====== 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:

  * [[cardio:hypertension:start|Hypertension]]
  * [[cardio:heart_failure:start|Heart Failure]]
  * Volume overload states

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===== Nephron-Based Physiology =====

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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[[cardio:diuretics:carbonic_anhydrase:start|Carbonic Anhydrase Inhibitors]]

Weak Diuretic Effect

Agents:
  * [[cardio:diuretics:acetazolamide|Acetazolamide]]
  * Methazolamide
  * Dichlorphenamide

Effect:
  * ↓ HCO₃⁻ reabsorption
  * Mild natriuresis
  * Metabolic acidosis

Clinical Use:
  * Glaucoma
  * Altitude sickness
  * Metabolic alkalosis
  * Periodic paralysis

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[[cardio:diuretics:loop:start|Loop Diuretics]]

Very Strong Diuresis

Agents:
  * [[cardio:diuretics:furosemide|Furosemide]]
  * [[cardio:diuretics:torsemide|Torsemide]]
  * [[cardio:diuretics:bumetanide|Bumetanide]]

Clinical Role:
  * Acute pulmonary edema
  * Decompensated [[cardio:heart_failure:start|Heart Failure]]
  * Advanced CKD
  * Severe volume overload

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[[cardio:diuretics:thiazide:start|Thiazide & Thiazide-Like Diuretics]]

Long-term vascular remodeling benefits.

Agents:
  * [[cardio:diuretics:hydrochlorothiazide|Hydrochlorothiazide]]
  * [[cardio:diuretics:chlorthalidone|Chlorthalidone]]
  * [[cardio:diuretics:indapamide|Indapamide]]

Clinical Role:
  * First-line therapy for [[cardio:hypertension:start|Hypertension]]
  * Mild edema

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[[cardio:diuretics:mra|Potassium-Sparing Diuretics]]

---- Mineralocorticoid Receptor Antagonists (MRAs)

  * [[cardio:hf:spironolactone|Spironolactone]]
  * [[cardio:hf:eplerenone|Eplerenone]]

Block aldosterone receptor.

Used in:
  * HFrEF (mortality benefit)
  * Resistant [[cardio:hypertension:start|Hypertension]]

---- Direct ENaC Blockers

  * [[cardio:diuretics:amiloride|Amiloride]]
  * [[cardio:diuretics:triamterene|Triamterene]]

Block epithelial sodium channel.

Electrolytes:
  * ↑ K⁺ (risk of hyperkalemia)

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[[cardio:diuretics:osmotic:start|Osmotic Diuretics]]

Agent:
  * [[cardio:diuretics:mannitol|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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===== Electrolyte Comparison =====

Loop Diuretics:
  * ↓ K⁺
  * ↓ Mg²⁺
  * ↓ Ca²⁺

Thiazides:
  * ↓ K⁺
  * ↑ Ca²⁺

MRAs:
  * ↑ K⁺

Carbonic Anhydrase Inhibitors:
  * ↓ HCO₃⁻

Monitoring electrolytes is essential.

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===== Diuretics in Cardiovascular Strategy =====

Hypertension:
  * [[cardio:diuretics:chlorthalidone|Chlorthalidone]] preferred over [[cardio:diuretics:hydrochlorothiazide|HCTZ]]

Heart Failure:
  * [[cardio:diuretics:loop:start|Loop Diuretics]] for congestion
  * [[cardio:hf:spironolactone|Spironolactone]] for mortality reduction

Resistant Hypertension:
  * Add [[cardio:hf:spironolactone|Spironolactone]]

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===== Clinical Pearls =====

  * 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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===== Related =====

  * [[cardio:hypertension:start|Hypertension]]
  * [[cardio:heart_failure:start|Heart Failure]]
  * [[cardio:intro:start|Cardiovascular Pharmacology]]