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.
Sodium Channel Blockers prolong phase 0 (rapid sodium influx into the cell) of the cardiac action potential; effects on QTc are variable by subclass.
Beta-blockers decrease conduction velocity; slow conduction through the AV node.
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
Non-dihydropyridine calcium channel blockers (diltiazem, verapamil) decrease conduction velocity; slow conduction through the AV node.
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.
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.
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 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.
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.
|||Shanmugasundaram M,Lotun K, Refractory Out of Hospital Cardiac Arrest. Current cardiology reviews. 2018 [PubMed PMID: 29737259]|
|||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 PMID: 29104235]|
|||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 PMID: 28990149]|
|||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 PMID: 29142794]|
|||Irizarry-Alvarado JM, Perioperative Management of Beta Blockers and Other Antiarrhythmic Medications. Current clinical pharmacology. 2017 [PubMed PMID: 28847276]|
|||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 PMID: 28610942]|
|||MacIntyre CJ,Sapp JL, Treatment of persistent ventricular tachycardia: Drugs or ablation? Trends in cardiovascular medicine. 2017 Oct [PubMed PMID: 28625728]|
|||Beaty RS,Moffett BS,Hall S,Kim J, Evaluating the Safety of Intraoperative Antiarrhythmics in Pediatric Cardiac Surgery Patients. Pediatric cardiology. 2015 Oct [PubMed PMID: 25981562]|