Agents Used in Cardiac Arrhythmias By M.D. , Ph.D. Shahid Beheshti University of Medical Science
Agents Used in Cardiac Arrhythmias Introduction Arrhythmia precipitating factors Antiarrhythmic Mechanisms Principles of therapy Classification of Antiarrhythmics Specific Antiarrhythmic Agents Miscellaneous Antiarrhythmic Agents Important Antiarrhythmic patterns Drug Pictures
introduction Arrhythmias consist of abnormality in the site of origin of the impulse, its rate or regularity, or its conduction. Cardiac arrhythmias occurring in 25% of patients treated with digitalis and over 80% of patients with acute myocardial infarction. All arrhythmias result from: Disturbances in impulse formation. Disturbances in impulse conduction (reentry). Both of the above.
Disturbances of Impulse Conduction Reentry (circus movement), in which one impulse reenters and excites areas of the heart more than once. In order for reentry to occur, three conditions must coexist: An obstacle (anatomic or physiologic). Unidirectional block at some point in the circuit. Conduction time around the circuit must be long enough so that the retrograde impulse does not enter refractory tissue.
Arrhythmia precipitating factors Ischemia, hypoxia Acidosis or alkalosis Electrolyte abnormalities Excessive catecholamine exposure, autonomic influences Drug toxicity Overstretching of cardiac fibers The presence of scarred or otherwise diseased tissue
Antiarrhythmic Mechanisms Antiarrhythmic drugs decrease the automaticity of ectopic pacemakers more than that of the sinoatrial node. They reduce conduction and excitability and increase the refractory period to a greater extent in depolarized tissue than in normally polarized tissue. This is accomplished by selectively blocking the ion channels of depolarized cells.
Principles of therapy The margin between efficacy and toxicity is particularly narrow for antiarrhythmic drugs. A drug that is antiarrhythmic may become "proarrhythmic" in the case of: High dose of antiarrhythmic drug Fast heart rates (more development of block) Acidosis (slower recovery from block) Hyperkalemia Ischemia.
Principles of therapy Precipitating factors must be eliminated if possible. A firm arrhythmia diagnosis should be established. The mere identification of an abnormality of cardiac rhythm does not necessarily require that the arrhythmia be treated.
Principles of therapy The urgency of the clinical situation determines the route and rate of drug initiation. Drug therapy can be considered effective when the target arrhythmia is suppressed. Conversely, drug therapy should not be considered ineffective unless toxicities occur at a time when arrhythmias are not suppressed.
Classification of Antiarrhythmics Blocking sodium channel. Blocking of sympathetic effects in the heart. Prolonging the effective refractory period. Blocking calcium channel.
Schematic diagram of the ion permeability changes and transport processes thatoccur during an action potential and the diastolic period following it. The size andweight of the arrows indicate approximate magnitudes of the ion channelcurrents; arrows pointing down indicate inward (depolarizing) membranecurrents, arrows pointing up indicate outward (repolarizing) membrane currents.Multiple subtypes of potassium and calcium currents, with different sensitivitiesto blocking drugs, have been identified. Chloride currents (dotted arrows)produce both inward and outward membrane currents during the cardiac actionpotential.
Sodium Channel-Blocking Drugs (Class 1) Quinidine (subgroup 1a): Quinidine prolongs the QRS duration by blockade of activated sodium channels. Quinidine also blocks most types of potassium channels. Its major cardiac effects are excessive QT interval prolongation and induction of torsade de pointes arrhythmia, and syncope.
Sodium Channel-Blocking Drugs (Class 1) Procainamide (subgroup 1a): The electrophysiologic effects of procainamide are similar to those of quinidine. Can cause hypotension, particularly with intravenous use. Hypotension is usually associated with excessively rapid procainamide infusion or the presence of severe underlying left ventricular dysfunction.
Sodium Channel-Blocking Drugs (Class 1) Procainamide (subgroup 1a) Procainamide is effective against most atrial and ventricular arrhythmias. Procainamide is the drug of second choice (after lidocaine) in CCUs for sustained ventricular arrhythmias associated with acute myocardial infarction.
Sodium Channel-Blocking Drugs (Class 1) Lidocaine (Subgroup 1b) Lidocaine blocks activated and inactivated sodium channels with rapid kinetics. Lidocaine is one of the least cardiotoxic of the currently used sodium channel blockers. Lidocaines most common adverse effects are neurologic. These occur most commonly in elderly when a bolus of the drug is given too rapidly.
Calcium Channel-Blocking Drugs (Class 4) Verapamil Verapamil blocks both activated and inactivated L- type calcium channels. its effect is more marked in the sinoatrial and atrioventricular nodes. A common error is to administer intravenous verapamil to a patient with ventricular tachycardia misdiagnosed as supraventricular tachycardia which causes hypotension and ventricular fibrillation.
Calcium Channel-Blocking Drugs (Class 4) Verapamil In patients with sinus node disease, verapamil can precipitate sinus arrest. Parenteral verapamil can be used to terminate supraventricular tachycardia, (but adenosine is the agent of first choice). Supraventricular tachycardia is the major arrhythmia indication for verapamil. Verapamil can also reduce the ventricular rate in atrial fibrillation and flutter.
Adenosine Its half-life in the blood is less than 10 seconds. Adenosine is the drug of choice for prompt conversion of paroxysmal supraventricular tachycardia to sinus rhythm. Adenosine causes flushing in about 20% of patients and shortness of breath or chest burning (related to bronchospasm) in over 10%.
Magnesium Magnesium therapy is indicated in patients with digitalis-induced arrhythmias if hypomagnesemia is present It is also indicated in some patients with torsade de pointes even if serum magnesium is normal.
Potassium The effects of hyperkalemia is: A resting potential depolarizing action. A membrane potential stabilizing action, caused by increased potassium permeability. Hyperkalemia depresses ectopic pacemakers (severe hyperkalemia is required to suppress the sinoatrial node) and slows conduction. Hypokalemia results in an increased risk of early and delayed afterdepolarizations, and ectopic pacemaker activity, especially in the presence of digitalis.
Sodium Channel-Blocking Drugs (Class 1) Quinidine (Subgroup 1a): Gastrointestinal side effects of diarrhea, nausea, and vomiting are observed in half of patients. A syndrome of headache, dizziness, and tinnitus (Cinchonism) is observed at toxic drug concentrations. Quinidine is used for the maintenance of normal sinus rhythm in patients with atrial flutter or fibrillation.