Update in Diuretic Therapy: Clinical Pharmacology
Summary
All diuretics except spironolactone exert their effects from the lumen of the nephron. Thus, to exert an effect, they must reach the urine. Pharmacokinetics (PK) describes this access. Different edematous disorders can affect access to this site of action and therein affect response to a diuretic. In addition, once a diuretic reaches the site of action, a response ensues. The characteristics of this response that can be affected by a patient's clinical condition are described by the pharmacodynamics (PD) of a diuretic. To understand the mechanisms of abnormal response to a diuretic one must dissect its PK and PD in different edematous disorders. For example, in patients with renal insufficiency, the mechanism of poor diuretic response is PK. In contrast, in patients with cirrhosis or in those with congestive heart failure, it is PD. In patients with nephrotic syndrome, both PK and PD are operative. These different mechanisms mandate differences in therapeutic strategy, as explained in this article.
Keywords: Diuretic, edema, renal insufficiency, nephrotic syndrome, cirrhosis, congestive heart failure
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Supported by the General Clinical Research Center (MO1 RR00750) and R01 DK 37994 and R01 AG 07631.
PII: S0270-9295(11)00132-X
doi:10.1016/j.semnephrol.2011.09.003
© 2011 Elsevier Inc. All rights reserved.
