Historical perspective of low- vs. high-dose diuretics

In the 50 years since the introduction of cholorothiazide by Fries and Wilson for the treatment of hypertension, numerous thiazide and thiazide-like diuretics have been marketed. Orally-administered diuretics enhanced the therapeutic efficacy of extant antihypertensive medications and reduced the doses required; adverse effects were thereby reduced as well. Initially, high doses of diuretics were employed at least in part because of the misconception that substantial natriuresis was required for their antihypertensive effect. As the long-term vasodilating effects of the thiazides became appreciated, it was possible to separate antihypertensive dose-response from natriuretic dose-response. As ever lower doses of thiazides were proven to be effective, most of their associated biochemical side and adverse effects were also reduced. Fifty years later, thiazide diuretics maintain a key role in the treatment of hypertension-especially in combination with one or more non-diuretic drugs.