Hydrochlorothiazide (DB00999): A Comprehensive Pharmacological and Clinical Monograph

I. Introduction and Drug Profile

1.1. Overview and Historical Context

Hydrochlorothiazide (HCTZ) is a prototypical diuretic of the thiazide class, which has served as a cornerstone in the management of hypertension and edema for over six decades.[1] Since its approval by the U.S. Food and Drug Administration (FDA) on February 12, 1959, HCTZ has become one of the most widely prescribed medications in cardiovascular medicine, valued for its efficacy, low cost, and extensive clinical experience.[3]

Historically, thiazide diuretics represented a major breakthrough in the treatment of hypertension, offering a reliable oral agent that could effectively control blood pressure and reduce the morbidity associated with fluid overload.[1] HCTZ remains the most commonly prescribed thiazide diuretic worldwide.[3] However, its role, particularly as a first-line monotherapy for hypertension, has been subject to re-evaluation in recent years. Its use in this capacity is gradually declining in favor of newer antihypertensive classes, such as angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs).[3] Despite this trend, the prevalence of HCTZ remains exceptionally high, largely due to its formulation in numerous fixed-dose combination products, where it acts synergistically with other antihypertensive agents to achieve greater blood pressure control.[3]

1.2. Chemical and Physical Properties

Hydrochlorothiazide is classified as a small molecule drug.[3] Chemically, it is a benzothiadiazine, specifically the 3,4-dihydro derivative of chlorothiazide, and is characterized by the presence of a sulfonamide group and an organochlorine component.[4] This sulfonamide moiety is critical for its diuretic activity and is also the basis for potential hypersensitivity reactions in individuals with a sulfa allergy.