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EspañolAntiarrhythmics: Uses, common brands, and safety info
Fluttering sensations in the chest or a passing emptiness that feels like a skipped heartbeat are often harmless, but if they persist, they may be a sign of a medical condition called an arrhythmia. An arrhythmia can describe an irregular heartbeat that is abnormally fast or abnormally slow. This article will focus on medications that treat irregular or fast heart rhythms. It will list the different brand and generic names, outline how the drugs work, and cover their uses, safety considerations, and costs.
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List of antiarrhythmics
What are antiarrhythmics?
Antiarrhythmic drugs help restore and maintain a correct heart rhythm by changing the electrical conduction that is responsible for making the heart muscles contract. Antiarrhythmics are used to correct a heart rhythm that beats too quickly and irregularly (atropine is used in cases where the heart beats too slowly). Antiarrhythmics are usually taken orally as capsules, but they may also be injected intravenously in a health care setting.
How do antiarrhythmics work?
Electrical signals travel through the heart and determine how the heart contracts. The signal begins in a group of cells called pacemakers cells located at the sinoatrial (SA) node at the top of the heart. These cells send out electrical signals that travel down the heart. The signal triggers the atria (upper heart chambers) to contract. The signal then arrives at the AV node located beneath the atria, where it slows momentarily before traveling to the ventricles (lower chambers), causing them to contract.
How does the electrical signal cause heart muscle contraction? A voltage is created when there is a difference in electrical charge at different ends of a conductive material. In the case of a cell, a voltage exists across the cell membrane. The difference in charge across the cell membrane is due to the types of charged ions that exist inside and outside of the cell. Examples of these charged ions include potassium, calcium, and sodium ions. The voltage that exists across the cell membrane causes these ions to move in and out of the cell when “gates” in the cell membrane open. When enough calcium flows inside cardiac muscle cells, it induces the muscle cell to contract. Thus, as the electric signal travels from cell to cell, the voltage across cell membranes also changes, affecting the flow of calcium into cells and ultimately controlling the contraction of muscle cells.
The change in voltage across a cell membrane is called an action potential. An action potential in one cell can result in another action potential in an adjacent cell, allowing the electrical signal to travel. A single cell’s action potential is partly determined by the opening and closing of “channels” or “gates” that allow certain types of ions in and out of the cell. Different classes of antiarrhythmic drugs affect different ion channels, slowing down the electrical signal in different ways.
What are antiarrhythmics used for?
Paroxysmal atrial fibrillation
Persistent atrial fibrillation
Permanent atrial fibrillation
Brugada syndrome
Ventricular fibrillation
Ventricular tachycardia
Premature ventricular beats (PVCs)
Premature atrial contractions (PACs)
AV nodal reentrant tachycardia (AVNRT)
Atrial tachycardia
Paroxysmal supraventricular tachycardia (PSVT)
Wolff-Parkinson-White (WPW) treatment
Long QT syndrome
Sinus tachycardia
Torsade de Pointes
Types of antiarrhythmics
Class I antiarrhythmic drugs
Class I antiarrhythmic drugs block sodium channels located in the cell membrane. This slows down the conduction of the electrical signal from one cell to another. Some class I antiarrhythmic drugs can also affect the time a single cell must wait before a new action potential can be initiated following the previous action potential (effective refractory period). Both effects can prevent abnormal conduction such as reentry (an abnormality in which a second electrical signal is generated in the opposite direction). Class I antiarrhythmic drugs can be further divided into class Ia, Ib, and Ic agents depending on their specific effects on the action potential.
Examples of drugs in this class include:
Disopyramide
Flecainide
Lidocaine
Mexiletine
Phenytoin
Procainamide
Propafenone
Quinidine
Class II antiarrhythmic drugs
Class II antiarrhythmic drugs block the activity of beta-1 adrenergic receptors located in the heart. They are also called beta-blockers. The primary effect of beta-1 adrenergic function is to increase heart rate and contractility. Thus, preventing the activity of these receptors slows down the rate of heart contractions.
Examples of antiarrhythmics in this class include:
Atenolol
Esmolol
Propranolol
metoprolol
Class III antiarrhythmic drugs
Class III antiarrhythmic drugs block potassium channels located in the cell membrane. Unlike class I agents, these do not slow down the conduction of a single electrical signal. Rather, they increase the effective refractory period (ERP) which prolongs the time before another action potential can occur. During this time, the cell remains “unexcitable.” This prevents premature conduction and repetitive patterns of electrical signaling that can cause rapid heartbeats.
Amiodarone
Ibutilide
Sotalol
Dofetilide
dronedarone
Class IV antiarrhythmic drugs
Class IV antiarrhythmic drugs block the activity of calcium channels located in the heart. They are also called calcium channel blockers. By blocking the entry of calcium ions into cells, these drugs cause heart muscle relaxation, slower conduction of electric signals through the heart, and a decreased heart rate. Calcium channel blockers also lower the rate of electrical signs firing from the pacemaker cells.
Class IV antiarrhythmic drugs include two calcium channel blockers:
Diltiazem
verapamil
Miscellaneous antiarrhythmic drugs
Some antiarrhythmic drugs have unique properties which prevent easy classification. These drugs are referred to as Class V or miscellaneous antiarrhythmic drugs. Digoxin decreases the firing rate at the SA node, and both digoxin and adenosine decrease the conduction of electrical signs through the AV node, albeit by different mechanisms. Magnesium sulfate supports the function of the sodium-potassium pumps in cell membranes, which is vital for maintaining normal electrical conduction through the heart.
Who can take antiarrhythmics?
Can infants, children, and adolescents take antiarrhythmics?
While many rhythm disturbances in children are benign and do not require medical treatment, serious arrhythmias do occur in children of all ages. Sinus tachycardia is the most reported arrhythmia among children, followed by supraventricular tachycardia. Many antiarrhythmics are safe and effective for the treatment of hypertension in children. Drugs such as adenosine and amiodarone have been used in pediatric patients for many decades. Antiarrhythmics commonly used in children include adenosine, lidocaine, flecainide, propafenone, verapamil, digoxin, and amiodarone. Most antiarrhythmics are safe to use in children, but their use may be considered “off-label” by the FDA. However, some antiarrhythmic drugs are contraindicated in certain age groups. For example, verapamil should not be used in children younger than one year due to possible fatalities from low blood pressure.
Can adult men and women take antiarrhythmics?
Antiarrhythmics are generally considered safe and effective for use in men and women. The most common side effects are fatigue, dizziness, headache, shortness of breath, and heart palpitations. Some patients may experience less tolerable side effects. It is important to consult a healthcare provider about troublesome side effects so that treatment can be adjusted accordingly.
Can you take antiarrhythmics while pregnant or breastfeeding?
Most antiarrhythmic drugs are compatible with pregnancy and while breastfeeding. However, caution is advised while using many of these agents due to possible risks such as intrauterine growth restriction or neonatal adverse effects. Amiodarone and atenolol have the highest risk for fetal harm during pregnancy or infant harm while breastfeeding. Patients should have a conversation about risks versus benefits with a doctor. Using amiodarone while pregnant increases the risk of congenital goiter and thyroid abnormalities and neonatal adverse effects, incl. bradycardia and QT interval prolongation. Long-term use is contraindicated while breastfeeding.
Monitor infants closely with short-term use while breastfeeding. There exists a possible risk of teratogenicity (birth defects) when using atenolol during pregnancy, based on limited or conflicting human data. There is also an increased risk of intrauterine growth restriction and other neonatal adverse effects, including bradycardia and hypoglycemia. Consider an agent other than atenolol while breastfeeding due to the possible risk of bradycardia, cyanosis, and hypothermia. Other drugs that may warrant an alternative option during breastfeeding include verapamil, sotalol, bisoprolol, and nebivolol.
Can seniors take antiarrhythmics?
Extra caution is required when using antiarrhythmics in elderly patients due to age-related changes in drug absorption, metabolism, and elimination. For example, the bioavailability of propranolol and lidocaine can be significantly higher in older patients, which may require doses to be reduced. Amiodarone and digoxin may also require dose adjustments because they distribute throughout the body differently in older patients compared to young patients. This is due to changes in body fat, lean muscle, and water proportions in older patients. Elderly patients are more susceptible to common side effects of these drugs, such as bradycardia, orthostatic hypotension, urinary retention, and falls.
Patient with liver or kidney impairment
Many antiarrhythmic drugs are eliminated from the body through the liver. If liver function is impaired, drugs may accumulate and cause dangerous side effects. Other drugs in this class such as sotalol, disopyramide, and procainamide are primarily eliminated through the kidneys. Antiarrhythmic drugs require precise dosing and drug concentrations must be maintained within a narrow window. Therefore, patients with liver or kidney impairment often require special dose adjustments or may not be able to take certain antiarrhythmic drugs if organ function is severely compromised.
Are antiarrhythmics safe?
A black box warning, or “boxed warning,” is an FDA warning to alert consumers about serious or life-threatening side effects the drug may have. These are found on the package insert for prescription drugs, this is the most serious warning given by the FDA. It is important to be aware of the black box warnings that apply to some antiarrhythmics, listed below:
Disopyramide and mexiletine: Restrict use to life-threatening ventricular arrhythmias, no survival benefit in patients without life-threatening arrhythmias. Excessive mortality or nonfatal cardiac arrest rate has occurred in patients with asymptomatic, non-life-threatening ventricular arrhythmias with myocardial infarction six days to two years prior.
Propafenone and flecainide: Class IC antiarrhythmics should be avoided in patients with non-life-threatening ventricular arrhythmias. No survival benefit in patients without life-threatening arrhythmias. Excessive mortality or nonfatal cardiac arrest rate has occurred in patients with asymptomatic, non-life-threatening ventricular arrhythmias with myocardial infarction six days to two years prior.
Flecainide carries an additional black box warning about proarrhythmic effects, specifically ventricular proarrhythmic effects in atrial fibrillation/flutter. It is not recommended for chronic atrial fibrillation.
Phenytoin: Intravenous infusion rate should not exceed 50 mg/min in adults or 1-3 mg/kg/min (or 50 mg/min, whichever is slower) in pediatric patients due to increased risk of severe hypotension and cardiac arrhythmias above recommended infusion rate, but events have also been reported at or below this recommended rate.
Amiodarone: Restrict use to life-threatening arrhythmias due to drug-associated toxicity; start treatment in a clinical setting with available continuous ECG and cardiac resuscitation capabilities. Lung disease occurs in 10-17% of patients; abnormal diffusion capacity without symptoms is more common; fatal in 10% of patients. Providers should obtain a baseline chest x-ray and pulmonary function tests, including diffusion capacity, and must repeat history, physical exam, and chest x-ray every 3-6 months. Amiodarone can cause mild liver damage; overt liver failure has also occurred in some patients with few fatal cases. Providers must obtain baseline and periodic liver function tests (LFTS). Discontinue if there are signs or symptoms of liver injury. In 2-5% of patients taking amiodarone, arrhythmias worsened, significant heart block, or sinus bradycardia (slow heart rate) occurred. Effects were prolonged compared to other antiarrhythmics.
Metoprolol and atenolol: Following abrupt cessation of therapy with certain beta-blocking agents, an increased incidence of angina pectoris and, in some cases, myocardial infarction have occurred. When discontinuing chronically administered beta-blockers, particularly in patients with ischemic heart disease, the dosage should be gradually reduced over a period of 1-2 weeks and the patient should be carefully monitored.
Dofetilide: Patients starting or restarting treatment with dofetilide should be placed in a facility that provides creatinine clearance and continuous ECG monitoring and cardiac resuscitation for at least three days to minimize arrhythmia risk.
Procainamide: Restrict use to life-threatening ventricular arrhythmias, no survival benefit in patients w/o life-threatening arrhythmias. The prolonged administration of procainamide frequently leads to the development of a positive antinuclear antibody (ANA) test, with or without symptoms of lupus erythematosus-like syndrome. If a positive ANA titer develops, the benefits vs risks of continued procainamide therapy should be assessed. Blood dyscrasias which may be life-threatening have been reported. Use caution in patients with pre-existing marrow failure or cytopenia of any type.
Dronedarone: Do not use in patients with symptomatic heart failure and recent decompensation requiring hospitalization, NYHA Class IV heart failure, or permanent atrial fibrillation. The risk of death doubled in patients with decompensated heart failure or NYHA Class IV heart failure. The risk of death, stroke, and hospitalization for heart failure doubled in patients with permanent atrial fibrillation.
Ibutilide: Ibutilide can cause potentially fatal arrhythmias such as polymorphic VT (Torsade de pointes). These arrhythmias may or may not be associated with measurable QT prolongation. It is essential that ibutilide be administered in a setting with continuous ECG monitoring & personnel trained in identifying & treating acute polymorphic ventricular arrhythmias. Patients with atrial fibrillation of more than 2-3 days duration must be properly anticoagulated (for 2 weeks) before using ibutilide for sinus conversion.
Sotalol: To minimize the risk of induced arrhythmia, patients should be placed in a facility that can provide continuous ECG monitoring, calculations of creatinine clearance, and cardiac resuscitation for a minimum of three days when starting therapy with Sotalol.
Recalls
Restrictions
Do not take any of the antiarrhythmics listed below, if you have any of these symptoms or medical conditions:
A severe sinus-node dysfunction, second- or third-degree atrioventricular block, or episodes of bradycardia causing syncope (without a pacemaker).
Do not take quinidine if you have a heart rhythm dependent upon an ectopic pacemaker. Those who have conditions that make them adversely affected by anticholinergic agents (i.e., myasthenia gravis) should not take quinidine.
Do not take procainamide if you have a complete heart block, systemic lupus erythematosus, or history of torsade de pointes.
Do not take lidocaine if you have a hypersensitivity to amide local anesthetics.
Do not take propranolol if you have sinus bradycardia or greater than first-degree block, or bronchial asthma. Patients in cardiogenic shock should not receive propranolol.
Do not take atenolol or metoprolol if you have sinus bradycardia, asthma, second- or third-degree heart block, or overt cardiac failure. Patients in cardiogenic shock should not receive atenolol or metoprolol.
Do not take sotalol if you have sinus bradycardia, second- or third-degree heart block, long QT syndrome, heart failure, bronchial asthma, uncorrected hypokalemia, or uncorrected hypomagnesemia. Patients in cardiogenic shock should not receive sotalol.
Do not take verapamil if you have severe hypotension, second- or third-degree heart block, severe congestive heart failure, sick sinus syndrome (unless you have an artificial pacemaker), or severe left ventricular dysfunction. Patients in cardiogenic shock should not receive verapamil.
Do not take diltiazem if you have low blood pressure, second- or third-degree heart block, acute myocardial infarction, pulmonary congestion, or sick sinus syndrome (except in the presence of a functioning ventricular pacemaker). Do not take diltiazem if you are breastfeeding.
Do not take adenosine if you have sinus node diseases such as sick sinus syndrome or symptomatic bradycardia, or if you have second- or third-degree heart block (except in patients with a functioning artificial pacemaker).
Are antiarrhythmics controlled substances?
No, antiarrhythmics are not controlled substances.
Common antiarrhythmics side effects
Fatigue
Nausea
Shortness of breath
Heart palpitations
Chest pain
Syncope (fainting)
Visual disturbances
Dizziness
Headache
Changes in thyroid levels
Individual antiarrhythmic drugs may have additional side effects not included in the above list.
How much do antiarrhythmics cost?
Antiarrhythmic drugs are a relatively inexpensive class of medications because generic versions exist for each drug in this class. Most generics cost less than $100 for a 30 day supply and can be even less expensive with a SingleCare discount card. For example, the retail price of brand name Betapace is over $1000. However, the generic version costs less than $50, and can be as low as $10, with a sotalol SingleCare coupon.