The positive inotropic effect of digoxin results from inhibition of which target, leading to what intracellular change?

• A Inhibition of sarcolemmal Ca2+ ATPase, increasing cytosolic calcium influx
• B Inhibition of phosphodiesterase-3, reducing Ca2+ reuptake into the sarcoplasmic reticulum
• C Activation of adenylate cyclase, raising cAMP and enhancing Ca2+ channel opening
• D Inhibition of Na+/K+-ATPase, raising intracellular Na+ and secondarily increasing intracellular Ca2+ ✓

Explanation

Digoxin binds the alpha subunit of Na+/K+-ATPase. The resulting rise in intracellular sodium reduces the transmembrane sodium gradient, so the sodium-calcium exchanger exports less calcium during diastole. Intracellular calcium rises, more calcium is taken up by the sarcoplasmic reticulum, and systolic calcium release increases. Options A and B describe unrelated targets, and option C describes beta-adrenergic stimulation, the pathway of dobutamine rather than digoxin.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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