Antiarrhythmics Poisons with occasionally beneficial side effects

The Plan  Normal Rhythm Physiology  Antiarrhythmic Characteristics  Common Arrhythmias  Cases

AV SA

What Kind of Channels? Ca ++ Na + / K + ! What kind of Channels? Na + / K + Na + depolarize K + repolarize Na + / K + Na + depolarize K + repolarize Ca ++ What Kind of Channels? SA AV

Class I – Sodium Channel blockers  Ia Quinidine, procainamide, disopyramide  Ib - Lidocaine Lidocaine easier to use quickly, less proarrhythmic  Ic – Flecainide, Propafenone More effective, more proarrhythmic

Class I  Effect on SA node  Effect on AV node  Effect on Conduction / Automaticity  Used for: Converting and maintaining atrial and ventricular arrhythmias

CAST  Cardiac Arrhythmia Suppression Trial

Class II: Beta Blockers Valium for the Heart

Class I I  Effect on SA node  Effect on AV node  Effect on Conduction / Automaticity  AND….  Used for A. Fib rate control, SVT and adjunct for ventricular arrhythmias

Howard Kyle Baker

Howard Flashback: What was the CAST trial?

Class III: K+ Channel Blockers

Class I I I  Effect on SA node  Effect on AV node  Effect on Conduction / Automaticity  Effect on Refractory Period  Used for Atrial (low dose) & Ventricular (higher dose)arrhythmia conversion and maintenance

Class III: K+ Channel Blockers  Sotalol  Ibutilide  Dofetilide  Amiodarone  Sotalol d-Class III l-Beta Blocker  Sotalol  Amiodarone Class I Na + blockade Alpha and Beta blockade Class III Predominates Calcium blockade

Class I I I - Sotalol  Effect on SA node  Effect on AV node  Effect on Conduction / Automaticity  Effect on Refractory Period

Class I I I - Amiodarone  EVERYTHING Skip Side Effects and Drug Interactions. We’ll come back.

Class IV: Calcium Channel Blockers  Verapamil  Diltiazem  Dihydropyridines

Class I V  Effect on SA node  Effect on AV node  Effect on Conduction / Automaticity  Effect on Refractory Period  Used for A. Fib rate control and SVT

“Others”  Digoxin  Vagal Side Effect Slows SA and AV Node (A.Fib Rate Control) Problem: It can be overridden by sympathetic stimulation  Adenosine  Slows S-A and A-V node  Lasts minutes  Vasodilates SE: Chest tightness, tingling, apprehension, hypotension

Which node is the pacemaker

What does the AV node do?

Name a calcium blocker that would not be used in A.Fib

HOW ARE WE DOING? What was the muddiest point?

Common Arrhythmias

Atrial Fibrillation

Usually 2:1 or 3:1 300 to 600 /Minute SA AV Irregularly Irregular

 Rate Rhythm

A. Fib rate=250 Normal Sinus Rhythm A Fib rate= 100

A. Fib: Rate vs. Rhythm  Two Options for Chronic A.Fib management  Maintain Normal Sinus Rhythm  Control Ventricular Rate  Double blind Trial to Compare  21.3% vs 23.8% mortality with more hospitalizations in rhythm control group.

A. Fib: Rate vs. Rhythm  Equal Mortality  Rate control much less toxicity and trouble than rhythm control  However, Rate control does require warfarin (more later)

What is Rate control in A.Fib

What is Rhythm control in A.Fib

A. Fib: Rate vs. Rhythm  If you decide to do Rhythm anyway

Acute Conversion Options: Propafenone (Rhythmol) 1x 600mg oral dose Ibutilide 1mg IV over 10 minutes MRx1 (proarrhythmic) Amiodarone (various IV regimens) Dofetilide (requires documented training TdP )

How do you recognize “hemodynamically unstable”?

Acute Conversion of A Fib  Torsades de Pointes is always a risk  Perhaps lowest risk with amiodarone

Torsades caused by other drugs  Tricyclics  Erythromycin  TMP/SMX  Haldol and other antipsychotics?  Quinine  Moxifloxacin

Rate vs. Rhythm  Chronic Rhythm Control Drugs  Amiodarone  Propafenone  Class 1a

Rate vs. Rhythm  Rate Control Drugs  Beta Blockers  Calcium Blockers (Non-)  Digoxin  NOT ADENOSINE  Why?

Atrial Fibrllation Cookbook  Disclaimers  Recommendation 1: Rate control preferred

Atrial Fibrllation Cookbook  Recommendation 2: Anticoagulate almost everyone (more on that in a minute)

Atrial Fibrllation Cookbook  Recommendation 3: Rate control drugs:  atenolol,  metoprolol,  diltiazem,  verapamil  (drugs listed alphabetically by class).  Digoxin is a second line agent

Why is digoxin second line?

Atrial Fibrllation Cookbook  Recommendation 4: For those patients who elect to undergo acute cardioversion  Shock or Poison

Atrial Fibrllation Cookbook  Recommendation 5: Do a trans-esophageal echo to rule out a clot OR anticoagulate three weeks prior to cardioversion.

Atrial Fibrllation Cookbook  Recommendation 6: In a selected group of patients whose quality of life is compromised by atrial fibrillation, the recommended pharmacologic agents for rhythm maintenance are amiodarone, disopyramide, propafenone, and sotalol (drugs listed in alphabetical order). The choice of agent predominantly depends on specific risk of side effects based on patient characteristics.

Atrial Fibrllation  If you don’t die of ventricular tachycardia, what is the next worst thing caused by A. Fib?  Why?

A. Fib: Stroke Risk

A. Fib and Anticoagulation  STROKE with Atrial Fibrillation:  5% per year  On Warfarin: 1-2% per year  Goal INR = 2.5 (2.0 – 3.0)  More risk factors = More strokes  More warfarin benefit

CHADS2  CHF  Hypertension  Age greater than 75  Diabetes  Stroke or TIA history (2 points)

CHADS2 Stroke rate/year

“Chest Guidelines” CHEST / 126 / 3 / SEPTEMBER, 2004 SUPPLEMENT 449S In patients with persistent or paroxysmal AF at high risk of stroke (ie, having any of the following features: prior ischemic stroke, TIA, or systemic embolism, age >75 years, impaired systolic function and/or congestive heart failure, hypertension, or diabetes Warfarin (target INR, 2.5; range, 2.0 to 3.0)

“Chest Guidelines” In patients with persistent AF age 65 to 75 years, in the absence of other risk factors (intermediate risk), Warfarin OR Aspirin 325mg/day

“Chest Guidelines” In patients with persistent AF < 65 with no other risk factors, Aspirin OR no anticoagulant

“Chest Guidelines” In patients in Atrial Fibrillation for >48 hours or for unknown duration:  Anticoagulate for 3 weeks before cardioversion  Anticoagulate for 5 days and confirm absence of thrombus with TEE before cardioversion

What is the biggest risk factor for Stroke in A.Fib patients”?

Between 65 and 75 y.o. with no risk factors”?

Supraventricular Tachycardia A Young Persons Disease

Supraventricular Tachycardia

Beware WPW

Treatment for SVT Carotid Massage Valsalva Adenosine Verapamil / Diltiazem

Managing SVT

V. Fib and V.Tach The Patient Killers

Ventricular Fibrillation

Ventricular Fibrillation SA

ACLS protocol  See Dr. deVoest or Dr. Aykroyd

Ventricular Tachycardia

Ventricular Tachycardia  Na/K Channels  Class 1A, B, C  Class III  Na/K Channels  Class 1A, B, C  Class III SA

Are Your Needs Being Met?

Arrhythmias in the Real World

Acute Atrial Fibrillation

 AF is a 72 year old white female appearing older than her stated age.  PMH: Hypertension Mild COPD Hypothyroidism  Pulse: 140  Irregularly Irregular rhythm (A.Fib)

Acute A.Fib (AF)  Drugs: Levoxyl 150 mcg  Pravachol 20mg  Zestril (Lisinopril) 40mg  Combivent  HCTZ 25mg daily

Case #1  What should you ask about the patient’s condition ?  Are there any laboratory values that would be helpful?  Hint: Hyperthyroidism causes A.Fib.

Case #1:Acute A.Fib (Carol)  Pertinent Labs: TSH 0.1 EF = 18%

Acute A.Fib (Carol)  What interventions could we make (brainstorm, don’t hold back!)  What if that doesn’t work?  Does she need anticoagulation?  What interventions could we make (brainstorm, don’t hold back!)  What if that doesn’t work?  Does she need anticoagulation?

Chronic Atrial Fibrillation

#2 Chronic A Fib  Drugs  Cordarone 200mg daily  Synthroid 100mcg daily  Aspirin daily  Zestril 40mg daily  HCTZ 25mg daily  Why Synthroid?  What monitoring would you recommend?/???????????????????????

Amiodarone Side Effects Pages 4 and 5  Bradycardia (beta blocker)  Pulmonary Fibrosis  Hyper or Hypothyroidism  Peripheral Neuropathy  Corneal Deposits  Tremor  Ataxia  Blue/Gray skin

Amiodarone monitoring  Normal Sinus Rhythm?  Baseline PFT  LFT’s  TSH  Ophthalmologic exams  QT interval  Bradycardia  Drug Interactions

Amiodarone Interactions? 1A2  Theo 2C9  Warfarin  Diazepam  Phenytoin 2D6  TCA’s  SSRI’s  Beta Blockers 3A4  Everything Else  Statins  Calcium Blockers  Amiodarone

Amiodarone Interactions? QT Prolonging Drugs  Ia, Ic and III antiarrhythmics  Antipsychotics  Tricyclics  Spar, Moxi, Clari, Ery, TMP, Keto and Dopey

#3 Atrial Fibrillation  Carol #2 is a 56 year old lady with hx of A. Fib for 5 yrs and multiple medical problems.  She is on several antihypertensives and Procainamide 750 mg TID.  Her pulse is 85 and irregularly irregular  Evaluate:

#4 Acute SVT The Case of the Stressed Out Student

Acute SVT  BD is a 22 year old Asian pharmacy student who developed dizziness and shortness of breath on medical rounds  In the ER his pulse was approx. 140 and a subsequent EKG showed SVT at a rate of 160/min.  What do you need to know?  What treatment options are there? At least it wasn’t ugly SVT

Acute SVT Tx  DC Cardioversion if unstable  Valsalva maneuver or Carotid Massage  Verapamil  Diltiazem  Adenosine

Antiarrhythmics Poisons with occasionally beneficial side effects

Sponsorship, Disclaimers, etc.