Q48: Please describe the action of cardiac glycosides?

Answer:

CARDIAC GLYCOSIDES

The cardiac glycosides are an important class of naturally occurring drugs whose actions include both beneficial and toxic effects on the heart. Plants containing cardiac steroids have been used as poisons and heart drugs at least since 1500 B.C. Throughout history these plants or their extracts have been variously used as arrow poisons, emetics, diuretics, and heart tonics. Cardiac steroids are widely used in the modern treatment of congestive heart failure and for treatment of atrial fibrillation and flutter. Yet their toxicity remains a serious problem.

 Mode of action

All cardiac glycosides are highly selective inhibitors of the active transport of Na and K across cell membranes, by binding to specific site of Na-K-ATPase, the enzymatic equivalent of the cellular Na-“pump”. This inhibition causes activation of Na-Ca-exchanger and increase of intracellular Ca levels, which interact with contractile proteins of myocardial cells and increasing the contractility of cardiac muscle.

Effects

1)     Positive inotropic effect – increasing of the heart velocity and contractility.

2)     Negative chronotropic effect – decreasing of heart automatisity and increasing maximal diastolic resting membrane potential in sino-atrial and atrio-ventricular nodes, causing in this way decreased heart conduction.

3)     Vasoconstriction in rapid IV administration –  transient effect, via inhibition of Na-K-ATPase and increasing of Ca entry cause effect on vascular smooth muscles.

Pharmacokinetics and dosing

Digoxin’s half-life is 48 hours, this permits a once-a-day dosing; then the drug is started, during first week loading dose is given (“digitalisation”), then the treatment is continued with maintenance doses.

Digoxin excreted mainly with urine (most part is unchanged). Tissue reservoir of digoxin is skeletal muscles, so dosing should be based on estimated lean body mass. Monitoring is required during administration (target serum concentration is about 1.0 nanogramm/ml).