Extracardiac and coronary vascular effects of digitalis

The administration of digitalis glycosides causes a variety of extracardiac effects. In both normal human subjects and in other species, digitalis increases smooth muscle tone of resistance and capacitance vessels. The vasoconstriction is mediated, in part, by a direct action of these glycosides on smooth muscle and, in part, by an increase in alpha-adrenergic tone. Constriction of coronary and splanchnic vessels may lead to myocardial or mesenteric ischemia. In contrast to normal subjects, patients with congestive heart failure demonstrate arteriolar and venodilation in response to these glycosides, possibly because the myocardial effect, to increase cardiac output and peripheral blood flow, overcomes the vasoconstrictor properties of these drugs. Other important actions of digitalis glycosides occur in the central and peripheral nervous systems. Their effects on the area postrema of the medulla oblongata are largely responsible for the alpha-adrenergic-mediated peripheral vasoconstriction, as well as the nausea and vomiting that frequently accompany digitalis intoxication. Actions of glycosides on the cerebral cortex are responsible for the wide range of neurotoxic effects that range from visual disturbances and headaches to seizures and coma. Finally, peripheral neurologic effects of digitalis glycosides on baroreceptor and cardiac afferent fibers may: improve the depressed function of these receptors in the situation of heart failure, and reflexly lower peripheral vascular resistance, thereby partially preventing the vascular constrictor action of these glycosides.