Pharmacology Review

Abstract

After completing this article, readers should be able to: 1. Review the actions of the diuretic agents commonly used in neonates. 2. Delineate the adverse effects of diuretic therapy. 3. Determine the roles of diuretics in therapy. Diuretics represent one of the most common classes of drugs administered to sick neonates and infants. Unwanted fluid retention arising from myriad neonatal disorders can and does complicate the optimal care of sick infants. To appreciate the many factors that influence a patient’s response to diuretic therapy and clinical and laboratory monitoring, we direct readers to the article “The Ontogeny of Human Kidney Development: Influence on Neonatal Diuretic Therapy” in this issue. All the clinically relevant diuretics, with the exception of aldosterone receptor antagonists (eg, spironolactone), must achieve sufficient free drug concentrations within the renal tubular lumen to reach their sites of action. Thus, diuretic effectiveness ultimately is guided by the functional capacity of the kidney, which clearly is influenced by infants’ gestational and postnatal ages. This article addresses the most common diuretics used in the neonate and young infant, focusing on the pharmacokinetic and pharmacodynamic characteristics of each drug relative to the infant’s postconceptional age and other factors that influence the infant’s overall response to therapy. ### “Loop” or “High Ceiling” Diuretics All diuretics, with the exception of spironolactone, must reach the renal tubular lumen to exert their pharmacologic effect. A lower renal blood flow (RBF) in preterm infants reduces the amount of drug delivered to the kidney, potentially limiting diuretic effectiveness. Highly protein-bound, loop diuretics (Table 1) are filtered minimally at the glomerulus. Instead, these agents are carried to the proximal tubule where they are actively secreted into the lumen via the organic acid transport pump. Luminal flow then carries the loop diuretics to their sites of action. | Loop Diuretics | || | •Bumetanide | | •Furosemide | | •Torsemide | | Thiazide Diuretics | | •Chlorothiazide | | •Chlorthalidone | | •Hydrochlorothiazide | | •Indapamide | | •Metolazone | | Aldosterone Antagonists | | •Eplerenone | | •Spironolactone | Table 1. Commonly Used Diuretic Drugs in Preterm and Newborn Infants Loop diuretics bind …