Digoxin tissue binding

Quinidine [HP] Increased digoxin plasma concentrations displaces digoxin from tissue binding sites. 

Drugs that show extensive tissue binding are said to have an apparent volume of distribution many times the total body size. For example, digoxin (see Chapter 35), which binds to plasma protein to the extent of 23%, has an apparent volume of distribution of 8 1/kg. The volume of distribution of drugs that do not bind to plasma or tissue proteins varies between the extracellular fluid volume (16 liters) and the total body water (42 liters). Insulin, sodium, and iodine are confined to the extracellular water, whereas caffeine and ethanol are distributed in the total body water. 

This presumably reflects a reduction in tissue levels of Na/K-ATPase, an enzyme that represents a major tissue-binding site for digoxin (28). In other cases in which distribution volume is decreased in patients with impaired renal function, the relationship between the degree of renal insufficiency and reduction in distribution volume has not been characterized nor have plausible mechanisms been proposed. 

Chapter 15, this leads to interactions between compounds that compete for the same binding sites on serum albumin. However, coadministered compounds also may compete for tissue binding sites, as demonstrated by the interaction between quinidine and digoxin (11). The extent of drug distribution across a membrane will depend on the relative affinity of competing compounds for both plasma and tissue binding sites. 

Interaction with digoxin (by displacement from tissue binding sites and interference with its... 

Examples of changes in tissue binding are the tissue displacement of digoxin by quinidinef" and the decrease in tissue binding of digoxin in uremia.As a result in both cases, the volume of distribution of digoxin is decreased. 

Decrease in renal clearance SDC may increase 30 0% Inhibits P-glycoprotein resulting in decrease in renal and nonrenal clearance also displacement of digoxin from tissue binding sites with decrease in the volume of distribution SDC generally increases about twofold. Decrease in renal and nonrenal clearance also... 

Altered tissue binding may also affect the apparent volume of distribution of a drug. For example, the distribution volume of digoxin has been reported to be reduced by 30% to 50% from normal values in patients with renal disease. It has been postulated that this reduction in the distribution volume is secondary to a decrease in tissue... 

It is also possible that drug binding to tissues rather than to plasma proteins is decreased in renal failure. This apparently occurs with digoxin, which has extensive tissue binding but little plasma protein binding. Under these circumstances, the decreased tissue binding of digoxin leads to a decreased body content of the... 

Of the following diuretic agents, which would be least likely to indirectly cause an increased binding of digoxin to cardiac tissue sodium-potassium-adenosine triphosphatase (Na K ATPase) ... 

In the case of digoxin we can visualize what is happening. The site of action and binding site of digoxin is to tissue Na+K+ATPase. This enzyme is distributed very widely in tissues, and particularly in excitable tissue, which depends on it to restore sodium/potassium balance to resting levels after excitation. Digoxin preferentially distributes therefore to these tissues, and a disproportionately small component is left in the plasma compartment from which we sample. 

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