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Chapter 49. Antidysrhythmic Drugs. Dysrhythmia. Dysrhythmia An abnormality in the rhythm of the heartbeat (also known as arrhythmias) Arises from impulse formation disturbances Tachydysrhythmias: SVT and ventricular Bradydysrhythmias
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Chapter 49 Antidysrhythmic Drugs
Dysrhythmia Dysrhythmia An abnormality in the rhythm of the heartbeat (also known as arrhythmias) Arises from impulse formation disturbances Tachydysrhythmias: SVT and ventricular Bradydysrhythmias Virtually all drugs that treat dysrhythmias can also cause dysrhythmias
Antidysrhythmic Drugs • Electrical properties of the heart • Generation of dysrhythmias • Classification of antidysrhythmic drugs • Prodysrhythmic effects of antidysrhythmic drugs • Overview of common dysrhythmias and their treatment
Electrical Properties of the Heart • Impulse conduction: pathways and timing • Sinoatrial (SA) node:pacemaker of heart • Atrioventricular (AV) node • His-Purkinje system
Cardiac Action Potentials • Fast potentials • Occur in fibers of the His-Purkinje system and in atrial and ventricular muscle • Five distinct phases • Phase 0:depolarization • Phase 1:(partial) repolarization • Phase 2:plateau • Phase 3:repolarization • Phase 4:stable potential
Cardiac Action Potentials • Slow potentials • Occur in cells of the SA node and AV node • Three features of special significance • Phase 0:slow depolarization • Mediated by calcium influx • Phases 1, 2, and 3 • Phase 1 absent • Phases 2 and 3 not significant • Phase 4:depolarization
Fig.49–2. Ion fluxes during cardiac action potentials and effects of antidysrhythmic drugs.
The Electrocardiogram • Provides a graphic representation of cardiac electrical activity • Major components of an ECG • P wave • Depolarization in the atria • QRS complex • Depolarization of the ventricles • T wave • Repolarization of the ventricles • Three other components • PR interval • QT interval • ST segment
Generation of Dysrhythmias • Two fundamental causes • Disturbances of automaticity • Disturbances of conduction • Atrioventricular block • Reentry (recirculating activation)
Classification of Antidysrhythmic Drugs • Vaughan Williams classification • Class I: sodium channel blockers • Class II: beta blockers • Class III: potassium channel blockers • Class IV: calcium channel blockers • Other: adenosine, digoxin, and ibutilide
Common Dysrhythmias and Their Treatment • Supraventricular • Impulse arises above the ventricle • Atrial fibrillation • Atrial flutter • Sustained supraventricular tachycardia (SVT)
Common Dysrhythmias and Their Treatment • Ventricular • Sustained ventricular tachycardia • Ventricular fibrillation • Ventricular premature beats • Digoxin-induced ventricular dysrhythmias • Torsades de pointes
Principles of Antidysrhythmic Drug Therapy • Balancing risks and benefits • Consider properties of dysrhythmias • Sustained vs. nonsustained • Asymptomatic vs. symptomatic • Supraventricular vs. ventricular • Acute and long-term treatment phases • Minimizing risk
Class I: Sodium Channel Blockers • Class IA agents • Class IB agents • Class IC agents
Class IA Agents • Quinidine • Effects on the heart • Blocks sodium channels • Slows impulse conduction • Delays repolarization • Blocks vagal input to the heart • Effects on ECG • Widens the QRS complex • Prolongs the QT interval • Therapeutic uses • Used against supraventricular and ventricular dysrhythmias
Class IA Agents • Quinidine (cont’d) • Adverse effects • Diarrhea • Cinchonism • Cardiotoxicity • Arterial embolism • Alpha-adrenergic blockade, resulting in hypotension • Hypersensitivity reactions • Drug interactions • Digoxin
Other Class IA Agents • Procainamide (Procanbid) • Similar to quinidine • Only weakly anticholinergic • Adverse effects: symptoms of systemic lupus erythematosus • Disopyramide (Norpace) • Similar to quinidine • Prominent side effects have limited its use
Class IB Agents • Lidocaine (Xylocaine) • Effects on the heart and ECG • Blocks cardiac sodium channels • Slows conduction in the atria, ventricles, and His-Purkinje system • Reduces automaticity in the ventricles and His-Purkinje system • Accelerates repolarization • Adverse effects • CNS effects • Drowsiness • Confusion • Paresthesias
Class IB Agents • Other class IB agents • Phenytoin • Antiseizure medication also used to treat digoxin-induced dysrhythmias • Mexiletine • Oral analog of lidocaine • Used for symptomatic ventricular dysrhythmias
Class IC Agents • Block cardiac sodium channels • Delay ventricular repolarization • All class IC agents can exacerbate existing dysrhythmias and create new ones • Two class IC agents • Flecainide • Propafenone
Class II: Beta Blockers • Beta-adrenergic blocking agents • Only four approved for treating dysrhythmias • Propranolol • Acebutolol • Esmolol • Sotalol
Class II: Beta Blockers • Propranolol (Inderal): nonselective beta-adrenergic antagonist • Effects on the heart and ECG • Decreased automaticity of the SA node • Decreased velocity of conduction through the AV node • Decreased myocardial contractility • Therapeutic use • Dysrhythmias caused by excessive sympathetic stimulation • Supraventricular tachydysrhythmias • Suppression of excessive discharge • Slowing of ventricular rate
Class II: Beta Blockers • Propranolol (Inderal) (cont’d) • Adverse effects • Heart block • Heart failure • AV block • Sinus arrest • Hypotension • Bronchospasm (in asthma patients) • Other class II: beta blockers • Acebutolol (Sectral) • Esmolol (Brevibloc)
Class III: Potassium Channel Blockers • Amiodarone (Cordarone, Pacerone) • Therapeutic use • For life-threatening ventricular dysrhythmias only • Recurrent ventricular fibrillation • Recurrent hemodynamically unstable ventricular tachycardia
Class III: Potassium Channel Blockers • Amiodarone (Cordarone, Pacerone) (cont’d) • Effects on the heart and ECG • Reduced automaticity in the SA node • Reduced contractility • Reduced conduction velocity • QRS widening • Prolongation of the PR and QT intervals
Class III: Potassium Channel Blockers • Amiodarone (Cordarone, Pacerone) (cont’d) • Adverse effects • Protracted half-life • Pulmonary toxicity • Cardiotoxicity • Toxicity in pregnancy and breast-feeding • Corneal microdeposits • Optic neuropathy
Class III: Potassium Channel Blockers • Amiodarone (Cordarone, Pacerone) (cont’d) • Drug interactions (increases levels) • Quinidine • Diltiazem • Cyclosporine • Digoxin • Procainamide • Diltiazem • Phenytoin • Warfarin • Lovastatin, simvastatin, atorvastatin
Class III: Potassium Channel Blockers • Amiodarone levels can be increased by grapefruit juice and by inhibitors of CYP3A4. Toxicity can result • Amiodarone levels can be reduced by cholestyramine (which decreases amiodarone absorption) and by agents that induce CYP3A4 (eg, St. John’s wort, rifampin)
Class III: Potassium Channel Blockers • The risk of severe dysrhythmias is increased by diuretics (because they can reduce levels of potassium and magnesium) and by drugs that prolong the QT interval, of which there are many (see Chapter 7) • Combining amiodarone with a beta blocker, verapamil, or diltiazem can lead to excessive slowing of heart rate
Class III: Potassium Channel Blockers • Dronedarone (Multaq) • Derivative of amiodarone approved in 2009 • Effects on the heart and ECG • Pharmacokinetics • Adverse effects • Common side effects • Cardiac effects in severe heart failure • Liver toxicity • Toxicity in pregnancy and breast-feeding • Drug interactions • Multiple—many involve CYP3A4
Class III: Potassium Channel Blockers • Sotalol (Betapace) • Combined class II and class III properties • Beta blocker that also delays repolarization • Dofetilide (Tikosyn) • Oral class III antidysrhythmic • Predisposes patient to torsades de pointes • Ibutilide (Covert) • Class III agent • IV agent used to terminate atrial flutter/fibrillation
Class IV: Calcium Channel Blockers • Verapamil (Calan, Isoptin, Verelan) and diltiazem (Cardizem) • Reduce SA nodal automaticity • Delay AV nodal conduction • Reduce myocardial contractility • Therapeutic uses • Slow ventricular rate (atrial fibrillation or atrial flutter) • Terminate SVT caused by an AV nodal reentrant circuit
Class IV: Calcium Channel Blockers • Verapamil (Calan, Isoptin, Verelan) and diltiazem (Cardizem) (cont’d) • Adverse effects • Bradycardia • Hypotension • AV block • Heart failure • Peripheral edema • Constipation • Can elevate digoxin levels • Increased risk when combined with a beta blocker
Other Antidysrhythmic Drugs • Adenosine (Adenocard) • Effects on the heart and ECG • Decreases automaticity in the SA node • Slows conduction through the AV node • Prolongation of PR interval • Therapeutic use: termination of paroxysmal SVT
Other Antidysrhythmic Drugs • Adenosine (Adenocard) (cont’d) • Adverse effects • Sinus bradycardia • Dyspnea • Hypotension • Facial flushing • Chest discomfort • Drug interactions • Methylxanthines • Dipyridamole
Other Antidysrhythmic Drugs • Digoxin (Lanoxin) • Primary indication is heart failure • Also used to treat supraventricular dysrhythmias (inactive against ventricular dysrhythmias) • Suppresses dysrhythmias by decreasing conduction through AV node and automaticity in the SA node • QT interval may be shortened • Adverse effect: cardiotoxicity • Risk increased by hypokalemia
Nondrug Treatment of Dysrhythmias • Implantable cardioverter-defibrillators • Radiofrequency catheter ablation