MCQ Quiz: Pharmacology of Inotropic Agents

Inotropic agents are a class of drugs that modify the force or energy of myocardial contraction. Positive inotropes increase contractility, while negative inotropes decrease it. These agents play a crucial role in the management of various cardiovascular conditions, particularly acute decompensated heart failure and cardiogenic shock, where an increase in cardiac output is desired. For PharmD students, a comprehensive understanding of the pharmacology of inotropic agents—including their diverse mechanisms of action, pharmacokinetic and pharmacodynamic properties, therapeutic indications, adverse effects, and monitoring parameters—is vital for ensuring their safe and effective use in critical patient care scenarios. This MCQ quiz will test your knowledge on these important pharmacological principles.

1. Positive inotropic agents primarily work by increasing the intracellular concentration of which ion in cardiomyocytes, or by sensitizing contractile proteins to it?

• A. Sodium (Na+)
• B. Potassium (K+)
• C. Calcium (Ca2+)
• D. Magnesium (Mg2+)

Answer: C. Calcium (Ca2+)

2. Digoxin, a cardiac glycoside, exerts its positive inotropic effect by inhibiting which enzyme?

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

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

3. Inhibition of the Na+/K+-ATPase pump by digoxin leads to an increase in intracellular sodium, which subsequently causes:

• A. Decreased activity of the Na+/Ca2+ exchanger, leading to increased intracellular calcium.
• B. Increased activity of the Na+/Ca2+ exchanger, leading to decreased intracellular calcium.
• C. Direct activation of ryanodine receptors.
• D. Inhibition of L-type calcium channels.

Answer: A. Decreased activity of the Na+/Ca2+ exchanger, leading to increased intracellular calcium. (Increased intracellular Na+ reduces the gradient for Na+ entry via NCX, thus reducing Ca2+ efflux).

4. Dobutamine is a synthetic catecholamine that primarily acts as a(n):

• A. Alpha-1 adrenergic agonist
• B. Beta-1 adrenergic agonist, with some beta-2 and alpha-1 activity
• C. Dopamine D1 receptor agonist
• D. Non-selective beta-blocker

Answer: B. Beta-1 adrenergic agonist, with some beta-2 and alpha-1 activity

5. The primary therapeutic effect of dobutamine in acute decompensated heart failure is:

• A. Significant vasoconstriction
• B. Increased myocardial contractility (positive inotropy) with some vasodilation
• C. Decreased heart rate
• D. Inhibition of the renin-angiotensin system

Answer: B. Increased myocardial contractility (positive inotropy) with some vasodilation

6. Dopamine exerts dose-dependent pharmacological effects. At low doses (e.g., 1-3 mcg/kg/min), it primarily stimulates:

• A. Alpha-1 receptors, causing vasoconstriction
• B. Beta-1 receptors, increasing heart rate and contractility
• C. Dopamine D1 receptors in renal, mesenteric, and coronary vasculature, causing vasodilation
• D. Beta-2 receptors, causing bronchodilation

Answer: C. Dopamine D1 receptors in renal, mesenteric, and coronary vasculature, causing vasodilation

7. At moderate doses (e.g., 3-10 mcg/kg/min), dopamine primarily stimulates which receptors, leading to increased cardiac contractility and output?

• A. Dopamine D1 receptors
• B. Beta-1 adrenergic receptors
• C. Alpha-1 adrenergic receptors
• D. Muscarinic M2 receptors

Answer: B. Beta-1 adrenergic receptors

8. Milrinone and inamrinone (amrinone) are phosphodiesterase-3 (PDE3) inhibitors. Inhibition of PDE3 in cardiomyocytes leads to:

• A. Decreased intracellular cyclic AMP (cAMP)
• B. Increased intracellular cyclic AMP (cAMP), leading to increased calcium influx and positive inotropy
• C. Inhibition of the Na+/K+-ATPase pump
• D. Blockade of beta-adrenergic receptors

Answer: B. Increased intracellular cyclic AMP (cAMP), leading to increased calcium influx and positive inotropy

9. In addition to their positive inotropic effects, PDE3 inhibitors like milrinone also cause:

• A. Significant vasoconstriction
• B. Vasodilation (acting as “inodilators”)
• C. Bradycardia
• D. Bronchoconstriction

Answer: B. Vasodilation (acting as “inodilators”)

10. Levosimendan is an inotropic agent (not widely available in the US) that belongs to which class?

• A. Cardiac glycoside
• B. Beta-adrenergic agonist
• C. Calcium sensitizer
• D. Phosphodiesterase inhibitor

Answer: C. Calcium sensitizer

11. The mechanism of action of levosimendan as a calcium sensitizer involves:

• A. Increasing intracellular calcium concentration.
• B. Binding to cardiac troponin C and increasing the sensitivity of the myofilaments to existing calcium.
• C. Inhibiting PDE3.
• D. Stimulating beta-1 receptors.

Answer: B. Binding to cardiac troponin C and increasing the sensitivity of the myofilaments to existing calcium.

12. A major therapeutic use of digoxin, besides HFrEF with persistent symptoms, is:

• A. Management of acute hypertension
• B. Rate control in atrial fibrillation
• C. Prevention of ventricular arrhythmias
• D. Treatment of severe bradycardia

Answer: B. Rate control in atrial fibrillation (due to its vagomimetic effects slowing AV nodal conduction).

13. Which of the following is a characteristic pharmacokinetic property of digoxin?

• A. Primarily hepatic metabolism with short half-life
• B. Large volume of distribution, long half-life, and primary renal excretion of unchanged drug
• C. Poor oral bioavailability requiring IV administration only
• D. Extensive binding to plasma proteins (>90%)

Answer: B. Large volume of distribution, long half-life, and primary renal excretion of unchanged drug

14. A common and potentially serious adverse effect of digoxin toxicity is:

• A. Hypertension
• B. Tachyphylaxis
• C. Cardiac arrhythmias (e.g., ventricular ectopy, AV block, bradycardia)
• D. Hyperkalemia

Answer: C. Cardiac arrhythmias (e.g., ventricular ectopy, AV block, bradycardia)

15. Which electrolyte imbalance significantly predisposes a patient to digoxin toxicity?

• A. Hyperkalemia
• B. Hypokalemia
• C. Hypercalcemia
• D. Hyponatremia

Answer: B. Hypokalemia (as K+ competes with digoxin for binding to Na+/K+-ATPase).

16. The therapeutic range for serum digoxin concentrations when used for HFrEF is generally narrow, typically aimed at:

• A. 2.0 – 3.0 ng/mL
• B. 0.5 – 0.9 ng/mL (lower end for HF, higher for AF rate control may differ)
• C. 5.0 – 10.0 ng/mL
• D. Serum levels are not useful for monitoring digoxin.

Answer: B. 0.5 – 0.9 ng/mL (Current guidelines often aim for lower concentrations for HF).

17. Dobutamine and dopamine are administered via which route due to their rapid metabolism and poor oral bioavailability?

• A. Oral
• B. Transdermal
• C. Intravenous infusion
• D. Intramuscular

Answer: C. Intravenous infusion

18. Tachycardia and arrhythmias are common dose-limiting side effects of which class of inotropic agents?

• A. Cardiac glycosides at therapeutic doses for HF
• B. Beta-adrenergic agonists (e.g., dobutamine, dopamine at moderate-high doses)
• C. Calcium sensitizers
• D. Only PDE3 inhibitors

Answer: B. Beta-adrenergic agonists (e.g., dobutamine, dopamine at moderate-high doses) (PDE3 inhibitors also cause arrhythmias).

19. Thrombocytopenia is a notable adverse effect, particularly associated with which older PDE3 inhibitor?

• A. Milrinone
• B. Inamrinone (formerly amrinone)
• C. Dobutamine
• D. Digoxin

Answer: B. Inamrinone (formerly amrinone)

20. What is the specific antidote for severe digoxin toxicity?

• A. Protamine sulfate
• B. N-acetylcysteine
• C. Digoxin-specific antibody fragments (DigiFab/Digibind)
• D. Glucagon

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

21. Long-term continuous therapy with positive inotropes (other than digoxin in selected patients) in chronic heart failure has generally been associated with:

• A. Improved long-term survival
• B. Increased mortality and adverse events
• C. No significant impact on outcomes
• D. Reversal of cardiac remodeling

Answer: B. Increased mortality and adverse events

22. Isoproterenol is a non-selective beta-adrenergic agonist. Its cardiovascular effects include:

• A. Positive inotropy, positive chronotropy, and peripheral vasoconstriction
• B. Positive inotropy, positive chronotropy, and peripheral vasodilation
• C. Negative inotropy, negative chronotropy, and vasodilation
• D. Negative inotropy, positive chronotropy, and vasoconstriction

Answer: B. Positive inotropy, positive chronotropy, and peripheral vasodilation (due to beta-2 agonism).

23. The positive inotropic effect of beta-1 adrenergic agonists like dobutamine is mediated by an increase in intracellular:

• A. cGMP
• B. cAMP, leading to protein kinase A activation and phosphorylation of calcium channels
• C. Sodium
• D. Potassium

Answer: B. cAMP, leading to protein kinase A activation and phosphorylation of calcium channels

24. Which of the following best describes the primary use of intravenous positive inotropes like dobutamine or milrinone in heart failure?

• A. Long-term oral maintenance therapy for all HFrEF patients.
• B. Short-term management of acute decompensated heart failure with cardiogenic shock or severe systolic dysfunction and end-organ hypoperfusion.
• C. First-line therapy for hypertension.
• D. Prevention of arrhythmias.

Answer: B. Short-term management of acute decompensated heart failure with cardiogenic shock or severe systolic dysfunction and end-organ hypoperfusion.

25. Digoxin’s neurohormonal modulating effects in heart failure, which may contribute to its benefits at low doses, include:

• A. Activation of the RAAS system.
• B. Increased sympathetic nervous system activity.
• C. Sensitization of baroreflexes and reduction in sympathetic outflow (vagomimetic effects).
• D. Inhibition of natriuretic peptide release.

Answer: C. Sensitization of baroreflexes and reduction in sympathetic outflow (vagomimetic effects).

26. Why should serum potassium levels be carefully monitored and maintained within the normal range for patients receiving digoxin?

• A. Hyperkalemia increases the risk of digoxin toxicity.
• B. Hypokalemia inhibits the binding of digoxin to Na+/K+-ATPase, reducing its effect.
• C. Hypokalemia enhances the binding of digoxin to Na+/K+-ATPase and inhibits its activity, increasing the risk of toxicity.
• D. Digoxin directly causes potassium excretion.

Answer: C. Hypokalemia enhances the binding of digoxin to Na+/K+-ATPase and inhibits its activity, increasing the risk of toxicity.

27. A potential advantage of calcium sensitizers like levosimendan over traditional inotropes that increase intracellular calcium is:

• A. They cause a greater increase in myocardial oxygen consumption.
• B. They produce positive inotropy with less increase in intracellular calcium concentration, potentially reducing the risk of calcium overload-induced arrhythmias and ischemia.
• C. They are administered orally with excellent bioavailability.
• D. They have no vasodilatory effects.

Answer: B. They produce positive inotropy with less increase in intracellular calcium concentration, potentially reducing the risk of calcium overload-induced arrhythmias and ischemia.

28. Which inotropic agent is a naturally occurring catecholamine that can also be used as a vasopressor at higher doses due to alpha-1 agonism?

• A. Dobutamine
• B. Milrinone
• C. Dopamine
• D. Digoxin

Answer: C. Dopamine

29. Patients receiving continuous infusions of dobutamine or milrinone require continuous monitoring of:

• A. Serum digoxin levels
• B. Blood pressure, heart rate, ECG, and fluid status/renal function
• C. Prothrombin time (INR)
• D. Liver function tests primarily

Answer: B. Blood pressure, heart rate, ECG, and fluid status/renal function

30. The term “inodilator” is often used to describe PDE3 inhibitors like milrinone because they possess both:

• A. Positive inotropic and negative chronotropic effects
• B. Positive inotropic and vasoconstrictor effects
• C. Positive inotropic and vasodilatory effects
• D. Negative inotropic and vasodilatory effects

Answer: C. Positive inotropic and vasodilatory effects

31. What is the primary reason for the narrow therapeutic index of digoxin?

• A. Its rapid and unpredictable metabolism.
• B. The therapeutic dose is close to the dose that can cause significant toxicity, particularly arrhythmias.
• C. Its extensive first-pass effect.
• D. Its complete lack of protein binding.

Answer: B. The therapeutic dose is close to the dose that can cause significant toxicity, particularly arrhythmias.

32. The use of digoxin is generally cautioned or requires dose reduction in patients with:

• A. Severe hepatic impairment
• B. Impaired renal function, as it is primarily renally eliminated
• C. Hyperthyroidism
• D. Obesity

Answer: B. Impaired renal function, as it is primarily renally eliminated

33. Which class of drugs, when co-administered with digoxin, can significantly increase digoxin levels by inhibiting P-glycoprotein and/or reducing its clearance?

• A. ACE inhibitors
• B. Beta-blockers like propranolol
• C. Certain antiarrhythmics (e.g., amiodarone, verapamil, quinidine) and antibiotics (e.g., clarithromycin)
• D. Loop diuretics

Answer: C. Certain antiarrhythmics (e.g., amiodarone, verapamil, quinidine) and antibiotics (e.g., clarithromycin)

34. “Tachyphylaxis” or tolerance can develop with prolonged continuous infusion of which class of inotropes due to receptor downregulation or desensitization?

• A. Cardiac glycosides
• B. Beta-adrenergic agonists (e.g., dobutamine)
• C. PDE3 inhibitors
• D. Calcium sensitizers

Answer: B. Beta-adrenergic agonists (e.g., dobutamine)

35. Visual disturbances, such as blurred vision or yellow/green halos around objects (xanthopsia), are characteristic signs of toxicity with:

• A. Dobutamine
• B. Milrinone
• C. Digoxin
• D. Levosimendan

Answer: C. Digoxin

36. Which inotropic agent would be most appropriate for a patient in cardiogenic shock with severe hypotension requiring some vasopressor support in addition to inotropy?

• A. Milrinone (due to vasodilation)
• B. Dobutamine (can cause some vasodilation)
• C. Dopamine (at moderate to high doses, due to alpha-1 effects)
• D. Digoxin (slow onset, not for acute shock)

Answer: C. Dopamine (at moderate to high doses, due to alpha-1 effects)

37. In patients with heart failure, digoxin is typically added to standard therapy (ACEi/ARB/ARNI, beta-blocker, aldosterone antagonist) primarily to:

• A. Improve survival as a first-line agent.
• B. Reduce symptoms and potentially hospitalizations in HFrEF patients who remain symptomatic, or for rate control in AFib.
• C. Actively reverse cardiac remodeling.
• D. Replace the need for diuretics.

Answer: B. Reduce symptoms and potentially hospitalizations in HFrEF patients who remain symptomatic, or for rate control in AFib.

38. The positive inotropic effect of PDE3 inhibitors is dependent on baseline levels of sympathetic tone or beta-agonist stimulation because:

• A. PDE3 inhibitors directly activate beta-receptors.
• B. They prevent the breakdown of cAMP, and cAMP levels are increased by beta-agonist stimulation.
• C. They require PDE3 to be phosphorylated by protein kinase C.
• D. They only work in the presence of high intracellular calcium.

Answer: B. They prevent the breakdown of cAMP, and cAMP levels are increased by beta-agonist stimulation.

39. Which statement accurately describes the current role of Inamrinone (Amrinone)?

• A. It is a first-line oral inotrope for chronic heart failure.
• B. Its use is very limited due to a higher incidence of adverse effects (e.g., thrombocytopenia, hepatotoxicity) compared to milrinone.
• C. It is preferred over milrinone for its better safety profile.
• D. It is a selective beta-1 agonist.

Answer: B. Its use is very limited due to a higher incidence of adverse effects (e.g., thrombocytopenia, hepatotoxicity) compared to milrinone.

40. Hypomagnesemia can exacerbate digoxin toxicity because magnesium is important for:

• A. The metabolism of digoxin.
• B. The function of the Na+/K+-ATPase pump, and low Mg2+ can impair its activity, similar to hypokalemia.
• C. The absorption of digoxin.
• D. The renal excretion of digoxin.

Answer: B. The function of the Na+/K+-ATPase pump, and low Mg2+ can impair its activity, similar to hypokalemia.

41. The main difference in the site of action between cardiac glycosides and beta-adrenergic agonists in producing positive inotropy is:

• A. Cardiac glycosides increase cAMP; beta-agonists inhibit Na+/K+-ATPase.
• B. Cardiac glycosides inhibit Na+/K+-ATPase; beta-agonists stimulate adenylyl cyclase to increase cAMP.
• C. Both directly open calcium channels.
• D. Both sensitize troponin C to calcium.

Answer: B. Cardiac glycosides inhibit Na+/K+-ATPase; beta-agonists stimulate adenylyl cyclase to increase cAMP.

42. In acute decompensated heart failure, if a patient is “cold and dry” (hypoperfused without congestion), which pharmacological approach might be considered first if IV fluids are not sufficient or appropriate?

• A. High-dose IV loop diuretics
• B. An IV positive inotrope (e.g., dobutamine) or vasopressor if hypotensive
• C. Oral beta-blocker initiation
• D. IV nitrates

Answer: B. An IV positive inotrope (e.g., dobutamine) or vasopressor if hypotensive

43. Which of the following is a primary concern when using dobutamine in a patient with acute myocardial infarction and cardiogenic shock?

• A. Significant bradycardia
• B. Potential to increase myocardial oxygen demand and worsen ischemia
• C. Severe bronchoconstriction
• D. Hyperkalemia

Answer: B. Potential to increase myocardial oxygen demand and worsen ischemia

44. The loading dose of digoxin is administered to:

• A. Rapidly achieve therapeutic serum concentrations due to its large volume of distribution and long half-life.
• B. Prevent gastrointestinal absorption issues.
• C. Assess for allergic reactions.
• D. Minimize the risk of arrhythmias.

Answer: A. Rapidly achieve therapeutic serum concentrations due to its large volume of distribution and long half-life.

45. Which inotropic agent directly increases heart rate significantly due to its potent beta-1 and beta-2 agonist activity?

• A. Digoxin
• B. Milrinone
• C. Isoproterenol
• D. Levosimendan

Answer: C. Isoproterenol

46. The vasodilatory effect of milrinone is beneficial in acute heart failure as it:

• A. Increases preload significantly.
• B. Reduces both preload and afterload, improving cardiac output.
• C. Causes selective renal vasoconstriction.
• D. Increases systemic vascular resistance.

Answer: B. Reduces both preload and afterload, improving cardiac output.

47. What is the primary rationale for the very limited or short-term use of most IV positive inotropes (except digoxin in specific chronic scenarios) in heart failure management?

• A. They are extremely expensive.
• B. They lack significant positive inotropic effects.
• C. Concerns about increased arrhythmias and long-term mortality despite short-term hemodynamic benefits.
• D. They are only effective when given orally.

Answer: C. Concerns about increased arrhythmias and long-term mortality despite short-term hemodynamic benefits.

48. The effect of digoxin on the atrioventricular (AV) node, which is useful for rate control in atrial fibrillation, is primarily due to:

• A. Direct stimulation of sympathetic nerves.
• B. Its vagomimetic action (increased parasympathetic tone), which slows AV nodal conduction and prolongs the refractory period.
• C. Inhibition of calcium channels in the AV node.
• D. Beta-1 adrenergic blockade.

Answer: B. Its vagomimetic action (increased parasympathetic tone), which slows AV nodal conduction and prolongs the refractory period.

49. If a patient on digoxin develops severe bradycardia or high-degree AV block, what is the first step in management?

• A. Increase the digoxin dose.
• B. Withhold digoxin and assess for toxicity; consider atropine or pacing if hemodynamically unstable.
• C. Administer a beta-blocker.
• D. Start an IV infusion of milrinone.

Answer: B. Withhold digoxin and assess for toxicity; consider atropine or pacing if hemodynamically unstable.

50. The choice of inotropic agent in acute decompensated heart failure often depends on the patient’s hemodynamic profile, specifically their:

• A. Baseline cholesterol levels
• B. Blood pressure, evidence of congestion, and peripheral perfusion status
• C. Age and gender only
• D. Preferred route of administration

Answer: B. Blood pressure, evidence of congestion, and peripheral perfusion status