540 Week 4 May 20 Pharm Part 1 Notes on Antiarrhythmics and Antianginals

Arrhythmias and Angina Medications

Overview

• This lecture covers medications for arrhythmias and angina.

• Key aspects include mechanisms of action, contraindications, and drug interactions.

• Arrhythmias are abnormal heartbeats or heart rhythms.

  • Tachyarrhythmia: Heart rate of $100$ beats per minute or faster.

  • Bradyarrhythmia: Heart rate less than $60$ beats per minute.

• Antiarrhythmics are used less frequently due to interventions like ICDs (implantable cardioverter-defibrillators) and ablation.

Impulse Generation and Action Potential

• Understanding action potential is crucial for understanding how antiarrhythmics work.

• Action potential involves a cell going from a negative to a positive charge.

• Phases of Action Potential:

  • Involve the movement of ions across the cell membrane.

  • Sodium ($Na^+$) influx.

  • Potassium ($K^+$) efflux.

  • Calcium ($Ca^{2+}$) influx.

• Conduction Velocity: Regulation of action potential.

• Refractory Period: Time during which a cardiac cell cannot or may not propagate another action potential.

  • Absolute Refractory Period: Cardiac cell cannot propagate an action potential.

  • Relative Refractory Period: Cardiac cell may propagate an action potential, but requires a strong electrical stimulus.

Chemical Level of Action Potential

• Phase 0: Dramatic increase in cell potential from negative to positive due to sodium ions rushing into the cell.

• Calcium also rushes in during phase 0.

• As the action potential decreases, potassium exits the cell, and sodium leaves.

• Repolarization occurs as the cell becomes more negative.

Vaughan Williams Classification of Antiarrhythmic Drugs

• Four main classes of antiarrhythmics:

  • Class I: Sodium channel blockers

  • Class II: Beta-adrenergic antagonists (beta blockers)

  • Class III: Potassium channel blockers

  • Class IV: Calcium channel blockers

• Other antiarrhythmics:

  • Digoxin

  • Adenosine

Class I: Sodium Channel Blockers

• Block sodium channels, decreasing the action potential.

• Subclasses:

  • Class IA

  • Class IB

  • Class IC

Class II: Beta Blockers

• Beta-adrenergic antagonists that block calcium.

• Block beta-1 receptors on the heart.

Class III: Potassium Channel Blockers

• Prolong the action potential duration by blocking potassium channels.

Class IV: Calcium Channel Blockers

• Calcium channel antagonists.

Detailed Look at Class I Drugs

Effects on Action Potential

• All Class I drugs block sodium channels, preventing sodium from entering the cell.

• They affect cardiac conduction velocity, refractory period, and automaticity.

• Class IA: E.g., disopyramide, procainamide, and quinidine.

• Class IB: E.g., lidocaine, mexiletine.

• Class IC: E.g., flecainide, propafenone.

• Quinidine is no longer being manufactured but may be included for completeness.

Cardiac Conduction Velocity

• Refers to the speed at which electrical signals travel through the heart's muscle tissue.

Refractory Period

• The time interval during which cardiac muscles respond to electrical stimuli contracts.

• Increasing the refractory period slows the heart rate.

Automaticity

• The ability for heart cells to spontaneously generate electrical impulses.

• Class I drugs decrease automaticity, which is important for treating tachyarrhythmias.

Action Potential Slope

• Class I drugs affect the slope of phase 0 of the action potential.

• Class IC drugs (e.g., flecainide) have the strongest effect, followed by Class IA, and then Class IB (weakest).

• Remember the order as CAB (C strong, A moderate, B weak).

Class IA Antiarrhythmics

• Examples: Procainamide, disopyramide, quinidine (not used much anymore).

• Mnemonic: Pretty Darn Quick.

• Used for supraventricular, ventricular, and autonomic arrhythmias.

• Also used for reentry arrhythmias, where electrical signals stray from their usual course.

• Slow conduction velocity and increase refractory period.

Procainamide

• Can cause lupus-like syndrome and hypotension.

• May cause Torsades de pointes (a type of ventricular tachycardia).

• Not a preferred medication for any arrhythmia.

• Caution in heart failure and elderly patients.

Disopyramide

• Rarely indicated and has negative inotropic and anticholinergic side effects.

• Anticholinergic side effects: Can't see, can't pee.

• Caution in heart failure and elderly patients.

Class IB Antiarrhythmics

• Examples: Lidocaine and mexiletine.

• Lidocaine is given IV, primarily for ischemic tissue.

• Used for ventricular tachycardia and fibrillation (V-tach, V-fib).

• Commonly found in crash carts.

• Side effects of lidocaine: Nervousness, tremors.

• Mexiletine is given orally.

• Used for suppression of life-threatening ventricular arrhythmias.

• Side effects of mexiletine: Seizures, blood dyscrasias, hepatic effects.

Class IC Antiarrhythmics

• Examples: Flecainide and propafenone.

• Have the strongest effect on the action potential and sodium blockade.

• Used for supraventricular and life-threatening ventricular arrhythmias.

• Antiarrhythmics can sometimes cause arrhythmias.

• Propafenone has a metallic taste.

• Can cause heart block and bradycardia.

Class II Antiarrhythmics: Beta Blockers

• Beta-adrenergic antagonists.

• Examples: Metoprolol, propranolol, esmolol.

• Esmolol (Brevibloc) is given IV and is primarily indicated for antiarrhythmic use, especially supraventricular arrhythmias.

• Slows the heart rate and decreases AV node conduction velocity, and increases AV node refractory period.

• Short-acting IV product.

Class III Antiarrhythmics: Potassium Channel Blockers

• Amiodarone is the most utilized.

• Affect potassium channels, prolonging action potential.

• Increase refractory period.

• Drugs in this class: Amiodarone, ibutilide, dofetilide, sotalol, dronedarone.

• Mnemonic: