MCQ Quiz: Pharmacology of Glycosides (Cardiac Glycosides)

Cardiac glycosides, exemplified by digoxin, are a class of drugs historically derived from plant sources like Digitalis purpurea and Digitalis lanata. They have been used for centuries to treat heart conditions and are known for their distinct effects on myocardial contractility and cardiac electrophysiology. For PharmD students, a thorough understanding of the pharmacology of cardiac glycosides—including their intricate mechanism of action, pharmacokinetic nuances, therapeutic applications in heart failure and atrial fibrillation, narrow therapeutic index, and potential for toxicity—is crucial for ensuring their safe and effective use in clinical practice. This MCQ quiz will test your knowledge on these important pharmacological aspects.

1. Cardiac glycosides, such as digoxin, exert their primary positive inotropic effect by inhibiting which cellular enzyme?

• A. Adenylyl cyclase
• B. Na+/K+-ATPase pump
• C. Phosphodiesterase-3 (PDE3)
• D. HMG-CoA reductase

Answer: B. Na+/K+-ATPase pump

2. The inhibition of the Na+/K+-ATPase pump by digoxin directly leads to an increase in intracellular:

• A. Potassium ion concentration
• B. Sodium ion concentration
• C. Cyclic AMP (cAMP)
• D. Nitric oxide

Answer: B. Sodium ion concentration

3. The rise in intracellular sodium due to Na+/K+-ATPase inhibition by digoxin subsequently causes:

• A. Increased activity of the Na+/Ca2+ exchanger, leading to decreased intracellular calcium.
• B. Decreased efflux (or increased influx) of calcium via the Na+/Ca2+ exchanger, leading to increased intracellular calcium.
• C. Direct opening of L-type calcium channels.
• D. Inhibition of ryanodine receptors on the sarcoplasmic reticulum.

Answer: B. Decreased efflux (or increased influx) of calcium via the Na+/Ca2+ exchanger, leading to increased intracellular calcium.

4. The increased intracellular calcium concentration available to the contractile proteins in cardiomyocytes results in which pharmacodynamic effect of digoxin?

• A. Negative inotropy (decreased contractility)
• B. Positive inotropy (increased contractility)
• C. Vasodilation
• D. Negative chronotropy only via direct SA node effect

Answer: B. Positive inotropy (increased contractility)

5. Besides its inotropic effects, digoxin also exhibits neurohormonal effects, including:

• A. Activation of the sympathetic nervous system and renin-angiotensin-aldosterone system.
• B. Vagomimetic actions (enhanced parasympathetic tone) leading to decreased heart rate and slowed AV nodal conduction.
• C. Direct stimulation of beta-1 adrenergic receptors.
• D. Inhibition of neprilysin.

Answer: B. Vagomimetic actions (enhanced parasympathetic tone) leading to decreased heart rate and slowed AV nodal conduction.

6. Which of the following ECG changes is commonly associated with therapeutic levels of digoxin?

• A. ST-segment elevation and peaked T waves
• B. PR interval prolongation, ST segment depression (scooping), and T wave inversion or flattening
• C. QRS complex widening and QT interval prolongation
• D. Sinus tachycardia and increased P wave amplitude

Answer: B. PR interval prolongation, ST segment depression (scooping), and T wave inversion or flattening

7. Digoxin is primarily used in current clinical practice for which two main indications?

• A. Acute myocardial infarction and hypertension
• B. Heart failure with reduced ejection fraction (HFrEF) for symptom improvement/hospitalization reduction, and ventricular rate control in atrial fibrillation
• C. Prevention of deep vein thrombosis and pulmonary embolism
• D. Hyperlipidemia and stable angina

Answer: B. Heart failure with reduced ejection fraction (HFrEF) for symptom improvement/hospitalization reduction, and ventricular rate control in atrial fibrillation

8. The oral bioavailability of digoxin can be variable and is known to be affected by:

• A. Co-administration with antacids or cholestyramine (decreased absorption).
• B. Hepatic first-pass metabolism primarily.
• C. Its classification as a highly water-soluble drug.
• D. Its inability to bind to P-glycoprotein.

Answer: A. Co-administration with antacids or cholestyramine (decreased absorption).

9. Digoxin has a large volume of distribution, meaning it distributes extensively into:

• A. Adipose tissue primarily
• B. Tissues such as skeletal muscle, heart, and kidney, rather than remaining confined to the plasma
• C. Cerebrospinal fluid
• D. Plasma proteins, leading to high protein binding

Answer: B. Tissues such as skeletal muscle, heart, and kidney, rather than remaining confined to the plasma

10. The primary route of elimination for digoxin is:

• A. Hepatic metabolism by CYP3A4
• B. Renal excretion, largely as unchanged drug
• C. Biliary excretion followed by enterohepatic recirculation
• D. Pulmonary exhalation

Answer: B. Renal excretion, largely as unchanged drug

11. Which of the following is a common gastrointestinal adverse effect of digoxin, often an early sign of toxicity?

• A. Constipation
• B. Increased appetite
• C. Anorexia, nausea, and vomiting
• D. Dry mouth

Answer: C. Anorexia, nausea, and vomiting

12. Neurological and CNS side effects of digoxin toxicity can include:

• A. Euphoria and increased energy
• B. Seizures as a common early sign
• C. Fatigue, confusion, weakness, and visual disturbances (e.g., xanthopsia)
• D. Insomnia and restlessness

Answer: C. Fatigue, confusion, weakness, and visual disturbances (e.g., xanthopsia)

13. Xanthopsia, a visual disturbance sometimes seen with digoxin toxicity, refers to:

• A. Seeing blue halos around objects
• B. Double vision
• C. Seeing yellow or green discoloration of objects/vision
• D. Complete loss of vision

Answer: C. Seeing yellow or green discoloration of objects/vision

14. The most serious adverse effects of digoxin toxicity involve the:

• A. Liver
• B. Kidneys
• C. Heart (cardiac arrhythmias, including bradyarrhythmias and ventricular tachyarrhythmias)
• D. Lungs

Answer: C. Heart (cardiac arrhythmias, including bradyarrhythmias and ventricular tachyarrhythmias)

15. Which electrolyte imbalance significantly sensitizes the myocardium to the toxic effects of digoxin and must be corrected?

• A. Hypernatremia
• B. Hypokalemia
• C. Hypocalcemia
• D. Hyperphosphatemia

Answer: B. Hypokalemia

16. In addition to hypokalemia, which other electrolyte imbalance can potentiate digoxin toxicity?

• A. Hyponatremia
• B. Hypomagnesemia and hypercalcemia
• C. Hypophosphatemia
• D. Hyperchloremia

Answer: B. Hypomagnesemia and hypercalcemia

17. The therapeutic serum digoxin concentration range for heart failure is generally considered to be:

• A. 2.0 – 3.5 ng/mL
• B. 0.5 – 0.9 ng/mL
• C. 1.5 – 2.0 ng/mL
• D. > 2.0 ng/mL for optimal effect

Answer: B. 0.5 – 0.9 ng/mL (Higher levels may be targeted for rate control in AFib, but for HF, lower levels are preferred).

18. When should blood samples for monitoring serum digoxin concentrations ideally be drawn?

• A. Immediately after an oral dose (peak level)
• B. At least 6-8 hours after the last dose (oral or IV) to allow for tissue distribution
• C. During the night while the patient is sleeping
• D. Only when signs of toxicity are present

Answer: B. At least 6-8 hours after the last dose (oral or IV) to allow for tissue distribution

19. Amiodarone, when co-administered with digoxin, can lead to increased digoxin levels primarily by:

• A. Inducing digoxin metabolism via CYP3A4.
• B. Inhibiting P-glycoprotein (P-gp) efflux transporter and reducing renal clearance of digoxin.
• C. Increasing the oral bioavailability of digoxin only.
• D. Displacing digoxin from plasma protein binding sites.

Answer: B. Inhibiting P-glycoprotein (P-gp) efflux transporter and reducing renal clearance of digoxin.

20. The specific antidote for life-threatening digoxin toxicity is:

• A. IV Potassium chloride
• B. Atropine
• C. Digoxin-specific antibody fragments (DigiFab)
• D. N-acetylcysteine

Answer: C. Digoxin-specific antibody fragments (DigiFab)

21. For which type of cardiac arrhythmia is digoxin primarily used for ventricular rate control?

• A. Ventricular tachycardia
• B. Atrial fibrillation and atrial flutter
• C. Sinus bradycardia
• D. Wolff-Parkinson-White syndrome with AF (digoxin is contraindicated here)

Answer: B. Atrial fibrillation and atrial flutter

22. The negative chronotropic effect of digoxin (slowing of heart rate) is primarily due to its:

• A. Direct inhibition of the SA node pacemaker cells.
• B. Increased sympathetic nervous system activity.
• C. Vagomimetic effect, which increases parasympathetic tone to the SA and AV nodes.
• D. Beta-adrenergic blocking properties.

Answer: C. Vagomimetic effect, which increases parasympathetic tone to the SA and AV nodes.

23. In HFrEF, digoxin is generally considered for patients who:

• A. Are asymptomatic and have normal LVEF.
• B. Remain symptomatic despite optimal therapy with ACE inhibitors/ARBs/ARNIs, beta-blockers, and aldosterone antagonists.
• C. Have severe renal impairment as a first-line agent.
• D. Are intolerant to all other heart failure medications.

Answer: B. Remain symptomatic despite optimal therapy with ACE inhibitors/ARBs/ARNIs, beta-blockers, and aldosterone antagonists.

24. Which of the following conditions can decrease the renal clearance of digoxin, necessitating dose adjustment?

• A. Hyperthyroidism
• B. Renal impairment (reduced GFR)
• C. Fever
• D. Young age with normal renal function

Answer: B. Renal impairment (reduced GFR)

25. The interaction between digoxin and loop or thiazide diuretics is significant because these diuretics can cause:

• A. Hyperkalemia, reducing digoxin efficacy.
• B. Hypokalemia and hypomagnesemia, increasing the risk of digoxin toxicity.
• C. Increased renal clearance of digoxin.
• D. Inhibition of digoxin absorption.

Answer: B. Hypokalemia and hypomagnesemia, increasing the risk of digoxin toxicity.

26. What is the primary mechanism by which increased intracellular calcium enhances myocardial contractility?

• A. It directly activates myosin ATPase.
• B. It increases the number of available actin-myosin cross-bridges by binding to troponin C, relieving the inhibitory effect of the troponin-tropomyosin complex.
• C. It causes vasodilation of coronary arteries.
• D. It prolongs the action potential duration.

Answer: B. It increases the number of available actin-myosin cross-bridges by binding to troponin C, relieving the inhibitory effect of the troponin-tropomyosin complex.

27. “Loading doses” of digoxin are sometimes used to:

• A. Minimize the risk of toxicity.
• B. Achieve therapeutic steady-state concentrations more rapidly due to its long half-life and large volume of distribution.
• C. Bypass hepatic metabolism.
• D. Improve its oral bioavailability.

Answer: B. Achieve therapeutic steady-state concentrations more rapidly due to its long half-life and large volume of distribution.

28. Which of the following patient populations is generally more sensitive to the effects of digoxin and may require lower doses?

• A. Young, healthy adults
• B. Obese patients
• C. Elderly patients and those with low body weight or renal dysfunction
• D. Patients with hyperthyroidism

Answer: C. Elderly patients and those with low body weight or renal dysfunction

29. The term “digitalis toxicity” refers to adverse effects caused by which class of drugs?

• A. Beta-blockers
• B. Calcium channel blockers
• C. Cardiac glycosides (e.g., digoxin)
• D. ACE inhibitors

Answer: C. Cardiac glycosides (e.g., digoxin)

30. Which statement is TRUE regarding the effect of digoxin on long-term mortality in HFrEF patients in major clinical trials?

• A. It consistently shows a significant mortality benefit as monotherapy.
• B. It generally has a neutral effect on mortality but can reduce hospitalizations for heart failure.
• C. It consistently increases mortality in all HFrEF patients.
• D. It is primarily used for its mortality benefit in HFpEF.

Answer: B. It generally has a neutral effect on mortality but can reduce hospitalizations for heart failure.

31. The electrophysiological effect of digoxin on the AV node is primarily:

• A. Increased conduction velocity (positive dromotropic effect)
• B. Decreased conduction velocity and increased refractory period (negative dromotropic effect)
• C. No significant effect on AV nodal conduction
• D. Shortening of the refractory period

Answer: B. Decreased conduction velocity and increased refractory period (negative dromotropic effect)

32. Which of the following symptoms should prompt a pharmacist to suspect potential digoxin toxicity in a patient?

• A. Sudden onset of hypertension and tachycardia
• B. New onset of anorexia, nausea, visual disturbances, and bradycardia or palpitations
• C. Improved exercise tolerance and resolution of edema
• D. Polyuria and excessive thirst

Answer: B. New onset of anorexia, nausea, visual disturbances, and bradycardia or palpitations

33. P-glycoprotein (P-gp) is an efflux transporter found in the intestines, kidneys, and other tissues. Digoxin is a substrate for P-gp. This means that P-gp inhibitors can:

• A. Decrease digoxin absorption and serum levels.
• B. Increase digoxin absorption and serum levels by reducing its efflux.
• C. Have no effect on digoxin pharmacokinetics.
• D. Enhance the renal excretion of digoxin.

Answer: B. Increase digoxin absorption and serum levels by reducing its efflux.

34. Hypercalcemia can potentiate digoxin-induced arrhythmias because calcium:

• A. Competes with digoxin for binding to Na+/K+-ATPase.
• B. Accelerates the metabolism of digoxin.
• C. Can overload intracellular calcium stores when combined with digoxin’s effect, increasing the risk of delayed afterdepolarizations.
• D. Inhibits the vagomimetic effects of digoxin.

Answer: C. Can overload intracellular calcium stores when combined with digoxin’s effect, increasing the risk of delayed afterdepolarizations.

35. What is the approximate elimination half-life of digoxin in a patient with normal renal function?

• A. 2-4 hours
• B. 12-18 hours
• C. 36-48 hours
• D. 5-7 days

Answer: C. 36-48 hours

36. If a patient on digoxin therapy experiences severe, life-threatening arrhythmias (e.g., ventricular tachycardia, complete heart block), the most appropriate specific intervention is:

• A. Administration of IV potassium
• B. Administration of digoxin-specific antibody fragments (DigiFab)
• C. Cardioversion as the sole therapy
• D. Administration of a beta-blocker

Answer: B. Administration of digoxin-specific antibody fragments (DigiFab)

37. Which of the following is NOT a typical goal when using digoxin for rate control in atrial fibrillation?

• A. To slow the ventricular response rate.
• B. To convert atrial fibrillation to normal sinus rhythm (digoxin is not effective for this).
• C. To improve symptoms related to rapid ventricular rates.
• D. To reduce the risk of tachycardia-induced cardiomyopathy.

Answer: B. To convert atrial fibrillation to normal sinus rhythm (digoxin is not effective for this).

38. The positive inotropic effect of digoxin is most evident in:

• A. A healthy, non-failing heart.
• B. The failing myocardium where contractility is impaired.
• C. Conditions of severe bradycardia.
• D. Patients with hyperthyroidism.

Answer: B. The failing myocardium where contractility is impaired.

39. “Digitalizing dose” refers to:

• A. The daily maintenance dose of digoxin.
• B. An initial series of larger doses (loading dose) given to rapidly achieve therapeutic tissue concentrations.
• C. The dose at which toxicity first appears.
• D. The dose used for managing digoxin overdose.

Answer: B. An initial series of larger doses (loading dose) given to rapidly achieve therapeutic tissue concentrations.

40. Which parameter is most crucial for determining the maintenance dose of digoxin?

• A. Liver function
• B. Renal function (creatinine clearance) and lean body weight
• C. Serum albumin levels
• D. Age alone

Answer: B. Renal function (creatinine clearance) and lean body weight

41. The mechanism of action of digoxin involves all the following steps EXCEPT:

• A. Inhibition of Na+/K+-ATPase
• B. Increase in intracellular Na+
• C. Decrease in Na+/Ca2+ exchange leading to increased intracellular Ca2+
• D. Direct stimulation of beta-1 adrenergic receptors

Answer: D. Direct stimulation of beta-1 adrenergic receptors

42. Why is it important to measure serum digoxin levels at trough, just before the next dose, or at least 6-8 hours after the last dose?

• A. To capture the peak effect of the drug.
• B. To allow for complete absorption and distribution from plasma into tissues, reflecting steady-state tissue concentrations more accurately.
• C. Because digoxin is only active at trough concentrations.
• D. To minimize interference from other medications.

Answer: B. To allow for complete absorption and distribution from plasma into tissues, reflecting steady-state tissue concentrations more accurately.

43. In atrial fibrillation, digoxin is often less effective for rate control during exercise compared to at rest because:

• A. Its effect is primarily on sympathetic tone, which is overridden by exercise.
• B. Its effect on AV nodal conduction is primarily vagally mediated, and vagal tone is withdrawn during exercise, while sympathetic drive increases.
• C. It is rapidly metabolized during exercise.
• D. It causes bronchoconstriction during exercise.

Answer: B. Its effect on AV nodal conduction is primarily vagally mediated, and vagal tone is withdrawn during exercise, while sympathetic drive increases.

44. The term “glycoside” in cardiac glycoside refers to the chemical structure containing:

• A. A peptide bond
• B. A sugar moiety (glycone) attached to a non-sugar moiety (aglycone or genin)
• C. A purine or pyrimidine base
• D. A sulfhydryl group

Answer: B. A sugar moiety (glycone) attached to a non-sugar moiety (aglycone or genin)

45. The aglycone (genin) part of the digoxin molecule is primarily responsible for its:

• A. Water solubility
• B. Pharmacological activity (binding to Na+/K+-ATPase)
• C. Rate of renal excretion
• D. Antigenicity

Answer: B. Pharmacological activity (binding to Na+/K+-ATPase)

46. Which of the following is a crucial piece of information a pharmacist should gather before dispensing digoxin to a new patient?

• A. Patient’s favorite food
• B. Baseline renal function and serum electrolyte levels (especially potassium)
• C. Patient’s height only
• D. History of seasonal allergies

Answer: B. Baseline renal function and serum electrolyte levels (especially potassium)

47. The primary source of digoxin and digitoxin (another cardiac glycoside, less commonly used) is:

• A. Synthetic laboratory production only
• B. Animal tissues
• C. Plants of the Digitalis species (e.g., Digitalis lanata, Digitalis purpurea)
• D. Marine organisms

Answer: C. Plants of the Digitalis species (e.g., Digitalis lanata, Digitalis purpurea)

48. Which statement is generally true about the use of digoxin in HFpEF (Heart Failure with preserved Ejection Fraction)?

• A. It is a first-line agent and improves mortality.
• B. It has no role and is contraindicated.
• C. Its role is not well established for improving outcomes in HFpEF; it may be used for rate control if concomitant atrial fibrillation is present.
• D. It is more effective in HFpEF than in HFrEF.

Answer: C. Its role is not well established for improving outcomes in HFpEF; it may be used for rate control if concomitant atrial fibrillation is present.

49. Patients taking digoxin should be counseled to report which symptoms that might indicate toxicity?

• A. Increased energy and improved appetite
• B. Unexplained nausea, vomiting, changes in vision, or unusually slow/irregular heartbeat
• C. Frequent urination and thirst
• D. Darkening of the skin

Answer: B. Unexplained nausea, vomiting, changes in vision, or unusually slow/irregular heartbeat

50. The pharmacodynamic effects of digoxin on cardiac electrophysiology (e.g., slowing AV conduction) make it useful for certain arrhythmias, but also contribute to its risk of causing what at toxic levels?

• A. Severe hypertension
• B. Proarrhythmic effects, including various forms of heart block and tachyarrhythmias
• C. Bronchodilation
• D. Enhanced renal perfusion

Answer: B. Proarrhythmic effects, including various forms of heart block and tachyarrhythmias