9.4 : Antihypertensive Drugs: Thiazide-Class Diuretics

Thiazide diuretics are sulfonamide derivatives featuring a benzothiadiazine ring system in their molecular structure. Based on this structure, thiazide diuretics can be categorized into two groups: thiazide-type and thiazide-like diuretics. Thiazide-type diuretics, including hydrochlorothiazide and chlorothiazide, consist of a benzothiadiazine backbone with an attached sulfonamide group. Thiazide-like diuretics, such as chlorthalidone and indapamide, lack the thiazide ring but demonstrate similar pharmacological properties to thiazide-type diuretics. The primary mechanism of action for thiazide diuretics involves inhibiting the sodium-chloride symporter on the luminal membrane of epithelial cells lining the distal convoluted tubule within the nephron. This interaction prevents sodium and chloride ions from being transported across the cell membrane, reducing their reabsorption into the bloodstream. The ions in the lumen attract more water, causing diuresis and increased urine excretion. This increased urine output reduces blood volume, decreasing cardiac output and lowering blood pressure. Additionally, thiazides indirectly reduce calcium influx into vascular smooth muscle cells, promoting muscle relaxation and reducing peripheral resistance, further reducing blood pressure. Thiazide diuretics must be excreted into the tubular lumen to achieve significant diuretic effects. However, their efficacy is diminished in patients with impaired renal function, such as those with a decreased glomerular filtration rate and compromised tubular secretion.