Tim Humlicek, PharmD, BCPS - PowerPoint Presentation

Slide1

Tim Humlicek, PharmD, BCPSTexas Children’s Hospital

Antiarrhythmic MedicationsSlide2

Understand the underlying theory for the use of antiarrhythmic medications

Understand

the mechanism of action for commonly used antiarrhythmic medications used in pediatric cardiac intensive careRecommend a plan to monitor patients on antiarrhythmic medications

ObjectivesSlide3
Slide4

Arrhythmias of sinus origin

Sinus Tachycardia, Sinus Bradycardia, Sinus Arrest,

Asystole Conduction blocksAV Blocks (First Degree; Second Degree:

Wenckebach

,

Mobitz Type 2; Third Degree; Bundle Branch Blocks; Hemiblocks)Ectopic rhythmsSupraventricular & ventricular arrhythmiasPre-excitationWolff-Parkinson-White Syndrome, Lown-Ganong-Levine Syndrome

Types of ArrhythmiasSlide5

Abnormally high heart rate originating above the Bundle of His

Narrow QRS complex

Can be re-entrant or focal (i.e. ectopic focus)Re-entrant ~90% of SVT

Can be incessant or paroxysmal (burst from seconds to minutes)

Morbidity:

Heart failureOther arrhythmiasSupraventricular Tachycardia (SVT)Slide6

Re-entrant arrhythmia

AV Node

Common type of SVTAge > 2 yearsMorbidityPalpitations, chest painHeart failureRe-entrant Tachycardia (AVNRT)Slide7

Re-entrant arrhythmia

Orthodromic

AntidromicMost common type of SVTNeonates and infantsMorbidityOther arrhythmiasHeart failureRe-entrant Tachycardia (AVRT)Slide8

Atrial ectopic focus/foci

“wandering pacemaker”Incessant SVTApproximately 10% of all SVTs

Adenosine can be

diagnostic

Treatment challenges<3 Years oldMorbidity:Tachycardia induced cardiomyopathyHeart FailureOther arrhythmiasAtrial TachycardiaSlide9

Re-entrant arrhythmia

ECG evidence of ventricular pre-excitation, slurred QRS upstroke (delta wave), short PR interval, wide QRS complex.

Also known as ‘pre-excitation’The ventricles become polarized before conduction in the primary pathway occursChildren with congenital heart disease

Ebstein’s

anomaly

Morbidity:Heart FailureOther arrhythmiasUse of digoxin is contraindicatedWolff-Parkinson-WhiteSlide10

Incessant (i.e. hemodynamic compromise)

Vagal maneuvers (i.e. ice to face)

Adenosine  β-antagonists (ie propranolol

)

Paroxysmal

Beta-blockers (i.e. propranolol)Second line:Amiodarone, procainamide, sotalol, & flecainideUse agent with fewest potential adverse eventsPharmacotherapy of SVTSlide11

Primarily a post-operative arrhythmia

Ectopic focus at the His/Purkinje junction

Increased heart rate  decreased cardiac outputStimulated by catecholamine release

Self-limiting

Typically resolves within 72 hours after surgery

PharmacotherapySedation and analgesiaAmiodaroneLimit patient movementNeuromuscular blockade, lower body temperatureJunctional Ectopic TachycardiaSlide12

Atrial Fibrillation / Atrial Flutter

Re-entrant arrhythmia

Atrial flutter: singleAtrial fibrillation: multiple

Rare in neonates / infants

More common in older patients

Fontan procedure (may also include IART / ‘Scar Flutter’)PharmacotherapyLimited, as most patients respond to cardioversionβ-antagonists if patients do not respond to cardioversionSlide13

Automaticity

Pacemaker cells

SA / AV node, ectopic sitesDecrease automaticity – decrease heart rateRefractory Period

Time to recharge

Increase refractory period – decrease heart rate

Conduction VelocitySpeed of impulseDecrease conduction velocity – decrease heart rateAntiarrhythmic Mechanism(s)Slide14

Class I

Sodium

Channel Antagonists (depress phase 0)Subtypes: 1a, 1b, 1cClass II

Beta-blockers (decreases slope of phase 4)

Class III

Potassium Channel Antagonists (prolongs phase 3)Class IVCalcium Channel Antagonists (prolong phase 2)DigoxinAdenosineVaughn-Williams ClassificationSlide15

Procainamide

Mechanism:

Class Ia (moderate blockade)Dosing: I.V.: LD 3-6 mg/kg (maximum 100mg), followed by infusion 20-80 mcg/kg/min

Monitoring:

Monitor procainamide (4-10 mcg/mL) and

NAPA levels (6-20 mcg/mL)High NAPA:Proc ratio – fast acetylatorLidocaine Mechanism: Class Ib (weakest blockade)Dosing:

I.V.: 1 mg/kg bolus; infusion: 20-50 mcg/kg/minute

Monitoring:

Monitor

lidocaine

levels (1.5-5 mcg/mL)

Flecainide

Mechanism:

Class

Ic

(strongest blockade)

Dosing:

Oral: 100-120 mg/m

2

/DAY divided every 8-12 hours

Monitoring:

Monitor

flecainide

troughs (200-1000

ng

/mL) – conjunction

with

ECG

Class I (Sodium Channel)Slide16

Propranolol

Dosing:

I.V.: 0.01-0.1 mg/kg/DOSE Q6-8hrs; Oral: 1-4 mg/kg/DOSE Q6-8hrsSpecial Formulations: c

ommercially

available liquid (4 mg/ml)

MetoprololDosing: Oral: 1-6 mg/kg/DAY Q12hoursSpecial Formulations: Compounded liquid (10 mg/mL tartrate) – extended release tablets available (succinate)AtenololDosing: Oral: 0.5-2 mg/kg/DAY (maximum 100 mg/DAY)Special Formulations: Compounded liquid (2 mg/mL)

Esmolol

Dosing:

I.V. Infusion: 150

– 1000 mcg/kg/min

Class I

I

(

β

-Antagonists)Slide17

Amiodarone

Mechanism:

Primary action is to prolong refractory period (K+ channel)Calcium channel blockadeβ-Antagonists

Na

+ Channel blockade

Dosing:IV Infusion: 10-20 mg/kg/DAY for 10-14 days, then maintenance dosing (oral): 2.5-5 mg/kg/DAYMonitoringCan cause hypotension on IV administration (Polysorbate 80)Hepatic injury, hypothyroidism, corneal deposits, skin sensitivityClass III (Potassium Channel)Slide18

Sotalol

Mechanism

K+ channel blockade (increasing refractory period)Beta-blockade (decrease automaticity)

Dosing

120-200 mg/m2/day divided 2-3 times daily

FormulationsOral and IV (new) formulations availableMonitoringQT prolongation / Torsades des PointesFemales > MalesClass III (Potassium Channel)Slide19

Mechanism: Centrally acting (myocardium) calcium channel

blockade

Not typically used in pediatric patientsDosing:

Verapamil

IV: 0.1-0.3 mg/kg (maximum 5-10 mg in children) every 30 minutes as needed

DiltiazemIV: 0.25 mg/kg (15-20 mg) up to 0.35 mg/kg (20-25 mg); infusions: 10-15 mg/hourUse: Some children, adolescents, and adults with atrial fibrillation/flutterDo not use in patients < 1 year of ageCardiovascular collapse has been noted in patients Class IV (Calcium

Channel)Slide20

Mechanism: AV

node

Decreases automaticityDosing: IV:

3.75-7.5 mcg/kg/DAY divided every 12 hours

Oral: 5-10 mcg/kg/DAY divided every 12 hours

Changes in exposureDrug-drug interactions, renal functionDigoxin toxicitySigns and symptoms under recognizedMonitoring: serum concentrations are rarely usefulPoor correlation with toxicityUse: primarily to treat SVT in infantsDigoxinSlide21

Mechanism:

Blocks AV node

‘Re-sets’ re-entrant circuit SVTDosing

IV: 0.05-0.1 mg/kg to maximum of 0.2 mg/kg (or 12 mg)

Administration: rapid IV push

Inject at site closest to heartMust travel through circulation to coronary arteriesMonitoringECG should show ‘sinus pause’Not effective – likely an ectopic focusUse: Hemodynamically unstable patients with SVTShort half-life: 5-10 secondsMetabolized by red blood cells

AdenosineSlide22

Understand the underlying theory for the use of antiarrhythmic medications

Understand

the mechanism of action for commonly used antiarrhythmic medications used in pediatric cardiac intensive careRecommend a plan to monitor patients on antiarrhythmic medications

ObjectivesSlide23