The three main actions of cardiac glycosides are: positive inotropic: increases contractibility of the myocardial muscle negative dromotropic: delays atrioventricular conduction of the AV-node against highly frequent stimulation (e.g. supraventricular fibrillation) negative chronotropic: decreased sinus rhythm 1 and 2 are caused by an increase in Ca2+ion concentration in the myocardium and excitable cells. Cardiac glycosides bind to the Na+/K+-ATPase pump and inhibit its action. This results in a reduced outflow of Na+ions, increasing the intracellular Na+concentration and thus leaving more intracellular Na+ available for passive exchange with Ca2+. Due to the rise of intracellular Ca2+concentration, more Ca2+ is stored in the sarcoplasmic reticulum. Hence, more Ca2+ is available for each action potential, which increases the myocardial contraction force and the stroke volume. Inhibition of the Na+/K+-ATPase pump causes a prolongation of the action potential and rest phase of the excitable cells. This alters the electrical activity of the heart and decreases cardiac conduction
velocity (dromotropic effect). In contrast, the negative chronotropic effects (3) are due to increased sensitivity of the baroreflex by inhibition of vagal tone and sympathetic influence over time. Digoxin decreases plasma levels of norepinephrine and renin, which are elevated in heart failure. Cardiac glycosides have a narrow therapeutic window and therapeutic drug monitoring is therefore often necessary. Dosage adjustments are necessary in children and the elderly. Digoxin elimination is entirely renal. Indications: supraventricular rhythm disorders (like atrial fibrillation) and heart failure with insufficient contractions on standard therapy. Adverse effects may be signs of overdosing: GI-problems (anorexia, nausea, vomiting), cardiac symptoms (ventricular extrasystoles, AV-blocks), neural symptoms (fatigue, confusion, headache, dizziness). Beware for interactions with other drugs because of the narrow therapeutic window. For example, diuretics lower plasma [K+] and thus increase sensitivity for cardiac glycosides. Increasing Ca2+ levels requires careful monitoring.
What is NOT true about digoxin toxicity
Extra info: Unfortunately, patients do not develop tolerance to the adverse effects of digoxin. Digoxin toxicity correlates with serum concentration.
Mr R is CHF-patient and takes digoxin 0.25 mg per day. He complains that he recently become nauseous after taking his digoxin. The CHF has been well-controlled. How would you treat Mr R's CHF?
Extra info: Mr R seems to be suffering from adverse effects of the digoxin. His CHF is well-controlled, so you should first lower the dose of digoxin. Research on this dosing item revealed that there is not difference in effectivity between 0.25 and 0.125mg.