====== Thiazide & Thiazide-Like Diuretics ======

Thiazide and thiazide-like diuretics inhibit sodium reabsorption in the distal convoluted tubule.

They are foundational therapy for:

  * [[cardio:hypertension:start|Hypertension]]
  * Mild edema
  * Calcium nephrolithiasis prevention

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

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===== Site of Action =====

Distal Convoluted Tubule

Target transporter:

  * Na⁺-Cl⁻ cotransporter (NCC)

Normal physiology:

  * Reabsorbs ~5% of filtered sodium
  * Regulated independently of RAAS in chronic states

Blocking NCC leads to:

  * ↓ Sodium reabsorption
  * ↓ Plasma volume
  * ↓ Blood pressure
  * ↑ Calcium reabsorption

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===== Thiazide vs Thiazide-Like =====

True Thiazides:

  * [[cardio:diuretics:hydrochlorothiazide|Hydrochlorothiazide]]

Thiazide-Like (Longer-Acting):

  * [[cardio:diuretics:chlorthalidone|Chlorthalidone]]
  * [[cardio:diuretics:indapamide|Indapamide]]

Key Difference:

  * Thiazide-like agents have longer half-life
  * Greater 24-hour BP control
  * Stronger outcome data

Chlorthalidone is generally preferred in hypertension.

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

Initial:

  * ↓ Plasma volume
  * ↓ Cardiac output

Chronic:

  * ↓ Systemic vascular resistance
  * Vascular remodeling effects

Long-term BP lowering is primarily due to:

  * Reduced peripheral resistance

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

  * ↓ Potassium
  * ↓ Sodium
  * ↑ Calcium
  * ↑ Uric acid
  * ↑ Glucose (mild)

Monitor:

  * Potassium
  * Sodium
  * Uric acid

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

Hypertension:

  * First-line agent
  * Often combined with:
      * [[cardio:raas:acei|ACE Inhibitors]]
      * [[cardio:raas:arb|ARBs]]
      * [[cardio:ccb:dhp|DHP Calcium Channel Blockers]]

Kidney Stones:

  * Reduce urinary calcium excretion

Edema:

  * Mild cases
  * Not effective in severe renal failure

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===== Renal Function Considerations =====

Less effective when:

  * eGFR < 30 mL/min (except metolazone, not listed here)

In advanced CKD:

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

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

  * Hypokalemia
  * Hyponatremia
  * Hyperuricemia (gout risk)
  * Mild hyperglycemia

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===== Thiazides vs Other Diuretics =====

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

  * Less potent
  * Better chronic BP control

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

  * Cause potassium loss
  * Stronger natriuresis

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

  * First-line for hypertension
  * Chlorthalidone preferred
  * Cause hypokalemia
  * Increase calcium retention
  * Long-term BP effect = vascular resistance reduction
  * Weak in advanced CKD

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===== Related =====

  * [[cardio:hypertension:start|Hypertension]]
  * [[cardio:diuretics:start|Diuretics]]
  * [[cardio:diuretics:loop:start|Loop Diuretics]]
  * [[cardio:diuretics:mra|Potassium-Sparing Diuretics]]