Pharmacology of Class I Antiarrhythmic Drugs

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Questions and Answers

What is the primary mechanism by which Class I drugs affect cardiomyocytes?

Decrease threshold of excitability

Block fast Na+ channels (correct)

Increase phase 4 depolarization of SA node

Inhibit potassium channels

Which Class IA drug is known to have significant GIT adverse effects?

Disopyramide

Lidocaine

Procainamide

Quinidine (correct)

What condition is associated with Procainamide use, particularly in slow acetylators?

Cardiac arrest

Diarrhea

Hypotension

SLE-like syndrome (correct)

Which drug is primarily approved for ventricular arrhythmias and has significant anti-cholinergic activity?

Disopyramide Signup and view all the answers

What is the main toxicity associated with Lidocaine?

Neurological effects Signup and view all the answers

Mexiletine's primary use is for which condition?

Ventricular arrhythmias after MI Signup and view all the answers

Which Class IB drug is not recommended for oral administration due to high first pass metabolism?

Lidocaine Signup and view all the answers

What effect do sodium-channel blockers in Class IA drugs have on reentry currents?

Abolish reentry currents Signup and view all the answers

What phase of a nodal action potential corresponds to spontaneous depolarization?

Phase 4 Signup and view all the answers

Which phase follows phase 0 in the action potential of a nodal cell?

Phase 3 Signup and view all the answers

What does the effective refractory period (ERP) prevent in cardiac cells?

Propagation of new action potentials Signup and view all the answers

What are the two main categories of arrhythmias?

Bradyarrhythmias and Tachyarrhythmias Signup and view all the answers

Which factors can lead to arrhythmias?

Both generation and conduction of electrical impulses Signup and view all the answers

What is the purpose of the ERP in cardiac function?

To prevent multiple, compounded action potentials Signup and view all the answers

Where do supraventricular arrhythmias originate?

From the atria Signup and view all the answers

Which drug is primarily used to suppress ventricular arrhythmias in the Class Ia category?

Procainamide Signup and view all the answers

Which monitoring modalities might be used to assess arrhythmias?

Holter monitor and 12-lead EKG Signup and view all the answers

What is the primary action of Amiodarone?

Prolongs refractory period Signup and view all the answers

Which drug in Class Ib is recognized for its ability to shorten action potentials?

Mexiletine Signup and view all the answers

Which of the following drugs is used to treat paroxysmal atrial tachycardia?

Adenosine Signup and view all the answers

What is the mechanism of action for Verapamil?

Block Ca+ channels Signup and view all the answers

What is the main effect of amiodarone on the sinus node automaticity?

It decreases automaticity Signup and view all the answers

Which adverse effect is specifically associated with amiodarone?

Pulmonary fibrosis Signup and view all the answers

What is the primary use of Ibutilide?

Atrial fibrillation and atrial flutter Signup and view all the answers

What is the mechanism of action of Class IV drugs?

Block L-type calcium channels Signup and view all the answers

Which drug is a potent inhibitor of K+-channels used in atrial fibrillation?

Dofetilide Signup and view all the answers

What is a common adverse effect of Sotalol?

Dyspnea Signup and view all the answers

How long is the half-life of amiodarone, which increases the risk of toxicity?

14-100 days Signup and view all the answers

Which statement is true about Bretylium?

It is used for ventricular arrhythmia after Lidocaine fails. Signup and view all the answers

What is a primary clinical use of Moricizine?

Management of life-threatening ventricular arrhythmias Signup and view all the answers

Which of the following statements is true regarding Class IC antiarrhythmics?

They act as potent Na+ channel blockers. Signup and view all the answers

What is one mechanism of action of Class II drugs (beta-blockers)?

They inhibit phase 4 depolarization of the SA node. Signup and view all the answers

What is a key adverse effect of Verapamil?

AV block Signup and view all the answers

Adenosine is primarily used for which type of arrhythmia?

Paroxysmal supraventricular tachycardia Signup and view all the answers

Which drug is NOT classified as a Class II antiarrhythmic?

Amiodarone Signup and view all the answers

What characterizes the mechanism of action of Class III antiarrhythmics?

They prolong action potential duration by slowing K+ or Na+ currents. Signup and view all the answers

What mechanism does Digoxin use to increase contractility?

Inhibition of Na+/K+-ATPase Signup and view all the answers

Which drug is used to treat bradyarrhythmias during a myocardial infarction?

Atropine Signup and view all the answers

Which of the following correctly describes Propafenone's action?

It has β-adrenoceptor antagonist activity. Signup and view all the answers

Which beta-blocker is specifically noted for its selectivity to β1-adrenoceptors?

Acebutolol Signup and view all the answers

Which effect is associated with the use of Atropine?

Increased sinus rate Signup and view all the answers

Amiodarone is structurally related to which hormone?

Thyroxine Signup and view all the answers

What is a potential adverse effect of Isoproterenol?

Tachycardia Signup and view all the answers

What action does Adenosine have on cardiac cells?

Hyperpolarizes cardiac cells Signup and view all the answers

What condition can Verapamil precipitate in diseased patients?

Sinus arrest Signup and view all the answers

Study Notes

Antiarrhythmic Drugs

Antiarrhythmic drugs are used to treat abnormal heart rhythms (arrhythmias).
Arrhythmias can be bradyarrhythmias (slow heart rhythms) or tachyarrhythmias (fast heart rhythms).
Tachyarrhythmias can be supraventricular (arising from above the ventricles) or ventricular (arising from the ventricles).
Arrhythmias are caused by abnormalities in the generation or conduction of electrical impulses, or both.
Physicians use EKGs, Holter monitors, and 12-lead EKGs to diagnose arrhythmias.

Electrical Activity of Cardiac Cells

Cardiac cells have specific action potential phases.
Phase 0 is depolarization.
Phase 3 is repolarization.
Phase 4 is spontaneous depolarization (pacemaker potential).
SA node cells have a pacemaker potential, triggering the heart's rhythmic contractions.

Action Potential of SA Pacemaker Cells

'Funny' sodium channels (If channels) are open, and closing K+ channels.
Transient Ca²⁺ (T-type) channels open, pushing the membrane potential to threshold.
Long-lasting Ca²⁺ (L-type) channels open, creating the action potential.
Opening of K⁺ channels, and closing of Ca²⁺ (L-type) channels, hyperpolarizes the cell.

Nodal Action Potentials

Phase 4 is spontaneous depolarization (pacemaker potential).
Phase 0 is the depolarization phase of the action potential, followed by phase 3.
Phase 3 is the repolarization phase; when fully repolarized, the cycle spontaneously repeats.

Action Potential of Cardiomyocytes

Transient K+ channels open and K+ efflux returns the membrane potential to 0mV.
Rapid Na+ influx through open fast Na+ channels.
Influx of Ca²⁺ through L-type Ca²⁺ channels is balanced by K+ efflux through delayed rectifier K+ channels.
Ca²⁺ channels close, delayed rectifier K+ channels remain open, returning the membrane potential to -90mV.
Na⁺, Ca²⁺ channels close; open K⁺ rectifier channels keep the membrane potential stable at about -90mV.
Effective refractory period (ERP) — a time when a cell cannot produce an action potential in response to stimulation.

Effective Refractory Period (ERP)

During the ERP, the cell cannot produce new action potentials, because fast sodium channels are not fully reactivated.
The ERP protects the heart from multiple, compounded action potentials.
The length of the ERP limits the heart's contraction rate.
Antiarrhythmic drugs can alter the ERP, affecting cellular excitability.

Arrhythmias and Classification

Arrhythmias are categorized as bradyarrhythmias (slow heart rates) and tachyarrhythmias (fast heart rates).
Tachyarrhythmias are further classified into supraventricular and ventricular types.

Antiarrhythmic Drug Classes

Class I (Sodium Channel Blockers): Quinidine, Procainamide, Disopyramide, Lidocaine, Mexiletine, Flecainide, Propafenone, Tocainide.
Class II (Beta-Blockers): Propranolol, Esmolol, Metoprolol, Atenolol
Class III (Potassium Channel Blockers): Amiodarone, Dofetilide, Sotalol.
Class IV (Calcium Channel Blockers): Verapamil, Diltiazem.
Class V (Miscellaneous): Adenosine, Digoxin, Bretylium

Class IA Antiarrhythmics (Quinidine, Procainamide, Disopyramide)

Quinidine: An alkaloid with adverse effects like diarrhea, nausea, vomiting, cinchonism and thrombocytopenia
Procainamide: Similar to Quinidine, safer for intravenous use. High risk of adverse effects in long-term use, including SLE-like syndrome.
Disopyramide: Primarily for ventricular arrhythmias. Has prominent anti-cholinergic activity.

Class IB Antiarrhythmics (Lidocaine)

Lidocaine: Least cardiotoxic, blocks inactivated sodium channels, preferred in ischemic areas; high first pass metabolism.
Toxicity often manifests as neurological symptoms (drowsiness, nystagmus, seizures).
Used for ventricular arrhythmias and those induced by digoxin.

Class IC Antiarrhythmics (Flecainide, Propafenone)

Flecainide: Orally active, used in ventricular tachyarrhythmias and sinus maintenance in patients with paroxysmal atrial fibrillation.
Propafenone: Similar to Quinidine in action, with beta-blocker activity; used in supraventricular and life-threatening ventricular arrhythmias.

Class II Antiarrhythmics (Beta-Blockers)

Beta-blockers, such as propranolol, acebutolol, and esmolol, inhibit phase 4 depolarization of the SA node and prolong AV node conduction.
They decrease heart rate (except for agents with intrinsic sympathomimetic activity) and contractility.
These are often used to prevent recurrent MI.

Class III Antiarrhythmics

Amiodarone: Structurally related to thyroxine, increases refractoriness and depresses sinus node automaticity, and slows conduction; long half-life.
Ibutilide: Used for atrial fibrillation and flutter, administered by intravenous infusion. Blocks slow inward Na+ currents.
Sotalol: Prolongs cardiac action potential and refractory period. Nonselective beta-blocker activity; used in atrial and life-threatening ventricular arrhythmias, sustained ventricular tachycardia.

Class IV Antiarrhythmics (Calcium Channel Blockers)

Verapamil: Blocks activated and inactivated slow calcium channels; has equipotent activity in AV and SA nodes and cardiac/vascular tissues. Prevents supraventricular tachycardia and atrial fibrillation.
Adverse effects include negative inotropic action, AV block (particularly in large doses), sinus arrest in diseased patients, and peripheral vasodilation.
Diltiazem: Similar action and use to verapamil but is not as potent.

Class V Antiarrhythmics (Adenosine)

Adenosine: Hyperpolarizes cardiac cells by increasing potassium efflux and decreasing calcium influx. Treatment of choice for paroxysmal supraventricular tachycardia and those linked to Wolff-Parkinson-White Syndrome.

Digoxin

Digoxin: Inhibits Na+/K+-ATPase leading to increased intracellular Na+, influencing the Na+/Ca²⁺ exchanger and enhancing contractility.
It slows conduction, controlling ventricular response in atrial flutter or fibrillation.
Elevated intracellular sodium and altered resting membrane potential can increase the risk of arrhythmias.

Other Drugs (Atropine, Isoproterenol)

Atropine: Blocks acetylcholine effects, elevates sinus rate and AV nodal/SA conduction. Decreases refractory period; used in bradyarrhythmias (often accompanying MI).
Isoproterenol: Stimulates beta-adrenergic receptors, increases heart rate and contractility; used in AV block. Can cause tachycardia, anginal attacks, headaches, dizziness, and tremors.

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Description

This quiz focuses on the pharmacological effects, side effects, and mechanisms of Class I antiarrhythmic drugs. It covers various aspects including specific drug interactions, conditions treated, adverse reactions, and the physiology of cardiac action potentials. Perfect for students studying cardiac pharmacology and arrhythmias.