====== 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 [[cardio:heart_failure:start|Heart Failure]]
  * Pulmonary edema
  * Advanced CKD with volume overload
  * Severe edema

→ [[cardio:diuretics:start|Diuretics]]

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===== 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

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===== Agents =====

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

All inhibit NKCC2.

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===== Hemodynamic Effects =====

Immediate:

  * Venodilation (before diuresis)
  * ↓ Preload

Later:

  * ↓ Plasma volume
  * ↓ Cardiac filling pressures

Primary cardiovascular effect:

  * Volume reduction

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===== Electrolyte Effects =====

  * ↓ Potassium
  * ↓ Magnesium
  * ↓ Calcium
  * ↓ Sodium

Metabolic Effects:

  * Metabolic alkalosis (contraction alkalosis)

Monitor:

  * Potassium
  * Magnesium
  * Renal function

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===== Clinical Use =====

Acute Pulmonary Edema:

  * Rapid IV administration

Decompensated HFrEF:

  * First-line for congestion
  * Combine with:
      * [[cardio:hf:spironolactone|Spironolactone]]
      * [[cardio:raas:acei|ACE Inhibitors]]
      * [[cardio:beta_blockers:start|Beta-Blockers]]
      * [[endocrine:sglt2:start|SGLT2 Inhibitors]]

Advanced CKD:

  * Effective even when eGFR < 30

Hypercalcemia:

  * Increase calcium excretion (with fluids)

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===== Loop Diuretics vs Thiazides =====

Compared to [[cardio:diuretics:thiazide:start|Thiazide Diuretics]]:

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

Thiazides:

  * Better chronic BP control
  * Increase calcium retention

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===== Adverse Effects =====

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

Risk increased with:

  * Aminoglycosides
  * Rapid IV administration

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===== 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

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===== 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)

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===== Related =====

  * [[cardio:heart_failure:start|Heart Failure]]
  * [[cardio:hypertension:start|Hypertension]]
  * [[cardio:diuretics:thiazide:start|Thiazide Diuretics]]
  * [[cardio:diuretics:mra|Potassium-Sparing Diuretics]]