Chapter: Modern Pharmacology with Clinical Applications: Antihypertensive Drugs

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Diuretics

The exact mechanisms by which diuretics lower blood pressure are not entirely understood.

DIURETICS

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 de-pend on the production of diuresis. High salt intake or low rates or glomerular filtration will eliminate the anti-hypertensive effects of the drugs.

The value of diuretics lies in their ability to reverse the NA+ retention commonly associated with many an-tihypertensive drugs that probably induce NA+ reten-tion and fluid volume expansion as a compensatory re-sponse 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 combi-nation 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 pa-tients with renal insufficiency. In this situation, the loop diuretics furosemide and bumetanide are recom-mended; they have greater intrinsic natriuretic potency than do the thiazides and do not depress renal blood flow.

 

In situations of known renin–angiotensin–aldos-terone involvement, such as in hypertension secondary to renal disease (i.e., renovascular hypertension), di-uretics probably should not be used because they fur-ther elevate plasma renin.

 

The K+ -sparing action of spironolactone, tri-amterene, and amiloride serves as the basis for their oc-casional 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.

 

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