Thiazide diuretics like hydrochlorothiazide (HCTZ) were derived from sulfonamides in the late 1950’s by chemists who were looking for a non-mercurial, orally active compound that would increase salt and water excretion by the kidneys safely for treatment of hypertension and edema.1-3 In 1949, the diuretic action, the excretion of salt and water, of sulfanilamide in patients with edema due to congestive heart failure was identified by Schwartz.4 Chlorothiazide was developed from this discovery.4 It is a substituted 1,3-benzene disulphonamide (6 - chloro - 7 - sulphamyl- 1,2,4-benzothiadiazine- 1, 1 -dioxide).5 One sulphonamide group is free, while the other is linked with an acyl-amino group (opposite the free sulphonamide group on the benzene nucleus) forming a benzothiadiazine ring.5
HCTZ (6-chloro-7-sulfamyl-3,4,dihydro-l,2,4, benzothiadiazine-1,1,-dioxide) is the 3,4,dihydro derivative of chlorothiazide wherein the 3,4 double bond is saturated by two hydrogen atoms.6 HCTZ is equally active to chlorothiazide in doses between 1/10th and 1/20th of chlorothiazide.7-9
References
- Novello FC, Sprague JM. Benzothiadiazine dioxides as novel diuretics. J Am Chem Soc 1957; 79 (8): 2028-2029.
- Ford RV, Moyer JH, Spurr CL. Clinical and laboratory observations on chlorothiazide (Diuril), an orally effective non-mercurial diuretic agent. AMA Arch Intern Med 1957; 100 (4): 582-596.
- Beyer KH, Jr., Baer JE. The site and mode of action of some sulfonamide-derived diuretics. Med Clin North Am 1975; 59 (3): 735-750.
- Schwartz WB. The effect of sulfanilamide on salt and water excretion in congestive heart failure. N Engl J Med 1949; 240 (5): 173-177.
- [Chlorothiazide]. Lancet 1959; 1 (7076): 768-769.
- Januszewicz W, Heinemann HO, Demartini FE, Laragh JH. A clinical study of the effects of hydrochlorothiazide on the renal excretion of electrolytes and free water. N Engl J Med 1959; 261 (6): 264-269.
- Smirk H, McQueen EG, Morrison RBI. Chlorothiazide and hydrochlorothiazide in management of hypertension. Br Med J 1960; 1 (5172): 515-518.
- Lee RE, Seligman AW, Clark MA, Rousseau PA. A comparison of the side effects and antihypertensive potency of chlorothiazide and hydrochlorothiazide. N Engl J Med 1960; 262: 1066-1068.
- Fleming PR, Zilva JF, Bayliss RI, Pirkis J. Hydrochlorothiazide; a comparison with chlorothiazide. Lancet 1959; 1 (7085): 1218-1221.
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