Diuretic-Related Side Effects: Development and Treatment

Domenic A. Sica, MD

In This Article

Abstract and Introduction

Diuretics are important therapeutic tools. First, they effectively reduce blood pressure and have been shown in numerous hypertension clinical trials to reduce both cardiovascular and cerebrovascular morbidity and mortality. In addition, their use has been equally effective in controlling cardiovascular events as angiotensin-converting enzyme inhibitors or calcium channel blockers. Diuretics are currently recommended by the Seventh Report of the Joint National Commission on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure report as first-line therapy for the treatment of hypertension. In addition, they remain an important aspect of congestive heart failure treatment in that they improve the congestive symptomatology, which typifies the more advanced stages of congestive heart failure. This article reviews the commonly encountered side effects with the various diuretic classes. Where indicated, the mechanistic basis and treatment of such side effects is further discussed.

The dose-response relationship for the antihypertensive effect of diuretics has been more fully characterized over the past 20 years. In the process, many of the supposed negative attributes of diuretics are less common than was first thought. In the early days of diuretic use, doses were unnecessarily high, with dosing driven by the belief that "If a little is good, more is better"; however, it was quickly recognized that the blood pressure (BP) lowering effect for a thiazide-type diuretic, such as hydrochlorothiazide (HCTZ), was relatively flat beyond a daily dose of 25 mg, and that at the higher dosages (100-200 mg/d), more negative metabolic experiences would occur.[2,3] At lower doses (HCTZ, 12.5-25.0 mg), the metabolic mischief seen with high-dose thiazide-type diuretic therapy was much less concerning, with the possible exception of new-onset diabetes.[3] Recent observations suggest that becoming a new-onset diabetic as a consequence of diuretic therapy carries a similar negative cardiovascular (CVR) risk as exists for the diabetic population in general.[4] This observation varies from that of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial,[5] where the CVR outcomes in either new-onset or already present diabetics were not worsened by diuretic therapy.