Class 2 Antiarrhythmics

Summary

Class 2 antiarrhythmics are beta blockers that have drug names that end in -lol.

By blocking beta receptors, these drugs decrease cAMP levels and decrease calcium currents entering heart cells. This lengthens phase 4 of the nodal action potential. Physiologically, this slows pacing in the SA node. This also slows conduction in the AV node and prolongs repolarization at the AV node, manifesting as an increase in the PR interval on an EKG. Class 2 antiarrhythmics also suppress abnormal pacemaker activity. Notably, Esmolol is a very short acting drug with effects lasting less than 30 minutes, which can be used when more precise control is needed.

Clinically, these drugs work as antiarrhythmics to treat various types of arrhythmias. Class 2 drugs can treat SVT and are most commonly used in the treatment of A-Fib, where they are used for rate control. They may also be used to prevent ventricular fibrillation post-MI, and to treat atrial flutter.

Side effects of the Class 2 antiarrhythmics include CNS depression, cardiovascular depression, as well as sleep alterations including nightmares and insomnia. Class 2 drugs can also cause unopposed alpha activity, bronchoconstriction, and impotence. These drugs may also mask the signs of hypoglycemia in diabetic patients. Propranolol has been implicated in vasospasm, while metoprolol can increase fat and cholesterol levels to cause hyperlipidemia. 

Overdoses of Class 2 antiarrhythmics can be treated with saline, atropine, and glucagon.

Key Points

• Class II Antiarrhythmics
  • Drug Names
    • Beta-Blockers (-lol ending)
      • Includes all drugs that block beta-1 receptors, including
        • Beta-1 selective blockers (atenolol, esmolol, metoprolol)
        • Non-selective blockers (timolol, propranolol)
        • Dual alpha and beta blockers (carvedilol, and labetalol)
  • Mechanism
    • Reduces cAMP & reduces Ca2+ currents
      • By blocking Gs signaling cascade
    • Lengthens slope of phase 4 (in Nodal AP)
      • Since nodal tissue has Ca2+-dependent action potentials (see: CV Pharmacology)
      • Slows Pacemaker at SA Node
      • Slows Conduction at AV Node
    • Prolongs repolarization at AV node
    • Increases PR interval
      • Manifestation of slowed conduction on EKG
    • Suppresses abnormal pacemakers
    • Esmolol is very-short acting (<30 minutes)
      • Can be used for more precise control of effects
  • Clinical Use
    • Treats arrhythmias (antiarrhythmic)
    • Treats supraventricular tachycardia (SVT)
      • Treats A-Fib (Atrial Fibrillation)
        • Used for (ventricular) rate control
          • Slowing conduction of atrial action potentials through the node prevents ventricular rate increase
      • Treats Atrial Flutter
    • Prevents ventricular arrhythmia post-MI
      • This is controversial and is mostly supported by historical studies showing a slight decrease in sudden cardiac death after MI
  • Side Effects
    • Acute effects are more important than chronic effects for antiarrhythmic function
    • CNS Depression (sedation)
    • Nightmares and Insomnia (sleep alterations)
    • Cardiovascular Depression (e.g. bradycardia, AV block, HF)
      • Due to beta-1 receptor blockade at heart
    • Unopposed alpha-1 agonism
      • Does not affect combined alpha and beta blockers (carvedilol and labetalol)
      • May worsen pheochromocytoma or cocaine toxicity if not given with alpha-blocker
    • Bronchospasm (exacerbation of COPD and asthma)
      • Due to beta-2 receptor blockade at bronchioles
      • May lead to acute exacerbation of COPD and Asthma
    • Impotence (Erectile dysfunction)
      • Decreases blood flow to the penis
    • Masks Hypoglycemia
      • Symptoms of hypoglycemia (e.g. tachycardia) may be less apparent to diabetics
    • Dyslipidemia (metoprolol)
      • May increase triglyceride levels on lipid panels
    • Vasospasm/constriction (propranolol)
      • This is thought to be a symptom of unopposed alpha-antagonism
      • May worsen vasospastic angina (Prinzmetal)
  • Reversal of Overdose
    • Saline
    • Atropine
    • Glucagon