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