Antiarrhythmic Medications

Article Author:
Gregory King
Article Editor:
Muhammad Hashmi
10/24/2019 8:26:40 AM
PubMed Link:
Antiarrhythmic Medications


The anti-arrhythmic medications have typically been categorized according to the Vaughan-Williams (VW) classification system. The system classifies the medications according to the main mechanism of action (although several of the agents retain properties from multiple classes). The VW classification is traditionally broken down into four main categories, with some references adding a fifth.[1][2][3]

Class I

Sodium Channel Blockers prolong phase 0 (rapid sodium influx into the cell) of the cardiac action potential; effects on QTc are variable by subclass.

  • Class Ia: Quinidine, procainamide, disopyramide is the most pro-arrhythmic of the sodium channel blockers; prolong the QTc interval; use is limited due to pro-arrhythmic potential. Disopyramide still used occasionally with hypertrophic obstructive cardiomyopathy (HOCM). Procainamide can be used as an agent to help unmask and diagnose Brugada syndrome in patients suspected of having Brugada, but without a definitive diagnosis.
  • Class Ib: Lidocaine, mexiletine shorten the QTc interval; used for ventricular arrhythmias only; not effective for atrial arrhythmias. Mexiletine is an oral analog of lidocaine. Its utility is limited due to a high rate of nausea and vomiting that typically does not abate with continued use.
  • Class Ic: Flecainide, propafenone - should not be used for patients with any "structural heart disease." The Cardiac Arrhythmia Suppression Trials (CAST I and II) showed increased mortality in patients who had a previous myocardial infarction who were administered class Ic agents (flecainide, encainide, moricizine) versus placebo when trying to reduce the frequency of premature ventricular contractions. The implications of this trial are that class IC agents are not routinely prescribed to patients with left ventricular dysfunction. This data essentially rules out the majority of ventricular arrhythmias for treatment with class IC agents. These agents produce no significant change to the QTc interval. Some patients may use the "pill in pocket" strategy. The pill in pocket refers to a treatment plan where the patient with paroxysmal atrial fibrillation does not take a regularly scheduled maintenance dose of the medication but instead carries a loading dose of the agent with them. If the patient feels an episode of atrial fibrillation start, he or she takes their loading dose of the respective treatment medication as a one-time dose and essentially attempts chemical cardioversion back to a more regular rhythm.

Class II

Beta-blockers decrease conduction velocity, slowing conduction through the AV node.

Class III

Potassium channel blockers decrease the rate of phase 3 of the cardiac action (potassium efflux out of the cell); phase 3 is the repolarization component of the action potential; by definition, all potassium channel blockers prolong the QTc interval 


  • Amiodarone is useful for atrial and ventricular arrhythmias; long half-life; side effects limit utility in the younger population. Side effects are wide-ranging and include corneal microdeposits of amiodarone, hypothyroidism, hyperthyroidism, pulmonary fibrosis, elevated liver function tests, nausea, and myopathy.
  • Dronedarone useful for atrial arrhythmias only; should not be used in a patient with severe heart failure or decompensated heart failure; should not be used in permanent atrial fibrillation (see Pallas trial).
  • Dofetilide used for atrial arrhythmias only; patients initiating dofetilide should be hospitalized for monitoring the QTc interval for 72 hours; must be aware of absolute drug interactions/contraindications (HCTZ, megestrol, trimethoprim, prochlorperazine, verapamil, cimetidine, ketoconazole, itraconazole); should keep magnesium greater than 2, potassium greater than 4; dose adjustments based on renal function; contraindicated for CrCl less than 20 ml per minute.
  • Sotalol effects of both class II and class III; non-cardioselective beta-blocker and potassium channel blocker; patients initiating sotalol should be hospitalized for monitoring the QTc interval for 72 hours;  should keep magnesium greater than 2, potassium greater than 4; dose adjust based on renal function; contraindicated for CrCl less than  40 ml per minute for atrial arrhythmias; very rarely used for ventricular arrhythmias; should not be used in a patient's with cardiogenic shock or decompensated heart failure; standard non-selective beta-blocker concerns apply (asthma, diabetes, CHF, etc.).
  • Ibutilide infused over 10 minutes for a maximum of 2 doses; patients require continuous monitoring for QTc prolongation or ventricular arrhythmia; used for atrial fibrillation or flutter only

Class IV

Non-dihydropyridine calcium channel blockers (diltiazem, verapamil)  decrease conduction velocity, slow conduction through the AV node.

Mechanism of Action

The cardiac action potential is the cycle of ion movement, which leads to successive depolarization and repolarization of the cardiac myocyte leading to muscle contraction. The resting phase of the cardiac myocyte has a resting membrane potential of negative 80 to negative 90 mV at baseline. The anti-arrhythmic medications essentially slow ion movement in various phases of the cardiac action potential and get broken down as follows.

Phase 0: "the depolarization" phase of the action potential; occurs by the rapid movement of sodium ions (Na+) into the cell along an electrochemical gradient, which leads to a membrane potential of approximately positive 30 mV.

Phase 1: "The notch"; initial repolarization phase of the action potential. Involves potassium (K+) ion movement

Phase 2: "The plateau" phase; this phase is a balance of inward calcium movement and outward K+ movement

Phase 3: "The repolarization" phase of the action potential; this phase is primarily caused by the movement of K+ ions along their electrochemical gradient out of the cell, essentially taking the positive charge of the K+ ion out of the cell. Restores the negative potential of the cardiac myocyte

Phase 4: Restoration of the Na/K ATPase, which restores the resting membrane potential of the cardiac myocyte.


Anti-arrhythmic medications have several areas of concern. First and foremost, most agents also have some degree of pro-arrhythmic potential. Practically speaking, while trying to suppress arrhythmias with the medications, the medications themselves, can lead to other (potentially more dangerous) arrhythmias. For example, the class Ia sodium channel blockers (quinidine, procainamide, and disopyramide) all effectively prolong the QTc interval and thus increase the risk of ventricular tachycardia (torsades de pointes). All K+ channel blockers share this potential side effect. The reason for this is quite simple if one compares the phases of the action potential to the ECG. The T wave on the ECG represents ventricular repolarization. Phase 3 of the action potential represents repolarization. If a K+ channel blocker is given, this prolongs phase 3 of the action potential in a charge over time manner. If the repolarization phase of the action potential is prolonged, the T-wave on the corresponding ECG also gets prolonged, which creates an elongated QTc interval.[4][5][6]

Adverse Effects

The clinical significance of the anti-arrhythmic medications lies in the type of arrhythmias that each drug or class can treat and what are the potential side effects of each overall classification or individual medication. The details of each are noted and discussed separately.


Nurses, pharmacists, and other healthcare workers who look after patients with heart disease should be very familiar with the different antiarrhythmic agents.

Each agent in the Vaughn Williams classification includes distinctive side effect profiles that require individual consideration. For example, procainamide may induce a lupus-like syndrome, while quinidine is known to produce cinchonism. The benefit of the classification is in the primary mechanism of action, and the broad, predictable side effects brought about by the primary mechanism. An example would include the class III K+ channel blockers or "repolarization" blockers producing a prolonged phase 3 of the action potential and by definition, also leading to a prolonged QT interval on the corresponding ECG. Amiodarone is an excellent antiarrhythmic agent, but long term use has correlations with corneal opacities, thyroid problems, and lung infiltrates. Only by being aware of the adverse effects can one reduce the morbidity associated with these agents.[7][8]

Enhancing Healthcare Team Outcomes

The cardiologist is generally responsible for starting the patient on an antiarrhythmic medication, but the patient requires monitoring by the primary care provider, nurse, and pharmacist. These medications are not benign, and all healthcare workers who look after patients on antiarrhythmic agents should be very familiar with the different antiarrhythmic agents and the arrhythmia treated. Cardiology specialty nurses are especially helpful in monitoring since they have the training to recognize adverse events and understand treatment goals, and can inform the specialist or other clinicians of any concerns. The pharmacist can also be a board-certified cardiology specialist and can assist in agent selection as well as ongoing monitoring, checking for drug interactions, and maintaining communication with the prescriber. All these are examples of interprofessional team dynamics that can drive positive outcomes for patients. [Level V]

Each agent in the Vaughn Williams classification includes distinctive side effect profiles that require individual monitoring. If there is ever a doubt about the medication, the clinician should seek a cardiology consult.


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