Anti-Arrhythmic Drugs: Class I
Sections
Anti-Arrhythmic Drugs Overview
- Arrhythmias are characterized by abnormal generation and/or conduction of electrical impulses, which produce abnormal rate and/or activation sequences in the cardiac tissue. Ultimately, this can reduce cardiac output.
Supraventricular Arrhythmias
Ventricular Arrhythmias
AV Node block - Class 1 drugs are sodium channel blockers; we'll focus on this group in this tutorial.
- Class 2 drugs comprise the beta blockers.
- Class 3 drugs include the potassium channel blockers.
- Class 4 drugs comprise the calcium channel blockers.
- Magnesium and adenosine are also used to treat arrhythmias.
- Paradoxically, anti-arrhythmic drugs can actually precipitate fatal arrhythmias; thus, the potential harm of these drugs may outweigh their potential benefits in some patients.
Action Potenial Review
Review
We draw a simplified diagram to show the phases of a normal action potential in the ventricles. To track the flow of key ions into and out of the cell, indicate the extracellular fluid and intracellular fluid of a ventricular myocyte; write Phases 0-4 along the top.
Phase 0 = Fast sodium channels open and ions quickly move into the cell, which causes rapid depolarization.
– Class 1 antiarrhythmics affect the slope of this line.
Phase 1 = Potassium channels open, which allows potassium ions to move out of the cell and cause early repolarization.
Phase 2 = The plateau phase; potassium continues to move out of the cell, and calcium move into it.
Phase 3 = As more potassium channels begin to open, and calcium channels close, Phase 3 is characterized by rapid repolarization.
Phase 4 = Resting phase, during which "leaky" potassium channels maintain resting membrane potential.
Effective refractory period is the time when new action potentials cannot be triggered.
Effects of Class 1 anti-arrhythmics on this curve
These drugs are fast-sodium channel blockers; they also have local anesthetic properties.
They slow the rate of Phase 0 depolarization and conduction velocity.
Class 1 drugs are further classified by their effects on the duration of action potentials.
Class 1a drugs prolong the duration of the action potential
Class 1b drugs shorten its duration
Class 1c drugs have minimal effect
Class 1 Details
Class 1a
Used to treat atrial and ventricular arrhythmias.
They are moderate sodium channel blockers, and also block some potassium channels.
They prolong the action potential duration, effective refractory period, QRS complex, and QT interval.
Examples and their most common side effects:
Procainamide is associated with hypotension; long term use is typically avoided because the drug can cause lupus-like syndrome, characterized by arthralgia and purpura.
It is generally considered the third best choice in myocardial infarction arrhythmias (behind amiodarone and lidocaine).
Quinidine is associated with gastrointestinal side effects, cinchonism (headache, dizziness, and tinnitus), and thrombocytopenia.
Disopyramide are due to its anticholinergic effects (for example, constipation, urine retention, dry mouth, blurred vision). Can worsen glaucoma, and is not suitable for patients with heart failure.
All Class 1a drugs can precipitate torsades de pointes.
Class 1b
Used to treat ventricular arrhythmias.
They are weak sodium channel blockers, and are selective for ischemic tissue and depolarized Purkinje fibers and ventricular myocytes.
These drugs shorten the action potential duration and effective refractory period, but have no effect on the QRS complex or QT interval.
Lidocaine is the prototypical class 1b drug; it is second in line to treat arrhythmias associated with myocardial infarction (behind amiodarone).
Lidocaine has low toxicity, but, in vulnerable patients or when given in high doses or administered too rapidly, it is associated with neurological, and, more rarely, cardiovascular side effects.
Neurological effects include paresthesia (tingling, "pins and needles," usually in the hands and feet), dizziness, and confusion.
Cardiovascular effects include sinus bradycardia, arrhythmias, and shock.
Phenytoin is often considered an honorary member of class 1b anti-arrhythmias; it is used to treat arrhythmias caused by digitalis.
Class 1c
We'll list characteristics for the prototypical drug, Flecainide; as we'll see, however, not all class 1c drugs have the same effects.
Used to treat supraventricular arrhythmias.
Strong sodium-channel blockers that also block some potassium channels.
Flecainide has no effect on the duration of action potentials or the effective refractory period; it prolongs the QRS complex with little effect on the QT interval.
Common side effects are dizziness, headaches, and visual disturbances, which may include blurred vision or difficulty focusing, or the appearance of flashing lights or spots.
Propafenone has similar side effects; it can exacerbate heart failure (propafenone also blocks beta channels and has negative inotropic effects).
Unlike flecainide, it is associated with prolonged QT intervals and effective refractory periods.
Moricizine is another class 1c anti-arrhythmic, but it is no longer used in the United States.
Class 1c drugs are pro-arrhythmic; they are not suitable for patients with structural heart disease.
References
- "2018 Focused Update on ACLS Use of Antiarrhythmic Drugs." American College of Cardiology. Accessed August 21, 2019. http%3a%2f%2fwww.acc.org%2flatest-in-cardiology%2ften-points-to-remember%2f2018%2f11%2f20%2f11%2f37%2f2018-american-heart-association-focused-update-on-acls.
- Andrikopoulos, George K, Sokratis Pastromas, and Stylianos Tzeis. "Flecainide: Current Status and Perspectives in Arrhythmia Management." World Journal of Cardiology 7, no. 2 (February 26, 2015): 76–85. https://doi.org/10.4330/wjc.v7.i2.76.
- Burashnikov, Alexander, and Charles Antzelevitcht. "Atrial-Selective Sodium Channel Block for the Treatment of Atrial Fibrillation." Expert Opinion on Emerging Drugs 14, no. 2 (June 2009): 233–49. https://doi.org/10.1517/14728210902997939.
- Bursell, Benjamin, Richard M. Ratzan, and Alan J. Smally. "Lidocaine Toxicity Misinterpreted as a Stroke." Western Journal of Emergency Medicine 10, no. 4 (November 2009): 292–94.
- "Disopyramide - FDA Prescribing Information, Side Effects and Uses." Drugs.com. Accessed August 22, 2019. https://www.drugs.com/pro/disopyramide.html.
- "Electrocardiography: Flecainide Toxicity." Accessed August 21, 2019. https://www.mdedge.com/clinicianreviews/article/167286/toxicology/electrocardiography-flecainide-toxicity.
- Greene, H.Leon, Dan M. Roden, Richard J. Katz, Raymond L. Woosley, David M. Salerno, and Richard W. Henthorn. "The Cardiac Arrhythmia Suppression Trial: First CAST … Then CAST-II." Journal of the American College of Cardiology 19, no. 5 (April 1992): 894–98. https://doi.org/10.1016/0735-1097(92)90267-Q.
- Hasan, Badar, Talal Asif, and Maryam Hasan. "Lidocaine-Induced Systemic Toxicity: A Case Report and Review of Literature." Cureus 9, no. 5. Accessed August 21, 2019. https://doi.org/10.7759/cureus.1275.
- Ikaheimo, Kirsi, Raimo Kettunen, and Maija Mantyjarvi. "Adverse Ocular Effects of Flecainide." Acta Ophthalmologica Scandinavica 79, no. 2 (April 2001): 175–76. https://doi.org/10.1034/j.1600-0420.2001.079002175.x.
- Jain, Dinesh K., Raj K. Arya, and Ashok K. Jain. "A Mathematical Model to Understand the Mechanisms of Action of Class 1 Antiarrhythmic Drugs." Indian Journal of Pharmacology 42, no. 3 (June 2010): 195–96. https://doi.org/10.4103/0253-7613.66848.
- Katzung, Bertram G. Basic & Clinical Pharmacology, 2018. http://www.vlebooks.com/vleweb/product/openreader?id=none&isbn=9781259641169.
- Katzung, Bertram G. Katzung & Trevor's Pharmacology Examination & Board Review. Twelfth edition. A Lange Medical Book. New York: McGraw Hill Education, 2019.
- Lei Ming, Wu Lin, Terrar Derek A., and Huang Christopher L.-H. "Modernized Classification of Cardiac Antiarrhythmic Drugs." Circulation 138, no. 17 (October 23, 2018): 1879–96. https://doi.org/10.1161/CIRCULATIONAHA.118.035455.
- Mccann, G. "Pharmacological Treatment of Significant Cardiac Arrhythmias." British Journal of Sports Medicine 34, no. 5 (October 1, 2000): 401–2. https://doi.org/10.1136/bjsm.34.5.401.
- "Medications for Arrhythmia." www.heart.org. Accessed August 21, 2019. https://www.heart.org/en/health-topics/arrhythmia/prevention--treatment-of-arrhythmia/medications-for-arrhythmia.
- Panchal, Ashish R., Katherine M. Berg, Peter J. Kudenchuk, Marina Del Rios, Karen G. Hirsch, Mark S. Link, Michael C. Kurz, et al. "2018 American Heart Association Focused Update on Advanced Cardiovascular Life Support Use of Antiarrhythmic Drugs During and Immediately After Cardiac Arrest: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care." Circulation 138, no. 23 (December 4, 2018). https://doi.org/10.1161/CIR.0000000000000613.
- "Rythmol (Propafenone): Side Effects, Interactions, Warning, Dosage & Uses." RxList. Accessed August 21, 2019. https://www.rxlist.com/rythmol-drug.htm.
- "Rythmol SR (Propafenone Hydrochloride) Dose, Indications, Adverse Effects, Interactions... from PDR.Net." Accessed August 21, 2019. https://www.pdr.net/drug-summary/Rythmol-SR-propafenone-hydrochloride-224.178.
- Singh, Bramah N. "Mechanism of Action of Antiarrhythmic Agents: Focus on Propafenone." Journal of Electrophysiology 1, no. 6 (December 1987): 503–16. https://doi.org/10.1111/j.1540-8167.1987.tb01442.x.
- Solhjoo, Mahdis, Chin H. Ho, Krati Chauhan, and William Gossman. "Drug-Induced Lupus Erythematosus." In StatPearls. Treasure Island (FL): StatPearls Publishing, 2019. http://www.ncbi.nlm.nih.gov/books/NBK441889/.
- Velasco, Sara Llamas, Fernando Sierra-Hidalgo, Rosa María Ceballos Rodríguez, Antonio José Méndez Guerreo, and Juan Ruiz Morales. "Flecainide-Induced Myoclonus." Clinical Neuropharmacology 37, no. 2 (April 2014): 65–66. https://doi.org/10.1097/WNF.0000000000000025.