Diuretics in the treatment of hypertension. Part 1: thiazide and thiazide-like diuretics.
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Universidad Complutense, School of Medicine, Department of Pharmacology , Madrid , Spain.
Juan
J
Tamargo
Julian
J
Segura
Luis M
LM
Ruilope
D000959:Antihypertensive Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D006973:Hypertension / Q000188:drug therapy*; D055118:Medication Adherence; D049993:Sodium Chloride Symporter Inhibitors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D049971:Thiazides / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*
D000959:Antihypertensive Agents; D049993:Sodium Chloride Symporter Inhibitors; D049971:Thiazides; D014665:Vasodilator Agents