Digoxin

Question 1

Digoxin

Answer 1

− Direct effect: inhibition of cardiac Na+-K+ ATPase
o Results in ↑ intracellular Na+
o ↓ Na+/Ca2+ exchange
o ↑ intracellular Ca2+
o ↑ Ca2+ release from sarcoplasmic reticulum
o ↑ actin-myosin interaction
o ↑ contractile force
− Indirect effect: inhibition of neuronal Na+-K+ ATPase
o Results in ↑ vagal activity
− Pharmacokinetics:
o Long t1/2: need loading dose (LD)
o Renal clearance: caution in renal impairment
o Tissue protein binding (large Vd): displacement by other drugs (verapamil, quinidine)
− Uses:
o CHF

                                                                                 o Supraventricular tachycardias, except Wolff-Parkinson-White syn- drome  − Side effects: o Early signs include anorexia, nausea, ECG changes o Later signs include disorientation, visual effects (halos) o In toxic doses, any cardiac arrhythmias − Management of toxicity o Use of Fab antibodies toward digoxin o Supportive therapy (electrolytes and antiarrhythmics class IB) − Drug interactions: o Diuretics: ↓ K+, ↓ Mg2+, ↑ Ca2+ o Quinidine and verapamil