This animation explains the positive inotropic mechanism of digoxin (a cardiac glycoside extracted from the plant Digitalis Lanata) and its pharmacological effects at molecular, tissue and systemic levels.
Digoxin is indicated in the treatment of atrial fibrillation, atrial flutter and heart failure (currently it is not a first line treatment).
This excerpt explains digoxin effects on cardiac contractility and autonomic regulation of the electrophysiologic properties of the heart.
From: Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy, 2nd edition. D.Golan
Digoxin is a selective inhibitor of the plasma membrane sodium pump.
Cardiac myocytes exposed to digoxin extrude less sodium, leading to a rise in intracellular sodium concentration. In turn, the increase in intracellular sodium concentration alters the equilibrium of the sodium–calcium exchanger: calcium efflux is decreased because the gradient for sodium entry is decreased, while calcium influx is increased because the gradient for sodium efflux is increased. The net result is a rise in the intracellular calcium concentration. In response to this rise, the SR of the digoxin-treated cell sequesters more calcium. When the digoxin-treated cell depolarizes in response to an action potential, there is more Ca2+ available to bind troponin C, and tension development during contraction is facilitated.
In addition to its effects on myocardial contractility, digoxin exerts autonomic effects through its binding to sodium pumps in the plasma membranes of neurons in the central and peripheral nervous systems. These effects include inhibition of sympathetic nervous outflow, sensitization of baroreceptors, and increased parasympathetic (vagal) tone. Digoxin also alters the electrophysiologic properties of the heart by a direct action on the cardiac conduction system. At therapeutic doses, digoxin decreases automaticity at the AV node, prolonging the effective refractory period of AV nodal tissue and slowing conduction velocity through the node. These combined vagotonic and electrophysiologic properties underlie the use of digoxin in the treatment of patients with atrial fibrillation and rapid ventricular response rates; both the decreased automaticity of AV nodal tissue and the decreased conduction velocity through the node increase the degree of AV block, and thereby decrease the ventricular response rate.
In contrast to its effects at the AV node, digoxin enhances automaticity of the infranodal (His–Purkinje) conduction system. These divergent effects at the AV node and His– Purkinje system explain the characteristic electrophysiologic disturbance of complete heart block with accelerated junctional or accelerated idioventricular escape rhythm (referred to as “regularized” atrial fibrillation) in patients with digoxin toxicity.
Digoxin is commonly marketed under the trade names Lanoxin, Digitek, and Lanoxicaps