Comparison of the canine tissue distribution of digoxin after acute and chronic administration: implications for digitalis therapy

Digoxin is often used as an antiarrhythmic and inotropic agent. It produces significant neuroexcitatory responses that influence both its therapeutic and toxic effects. Patients receiving digoxin can be separated into 2 groups: those who receive it acutely and those who receive it chronically. The therapeutic and toxic responses to digoxin vary between these groups. The neural tissue distribution of digoxin was compared in dogs after both acute and chronic injections. Acute administration of digitalis in this study was associated with preferential uptake of digoxin into peripheral sympathetic nerves. Chronic administration was associated with continued selective uptake into the central nervous system despite decreasing serum levels. Therefore, acute (experimental or suicidal) or chronic (maintenance) digoxin administration produces different neural responses. The peripheral sympathetic nervous system will be the primary area of interaction with acute digoxin administration and the central nervous system will have a greater involvement with chronic digoxin administration. Our results indicate that the uptake of digoxin into the peripheral nervous system and central nervous system depends upon the duration of digoxin administration. The time course of digoxin accumulation influences both its therapeutic and toxic actions.