Thiazide Diuretic

  • Thiazide Diuretics are a class of structurally-similar sulfonamides that all act to increase Na+Cl- excretion by inhibiting the NaCl Symporter in the early distal tubule (See: Early Distal Tubule Transport). These are some of the most commonly prescribed diuretics and are frequently used as a first line anti-hypertensives. The two most dangerous adverse effects of thiazides are hyponatremia and hypokalemia although these drugs can also yield "4 hypers", hypercalcemia, hyperuricemia, hyperglycemia, and hyperlipidemia.
Mechanism of Action
  • As mentioned, thiazides inhibit the action of the NaCl symporter present on the luminal membrane of the early distal tubule. By doing so, thiazides increase Na+Cl- excretion. Water follows these ions and ultimately yields a reduction in effective extracellular fluid volume that likely underlies thiazides' anti-hypertensive effects. In general, thiazides are fairly weak diuretics as over 90% of sodium is resorbed prior to reaching the early distal tubule where thiazides act.
Adverse Effects
  • Hyponatremia
  • Hypokalemia
    • Because of their effects on sodium described above, thiazides modestly increase the flow of urine to the late distal tubule and collecting duct. As discussed under "Distal Tubular Flow Rate" of the External Potassium Balance page, this increased fluid delivery to the late distal tubule enhances sodium/potassium exchange, leading to increased potassium excretion. In some patients this may result in hypokalemia.
  • Hypomagnesemia
    • Through cryptic mechanisms thiazides can yield increased urinary magnesium excretion and thus hypomagnesemia.
  • Hypercalcemia
    • Thiazide diuretics increase tubular calcium resorption and can result in hypercalcemia
  • Hyperuricemia
    • Thiazides increase tubular uric acid resorption and can lead to hyperuricemia which in the proper context can precipitate and attack of gout
  • Hyperglycemia
    • Thiazides can interfere with release of insulin and decrease tissue insulin sensitivity. Together these effects can yield hyperglycemia and thus thiazides should be used with caution in diabetics.
  • Hyperlipidemia
    • Thiazides can lead to moderate dysregulation of lipid metabolism, resulting in mild to moderate hyperlipidemia
Member Drugs
  • Hydrochlorothiazide
  • Chlorthalidone