Why are thiazide diuretics used more often than loop diuretics in the treatment of hypertension? Do thiazides have vasodilatory effects?
Thiazide diuretics are used most often because they are considered to be more effective than other classes. It has been shown that low dose thiazide diuretics decrease the risk of stroke, CAD, CHF, cardiovascular mortality and total mortality.1 It is generally accepted that thiazide diuretics are more effective in the treatment of hypertension than loop diuretics in patients with a CrCl of > 30 ml/min. The theory is suggested due to the longer duration of action of most thiazide diuretics compared with loop diuretics.2 With thiazide diuretics, twenty-four hour control is achieved with a once daily dosing. The usual twice daily dosing of loop diuretics required to achieve twenty-four hour control increases the risk of dehydration, hypokalemia, and hypernatremia. For this reason, there are more trials involving thiazide diuretics in the treatment of hypertension.
There is also a theory that thiazide diuretics may have an additional mechanism of action involving direct vasodilation via relaxation of the vasculature. There is no literature to suggest that this mechanism of action may also be related to the loop diuretics. The theory with thiazides is based on the fact that diazoxide (a nondiuretic benzothiadiazine used intravenously (IV) for hypertensive emergencies) has a direct vasodilator effect and is chemically similar to hydrochlorothiazide.2 There is some in vitro evidence to support that hydrochlorothiazide causes vasodilation through the activation of potassium channels in the vasculature. Although difficult to determine in vivo, there is some support for this theory, but it was only achieved via IV infusion into a patient’s forearm at doses higher than traditional oral therapeutic doses.3 Some controversy surrounds the theory of thiazide vasodilation. The question exists as to why thiazides are not effective in patients with poor renal function. If the mechanism of action involves direct vasodilation, thiazides should be effective in these patients, because vasodilation would not be affected by renal function. There are no factual conclusions regarding the direct vasodilatory effects of thiazides. Loop diuretics have never been included in the theory of direct vasodilation.