Digoxin's positive inotropic effect in heart failure is mediated through:
- A Direct activation of β1-adrenoceptors in cardiomyocytes, increasing cAMP
- B Inhibition of sarcolemmal Na+/K+-ATPase, raising intracellular Na+, which reduces Na+/Ca2+ exchanger activity and raises intracellular Ca2+ ✓
- C Phosphodiesterase III inhibition, increasing cAMP and calcium entry through L-type channels
- D Activation of cardiac ryanodine receptor (RyR2), increasing Ca2+ release from SR
Correct answer: B. Inhibition of sarcolemmal Na+/K+-ATPase, raising intracellular Na+, which reduces Na+/Ca2+ exchanger activity and raises intracellular Ca2+
Explanation
Digoxin inhibits the sarcolemmal Na+/K+-ATPase pump, causing intracellular Na+ accumulation. This raised [Na+]i reduces the driving force for the Na+/Ca2+ exchanger (NCX), which normally extrudes Ca2+ in exchange for Na+ influx. Less Ca2+ efflux results in higher intracellular [Ca2+], augmenting sarcomere activation and contractility. PDE-III inhibitors (milrinone, amrinone) raise cAMP; β1 agonists (dobutamine) do the same via receptor; RyR2 modulators are experimental.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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