michigan hypertension core curriculum - State of Michigan

Diuretics
Overview of Major Anti-Hypertensive Classes
William Repaskey, M.D.
While there are no fewer than eight distinct antihypertensive drug classes, diuretics remain a
major cornerstone of antihypertensive therapy. There are multiple reasons for this including the fact that
they are inexpensive, have a proven track record of effectiveness since their development in the 1950s,
and diuretics enhance the effectiveness of all other antihypertensive drug classes. Numerous studies
over many years have demonstrated their equal if not superior effect in preventing the cardiovascular
complications of hypertension. Most recently, the landmark ALLHAT study which involved 40,000
hypertensive individuals showed that diuretics appear to prevent cardiovascular complications
associated with hypertension as effectively as ACE inhibitors or calcium-channel blockers. 1 On the
basis of these types of studies that authors of the JNCVII national guidelines recommend that thiazides
be used as initial therapy for the treatment of uncomplicated hypertension in most patients. Thiazides
can be used either alone or combined with other classes of antihypertensive drugs with demonstrated
benefit (e.g., ACE inhibitors, angiotensin II receptor antagonists, beta blockers, and calcium-channel
blockers). 2 Of note, the ALLHAT trial did show that the majority of patients will require treatment with 2
or more agents to accomplish adequate blood pressure control 3 , so the typical approach to therapy in a
standard patient will employ a diuretic in combination with another agent. Diuretics effectively lower BP
in all population sub-groups and, as monotherapy, they lower BP on average as or more effectively than
other antihypertensive drug classes.
Pharmacology/Mechanism of Action
The clinically utilized diuretics are divided into 3 distinct subclasses based on their chemical
structure, target of activity, mechanism of action within the renal tubule, pharmacologic effect and side
effect profile. These subclasses include the thiazides, loop diuretics, and the potassium sparing and
aldosterone antagonist diuretics. All diuretics fundamentally promote excretion of sodium, chloride and
water from the body. Diuresis contracts the extracellular fluid volume and as a consequence, decreases
cardiac output. There is an initial, transient hypotensive effect, though homeostatic mechanisms,
including activation of the renin-angiotensin activating system, later return extracellular volume to pre-
NKFM & MDCH 185