Thiazide Diuretics

Summary

The drug names of thiazide diuretics include hydrochlorothiazide, while the drug names of thiazide-like diuretics include chlorthalidone, indapamide, and metolazone.

These drugs act in the distal convoluted tubule of the nephron, where they inhibit the reabsorption of sodium and chloride. This results in increased urine output and a reduced ability of the nephron to dilute urine.  Thiazide diuretics also enhance calcium reabsorption in the kidneys, which can raise calcium levels in the body.

Clinically, thiazide diuretics are used to treat conditions like hypertension, heart failure, osteoporosis, nephrogenic diabetes insipidus, and idiopathic hypercalciuria.

Potential side effects of thiazide diuretics include changes in electrolytes like hypercalcemia, hyperglycemia, hypokalemia and hyponatremia.  They can also cause metabolic changes like hyperlipidemia and metabolic alkalosis. Other side effects include hyperuricemia and gout, sulfa allergies, and increased lithium levels which can lead to toxicity in patients on lithium therapy.

Key Points

• Thiazide Diuretics
  • Drug Name
    • Hydrochlorothiazide (HCTZ)
    • Chlorthalidone
    • Indapamide
    • Metolazone
  • Mechanism
    • Acts on early distal convoluted tubule
    • Blocks Na+Cl- cotransporters
      • Decreases diluting capacity of nephron
      • Thiazide diuretics block Na+/CI- reabsorption in the distal tubule. This allows more Na- to reach the collecting tubule, enhancing K+ and H+ excretion.
    • Decreased urinary secretion of Ca2+ (↑ absorption of Ca2+)
  • Clinical Use
    • Treat hypertension
      • Especially in African Americans and elderly patients
      • Thiazide diuretics are presently the first line treatment for essential hypertension in the outpatient setting
    • Treat heart failure
      • e.g heart failure, cirrhosis, nephrotic syndrome, pulmonary edema
    • Treat idiopathic hypercalciuria
      • Due to increased calcium reabsorption
    • Treat osteoporosis
      • Due to increased calcium reabsorption
    • Treat nephrogenic DI
      • Mild hypovolemia induced by thiazides increases proximal tubule sodium and water reabsorption)
  • Side Effects
    • Metabolic alkalosis
      • Also known as contraction alkalosis, where compensatory increase in aldosterone causes increased H+ excretion
    • Hypokalemia
    • Hyponatremia
    • Hypercalcemia
      • Due to increased calcium reabsorption
    • Hyperuricemia (gout)
      • Thiazide diuretics can lead to hyperuricemia and precipitate an acute gout attack
    • Causes sulfa allergy
    • Hyperglycemia
    • Hyperlipidemia
    • Increased lithium toxicity
      • Lithium is filtered and reabsorbed at the proximal convoluted tubule by cation transporters (similar to sodium)
      • The hypovolemia and hyponatremia caused by thiazide diuretics can stimulate increased activity of the cation transporters, leading to increased lithium levels and potential toxicity.