide

Clinical Role:

• First-line therapy for Hypertension
• Mild edema

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Potassium-Sparing Diuretics

—- Mineralocorticoid Receptor Antagonists (MRAs)

• Spironolactone
• Eplerenone

Block aldosterone receptor.

Used in:

• HFrEF (mortality benefit)
• Resistant Hypertension

—- Direct ENaC Blockers

• Amiloride
• Triamterene

Block epithelial sodium channel.

Electrolytes:

• ↑ K⁺ (risk of hyperkalemia)

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Osmotic Diuretics

Agent:

• Mannitol

Mechanism:

• Increases tubular osmotic pressure
• Pulls water into lumen

Clinical Use:

• Cerebral edema
• Increased intracranial pressure

Not used for chronic hypertension.

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Loop Diuretics:

• ↓ K⁺
• ↓ Mg²⁺
• ↓ Ca²⁺

Thiazides:

• ↓ K⁺
• ↑ Ca²⁺

MRAs:

• ↑ K⁺

Carbonic Anhydrase Inhibitors:

• ↓ HCO₃⁻

Monitoring electrolytes is essential.

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Hypertension:

• Chlorthalidone preferred over HCTZ

Heart Failure:

• Loop Diuretics for congestion
• Spironolactone for mortality reduction

Resistant Hypertension:

• Add Spironolactone

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• Sodium drives water
• Loops are most potent
• Thiazides are best chronic BP agents
• MRAs reduce mortality in HFrEF
• Hyperkalemia risk with MRAs and ENaC blockers
• Electrolyte patterns define each class

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• Hypertension
• Heart Failure
• Cardiovascular Pharmacology