Diuretics in the Treatment of Hypertension. Part 1: Thiazide and Thiazide-Like Diuretics

Expert Opin Pharmacother. 2014 Mar;15(4):527-47. doi: 10.1517/14656566.2014.879118. Epub 2014 Jan 20.


Introduction: Thiazides and thiazide-like diuretics inhibit the electroneutral Na(+)-Cl(-) cotransporter located on the apical membrane of the early segment of the distal convoluted tubule. They have been widely prescribed over 60 years in the treatment of hypertension and various edematous states.

Areas covered: Thiazide diuretics reduce blood pressure (BP), although the mechanisms by which they chronically lower BP remain unknown. These drugs present a flat dose-response curve that explains why when prescribed at high doses their use was associated with a wide range of adverse effects, particularly electrolyte changes and metabolic abnormalities that can be minimized at the low doses actually prescribed. This article reviews the clinical pharmacology of thiazide diuretics to provide an insight into the mechanisms involved in their antihypertensive and adverse effects, the determinants of drug response and the possible differences in their pharmacodynamic and pharmacokinetic properties in an attempt to improve their clinical use in the treatment of arterial hypertension.

Expert opinion: At low doses, thiazide diuretics remain as an effective and safe therapeutic alternative in the treatment of hypertension. Additionally, their ability to increase the efficacy of nearly all other classes of antihypertensives makes them a highly versatile therapeutic intervention in the treatment of hypertension.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Antihypertensive Agents / adverse effects
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use*
  • Humans
  • Hypertension / drug therapy*
  • Medication Adherence
  • Sodium Chloride Symporter Inhibitors / adverse effects
  • Sodium Chloride Symporter Inhibitors / pharmacology
  • Sodium Chloride Symporter Inhibitors / therapeutic use*
  • Thiazides / adverse effects
  • Thiazides / pharmacology
  • Thiazides / therapeutic use*
  • Vasodilator Agents / adverse effects
  • Vasodilator Agents / pharmacology
  • Vasodilator Agents / therapeutic use*


  • Antihypertensive Agents
  • Sodium Chloride Symporter Inhibitors
  • Thiazides
  • Vasodilator Agents