process of filtration is important to understanding the pharmacokinetics of diuretic action because most of these agents exert their inhibitory effect by blocking the entry of sodium from the urine into the cell. Therefore, these diuretics have to be present at sufficient concentrations within the tubular fluid to exert their inhibitory action on sodium transport. Most diuretics are variably bound to albumin and therefore are only partially filtered. They gain access to the tubular fluid by secretion into the proximal tubule (discussed later). In conditions of hemorrhage or liver disease resulting in hypoalbu-minemia, the concentration of albumin is reduced and the fraction of bound diuretic is altered. Although this may suggest that more of the diuretic is unbound (or free) and filtered at the glomerulus, this does not occur. The decrease in Starling forces, which govern the rate of fluid filtration across the glomerular and other capillaries, now results in greater entry of fluid into the interstitial space.
Most estimates of diuretic binding to albumin assume that the protein itself is not altered as part of the disease process. In renal failure, however, the number of binding sites on the protein may change, which in turn affects the pharmacokinetics and dynamics of the response to an administered diuretic. Another setting associated with diminished effective diuretic concentrations occurs in nephrotic syndrome. In this disease, protein escaping from the glomerulus into the tubules binds the diuretic within the lumen. The bound drug is unavailable to exert its inhibitory effect on sodium transport.
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