Diuretics are pharmacological agents that increase natriuresis through inhibition of tubular re-absorption of
sodium. The mechanisms and site of this inhibition differ with each
drug class, accounting for their additive effects on natriuresis increase and their hydroelectrolytic side effects. The response to a given
diuretic dose depends on the
diuretic concentration on the urine at its action site. This concentration may be decreased by pharmacokinetic factors such as encountered in
renal insufficiency or in
nephrotic syndrome. These resistance mechanisms of
diuretics may be corrected by dose increase, previous
diuretic fixation on
albumin or
warfarin administration. Once these mechanisms are opposed, the
diuretic concentration for maximal efficacy is reached at is action site and the natriuresis obtained as the normal maximal plateau. This is not the case when an oedematous systemic disease with effective
hypovolemia is present, like in
heart failure or
cirrhosis, or when chronic use of
loop diuretics has induced a
hypertrophy of the more distant part of the tubule. In theses cases, a pharmacodynamic resistance exists, resulting in a lower maximal natriuresis plateau in spite of adequate concentration of the
diuretic at its action site, even in the absence of pharmacokinetic resistance factors. The main indications of
diuretics are systemic oedematous disease and
hypertension. In the oedematous diseases,
diuretics indication is both straightforward and sufficient only if effective hypervolemia is present. The therapeutic approach is discussed according to the various clinical conditions and pathophysiological background. In uncomplicated
hypertension,
diuretics are the cornerstone of the
therapy. The most suitable
diuretic treatment for
hypertension is an association of low doses
thiazide (12.5-50 mg/day) with
potassium sparing diuretics. Rare indications of
diuretics are also reviewed.