Antiarrhythmic Pharmacology Linking Pharmacological Treatment to the Patient and the Rhythm Presented By: Karen Marzlin BSN, RN,C, CCRN-CMC CNEA 2009 1 The Electronics Action Potential of Cardiac Cells Phase 0: Rapid depolarization (beginning of QRS complex) Phase 1: Brief, rapid initiation of repolarization (QRS complex) 2 www.cardionursing.com 1
The Electronics Phase 2: Slowing of the repolarization (ST segment) Phase 3: Sudden acceleration in the rate of repolarization (T wave) Phase 4: Resting membrane potential (T-P segment) 3 4 www.cardionursing.com 2
5 Antiarrhythmic Medications Effecting the Action Potential Class I Fast sodium channel blockers IA:Quinidine, Procainamide, Disopyramide IB: Lidocaine, Mexiletine, Tocainide Class II??? IC: Flecainide, Propafenone Class III Potassium channel blockers Amiodarone, Ibutalide, Dofetalide, Sotalol Class IV Calcium channel blockers Verapamil, Diltiazem 6 www.cardionursing.com 3
Action Potential Actions Cautions Uses Drugs Class I A Antiarrhythmics Depresses Phase O of Action Potential Inhibits influx of sodium the fast channel of cardiac cell membrane Slows conduction widens QRS Increases the recovery period after repolarization; Effective refractory period prolonged, myocardium refractory after resting membrane potential has been restored (slightly prolongs QT) Decreases automaticity, excitability, conduction velocity (including accessory pathways) and contractility Net effect: suppresses atrial and ventricular ectopy Prolongs QT interval Mainly used in treatment of atrial fib / flutter Can also be used for ventricular tachycardia Quinidine Procainamide (Pronestyl) Disopyramide (Norpace) 7 Class I A Antiarrhythmics Quinidine Procainamide (Pronestyl) Disopyramide (Norpace) Effective antimalarial agent Anticholinergic effects Can increase ventricular rate in A fib / flutter Anticholinergic effects less pronounced ACLS Protocol Indications: Stable monomorphic or polymorphic VT with preserved ventricular function Can be used along with class IC drugs in WPW tachycardias Significant anticholinergic effects (limits uses) Can increase ventricular rate in A fib / flutter Significant negative inotropic effect Only used investigationally IV for refractory VT; Rapid IV dosing can decrease SVR 8 www.cardionursing.com 4
Action Potential Actions Cautions Uses Drugs Chart based on Lidocaine: Class I B Antiarrhythmics Blocks Phase O of Action Potential Inhibits influx of sodium the fast channel of cardiac cell membrane Increases the recovery period after repolarization; shortens refractory period (repolarization) unlike class IA drugs which lengthen it; Suppresses automaticity but not in the SA node; suppresses spontaneous depolarization in the ventricle inhibiting reentry mechanisms (some variations with other class I B medications) Acts preferentially on ischemic tissue; No anticholinergic properties Heavily metabolized in liver; toxicity manifested neurologically Acceptable for stable monomorphic or polymorphic VT (Acceptable for impaired ventricular function) Noy for prophylaxis of arrhythmias post infarction Lidocaine; Mexiletine (Mexitil); Tocainide (Tonocard) 9 Lidocaine Class I B Antiarrhythmics Parenteral administration only Can give via E-Tube during code Amiodorone considered first for pulseless ventricular tachycardia or ventricular fibrillation CNS: Effects confusion, numbness or tingling of lips or tongue, blurred vision Mexiletine (Mexitil) Tocainide (Tonocard) Used in treatment of life threatening ventricular arrhythmias Also used to treat diabetic neuropathy pain Tablets were discontinued on December 31 2003 Potential fatal hematological side effect of agranulocytosis 10 www.cardionursing.com 5
Action Potential Class I C Antiarrhythmics Potent inhibition of fast sodium channel; decrease in maximal rate of phase 0 depolarization Actions Increases recovery period after repolarization Slow His-Purkinge conduction and cause QRS widening PR and QT intervals are also usually prolonged Cautions Uses Drugs Proarrhythmic effects Life threatening ventricular arrhythmias Conversion to SR (Flecainide) Flecainide (Tambocor) Encainide (Enkaid) Moricizine (Ethomozine) Propofenone (Rhythmol) 11 Class I C Antiarrhythmics Flecainide (Tambocor) Encainide (Enkaid) Will slow conduction over accessory pathways in WPW tachycardias Not a first line agent for ventricular arrhythmias Used in atrial fibrillation CAST Trial: propensity for fatal proarrhythmic effects Not used post MI or with depressed LV function Discontinued in US in 1991; made available for compassionate care only to those on medication 12 www.cardionursing.com 6
Class I C Antiarrhythmics Moricizine (Ethmozine) Propafenone (Rhythmol) CAST studies: Reserved for life threatening ventricular arrhythmias Has properties of class I A and I B also Prolongs Pr, AV nodal conduction time and intraventricular conduction time Used in supraventricular arrhythmias and life threatening ventricular arrhythmias Also has small beta blocking actions Prolongs effective refractory period of accessory pathways Must be initiated in hospital setting to monitor ECG 13 Beta blockers A Closer Look at Antiarrhythmics Depresses SA node automaticity Increases refractory period of atrial and AV junctional tissue to slow conduction Inhibits sympathetic activity lol medications Sotalol (Class II and III) Class II 14 www.cardionursing.com 7
Class III Antiarrhythmics Action Potential Actions Cautions Uses Drugs Inhibits potassium ion fluxes during phase II and III of the action potential Directly on myocardium to delay repolarization (prolongs QT); prolongs effective refractory period in all cardiac tissue; By definition act only on repolarization phase and should not impact conduction Proarrhythmic Effects (amiodarone less) Drug dependent Amiodarone (Pacerone, Cordorone) Ibutilide (Corvert) pure class III Dofetilide (Tikosyn) pure class III Sotalol (Betapace) 15 Class III Antiarrhythmics Amiodarone (ARREST Trial) Approved for life threatening refractory ventricular arrhythmias; considered before lidocaine in pulseless VT or V fib; considered ahead of lidocaine for stable VT with impaired cardiac function; expanded to atrial and ventricular arrhythmias, conversion and maintenance of atrial fib Slows conduction in accessory pathways Originally marketed as anti-anginal (potent vasodilator) Relaxes smooth and cardiac muscle, reduces afterload and preload (well tolerated in heart failure and cardiomyoapthy) Proarrhythmias less frequent Is also a weak sodium channel blocker, also has effects similar to class II and IV, also has anticholinergic properties 16 www.cardionursing.com 8
Amiodarone Dosing Life-threatening ventricular arrhythmias Rapid loading infusion 150 mg administered at a rate of 15 mg/minute (over 10 minutes); initial infusion rate should not exceed 30 mg/minute The slow loading phase is 360 mg at a rate of 1 mg/minute (over 6 hours) First maintenance phase of the infusion is 540 mg at a rate of 0.5 mg/minute (over 18 hours). After the first 24 hours, maintenance infusion rate of 0.5 mg/minute should be continued; the rate of the maintenance infusion may be increased to achieve effective arrhythmia suppression. In the event of breakthrough episodes supplemental infusions of 150 mg administered at a rate of 15 mg/minute (over 10 minutes) may be given. For cardiac arrest secondary to pulseless ventricular tachycardia or ventricular fibrillation Initial adult loading dose is 300 mg (diluted in 20 30 ml of a compatible IV solution) given as a single dose, rapid IV 17 More on Amiodarone Nursing Considerations Peripheral IV concentration not to exceed 2mg/ml Oral administration / GI symptoms Severe adverse reactions (potentially lethal interstial pneumonitis CXR q 3-6 mos); less common in lower doses; Thyroid dysfunction is also a side effect (by weight amiodarone is 37% iodine) Toxic side effects increase with length of use 18 www.cardionursing.com 9
Ibutilide (Corvert) Dofetilide (Tykosin) Class III Antiarrhythmics Indicated for rapid conversion of atrial fib or flutter to sinus rhythm; IV use only; also facilitated cardioversion (Don t convert atrial fib or flutter of duration without anticoagulation) Rather than blocking outward potassium currents promotes influx of sodium through slow inward sodium channel More pure class III agent Conversion to and maintenance of SR in A fib and flutter Reserved for very symptomatic patients, monitored 3 days in hospital Widens the QT; cannot be given with many other drugs (prolong QT or inhibit metabolism or elimination); no negative inotropic effects, neutral effect on mortality from arrhythmias post MI and in in HF, can be used in this 19 population to prevent worsening HF from atrial fib Class III Antiarrhythmics Sotalol (Betapace R ) (Betapace AF ) Used in atrial arrhythmias and life threatening ventricular arrhythmias Indicated for stable monomorphic VT or Polymorphic VT with normal QT in ACLS protocol Non selective beta blocking agent with class III properties Significant class III effects are only seen at doses > 160 mg Proarrhythmic potential (prolonged QT) More effective in preventing reoccurring arrhythmias than several other drugs 20 www.cardionursing.com 10
New Antiarrhythmic Dronedarone (Multaq) Rejected by FDA 2006 Decision by April 30 2009 Decreases hospitalizations in atrial fib Safer alternative to amiodarone 21 Class IV Antiarrhythmics Phase II of Action Potential Depresses automaticity in the SA and AV Junction and increases the refractory period at the AV junction Decreases contractility Calcium Channel Blockers Verapamil (SA Node), Cardizem (AV Node) 22 www.cardionursing.com 11
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Exercise for Pro Arrhythmia Can expose pro arrhythmia with class I agents Will suppress pro arrhythmia with class III agents Increase HR = decreased pro arrhythmia 25 Initiation in Outpatient Setting Propafenone Absence of structural HD / SR Flecainide Absence of structural HD / SR Amiodarone Bradycardia biggest safety concern Absence of conduction system disease Sotolol In selected healthy patients 26 www.cardionursing.com 13
Outpatient Initiation Does not imply lack of monitoring Will be standard for new drug development Need to carefully dose and titrate 27 Non-classified Antiarrhythmics Adenosine Blocks conduction through AV Node Atropine Parasympatholytic Digitalis Cardiac Glycoside 28 www.cardionursing.com 14
Adenosine (Adenocard) Slows conduction through the AV Node Vasodilator Interrupts reentry pathways through the AV node and restores sinus rhythm Uses: Paroxsysmal SVT, AVNRT, Drug stress testing Side Effects: Headache, arrhythmias (blocks), SOB, chest pressure 29 Adenosine Nursing Considerations: Use cautiously in patients with asthma could cause bronchospasm Onset IV: Immediate Peak: 10 sec Duration 20-30 seconds Dosing for conversion of arrhythmia: 6mg IV rapid push If no change within 1-2 minutes repeat with 12mg rapid push Not indicated in WPW Fibrillation! 30 www.cardionursing.com 15
Digoxin Inhibits the NA+ and K+ membrane pump Increase in intracellular Na+ Enhances the Na+ and Ca++ exchange Leads to in intracellular Ca++ inotropic activity 31 Digoxin Digoxin also increases vagal activity and decreases conduction velocity through the AV node (sympathetic stimulation easily overrides the inhibitory effects of digoxin on AV node conduction) Calcium channel blockers are replacing digoxin as agent for rate control in atrial arrhythmias Digoxin no better than placebo in converting atrial fib to SR Digoxin decreases sympathetic outflow and decreases renin production Beneficial in heart faiure 32 www.cardionursing.com 16
Digoxin Indications HF Atrial arrhythmias (old indication) Contraindication / cautions MI Ventricular arrhythmias, HB, Sick Sinus Syndrome IHHS Electrolyte abnormalities (decreased K+, Ca++ and Mg++) 33 Digoxin Has a narrow therapeutic range Toxicity may occur at therapeutic levels Lower doses now routinely used 0.125 mg daily Amiodorone increases serum digoxin concentration (digoxin doses must be reduced if starting amiodarone) Multiple other medication interactions Dialysis is not effective with digoxin toxicity because of high tissue binding of digoxin 34 www.cardionursing.com 17
More About Digoxin Toxicity EKG Changes with Toxicity Increased automaticity with with impaired conduction is common (example: PAT with AV Block) Other Signs and Symptoms of Toxicity N & V, HA, Confusion Visual disturbances: halos, change in color perception 35 36 www.cardionursing.com 18
Patients Not Requiring Antiarrhythmics Because of proarrhythmias or exacerbations of existing arrhythmias antiarrhythmic therapy not indicated for: Asymptomatic atrial ectopy and unsustained SVT Asymptomatic ventricular ectopy without runs of VT Simple ventricular ectopy in AMI with no hemodynamic compromise Asymptomatic unsustained VT with no structural heart disease Asymptomatic WPW without known SVT Mildly symptomatic simple atrial or ventricular ectopy 37 Class Antiarrhythmics in Atrial Fibrillation Specific Medications Purpose of Medication Major Cardiac Side Effects Class I A Class I B Class I C Disopyramide Procainamide Quinidine Not used in atrial fibrillation Flecainide Propofenone Rhythm Control Rhythm Control Rhythm Control Rhythm Control Rhythm Control Torsade de pointes, HF Torsade de pointes Torsade de pointes Ventricular tachycardia, HF, Atrial Flutter Ventricular tachycardia, HF, Atrial Flutter Class II Beta Blockers Rate Control Class III Amiodarone Dofetilide Ibutilide Sotalol (also contains beta blocker) Rhythm / Rate Control Rhythm Control Rhythm Control Rhythm Control (also controls rate) Torsade de pointes (rare) * Organ toxicity Torsade de pointes Torsade de pointes Torsade de pointes, HF, Beta blocker side effects Class IV Calcium Channel Blockers Rate Control 38 www.cardionursing.com 19
Drugs Proven Most Effective for Pharmacological Cardioversion of Atrial Fibrillation (Class I Recommendation from ACC / AHA Guidelines Duration of Less than or Equal to 7 Days) Dofetilide * Flecainide Ibutilide Propofenone (* Also-class I recommendation for duration of Atrial Fibrillation > 7 days) 39 Medications Used to Maintain Sinus Rhythm in Patients with Atrial Fibrillation Amiodarone Disopyramide Dofetilide Flecainide Procainamide Propafenone Quinidine Sotalol 40 www.cardionursing.com 20
Medications Used to Maintain Sinus Rhythm in Special Patient Populations Special Patient Population Lone Atrial Fibrillation Medication Used to Maintain Sinus Rhythm Flecainide Propafenone Sotalol; Beta Blockers may also be tried Neurogenic Atrial Fibrillation Atrial Fibrillation in Heart Failure Disopyramide or flecainide (for vagal) Beta Blockers or sotalol (for adrenergic Amiodarone (less proarrhythmic effects) Dofetilide Atrial Fibrillation in Coronary Artery Disease Atrial fibrillation in Hypertensive Heart Disease with Left Ventricular Hypertrophy Sotalol (beta blocking properties) Propafenone (Class I C - does not prolong QT) Flecainide (Class I C - does not prolong QT) Amiodarone (if significant hypertrophy) 41 Emergency Antiarrhythmic Summary Atrial Fibrillation / Flutter Rate Control Normal LV (Class I Recommendations) Diltiazem Metoprolol Impaired LV (Class IIb Recommendations) Diltiazem Digoxin Amiodorone (Cordrone) (Class III) Conversion only if < 48 hour duration DC Cardioversion or Amiodrone (IIb) Other options only if LV preserved Ibutilide (Corvert) (Class III) Procainamide (Pronestyl) (Class IA) * Flecainide (Tambacor) (Class IC) * Propafenone (Rhythmol) (Class IC) * Not available in IV form in US 42 www.cardionursing.com 21
Emergency Antiarrhythmic Summary Atrial Fib in WPW DC Cardioversion if < 48 hours Preserved LV function Amiodarone Procainamide * Flecainide * Sotalol * Propofenone Impaired LV function Amiodorone only 43 Emergency Antiarrhythmic Summary Narrow Complex SVT (Initial Treatment) Vagal Adenosine 44 www.cardionursing.com 22
Emergency Antiarrhythmic Summary Stable Ventricular Tachycardia (Preserved LV Function) Monomorphic Procainamide Sotalol * Amiodarone Lidocaine Polymorphic Normal QT Beta Blockers (or) Lidocaine (or) Amiodarone (or) Procainide (or) Sotalol (or) Polymorphic Prolonged QT Magnesium (or) Lidocaine (or) Isoproterenol (or) Phenytoin (or) 45 Emergency Antiarrhythmic Summary Stable Ventricular Tachycardia (Monomorphic or Polymorphic: Normal or Prolonged QT) (Impaired Cardiac Function) * Amiodarone (or) Lidocaine 46 www.cardionursing.com 23
Summary New ACLS Guideline Changes Vasopressors or epinephrine for VF or pulseless VT when IV line in place Amiodarone preferred over lidocaine for VF and VT Epinephrine or vasopressin then atropine for asystole and PEA 47 Arrhythmias with ACS: ACC/AHA V-fib early in ACS Increase hospital mortality No increase in long term mortality Lidocaine prophylaxis Decrease V-fib Increase mortality Beta-blockers prophylaxis Decrease V-fib Correction of potassium and magnesium 48 www.cardionursing.com 24
Monomorphic VT: ACC/AHA DC cardioversion with sedation if unstable IV procainamide Stable VT Caution with CHF or severe LV dysfunction IV amiodarone Hemodynamically unstable Refractory to shock TTVP for pace termination Lidocaine if ischemia Class III: Calcium channel blockers in wide complex of unknown origin; especially if myocardial dysfunction 49 Repetitive Monomorphic VT: ACC/AHA IV amiodarone, beta-blocker, procainamide Generally idiopathic VT RV outflow tract May be provoked by exercise Beta-blockers or calcium channel blockers may be effective Ablation is successful treatment option 50 www.cardionursing.com 25
Polymorphic VT: ACC / AHA DC cardioversion with sedation when unstable IV beta-blockers if ischemia suspected Improve mortality IV amiodarone in absence of abnormal repolarization Urgent angiography to exclude ischemia Lidocaine may be reasonable if ischemia suspected 51 Class I Incessant VT VT Storm: ACC/AHA Revascularization and beta-blocker Followed by IV amiodarone or procainamide (if due to acute ischemia) Class IIa IV amiodarone or procainamide followed by VT ablation Important to understand substrate to target treatment 52 www.cardionursing.com 26
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