Thérapeutique diurétique

Abstract

Diuretics are pharmacological agents that increase natriuresis through inhibition of tubular re-absorption of sodium. The mechanism and site of this inhibition differ with each drug class, accounting for their additive effects on natriuresis increase and for their hydroelectrolytic side effects. The response to a given diuretic dose depends on the diuretic concentration in the urine at its action site. This concentration may be decreased by pharmacokinetic factors such as those encountered in renal insufficiency or in the 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 its action site and the natriuresis obtained has the normal maximal plateau. This is not the case when an oedematous systematic 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 distal parts of the tubule. In these 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, diuretic 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 dose thiazide (12.5-50 mg/day) with potassium sparing diuretics. Rare indications of diuretics are also reviewed.