PharmGKB summary: Diuretics pathway, pharmacodynamics

摘要

Diuretics are the most commonly prescribed drugs for hypertension in the USA [1]. Diuretics modulate the reabsorption of sodium in the kidney and affect the homeostasis of water and sodium and thus the volume of blood and blood pressure. From a pharmacogenomics perspective, the most well studied drug in this class is the thiazide diuretic hydrochlorothiazide (HGT). HCT is excreted primarily by renal elimination with greater than 95% of the drug recovered unchanged in the urine [2]. Therefore, pharmacodynamic genes have been the focus for studies of the variation in response to thiazide diuretics. Thiazide diuretics act by inhibiting the sodium chloride cotran-sporter, NGG, coded for by SLC12A3 [3]. Also acting on sodium regulation in the kidney, loop diuretics such as furosemide, target the sodium potassium chloride cotran-sporter (NKGC2, SLC12A1). In addition, another subclass of diuretics, potassium-sparing diuretics like amiloride, act on the sodium channel ENac, coded for by SCNN1 family of genes. Table 1 shows the common names and their corresponding HGNG gene symbols for the key transporters.