How Digitoxin increases the force of myocardial contraction (positive inotropic effect)
“The sodium-potassium (Na/K) ATPase pump exists in three isoforms in humans. The primary effect of digoxin is to inhibit membrane-bound α subunits of the Na/K ATPase pump mainly but not exclusively in the human myocardium. This inhibition promotes sodium-calcium exchange, which increases the intracellular calcium concentration, resulting in an increase in the force of myocardial contraction-positive inotropic effect.”
Mechanism of Digitoxin in Rate Control During A-fib, etc.
Digoxin acts as a vagotonic drug. It increases vagus (parasympathetic) tone in the AV node, slowing down conduction through it.
Digoxin “increases the vagal tone to the heart leading to decreased conduction velocity across the atrioventricular (AV) node and increased refractoriness of the AV node to impulses originating from the sinoatrial node (SA) node.”
Digoxin has additional neuro-hormonal effects. Studies have shown that such effects may also be secondary to inhibition of the Na/K ATPase pump. Neuro-hormonal effects of digoxin include attenuation of carotid sinus baroreceptor discharge sensitivity leading to decreased sympathetic nervous system activation, central vagal stimulation, and a direct sympatho-inhibitory effect on the myocardium. This increases the vagal tone to the heart leading to decreased conduction velocity across the atrioventricular (AV) node and increased refractoriness of the AV node to impulses originating from the sinoatrial node (SA) node. At therapeutic doses, digoxin does not appear to increase the risk of cardiac arrhythmias.8 However, toxic levels of digoxin are known to cause cardiac arrhythmias and also other central nervous system and gastrointestinal abnormalities. Digoxin toxicity leads to a high degree of AV block by its effect of increasing vagal tone to the heart. As a result, very few impulses originating from the SA node are conducted to the ventricles. In such cases, a slower pacemaker takes over the function of the SA node leading to junctional, sub-junctional, or ventricular arrhythmias.7 Digoxin toxicity has been documented to cause junctional rhythm with slow ventricular rate of < 100 beats/min in infants.7″AJP
References
AJP Rep. 2016 Mar; 6(1): e96–e98. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4737622/