antiarrhythmics poisons with occasionally beneficial side effects

AntiarrhythmicsAntiarrhythmics

Poisons with occasionally beneficial

side effects

The PlanThe Plan

Normal Rhythm PhysiologyAntiarrhythmic CharacteristicsCommon ArrhythmiasCases

AV

SA

What Kind of

Channels?

What Kind of

Channels?Ca++Ca++Na+/ K+ !Na+/ K+ !

What kind of

Channels?

What kind of

Channels?What kind of

Channels?

What kind of

Channels?

Na+ / K+

Na+ depolarize

K+ repolarize

Na+ / K+

Na+ depolarize

K+ repolarize

Ca++Ca++ What Kind of

Channels?

What Kind of

Channels?

SA

AV

Class I – Sodium Channel blockers

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 IClass I

Effect on SA node

Effect on AV node

Effect on Conduction / Automaticity

Used for: Converting and maintaining atrial and ventricular arrhythmias

CASTCAST

Cardiac Arrhythmia Suppression Trial

Class II: Beta BlockersClass II: Beta Blockers

Valium for the

Heart

Class I IClass I I

Effect on SA node

Effect on AV node


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 IClass I I I

Effect on SA node

Effect on AV node


Effect on Refractory Period

Used for Atrial (low dose) & Ventricular (higher dose)arrhythmia conversion and maintenance



SotalolIbutilideDofetilideAmiodarone

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 - SotalolClass I I I - Sotalol

Effect on SA node

Effect on AV node



Class I I I - AmiodaroneClass I I I - Amiodarone

EVERYTHING

Skip Side Effects and Drug Interactions. We’ll come back.

Class IV: Calcium Channel BlockersClass IV: Calcium Channel Blockers

VerapamilDiltiazemDihydropyridines

Class I VClass I V

Effect on SA node

Effect on AV node



Used for A. Fib rate control and SVT

“Others”“Others”

DigoxinVagal Side Effect

• Slows SA and AV Node (A.Fib Rate Control)

• Problem: It can be overridden by sympathetic stimulation

AdenosineSlows S-A and A-V nodeLasts minutesVasodilates

• 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?HOW ARE WE DOING?

What was the

muddiest point?

Common Arrhythmias

Common Arrhythmias

Atrial FibrillationAtrial Fibrillation

Atria

l

Fibril

lati

onUsually 2:1

or 3:1Usually 2:1

or 3:1

300 to 600 /Minute

300 to 600 /Minute

SA

AV

Irregularly

Irregular

http://www.tist.org/tist/aboutus/origins.php

Rate

Rhythm

http://www.learntheecg.com/ekg_strips

A. Fib rate=250

Normal Sinus Rhythm

A Fib rate= 100

A. Fib: Rate vs. RhythmA. Fib: Rate vs. Rhythm

Two Options for Chronic A.Fib managementMaintain Normal Sinus Rhythm Control Ventricular Rate

Double blind Trial to Compare21.3% vs 23.8% mortality with more

hospitalizations in rhythm control group.


Equal MortalityRate control much less toxicity and

trouble than rhythm controlHowever, Rate control does require

warfarin (more later)

What is Rate control in A.Fib

What is Rhythm control in A.Fib


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 FibTorsades 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. RhythmRate vs. Rhythm

Chronic Rhythm Control DrugsAmiodaronePropafenoneClass 1a

Rate vs. RhythmRate vs. Rhythm

Rate Control DrugsBeta BlockersCalcium Blockers (Non-)DigoxinNOT ADENOSINE

Why?

Atrial Fibrllation Cookbook


DisclaimersRecommendation 1: Rate control

preferred



Recommendation 2: Anticoagulate almost everyone (more on that in a minute)



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?



Recommendation 4: For those patients who elect to undergo acute cardioversion

Shock or Poison



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



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 FibrllationAtrial Fibrllation

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

Why?

A. Fib: Stroke RiskA. Fib: Stroke Risk

A. Fib: Stroke RiskA. Fib: Stroke Risk

http://www.mja.com.au/public/issues/186_04_190207/med11193_fm-1.jpg

A. Fib and Anticoagulation

A. Fib and Anticoagulation

STROKE with Atrial Fibrillation:5% per year On Warfarin: 1-2% per yearGoal INR = 2.5 (2.0 – 3.0)More risk factors = More strokes More warfarin benefit

CHADS2CHADS2

CHFHypertensionAge greater than 75DiabetesStroke or TIA history (2 points)

CHADS2CHADS2

Stroke rate/year0 1.91 2.82 4.03 5.94 8.55 12.56 18.2

“Chest Guidelines”www.chestjournal.org CHEST / 126 / 3 / SEPTEMBER, 2004 SUPPLEMENT 449S

“Chest Guidelines”www.chestjournal.org 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”“Chest Guidelines”

In patients with persistent AF age 65 to75 years, in the absence of other risk

factors (intermediate risk),

Warfarin OR Aspirin 325mg/day


In patients with persistent AF < 65 with no other risk factors,

Aspirin OR no anticoagulant


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

Supraventricular Tachycardia

A Young Persons Disease

Supra

vent

ricul

ar

Tach

ycar

dia

Beware WPW

Treatment for SVT

• Carotid Massage• Valsalva• Adenosine• Verapamil / Diltiazem

Managing SVTManaging SVT

V. Fib and V.TachV. Fib and V.Tach

The Patient Killers

Ventricular FibrillationVentricular Fibrillation

Ventr

icula

r

Fibril

latio

n

SA

ACLS protocolACLS protocol

See Dr. deVoest or Dr. Aykroyd

Ventricular Tachycardi

a

Ventricular Tachycardi

a

Ventr

icula

r

Tach

ycar

dia

Na/K ChannelsClass 1A, B, CClass III

Na/K ChannelsClass 1A, B, CClass III

SA

Are Your N

eeds

Being Met?

Arrhythmias in the Real World

Arrhythmias in the Real World

Acute Atrial

Fibrillation

Acute Atrial

Fibrillation

Acute Atrial FibrillationAcute Atrial Fibrillation

AF is a 72 year old white female appearing older than her stated age.

PMH: HypertensionMild COPDHypothyroidism

Pulse: 140Irregularly Irregular rhythm (A.Fib)

Acute A.Fib (AF)Acute A.Fib (AF)

Drugs:Levoxyl 150 mcg

Pravachol 20mgZestril (Lisinopril) 40mg Combivent

HCTZ 25mg daily

Case #1Case #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)Case #1:Acute A.Fib (Carol)

Pertinent Labs:TSH 0.1

EF = 18%

Acute A.Fib (Carol)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

Chronic Atrial

Fibrillation

#2 Chronic A Fib#2 Chronic A Fib

DrugsCordarone 200mg dailySynthroid 100mcg dailyAspirin dailyZestril 40mg dailyHCTZ 25mg daily

Why Synthroid?What monitoring would you

recommend?/???????????????????????

Amiodarone Side Effects Pages 4 and 5

Amiodarone Side Effects Pages 4 and 5

Bradycardia (beta blocker)Pulmonary FibrosisHyper or HypothyroidismPeripheral NeuropathyCorneal DepositsTremorAtaxiaBlue/Gray skin

http://www.code-d.com/papa-smurf/smurf-resources.php

Amiodarone monitoringAmiodarone monitoring

Normal Sinus Rhythm?Baseline PFTLFT’sTSHOphthalmologic examsQT intervalBradycardiaDrug Interactions

Amiodarone Interactions?Amiodarone Interactions?

1A2Theo

2C9 Warfarin Diazepam Phenytoin

2D6TCA’sSSRI’sBeta

Blockers

3A4 Everything

Else Statins Calcium

Blockers Amiodarone

Amiodarone Interactions?Amiodarone Interactions?QT Prolonging Drugs

Ia, Ic and III antiarrhythmicsAntipsychoticsTricyclicsSpar, Moxi, Clari, Ery, TMP,

Keto and Dopey

#3 Atrial Fibrillation#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

#4 Acute SVT

The Case of the Stressed Out Student

Acute SVTAcute 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

At least it wasn’t ugly SVT

Acute SVT TxAcute SVT Tx

DC Cardioversion if unstableValsalva maneuver or Carotid MassageVerapamilDiltiazemAdenosine

AntiarrhythmicsAntiarrhythmics

Poisons with occasionally beneficial

side effects

Sponsorship, Disclaimers, etc.

Sponsorship, Disclaimers, etc.

antiarrhythmics poisons with occasionally beneficial side effects

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