Antiarrhythmic Medications


Article Author:
Gregory King


Article Editor:
Jennifer McGuigan


Editors In Chief:
Casey Ciresi


Managing Editors:
Avais Raja
Orawan Chaigasame
Carrie Smith
Abdul Waheed
Khalid Alsayouri
Trevor Nezwek
Radia Jamil
Patrick Le
Anoosh Zafar Gondal
Saad Nazir
William Gossman
Hassam Zulfiqar
Hussain Sajjad
Steve Bhimji
Muhammad Hashmi
John Shell
Matthew Varacallo
Heba Mahdy
Ahmad Malik
Sarosh Vaqar
Mark Pellegrini
James Hughes
Beata Beatty
Beenish Sohail
Nazia Sadiq
Hajira Basit
Phillip Hynes


Updated:
3/8/2019 8:12:30 AM

Indications

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 4 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 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; slow conduction through the AV node.

Class III

Potassium channel blockers decrease 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 

Agents

  • Amiodarone 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's 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 adjust 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; patient must be continuously monitored 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 are 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.

Administration

The 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 is also 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.

Monitoring

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 which must be viewed individually. 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 producing a prolonged QT interval on the corresponding ECG. Amiodarone is an excellent antiarrhythmic agent but long term use has been associated 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 patient on an antiarrhythmic medication but the patient may be followed by the primary care provider, nurse practitioner or pharmacist. These medications are not benign and all healthcare workers who look after patients on antiarrhytmic agents should be very familiar with the different antiarrhythmic agents and the arrhythmia being treated.

Each agent in the Vaughn Williams classification includes distinctive side effect profiles which must be viewed individually. If there is ever a doubt about the medication, a cardiology consult should be sought.


Interested in Participating?

We are looking for contributors to author, edit, and peer review our vast library of review articles and multiple choice questions. In as little as 2-3 hours you can make a significant contribution to your specialty. In return for a small amount of your time, you will receive free access to all content and you will be published as an author or editor in eBooks, apps, online CME/CE activities, and an online Learning Management System for students, teachers, and program directors that allows access to review materials in over 500 specialties.

Improve Content - Become an Author or Editor

This is an academic project designed to provide inexpensive peer-reviewed Apps, eBooks, and very soon an online CME/CE system to help students identify weaknesses and improve knowledge. We would like you to consider being an author or editor. Please click here to learn more. Thank you for you for your interest, the StatPearls Publishing Editorial Team.

Antiarrhythmic Medications - Questions

Take a quiz of the questions on this article.

Take Quiz
Which of the following is false about anti-arrhythmic drugs?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which type of channels do class 1 antiarrhythmic drugs effect?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which statement about lidocaine is false?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following statements is false regarding class one antiarrhythmic agents?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What beta-blocker is also classified as a class III antiarrhythmic agent?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
What is the major mechanism of action of class III antiarrhythmic agents?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is used to manage the toxicity of class 1 antiarrhythmic agents?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a class 1C anti-arrhythmic agent?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Disopyramide belongs to what class of drugs?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
During admission assessment, a patient reports taking quinidine 4 times a day orally. Which of the following is true of this medication?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Flecainide is what class of anti-arrhythmic drug?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a potentially serious adverse effect of class I-C antiarrhythmic medications?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following classes of antiarrhythmic drugs works primarily by sodium channel blockade?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of following medications is a class II antiarrhythmic drug?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
The Vaughan Williams system classifies which group of drugs?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
After whom is the classification for cardiac antiarrhythmic drugs named?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following is a contraindication for class 1A, 1B, 1C antiarrhythmic drugs?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
Which of the following would be quinidine's most likely effect on phase 3 of the cardiac action potential?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up
A longer duration of phase 3 of the ventricular cardiac action potential would have which most likely effect on a 12-lead EKG and increase the likelihood of which clinical outcome?



Click Your Answer Below


Would you like to access teaching points and more information on this topic?

Improve Content - Become an Author or Editor and get free access to the entire database, free eBooks, as well as free CME/CE as it becomes available. If interested, please click on "Sign Up" to register.

Purchase- Want immediate access to questions, answers, and teaching points? They can be purchased above at Apps and eBooks.


Sign Up

Antiarrhythmic Medications - References

References

Shanmugasundaram M,Lotun K, Refractory Out of Hospital Cardiac Arrest. Current cardiology reviews. 2018     [PubMed]
Noss K,Aguero SM,Reinaker T, Assessment of Prescribing and Monitoring Habits for Patients Taking an Antiarrhythmic and Concomitant QTc-Prolonging Antibiotic. Pharmacy (Basel, Switzerland). 2017 Nov 1     [PubMed]
Lai E,Chung EH, Management of Arrhythmias in Athletes: Atrial Fibrillation, Premature Ventricular Contractions, and Ventricular Tachycardia. Current treatment options in cardiovascular medicine. 2017 Oct 9     [PubMed]
Amjad W,Qureshi W,Farooq A,Sohail U,Khatoon S,Pervaiz S,Narra P,Hasan SM,Ali F,Ullah A,Guttmann S, Gastrointestinal Side Effects of Antiarrhythmic Medications: A Review of Current Literature. Cureus. 2017 Sep 3     [PubMed]
Irizarry-Alvarado JM, Perioperative Management of Beta Blockers and Other Antiarrhythmic Medications. Current clinical pharmacology. 2017     [PubMed]
Long VP III,Carnes CA,Vecchiet J,Houmsse M,Hirsch A,Snider MJ, Evaluation of a pharmacist-managed electrolyte protocol in outpatients on antiarrhythmic medications. Journal of the American Pharmacists Association : JAPhA. 2017 Jul - Aug     [PubMed]
MacIntyre CJ,Sapp JL, Treatment of persistent ventricular tachycardia: Drugs or ablation? Trends in cardiovascular medicine. 2017 Oct     [PubMed]
Beaty RS,Moffett BS,Hall S,Kim J, Evaluating the Safety of Intraoperative Antiarrhythmics in Pediatric Cardiac Surgery Patients. Pediatric cardiology. 2015 Oct     [PubMed]

Disclaimer

The intent of StatPearls is to provide practice questions and explanations to assist you in identifying and resolving knowledge deficits. These questions and explanations are not intended to be a source of the knowledge base of all of medicine, nor is it intended to be a board or certification review of Nurse-Corrections (CCN). The authors or editors do not warrant the information is complete or accurate. The reader is encouraged to verify each answer and explanation in several references. All drug indications and dosages should be verified before administration.

StatPearls offers the most comprehensive database of free multiple-choice questions with explanations and short review chapters ever developed. This system helps physicians, medical students, dentists, nurses, pharmacists, and allied health professionals identify education deficits and learn new concepts. StatPearls is not a board or certification review system for Nurse-Corrections (CCN), it is a learning system that you can use to help improve your knowledge base of medicine for life-long learning. StatPearls will help you identify your weaknesses so that when you are ready to study for a board or certification exam in Nurse-Corrections (CCN), you will already be prepared.

Our content is updated continuously through a multi-step peer review process that will help you be prepared and review for a thorough knowledge of Nurse-Corrections (CCN). When it is time for the Nurse-Corrections (CCN) board and certification exam, you will already be ready. Besides online study quizzes, we also publish our peer-reviewed content in eBooks and mobile Apps. We also offer inexpensive CME/CE, so our content can be used to attain education credits while you study Nurse-Corrections (CCN).