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

They are foundational therapy for:

• Hypertension
• Mild edema
• Calcium nephrolithiasis prevention

→ Diuretics

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

True Thiazides:

• Hydrochlorothiazide

Thiazide-Like (Longer-Acting):

• Chlorthalidone
• Indapamide

Key Difference:

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

Chlorthalidone is generally preferred in hypertension.

Initial:

• ↓ Plasma volume
• ↓ Cardiac output

Chronic:

• ↓ Systemic vascular resistance
• Vascular remodeling effects

Long-term BP lowering is primarily due to:

• Reduced peripheral resistance

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

Monitor:

• Potassium
• Sodium
• Uric acid

Hypertension:

• First-line agent
• Often combined with:
  • ACE Inhibitors
  • ARBs
  • DHP Calcium Channel Blockers

Kidney Stones:

• Reduce urinary calcium excretion

Edema:

• Mild cases
• Not effective in severe renal failure

Less effective when:

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

In advanced CKD:

• Use Loop Diuretics

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

Compared to Loop Diuretics:

• Less potent
• Better chronic BP control

Compared to Potassium-Sparing Diuretics:

• Cause potassium loss
• Stronger natriuresis

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

• Hypertension
• Diuretics
• Loop Diuretics
• Potassium-Sparing Diuretics