Relation between concentrations of digoxin in the myocardium and in the plasma.

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Abstract
The clinical effects of digitalis glycosides apparently can be modified by many agents and circumstances. This variability of effect may not result solely from different plasma digoxin concentrations. Digitalis glycosides exert indirect effects upon the heart by actions on the autonomic nervous system. Therapeutic doses enhance vagal tone (sinus rate slowing, atrioventricular conduction slowing, decrease in automaticity of atrial ectopic pacemakers and decrease in refractory period of atrial muscle cells) and sensitize carotid sinus baroreceptors (at same level of blood pressure leading to increased efferent vagal activity and concomitant withdrawal of sympathetic tone), and high doses are sympathomimetric (increasing traffic in cardiac, phrenic, and peripheral sympathetic nerves). Smith presents some evidence for alterations in individual sensitivity to cardiac glycosides according to the following other factors: plasma electrolytes (K, Mg and Ca), adequacy of tissue oxygenation, acid-base balance, age, renal function, thyroid status, other drugs used concurrently and type and severity of the underlying heart disease. The measurement of plasma concentrations of cardiac glycosides can provide useful guidelines in patient care. Information obtained must always be interpreted in light of pharmacokinetic principles which apply to this group of drugs and with an awareness of the many factors that can modify an individual''s response to them.