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Practice EssentialsAntidysrhythmic medications are widely used to treat or prevent abnormalities in cardiac rhythms. They accomplish this through a number of mechanisms involving automaticity or ion channel dynamics, which in turn affect the propagation of the myocardial electrical impulse via change in conduction velocity or refractory period. Antidysrhythmics alter the propagation and mechanisms of cardiac rhythms, making toxicity from these agents highly lethal. In fact, antidysrythmics can be prodysrhythmic at both therapeutic and toxic serum concentrations. Additionally, the patients receiving these drugs may have a lower dysrhythmic threshold resulting from underlying cardiac conditions as well as other comorbidities, making them more suscpetible to toxicity. A thorough knowledge of this class of drugs is necessary for differentiating drug toxicity from primary disease. See also Beta-Blocker Toxicity and Calcium Channel Blocker Toxicity, as those topics are not covered in this article. Signs and symptomsToxicity from antidysrhythmic agents can be grouped in terms of clinical presentation and electrocardiographic (ECG) abnormalities, as follows:
ECG changes are as follows:
See Clinical Presentation for more detail. DiagnosisThe first and most important diagnostic tool in acute antidysrhythmic toxicity is electrocardiography. ECG changes such as QRS widening, QTc prolongation, and atrioventricular block should be ruled out. Serum electrolytes concentrations should be obtained, especially in patients taking antidysrhythmics that prolong the correct QT (QTc) interval. Serum drug concentrations are not likely to be helpful to the emergency physician treating a patient with acute antidysrhythmic drug toxicity, but concentrations of quinidine, lidocaine, and propafenone can be measured in the acute care setting. Chest radiographs and brain natriuretic peptide levels should be obtained in patients presenting with heart failure symptoms; Chest radiographs should also be obtained in patients taking amiodarone or dronedarone and presenting with pulmonary symptoms. Thyroid function tests should be obtained in patients taking amiodarone or dronedarone who present with signs and symptoms of hypothyroidism or hyperthyroidism. See Workup for more detail. ManagementAirway, breathing, and circulatory support; intravenous access; and ECG monitoring are of paramount importance. Treatment measures and the drugs for which they are appropriate are as follows:
See Treatment and Medication for more detail. BackgroundDespite the advent of interventional techniques such as catheter ablation and the implantable cardioverter-defibrillator in the treatment of supraventricular and ventricular tachycardia, antidysrhythmic drugs continue to play a significant role in treating and suppressing life-threatening dysrhythmias. The prodysrhythmic effects of many of these drugs also continue to present a major clinical problem, especially in the growing population of patients with underlying heart failure. When encountering a patient with dysrhythmias on antidysythmic drugs, the physician must maintain a broad differential diagnosis that includes not only drug toxicity but underlying ischemia, structural cardiac abnormalities, and conduction disturbances. Thus, understanding the adverse effects and electrocardiographic profiles of antidysrhythmic agents is critical for diagnosis and treatment of possibly life-threatening drug toxicity. This article discusses the major antidysrhythmic drugs within classes I, III and V, with specific attention to their adverse effects and clinical presentations in the setting of acute toxicity. Toxicity from class II and IV dysrhythmics is discussed elsewhere (see Beta-Blocker Toxicity and Calcium Channel Blocker Toxicity) For additional information, see Medscape's Cardiology Resource Center. For patient education resources, see the First Aid and Injuries Center, as well as Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home. PathophysiologyMost antidysrythmics may be categorized via the Vaughan-Williams classification system, based on their mechanism of activity (see the image below). Medications used to treat arrhythmias that have variable mechanisms have been included in class V; these include magnesium, digoxin, and adenosine. The Vaughn-Williams classes are as follows:
 Class I agents bind sodium channels reducing depolarization rate, which serves to slow and reduce the rate of rise of the action potential (phase 0). They also help to inhibit depolarization of neuronal cells, which provides local anesthesia. Class I agents also inhibit depolarization in atrial, ventricular, and Purkinje myocytes, thereby decreasing conduction velocity and automaticity. Class I agents are further categorized into A, B, or C subclasses, based on the degree of sodium channel blockade and effects on repolarization, as follows:
Class II agents indirectly blockade calcium channel opening by attenuating adrenergic activation. These agents block the proarrhythmic effects of catecholamines. Class III agents prolong refractoriness and delay repolarization by blocking potassium channels (phase 2, phase 3) leading to prolonged QTc intervals on the ECG. They have little direct effect on sodium channels. Class IV agents slow sinoatrial node pacemaker cell and atrioventricular conduction by direct blockade of L-type voltage-gated calcium channels. EtiologyClass IA antidysrhythmicsDisopyramide In addition to sodium and potassium channel blockade, disopyramide is a muscarinic antagonist. See the following:
Procainamide Procainamide blocks sodium and potassium channels, and its active metabolite prolongs the action potential duration of ventricular myocytes and Purkinje fibers. It is available in oral, intramuscular (IM), and intravenous (IV) forms. See the following:
Procainamide should be avoided in patients with myasthenia gravis. Quinidine In addition to blocking sodium and potassium channels, quinidine blocks alpha-adrenergic receptors and muscarinic receptors. Quinidine has the same antimalarial and antipyretic properties as quinine; in addition to its cardiologic indications, it is used for treatment of malaria, and as an illicit abortifacient. See the following:
Risk factors for quinidine toxicity are hepatic disease, renal insufficiency, and heart failure. Quinidine can cause sinus node depression in patients with sick sinus syndrome. Class IB antidysrhythmicsLidocaine Lidocaine is a derivative of cocaine that blocks fast sodium channels, leading to a modest reduction in the rate of phase 0 depolarization. See the following:
The therapeutic index of lidocaine is narrow. Toxicity may occur while a clinician is trying to achieve adequate local or regional anesthesia for repairing large lacerations or from pediatric ingestion of viscous lidocaine. Patients at greatest risk for iatrogenic toxicity are those with poor cardiac output or hepatic disease. Toxicity is potentiated in acidemic states (eg, hypercapnia during rapid sequence intubation, lactic acidosis following seizure). [5] Mexiletine Mexiletine is clinically equivalent to lidocaine in its mechanism of slowing the rate of phase 0 depolarization by blocking fast sodium channels, and it shortens the action potential duration of Purkinje fibers. It blocks the late sodium current, which may be useful for preventing delayed ventricular repolarization and torsade de pointes in long QT syndrome. [6]
Class IC antidysrhythmicsFlecainide Flecainide has a strong blocking effect on the rapid sodium channel, decreasing the rate of depolarization. Flecainide also slows conduction in all cardiac fibers, making it contraindicated in patients with second degree atrioventricular block and intraventricular conduction delay. In high concentrations, flecainide may block slow calcium channels and have negative inotropic effects. See the following:
Patients at risk for flecainide toxicity include those with renal insufficiency, decreased hepatic flow from compromised cardiac output, hyponatremia, and those taking medications that undergo CYP2D6 metabolism. Propafenone In addition to blocking fast sodium channels, propafenone is a weak beta-adrenergic antagonist and calcium channel blocker. See the following:
Patients at risk for propafenone toxicity include those with a polymorphism of CYP2D6 that slows metabolism, patients with hepatic dysfunction, and those taking drugs that interfere with CYP2D6 metabolism. Similarly to flecanaide, patients with structural heart disease and/or those being treated for ventricular rather than supraventricular arrhythmias are at higher risk for concerning severe cardiovascular complications such as arrtyhmia and cardiac arrest. Class III antidysrhythmics Amiodarone Amiodarone blocks fast sodium channels, beta-receptors, L-type calcium channels, and delayed rectifier potassium channels. It prolongs the effective refractory periods of all cardiac tissue. Additionally, amiodarone inhibits the conversion of thyroxine to triiodothyronine. See the following:
Amiodarone is well known to cause thyroid, liver, and pulmonary toxicity. It also has adverse CNS and skin side effects. Dronedarone Dronedarone is a noniodinated derivative of amiodarone, and like amiodarone it inhibits sodium channels, potassium channels, L-type calcium channels, and beta-receptors. Dronedarone also inhibits alpha1 receptors. Dronedarone is thought to cause less lung, liver, and thyroid toxicity than amiodarone. Use of this drug is contraindicated in any patient with an ejection fraction of less than 35% or class IV heart failure. See the following:
Hepatic dysfunction increases the risk of dronedarone toxicity. Higher mortality has been shown when dronedarone is given to patients with New York Heart Association class III or IV heart failure. Cases of interstial pneumonitis or bronchiolitis obliterans with organizing pneumonia (BOOP) have been reported in dronedarone users. [10] Despite a small increase in serum creatinine levels due to inhibition of tubular secretion, dronedarone does not impact the glomerular filtration rate and overall renal function, although it may affect the renal clearance of other medications and should be monitored in patients with preexisting renal dysfunction or on nephrotoxic medications. Furthermore renal failure may occur in setting of worsening heart failure due to dronedarone. [11] Sotalol Sotalol is a nonselective beta-adrenergic antagonist that prolongs the action potential and effective refractory period by blocking potassium channels. See the following:
Patients at risk for toxicity are those with renal dysfunction, with concomitant use of QTc-prolonging drugs, and women. [14] Ibutilide Ibutilide blocks the delayed rectifier potassium channel, prolonging repolarization. It also activates the slow inward sodium current. Ibutilide increases the refractory period of the accessory pathway, the His-Purkinje system, and the AV node. See the following:
The primary concern of ibutilide toxicity is its QT prolongation and increased risk for torsade de pointes. [15] Dofetilide Dofetilide prolongs the refractory period by blocking the delayed rectifier current. This drug effect is stronger in atrial than in ventricular tissue. See the following:
Patients at risk for toxicity are those with renal impairment, congenital long QT syndrome, electrolyte derangements (ie, hypocalcemia, hypomagnesemia, hypokalemia), and concurrent therapy with other QTc-prolonging drugs and drugs that inhibit the renal cation transport system. [16] Class V antidysrhythmicsAdenosine Adenosine is an extracellular signaling molecule that induces a short-duration heart block when used intravenously. Adenosine increases potassium conductance and shortens the atrial action potential duration and hyperpolarizes the myocyte membrane potential. Adenosine slows conduction in the AV node. See the following:
Adenosine is contraindicated in patients with sick sinus syndrome, second- and third-degree AV block, and atrial fibrillation down an accessory pathway (Wolff-Parkinson-White syndrome). EpidemiologyIn 2020, 1185 single exposures to antiarrhythmic drugs were reported to US poison control centers. Most exposures involved adults. There were 31 exposures resulting in major toxicity and 5 deaths. [17] Antidysrhythmic toxicity generally affects both sexes equally. However, with sotalol some studies have found that females are at higher risk for dysrhythmia (especially for torsade de pointes). [14] Prodysrhythmic effects occur more frequently in patients with underlying heart failure. Older patients, in general, have a higher risk for the development of dysrhythmias than younger patients. Drug-to-drug interactions are increasing, especially in elderly patients taking multiple antiarrhythmic drugs simultaneously.
Author Coauthor(s) Chief Editor Michael A Miller, MD Clinical Professor of Emergency Medicine, Medical Toxicologist, Department of Emergency Medicine, Texas A&M Health Sciences Center; CHRISTUS Spohn Emergency Medicine Residency Program Michael A Miller, MD is a member of the following medical societies: American College of Medical Toxicology Disclosure: Nothing to disclose. Additional Contributors Jennifer L Martindale, MD Clinical Assistant Professor, Department of Emergency Medicine, Kings County Hospital, State University of New York Downstate Medical Center Disclosure: Nothing to disclose. Denise Ammon, MD, MA Resident Physician, Department of Emergency Medicine, Kings County Hospital, State University of New York Downstate Medical Center Denise Ammon, MD, MA is a member of the following medical societies: American College of Emergency Physicians, American Medical Association, American Medical Student Association/Foundation, American Society of Anesthesiologists, Emergency Medicine Residents' Association Disclosure: Nothing to disclose. Acknowledgements Michael J Burns, MD Instructor, Department of Emergency Medicine, Harvard University Medical School, Beth Israel Deaconess Medical Center Michael J Burns, MD is a member of the following medical societies: American Academy of Clinical Toxicology, American College of Emergency Physicians, American College of Medical Toxicology, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT Associate Clinical Professor, Department of Surgery/Emergency Medicine and Toxicology, University of Texas School of Medicine at San Antonio; Medical and Managing Director, South Texas Poison Center Miguel C Fernandez, MD, FAAEM, FACEP, FACMT, FACCT is a member of the following medical societies: American Academy of Emergency Medicine, American College of Clinical Toxicologists, American College of Emergency Physicians, American College of Medical Toxicology, American College of Occupational and Environmental Medicine, Society for Academic Emergency Medicine, and Texas Medical Association Disclosure: Nothing to disclose. Joshua B Gaither, MD Fellow in Emergency Medicine Services, Prehospital and Disaster Care, Denver Health-University of Colorado Joshua B Gaither, MD is a member of the following medical societies: American College of Emergency Physicians, Society for Academic Emergency Medicine, and Wilderness Medical Society Disclosure: Nothing to disclose. Eileen C Quintana, MD Assistant Professor, Departments of Pediatrics and Emergency Medicine, St Christopher's Hospital for Children; Adjunct Clinical Professor, Departments of Pediatrics and Emergency Medicine, Temple University Hospital Eileen C Quintana, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Richard H Sinert, DO Professor of Emergency Medicine, Clinical Assistant Professor of Medicine, Research Director, State University of New York College of Medicine; Consulting Staff, Department of Emergency Medicine, Kings County Hospital Center Richard H Sinert, DO is a member of the following medical societies: American College of Physicians and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. Carin M Van Gelder, MD Assistant Professor, Department of Emergency Medicine, Yale University School of Medicine; EMS Medical Director, NHSHP and EMS Physician, SHARP Team; Attending Physician, Emergency Medicine, Yale-New Haven Medical Center Carin M Van Gelder, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, Massachusetts Medical Society, National Association of EMS Physicians, and Society for Academic Emergency Medicine Disclosure: Nothing to disclose. John T VanDeVoort, PharmD Regional Director of Pharmacy, Sacred Heart and St Joseph's Hospitals John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists Disclosure: Nothing to disclose. Which outcome may be the result of a drug drug interaction when quinidine and digoxin are administered concurrently?Clinical evidence indicates that there are increased electrophysiologic and inotropic effects as- sociated with the elevation of serum digoxin as a result of concurrent quinidine administration. This combination of drugs can cause signs and symptoms of digitalis toxicity.
Which is most important assessment to complete before the nurse administers an Antidysrhythmic medication?CHECK THE PATIENT'S BLOOD PRESSURE PRIOR TO ADMINISTERING AN ANTIDYSRHYTHMIC MEDICATION OR HEMODYNAMIC MEDICATION (like vasodilators). If systolic blood pressure is < 100 mm Hg or 30 mm Hg below baseline, then hold medication.
Which Antidysrhythmic drug is indicated for pulseless ventricular tachycardia?The vasopressor that is used for the treatment of VF/Pulseless VT is epinephrine. Epinephrine is primarily used for its vasoconstrictive effects.
Which electrocardiogram ECG change will the nurse monitor for when a patient is being treated with quinidine?EKG monitoring for prolongation of QT interval and QRS changes along with CBC, liver, and renal function testing should be done on a routine basis when giving quinidine as an IV infusion or for a prolonged period.
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The health care provider discontinues a patients quinidine and prescribes procainamide
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