[Diuretic resistance: mechanisms and therapeutic possibilities].
The diuretics, with the exception of spironolactone, act on the luminal (or apical) surface of the tubular cells of different segments of the nephron. In order to act, they must be secreted into the tubular lumen. This transfer of the drug to its site of action may be blocked by decreased renal blood flow, the saturation of the systems of tubular transport or fixation to the albumin present in the primary urine. All these pharmacokinetic abnormalities (observed in renal failure or the nephrotic syndrome) lead to diuretic resistance. Increasing the dosage, the repetition, intravenous administration, even as an infusion, are possible solutions. Resistance may be observed in the absence of pharmacokinetic abnormalities: in these cases, there is an abnormal response of the tubular cells to otherwise effective diuretic concentrations, or the activation of homeostatic mechanisms leading to sodium retention and preventing negativisation of the salt and water balance. These situations are often associated in cardiac failure or cirrhosis with oedema. Increasing the dosage is not a logical solution, but increasing the frequency of administration may be helpful. The importance of secondary hyperaldosteronism in cirrhotic oedema makes spironolactone the treatment of choice. In all cases, the addition of two mechanisms of inhibition of tubular reabsorption of sodium at different sites in the nephron often results in an effective diuresis: usually, this implies the addition of a thiazide (e.g. hydrochlorothiazide) to an initial prescription of a loop diuretic.
Imbs
J L
JL
Service d'hypertension artérielle, université Louis-Pasteur, Strasbourg.
Grima
M
M
Stephan
D
D
D004232:Diuretics / Q000493:pharmacokinetics / Q000494:pharmacology*; D004351:Drug Resistance; D004487:Edema; D005355:Fibrosis; D006333:Heart Failure / Q000188:drug therapy*; D006706:Homeostasis; D006801:Humans; D007684:Kidney Tubules / Q000187:drug effects* / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase
D004232:Diuretics; D000254:Sodium-Potassium-Exchanging ATPase
Résistance aux diurétiques. Mécanismes et possibilités thérapeutiques.