**Question:** In comparison to digoxin, digitoxin has ?

**Core Concept:** Digitoxin and digoxin are cardiac glycosides, which are drugs derived from the cardenolide group found in plants like Digitalis purpurea (Foxglove plant). They are used to treat heart failure by increasing the contractility of the heart muscle and reducing cardiac output.

**Why the Correct Answer is Right:** Digitoxin has higher lipophilicity compared to digoxin. Due to this, it accumulates more in the myocardial cells, leading to a higher degree of cardiac glycoside toxicity. The increased affinity for the sodium pump (Na+/K+-ATPase) is a consequence of the higher lipophilicity, which results in a higher level of inhibition of the pump. This leads to a higher degree of cardiac glycoside toxicity as well.

**Why Each Wrong Option is Incorrect:**

A. Lower potency: Although digitoxin is more lipophilic, digoxin has a higher potency, meaning it produces the desired therapeutic effect at lower concentrations. This is because digoxin has a higher affinity for the Na+/K+-ATPase than digitoxin.

B. Reduced toxicity: This is incorrect because digitoxin is more toxic than digoxin due to its higher lipophilicity and greater affinity for the Na+/K+-ATPase.

C. Increased potency: This is incorrect because digoxin has a higher potency than digitoxin, as mentioned above.

D. Enhanced efficacy: This is incorrect because despite being more toxic, digitoxin is less effective than digoxin due to its lower potency.

**Clinical Pearl:** Understanding the differences in pharmacokinetic properties of digitoxin and digoxin is crucial for proper dosing and monitoring in clinical practice. Regular monitoring of serum levels is necessary when prescribing these drugs to avoid toxicity.

**Correct Answer:** Digitoxin (Option C)

**Explanation:** Digitoxin is more toxic, lipophilic, and has a higher affinity for the Na+/K+-ATPase compared to digoxin. This results in a decrease in cardiac glycoside efficacy, despite increased toxicity.