Antiarrhythmic drugs are a diverse group of medications used to treat abnormalities in heart rhythm by modifying cardiac electrophysiology. They work by targeting ion channels, adrenergic receptors, or other mechanisms involved in the generation and conduction of electrical impulses within the heart. Given their potential for proarrhythmic effects and significant side effects, a thorough understanding of their pharmacology—including the Vaughan Williams classification, specific mechanisms of action, electrophysiological consequences, pharmacokinetic properties, therapeutic uses, and adverse drug reactions—is crucial for PharmD students to ensure safe and effective patient management. This MCQ quiz will test your knowledge of these critical pharmacological principles.
1. The Vaughan Williams classification system categorizes antiarrhythmic drugs primarily based on their dominant:
- A. Route of administration
- B. Electrophysiological mechanism of action on the cardiac action potential
- C. Chemical structure
- D. Cost-effectiveness
Answer: B. Electrophysiological mechanism of action on the cardiac action potential
2. Class I antiarrhythmic drugs primarily exert their effect by blocking which ion channels?
- A. Potassium (K+) channels
- B. Calcium (Ca2+) channels
- C. Sodium (Na+) channels
- D. Chloride (Cl-) channels
Answer: C. Sodium (Na+) channels
3. Quinidine, procainamide, and disopyramide belong to which subclass of Class I antiarrhythmics, characterized by moderate Na+ channel blockade and prolongation of repolarization?
- A. Class Ia
- B. Class Ib
- C. Class Ic
- D. Class Id
Answer: A. Class Ia
4. Lidocaine and mexiletine are Class Ib antiarrhythmics. They are characterized by:
- A. Strong Na+ channel blockade and marked slowing of conduction.
- B. Weak Na+ channel blockade, rapid association/dissociation, and often shortening of action potential duration in some tissues, with greater effect on ischemic tissue.
- C. Predominant potassium channel blockade.
- D. Beta-adrenergic receptor antagonism.
Answer: B. Weak Na+ channel blockade, rapid association/dissociation, and often shortening of action potential duration in some tissues, with greater effect on ischemic tissue.
5. Flecainide and propafenone are Class Ic antiarrhythmics. Their primary electrophysiological effect is:
- A. Significant prolongation of the action potential duration.
- B. Marked slowing of conduction velocity (Phase 0 depression) with minimal effect on action potential duration.
- C. Shortening of the effective refractory period.
- D. Beta-adrenergic blockade as their sole mechanism.
Answer: B. Marked slowing of conduction velocity (Phase 0 depression) with minimal effect on action potential duration.
6. Class II antiarrhythmic drugs are essentially:
- A. Potassium channel blockers
- B. Sodium channel blockers
- C. Calcium channel blockers
- D. Beta-adrenergic blockers
Answer: D. Beta-adrenergic blockers
7. The primary antiarrhythmic mechanism of beta-blockers (Class II) involves:
- A. Direct blockade of sodium channels.
- B. Antagonism of catecholamine effects on the heart, leading to decreased SA node automaticity and slowed AV nodal conduction.
- C. Prolongation of the QT interval by blocking potassium channels.
- D. Increasing intracellular calcium in cardiomyocytes.
Answer: B. Antagonism of catecholamine effects on the heart, leading to decreased SA node automaticity and slowed AV nodal conduction.
8. Class III antiarrhythmic drugs, such as amiodarone and sotalol, primarily exert their effect by:
- A. Blocking sodium channels
- B. Blocking beta-adrenergic receptors
- C. Blocking potassium channels, thereby prolonging repolarization (Phase 3) and the action potential duration
- D. Blocking calcium channels
Answer: C. Blocking potassium channels, thereby prolonging repolarization (Phase 3) and the action potential duration
9. Amiodarone is a unique Class III antiarrhythmic with complex pharmacology that also exhibits properties of which other Vaughan Williams classes?
- A. Only Class II
- B. Only Class IV
- C. Classes I, II, and IV, in addition to its primary Class III effects
- D. It has no properties overlapping with other classes.
Answer: C. Classes I, II, and IV, in addition to its primary Class III effects
10. Sotalol is a Class III antiarrhythmic that also possesses significant activity as a:
- A. Sodium channel blocker (Class I)
- B. Non-selective beta-adrenergic blocker (Class II)
- C. Calcium channel blocker (Class IV)
- D. Muscarinic receptor agonist
Answer: B. Non-selective beta-adrenergic blocker (Class II)
11. Class IV antiarrhythmic drugs, such as verapamil and diltiazem, primarily block which type of ion channels, especially in nodal tissue?
- A. Fast sodium channels
- B. L-type calcium channels
- C. Delayed rectifier potassium channels
- D. Inward rectifier potassium channels
Answer: B. L-type calcium channels
12. The primary electrophysiological effect of non-dihydropyridine calcium channel blockers (Class IV) on the AV node is:
- A. Shortening of the refractory period and increased conduction velocity.
- B. Prolongation of the refractory period and decreased conduction velocity.
- C. No significant effect on AV nodal function.
- D. Enhanced automaticity.
Answer: B. Prolongation of the refractory period and decreased conduction velocity.
13. Adenosine is an unclassified antiarrhythmic drug used for the acute termination of certain supraventricular tachycardias (SVTs). Its mechanism involves:
- A. Blocking sodium channels.
- B. Activating A1 adenosine receptors in the AV node, leading to K+ efflux, hyperpolarization, and slowed AV conduction.
- C. Inhibiting phosphodiesterase.
- D. Blocking beta-adrenergic receptors.
Answer: B. Activating A1 adenosine receptors in the AV node, leading to K+ efflux, hyperpolarization, and slowed AV conduction.
14. Digoxin, a cardiac glycoside, can be used as an antiarrhythmic for ventricular rate control in atrial fibrillation due to its:
- A. Direct beta-blocking effects.
- B. Vagomimetic effect, which slows AV nodal conduction and increases AV nodal refractoriness.
- C. Ability to prolong the QT interval.
- D. Sodium channel blocking properties.
Answer: B. Vagomimetic effect, which slows AV nodal conduction and increases AV nodal refractoriness.
15. “Use-dependence” is a property of some Class I antiarrhythmic drugs (especially Class Ic and some Ia) where their channel blocking effect is more pronounced at:
- A. Slower heart rates
- B. Faster heart rates (more channel openings)
- C. Rest (diastolic phase)
- D. Normal sinus rhythm only
Answer: B. Faster heart rates (more channel openings)
16. “Reverse use-dependence” is a characteristic of some Class III antiarrhythmic drugs (e.g., sotalol, dofetilide) where their effect of prolonging action potential duration (and QT interval) is more pronounced at:
- A. Faster heart rates
- B. Slower heart rates
- C. During exercise
- D. In the presence of hyperkalemia
Answer: B. Slower heart rates (This increases the risk of Torsades de Pointes at bradycardia).
17. A major dose-limiting adverse effect of quinidine (Class Ia) is “cinchonism,” which can manifest as:
- A. Hypertension and tachycardia
- B. Tinnitus, headache, dizziness, and visual disturbances
- C. Severe bronchoconstriction
- D. Hyperkalemia
Answer: B. Tinnitus, headache, dizziness, and visual disturbances
18. Procainamide (Class Ia) therapy can be associated with the development of drug-induced lupus erythematosus, characterized by the presence of:
- A. Anti-cyclic citrullinated peptide (anti-CCP) antibodies
- B. Antinuclear antibodies (ANA) and anti-histone antibodies
- C. Rheumatoid factor
- D. Anti-double-stranded DNA (anti-dsDNA) antibodies
Answer: B. Antinuclear antibodies (ANA) and anti-histone antibodies
19. Lidocaine (Class Ib) is primarily effective for treating which type of arrhythmias, especially in the setting of acute myocardial infarction?
- A. Atrial fibrillation
- B. Supraventricular tachycardias involving the AV node
- C. Ventricular arrhythmias (e.g., VT, PVCs)
- D. Sinus bradycardia
Answer: C. Ventricular arrhythmias (e.g., VT, PVCs)
20. The CAST (Cardiac Arrhythmia Suppression Trial) study showed that Class Ic antiarrhythmics (flecainide, encainide) in post-MI patients:
- A. Significantly reduced mortality.
- B. Increased mortality despite effective suppression of ventricular ectopy.
- C. Had no effect on mortality or arrhythmia suppression.
- D. Were superior to beta-blockers.
Answer: B. Increased mortality despite effective suppression of ventricular ectopy.
21. Amiodarone has a very long elimination half-life (weeks to months) and a large volume of distribution due to its:
- A. High water solubility
- B. Extensive lipophilicity and tissue accumulation
- C. Rapid renal excretion
- C. Lack of plasma protein binding
Answer: B. Extensive lipophilicity and tissue accumulation
22. Which of the following is a serious potential adverse effect of long-term amiodarone therapy requiring regular monitoring?
- A. Hypoglycemia
- B. Pulmonary toxicity (fibrosis, pneumonitis), thyroid dysfunction (hyper- or hypothyroidism), and hepatotoxicity
- C. Severe hypertension
- D. Renal failure
Answer: B. Pulmonary toxicity (fibrosis, pneumonitis), thyroid dysfunction (hyper- or hypothyroidism), and hepatotoxicity
23. Dofetilide and ibutilide are “pure” Class III antiarrhythmics that specifically block:
- A. Fast sodium channels
- B. L-type calcium channels
- C. The rapid component of the delayed rectifier potassium current (IKr)
- D. The inward rectifier potassium current (IK1)
Answer: C. The rapid component of the delayed rectifier potassium current (IKr)
24. Initiation of dofetilide therapy requires hospitalization for ECG monitoring primarily due to the risk of:
- A. Severe bradycardia
- B. Torsades de Pointes (TdP) related to QT prolongation
- C. Atrial fibrillation conversion to ventricular fibrillation
- D. Acute liver failure
Answer: B. Torsades de Pointes (TdP) related to QT prolongation
25. Dronedarone is a structural analogue of amiodarone designed to have less toxicity. However, it is contraindicated in patients with:
- A. Paroxysmal atrial fibrillation
- B. Permanent atrial fibrillation or severe/decompensated heart failure
- C. Hypertension
- D. Ischemic heart disease
Answer: B. Permanent atrial fibrillation or severe/decompensated heart failure
26. Verapamil and diltiazem (Class IV) are generally contraindicated or used with extreme caution in patients with:
- A. Hypertension and angina
- B. Severe left ventricular systolic dysfunction (HFrEF) or sick sinus syndrome/AV block (without a pacemaker)
- C. Paroxysmal supraventricular tachycardia
- D. Atrial flutter for rate control
Answer: B. Severe left ventricular systolic dysfunction (HFrEF) or sick sinus syndrome/AV block (without a pacemaker)
27. The pharmacokinetic profile of adenosine is characterized by an extremely short half-life (seconds) due to:
- A. Rapid hepatic metabolism by CYP3A4
- B. Rapid uptake by cells (e.g., red blood cells, endothelial cells) and metabolism by adenosine deaminase
- C. Excretion entirely by glomerular filtration
- D. High plasma protein binding
Answer: B. Rapid uptake by cells (e.g., red blood cells, endothelial cells) and metabolism by adenosine deaminase
28. Common transient adverse effects immediately following intravenous adenosine administration include:
- A. Hypertension, tachycardia, and euphoria
- B. Flushing, chest pain/pressure, dyspnea, and transient AV block/asystole
- C. Severe hyperkalemia and muscle weakness
- D. Prolonged QT interval and Torsades de Pointes
Answer: B. Flushing, chest pain/pressure, dyspnea, and transient AV block/asystole
29. Magnesium sulfate is used intravenously for the acute management of which specific arrhythmia?
- A. Atrial fibrillation with rapid ventricular response
- B. Sinus bradycardia
- C. Torsades de Pointes (TdP)
- D. Atrioventricular nodal reentrant tachycardia (AVNRT)
Answer: C. Torsades de Pointes (TdP)
30. The “proarrhythmic effect” of an antiarrhythmic drug refers to its potential to:
- A. Always convert an arrhythmia to sinus rhythm.
- B. Cause new arrhythmias or worsen existing arrhythmias.
- C. Prevent all future arrhythmias.
- D. Reduce the heart rate to safe levels.
Answer: B. Cause new arrhythmias or worsen existing arrhythmias.
31. Which of the following antiarrhythmic drug classes has the MOST significant effect on slowing conduction velocity in the His-Purkinje system and ventricular myocardium (Phase 0)?
- A. Class II (Beta-blockers)
- B. Class Ic (e.g., flecainide)
- C. Class IV (Calcium channel blockers)
- D. “Pure” Class III (e.g., dofetilide)
Answer: B. Class Ic (e.g., flecainide)
32. Propafenone (Class Ic) also possesses weak activity as a:
- A. Calcium channel blocker
- B. Beta-adrenergic blocker
- C. Potassium channel opener
- D. Muscarinic agonist
Answer: B. Beta-adrenergic blocker
33. Disopyramide (Class Ia) is known for its significant _________ effects, which can lead to dry mouth, urinary retention, and blurred vision.
- A. Beta-blocking
- B. Anticholinergic (muscarinic antagonist)
- C. Alpha-blocking
- D. Dopaminergic
Answer: B. Anticholinergic (muscarinic antagonist)
34. Which of these Class III antiarrhythmics requires dose adjustment based on renal function and QT interval monitoring during initiation?
- A. Amiodarone
- B. Dronedarone
- C. Dofetilide and Sotalol
- D. Ibutilide (IV only, QT monitored but dosing not primarily renal for acute use)
Answer: C. Dofetilide and Sotalol (Both are renally cleared and have QT prolongation risk).
35. Esmolol is a Class II antiarrhythmic (beta-blocker) with a very short duration of action primarily due to:
- A. Rapid hepatic metabolism by CYP enzymes.
- B. Hydrolysis by red blood cell esterases.
- C. Renal excretion as unchanged drug.
- D. High tissue distribution.
Answer: B. Hydrolysis by red blood cell esterases.
36. The primary therapeutic goal of using Class II or Class IV antiarrhythmics in atrial fibrillation is often:
- A. Conversion to sinus rhythm (rhythm control)
- B. Ventricular rate control by slowing AV nodal conduction
- C. Prevention of stroke
- D. Correction of electrolyte imbalances
Answer: B. Ventricular rate control by slowing AV nodal conduction
37. Which antiarrhythmic agent is known to contain iodine in its structure and can interfere with thyroid function tests?
- A. Sotalol
- B. Flecainide
- C. Amiodarone
- D. Verapamil
Answer: C. Amiodarone
38. A patient stabilized on warfarin therapy is initiated on amiodarone. The pharmacist should anticipate the need to:
- A. Increase the warfarin dose.
- B. Decrease the warfarin dose due to inhibition of warfarin metabolism by amiodarone.
- C. Make no changes to the warfarin dose.
- D. Discontinue warfarin.
Answer: B. Decrease the warfarin dose due to inhibition of warfarin metabolism by amiodarone. (Amiodarone inhibits CYP2C9 and other CYPs).
39. Which electrolyte abnormality is most likely to reduce the effectiveness of lidocaine for ventricular arrhythmias?
- A. Hypokalemia
- B. Hyperkalemia (can potentiate lidocaine toxicity or reduce efficacy by altering membrane potential)
- C. Hyponatremia
- D. Hypocalcemia
Answer: B. Hyperkalemia (High K+ can reduce Na+ channel availability and antagonize lidocaine’s effect or increase toxicity). Hypokalemia can also be problematic, but hyperkalemia is a classic interaction with lidocaine effect on Na+ channels.
40. The choice between a rate control strategy and a rhythm control strategy for atrial fibrillation depends on:
- A. Patient age only.
- B. A comprehensive assessment including patient symptoms, comorbidities, duration of AFib, and shared decision-making.
- C. The cost of the medications only.
- D. The preference of the cardiologist only.
Answer: B. A comprehensive assessment including patient symptoms, comorbidities, duration of AFib, and shared decision-making.
41. “Pill-in-the-pocket” approach for paroxysmal atrial fibrillation typically involves self-administration of which type(s) of antiarrhythmic drug upon symptom onset by carefully selected patients?
- A. Amiodarone or Sotalol
- B. Flecainide or Propafenone (Class Ic)
- C. Digoxin
- D. Verapamil
Answer: B. Flecainide or Propafenone (Class Ic) (Sometimes with a beta-blocker or CCB if not already on one).
42. The main difference in electrophysiological effect between Class Ia and Class Ib sodium channel blockers on action potential duration (APD) is:
- A. Class Ia shortens APD; Class Ib prolongs APD.
- B. Class Ia prolongs APD (due to K+ channel block); Class Ib often shortens APD or has little effect.
- C. Both markedly prolong APD.
- D. Neither affects APD.
Answer: B. Class Ia prolongs APD (due to K+ channel block); Class Ib often shortens APD or has little effect.
43. Which of the following antiarrhythmics is administered as an intravenous loading dose followed by a continuous infusion, primarily for acute ventricular arrhythmias?
- A. Mexiletine
- B. Propafenone
- C. Lidocaine
- D. Dofetilide
Answer: C. Lidocaine
44. The use of Class Ic antiarrhythmics (flecainide, propafenone) is generally contraindicated or used with extreme caution in patients with:
- A. Paroxysmal supraventricular tachycardia and no structural heart disease.
- B. Structural heart disease (e.g., prior MI, significant LV dysfunction) due to increased risk of proarrhythmia and mortality.
- C. Hypertension.
- D. Asthma.
Answer: B. Structural heart disease (e.g., prior MI, significant LV dysfunction) due to increased risk of proarrhythmia and mortality.
45. Which of the following is a key monitoring parameter when initiating or titrating sotalol?
- A. Serum sodium levels
- B. QT interval (for risk of TdP) and renal function (for dose adjustment)
- C. Liver function tests
- D. Platelet count
Answer: B. QT interval (for risk of TdP) and renal function (for dose adjustment)
46. The mechanism of “use-dependence” for Class I antiarrhythmics means they bind more effectively to sodium channels that are:
- A. In the resting state.
- B. Frequently opening (activated state) or in the inactivated state.
- C. Permanently closed.
- D. Located only in the SA node.
Answer: B. Frequently opening (activated state) or in the inactivated state.
47. Which antiarrhythmic drug is often used for pharmacological cardioversion of recent-onset atrial fibrillation?
- A. Digoxin
- B. Lidocaine
- C. Ibutilide (IV) or agents like Flecainide, Propafenone, Amiodarone
- D. Adenosine
Answer: C. Ibutilide (IV) or agents like Flecainide, Propafenone, Amiodarone
48. A common side effect of verapamil, particularly at higher doses, is:
- A. Diarrhea
- B. Constipation
- C. Tachycardia
- D. Dry cough
Answer: B. Constipation
49. What is the primary reason for the very short duration of action of adenosine?
- A. Rapid and extensive hepatic metabolism.
- B. Rapid uptake into red blood cells and endothelial cells and enzymatic degradation by adenosine deaminase.
- C. Slow IV infusion rate.
- D. Excretion entirely as unchanged drug in urine.
Answer: B. Rapid uptake into red blood cells and endothelial cells and enzymatic degradation by adenosine deaminase.
50. A pharmacist’s role in managing patients on antiarrhythmic therapy includes all of the following EXCEPT:
- A. Counseling on potential side effects and importance of adherence.
- B. Monitoring for drug interactions and efficacy (e.g., symptom control, ECG changes).
- C. Performing elective cardioversion procedures.
- D. Assisting with dose adjustments based on patient response, lab values, and guidelines.
Answer: C. Performing elective cardioversion procedures.