Mechanisms and pharmacogenetic signals underlying thiazide diuretics blood pressure response

Curr Opin Pharmacol. 2016 Apr:27:31-7. doi: 10.1016/j.coph.2016.01.005. Epub 2016 Feb 10.

Abstract

Thiazide (TZD) diuretics are among the most commonly prescribed antihypertensives globally; however their chronic blood pressure (BP) lowering mechanism remains unclear. Herein we discuss the current evidence regarding specific mechanisms regulating the antihypertensive effects of TZDs, suggesting that TZDs act via multiple complex and interacting mechanisms, including natriuresis with short term use and direct vasodilatory effects chronically. Additionally, we review pharmacogenomics signals that have been associated with TZDs BP-response in several cohorts (i.e. NEDD4L, PRKCA, EDNRA-GNAS, and YEATS4) and discuss how these genes might be related to TZD BP-response mechanism. Understanding the association between these genes and TZD BP mechanism might facilitate the development of new drugs and therapeutic approaches based on a deeper understanding of the determinants of BP-response.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antihypertensive Agents / pharmacology
  • Antihypertensive Agents / therapeutic use
  • Blood Pressure / drug effects*
  • Blood Pressure / genetics*
  • Diuretics / pharmacology*
  • Diuretics / therapeutic use*
  • Humans
  • Pharmacogenetics / methods
  • Signal Transduction / drug effects
  • Signal Transduction / genetics*
  • Thiazides / pharmacology*
  • Thiazides / therapeutic use*

Substances

  • Antihypertensive Agents
  • Diuretics
  • Thiazides