Learning Objective

Understand the mechanism, uses, side effects, and clinical considerations of thiazide diuretics and their effect on renal electrolyte handling.

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Drugs

• Hydrochlorothiazide
• Chlorthalidone
• Indapamide
• Metolazone

First line of treatment in HTN and should be discussed in M06.08.001, M06.08.002, and M06.08.003.

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Mechanism of Action:

Inhibit the Na⁺/Cl⁻ symporter in the distal convoluted tubule (DCT).

Results in:

• ↑ Na⁺ and Cl⁻ in the tubular lumen
• ↑ water excretion → diuresis

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Clinical Uses:

• Hypertension
• Congestive heart failure (CHF)
• Nephrolithiasis (calcium stones)
• Nephrogenic diabetes insipidus

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Common Side Effects:

Electrolyte disturbances:

• Hypokalemia
• Alkalosis
• Hypercalcemia

Metabolic effects:

• Hyperuricemia (via OAT secretion)
• Hyperglycemia
• Hyperlipidemia (except indapamide)

Sulfonamide hypersensitivity

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Drug Interactions / Cautions:

• Digoxin: ↑ risk of toxicity due to electrolyte disturbances
• Combining K⁺ Sparing diuretics with ACE inhibitors or ARBs may cause hyperkalemia

Clinical Note:

• Diuretics acting above the collecting duct (loop & thiazide) ↑ Na⁺ delivery to downstream segments → ↑ K⁺ and H⁺ excretion → hypokalemia and metabolic alkalosis.

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