Anti-Arrhythmic Drugs Overview

• Arrhythmias are characterized by abnormal generation and/or conduction of electrical impulses, which produce abnormal rate and/or activation sequences in the cardiac tissue. Ultimately, this can reduce cardiac output.
  Supraventricular Arrhythmias
  Ventricular Arrhythmias
  AV Node block
• Class 1 drugs are sodium channel blockers; we’ll focus on this group in this tutorial.
• Class 2 drugs comprise the beta blockers.
• Class 3 drugs include the potassium channel blockers.
• Class 4 drugs comprise the calcium channel blockers.
• Magnesium and adenosine are also used to treat arrhythmias.
• Paradoxically, anti-arrhythmic drugs can actually precipitate fatal arrhythmias; thus, the potential harm of these drugs may outweigh their potential benefits in some patients.

Action Potenial

Review

• Phase 0 = Fast sodium channels open and ions quickly move into the cell, which causes rapid depolarization.
  – Class 1 antiarrhythmics affect the slope of this line.
• Phase 1 = Potassium channels open, which allows potassium ions to move out of the cell and cause early repolarization.
• Phase 2 = The plateau phase; potassium continues to move out of the cell, and calcium move into it.
• Phase 3 = As more potassium channels begin to open, and calcium channels close, Phase 3 is characterized by rapid repolarization.
• Phase 4 = Resting phase, during which “leaky” potassium channels maintain resting membrane potential.
• Effective refractory period is the time when new action potentials cannot be triggered.

Effects of Class 1 anti-arrhythmics on this curve

• These drugs are fast-sodium channel blockers; they also have local anesthetic properties.
• They slow the rate of Phase 0 depolarization and conduction velocity.
• Class 1 drugs are further classified by their effects on the duration of action potentials.
  – Class 1a drugs prolong the duration of the action potential
  – Class 1b drugs shorten its duration
  – Class 1c drugs have minimal effect

Details

Class 1a

• Used to treat atrial and ventricular arrhythmias.
• Moderate sodium channel blockers, and also block some potassium channels.
• They prolong the action potential duration, effective refractory period, QRS complex, and QT interval.
• Examples and their most common side effects:
  – Procainamide is associated with hypotension; long term use is typically avoided because the drug can cause lupus-like syndrome, characterized by arthralgia and purpura.
  It is generally considered the third best choice in myocardial infarction arrhythmias (behind amiodarone and lidocaine).
  – Quinidine is associated with gastrointestinal side effects, cinchonism (headache, dizziness, and tinnitus), and thrombocytopenia.
  – Disopyramide are due to its anticholinergic effects (for example, constipation, urine retention, dry mouth, blurred vision). Can worsen glaucoma, and is not suitable for patients with heart failure.
• All Class 1a drugs can precipitate torsades de pointes.

Class 1b

• Used to treat ventricular arrhythmias.
• They are weak sodium channel blockers, and are selective for ischemic tissue and depolarized Purkinje fibers and ventricular myocytes.
• These drugs shorten the action potential duration and effective refractory period, but have no effect on the QRS complex or QT interval.
• Lidocaine is the prototypical class 1b drug; it is second in line to treat arrhythmias associated with myocardial infarction (behind amiodarone).
  – Lidocaine has low toxicity, but, in vulnerable patients or when given in high doses or administered too rapidly, it is associated with neurological, and, more rarely, cardiovascular side effects.
  – Neurological effects include paresthesia (tingling, “pins and needles,” usually in the hands and feet), dizziness, and confusion.
  – Cardiovascular effects include sinus bradycardia, arrhythmias, and shock.
• Phenytoin is often considered an honorary member of class 1b anti-arrhythmias; it is used to treat arrhythmias caused by digitalis.

Class 1c

• We’ll list characteristics for the prototypical drug, Flecainide; as we’ll see, however, not all class 1c drugs have the same effects.
• Used to treat supraventricular arrhythmias.
• Strong sodium-channel blockers that also block some potassium channels.
• Flecainide has no effect on the duration of action potentials or the effective refractory period; it prolongs the QRS complex with little effect on the QT interval.
• Common side effects are dizziness, headaches, and visual disturbances, which may include blurred vision or difficulty focusing, or the appearance of flashing lights or spots.
• Propafenone has similar side effects; it can exacerbate heart failure (propafenone also blocks beta channels and has negative inotropic effects).
  – Unlike flecainide, it is associated with prolonged QT intervals and effective refractory periods.
• Moricizine is another class 1c anti-arrhythmic, but it is no longer used in the United States.
• Class 1c drugs are pro-arrhythmic; they are not suitable for patients with structural heart disease.