| Biological Functions | The exact mechanisms by which diuretics lower blood
pressure are not entirely understood. Initially, diuretics
produce a mild degree of Na+ depletion, which leads to
a decrease in extracellular fluid volume and cardiac
output. The effectiveness of diuretic therapy in mild
hypertension may also involve either interference with
or blunting of cardiovascular reflexes. Regardless of
the details, there is general agreement that the blood
pressure–lowering effects of diuretics do ultimately depend
on the production of diuresis. High salt intake or
low rates or glomerular filtration will eliminate the antihypertensive
effects of the drugs.
The value of diuretics lies in their ability to reverse
the Na+ retention commonly associated with many antihypertensive
drugs that probably induce Na+ retention
and fluid volume expansion as a compensatory response
to blood pressure reduction.
When diuretic therapy is indicated for the treatment
of primary hypertension, the thiazide-type compounds
(e.g., chlorothiazide, hydrochlorothiazide) are generally
the drugs of choice. They can be used alone or in combination
with other antihypertensive agents. Approximately
30% of patients with mild hypertension may be treated
effectively with thiazide therapy alone.
Thiazide diuretics are not the drugs of choice in patients
with renal insufficiency. In this situation, the loop
diuretics furosemide and bumetanide are recommended;
they have greater intrinsic natriuretic potency
than do the thiazides and do not depress renal blood
flow.
In situations of known renin–angiotensin–aldosterone
involvement, such as in hypertension secondary
to renal disease (i.e., renovascular hypertension), diuretics
probably should not be used because they further
elevate plasma renin.
The K+-sparing action of spironolactone, triamterene,
and amiloride serves as the basis for their occasional
use in the therapy of primary hypertension.
The drugs can be employed in conjunction with other
types of diuretics to help alleviate the K+ loss caused by
them. Under these conditions, K+ balance is improved
while natriuresis is maintained. |