Seven Flashcards Preview

Cardiovascular > Seven > Flashcards

Flashcards in Seven Deck (26)
Loading flashcards...

Waht are the 3 mechanisms of arrhythmia?

} Enhanced automaticity

} Triggered activity

} Reentry


Explain how enhanced automaticity leads to arrhythmia?

} Due to accelerated firing of cells

} Often due to autonomic inputs, increased

sympathetic tone

} Can be due to medications

} Examples: Inappropriate sinus tachycardia,

accelerated junctional rhythm


What is triggered activity? How does it cause arrhythmias? In what patients does it occur?

} Often result from early and delayed


} Depolarizing currents generated by calcium influx

} Often occur in patients with coronary artery

disease or heart failure

◦ Cytosolic calcium overload from energy starvation


What are early after depolarizations? When do they occur? What are they related to? What about delayed after depolarizations?

Early Afterdepolarizations (EAD’s)

} Occur during phase 3 of the cardiac action

} Tend to be related to bradycardia

} Common mechanism to arrhythmia in Long QT

Delayed Afterdepolarization (DAD’s)

} Occur during phase 4 of the cardiac action

} Can be related to ischemia, drug effects (digoxin)

} Tends to be related to tachycardia

} Calcium influx from cell during phase 4 is
typical mechanism


What is reentry? What are some examples? What are 3 requirements?

} Most common mechanism of arrhythmia

} Continuous activation loop leading to arrhythmia

} Examples: atrial flutter, AVRT, AVNRT, scar
related ventricular tachycardia


◦ Two separate (anatomic or functional) pathways

◦ Separate conduction properties (fast/slow) in the two pathways

◦ Unidirectional block in fast pathway


Explain how AVRNT works?

} Common arrhythmia within the AV node

} Two separate pathways exist in the AV node (Fast

pathway and Slow pathway)

} Early activation causes block in the fast pathway

with conduction in the slow pathway

} When conduction passes through the slow

pathway, fast pathway has recovered excitability

and conduction occurs retrograde through the fast

pathway and back to the slow pathway


How do you stop or treat reentry? What are 3 general principles of antiarrhythmic drugs?

} Increase tissue refractory period

} Increase conduction rate through tissue

} General Principles

◦ Considerable risk in use

◦ High side effect profiles

◦ Proarrhythmia


List the Vaughn-Williams classification.

} Vaughan Williams Classification

◦ Class I – Sodium Channel Blockers
– Subclassified into A, B, C

◦ Class II – Beta-blockers

◦ Class III – Potassium Channel Blockers

◦ Class IV – Calcium Channel Blockers


What is use dependents? Reverse use dependents?

} Use dependence

◦ Trait of antiarrhythmics where drug blocks/binds more

with increased heart rates

– Example: Lidocaine

◦ Reverse use dependence

– Drug binds more in the open state, more effective at

decreased heart rates

– Example: Sotalol


List the different classes of antiarrhythmics, how they work, and examples of each.

} Class IA
◦ Moderate phase 0 depression
◦ Moderately slows conduction
◦ Prolongs repolarization
◦ Examples: Quinidine, Procainamide

} Class IB
◦ Minimal Phase 0 depression
◦ Minimal slowing of conduction
◦ Shorten Repolarization
– Blockade of slow sodium currents that continue through phase 2 of action potential
◦ Examples: Lidocaine, Mexiletine

} Class IC
◦ Marked Phase 0 depression
◦ Marked Slowing of conduction
◦ Minimal repolarization changes
◦ Prolong refractory period in AV node, accessory pathways
◦ Examples: Flecainide, Propafenone

Class II
} Reduce catecholaminergic effects on pacemaker cells
} Decrease conduction velocity in sinoatrial and AV nodes
◦ Increase effective refractory period in AV node
} Weak antiarrhythmic properties
} Examples: Metoprolol, Carvedilol, Propanolol

Class III Antiarrhythmics
} Potassium channel blockers
} Prolong refractoriness
} Examples: Sotalol, Amiodarone, Dofetilide

Class IV antiarrhythmics
} L-type calcium channel blockers
} Blocks/slows conduction through the AV node
} Weak antiarrhythmic properties
} Examples: Verapamil, diltiazem



Class IA

} Very rarely used, however still shows up occasionally on board exams

} Has sodium and potassium channel blocking properties

} Can be used for both atrial and ventricular arrhythmias

} Poorly tolerated due to GI side effects (Nausea, diarrhea)

} Liver clearance

} Serious side effects include proarrhythmia, thrombocytopenia, Cinchonism (CNS toxicity)

} Increases serum digoxin concentrations and should not be used in combination with digoxin

} Has been shown to increase mortality in patients with Atrial Fibrillation



Class IA

} Can be used for atrial and ventricular arrhythmias

} Oral and IV formulations
◦ Oral form no longer available in U.S.

} IV administration: Loading dose and maintenance

◦ Hypotension during loading dose is common
– Treat with IVF, discontinuation of loading dose, reduced rate of loading dose

} Acetylation in Liver (NAPA), Renal clearance

} Rarely used due to development of lupus syndrome
during long term administration

} Other serious side effects include agranulocytosis,
proarrhythmia (NAPA)



Class IA

} Can be used for atrial and ventricular arrhythmias
◦ Vagally mediated AF
◦ HCM with outflow tract obstruction

} Common side effects include anticholinergic effects
(constipation, dry mouth, urinary retention, blurred

} Serious side effects include worsening of CHF,

} Rarely used due to side effect profile

◦ Never use in patients with history of CHF or BPH

} Renal Clearance



} Blocks INA
} Rapid onset/offset kinetics
} Little effect on atrial tissue in open state

} Pro
◦ Effective for ischemic VT
– More effective at high rates, low pH, increased extracellular K, reduced membrane potential

} Con
◦ PO equivalent (mexillitine) low potency
◦ Side effects
◦ Elevates DFT
◦ After 24 hours, clearance of drug falls

} Administration
◦ IV bolus and gtt
◦ If bolus is ineffective, gtt is also likely to be ineffective
◦ Bolus needs to administered slowly to reduce likelihood of neurologic adverse effects

◦ Heart failure: lower loading/maintenance dosing

◦ Liver disease: lower maintenance dosing (cleared by liver)

} Monitoring
◦ Levels (steady state 8-10 hours)
◦ Neurotoxicity
◦ Malignant hyperthermia (rare)



} Similar to Lidocaine in properties

} Can affect sinus node in patients with disease, no
effect on normal sinus node

} Tablet form only

} Not generally useful in acute setting

} Limited potency

} Not very effective as monotherapy

} Often used as an adjunct with other antiarrhythmics for breakthrough

} Liver clearance, neurologic side effects

} Potential for treatment of LQT3?



} Used for atrial arrhythmias

} Prolongs PR, QRS, QT intervals

} Relatively well tolerated, but can cause dizziness,
headache, visual disturbances

} Black box warning
◦ Increased mortality in patients who are post MI
◦ Drug also known to exacerbate CHF and should not be
used in patients with history of CHF or structural heart

} Can produce atrial flutter with 1:1 conduction

} Increases pacing and defibrillation thresholds

} Liver clearance



} Used primarily for atrial arrhythmias

} Well tolerated, but can cause constipation,
metallic taste, visual blurring, dizziness, nausea

} Serious side effects include CHF, proarrhythmia

} Has same black box warning as Flecainide
◦ Probably less proarrhythmic than flecainide
◦ For all intensive purposes avoid in patients with history of MI, structural heart disease, CHF

} Like Flecainide, causes increased pacing and
defibrillation thresholds, and 1:1 atrial flutter

} A small portion of the population are slow propafenone metabolizers and can develop severe bradycardia


Beta Blockers

Metoprolol, Carvedilol, Propanolol

} Indications
◦ Arrhythmias caused or enhanced by increased
sympathetic tone
◦ Arrhythmias related to ischemia
◦ AV nodal dependent arrhythmias (AVNRT, AVRT)

} Side effects
◦ Bradycardia
◦ Hypotension
◦ AV block
◦ Depression, fatigue
◦ Bronchospasm in patients with reactive airway disease



} Class III antiarrhythmic
◦ Truly has Class I, II, III, and IV effects
◦ ‘Antiarrhythmic Shotgun’
◦ Prolongs APD and refractoriness
◦ Peripheral and coronary vasodilator
◦ Antiadrenergic actions
◦ Long half-life
◦ Hepatic metobolism
◦ In general the primary first line therapy for VT

} Prolongs QT interval however Torsades de Pointes is rare (<1%)
◦ Torsades de Pointes: Polymorphic ventricular tachycardia caused by QT prolongation
} Effective for atrial and ventricular arrhythmias
} Most effective drug available for AF suppression
◦ Especially effective in CHF patients

} Adverse Effects
◦ Phlebitis, severe cellulitis with peripheral IV administration
◦ Pulmonary fibrosis (1%-17%)
◦ Corneal microdeposits, optic neuritis
◦ Liver toxicity with rare progression to cirrhosis
◦ Photosensitivity, skin discoloration
◦ Hyper and Hypothyroidism
– Large iodine load
– Inhibits peripheral conversion of T4 to T3
◦ Tremor, ataxia
◦ Rare peripheral neuropathy, insomnia, memory disturbances, delirium
◦ Raises DFT

} Administration
◦ IV bolus and gtt
◦ PO loading dose, maintenance dose
} Monitoring
◦ Pulmonary: CXR (yearly), PFT w/ DLCO
◦ Thyroid: TSH, T4, T3 (q6 months)
◦ Liver: LFT’s (q6 months)
◦ Routine eye exams



Class III
} Specific blocker of Ikr
} Virtually no extracardiac pharmacologic effects
} Used for atrial arrhythmias, specifically atrial fibrillation

} Can only be prescribed by certified practioners

} Must be initiated in the hospital due to risk of QT

} Renal clearance

} Verapamil, HCTZ (among other drugs) interfere
with clearance and are contraindicated

Reverse use dependence
◦ Can lead to excessive QT prolongation and TdP post



} Used for acute conversion of atrial fibrillation/atrial

◦ IV formulation only
} Increases APD by blockade of Ikr
} Causes mild slowing of HR and AV node
} Most effective in recent onset-arrhythmias

} Reduces defibrillation threshold
◦ Useful for failed DCCV
} Can be used safely in patients on chronic amiodarone therapy

} Administration: 1mg over 10 minutes
◦ If unsuccessful, can be repeated x 1
◦ Dose should be reduced for patients less than 60kg
◦ Infusion should be stopped once cardioversion occurs
} Patients must be monitored on telemetry for 4
hours post infusion due to risk of TdP (3.6-8.3% of



} Nonspecific beta-blocker
} Prolongs repolarization
} Modest negative ionotropic effect
} Reverse use dependence

} Pro
◦ Well tolerated
◦ Limited side effect profile
◦ Improves DFT

} Con
◦ QT monitoring/Proarrhythmic
– Torsades risk 2%
◦ Contraindicated w/ renal disease and severe

} Administration

◦ PO dosing, generally BID

◦ Higher doses have more class III properties where lower
doses have more beta-blocking properties

} Monitoring
◦ Continuous telemetry monitoring during initiation/dose
increase w/ serial ECG for QT interval
◦ Renal function



} Noniodinated congener of amiodarone
◦ Class III agent, however blocks multiple ion channels
◦ Much shorter half life in comparison to amiodarone
◦ Not associated with significant tissue accumulation
◦ Relatively new medication, long term toxicity data not yet available
} Approved for rhythm control of atrial fibrillation and
atrial flutter
◦ Studies show more effective than compared to placebo
◦ Lost to amiodarone in head to head study

} Multiple drug-drug interactions
◦ Antifungals
◦ Calcium channel blockers
◦ QT prolonging medications
◦ Digoxin
◦ Warfarin, dabigatran, rivaroxaban
◦ Metoprolol
◦ Statins

} Side effects/Contraindications
◦ Not to be used as a rate control agent
◦ Class III/IV CHF
◦ Liver toxicity
◦ Lung toxicity
◦ GI effects


Calcium Channel blockers

Verapamil, diltiazem

} Indications
◦ Treatment of reentrant supraventricular arrhythmias
◦ Slowing conduction through the AV node to decrease
ventricular response to atrial arrhythmias (atrial
fibrillation, atrial flutter, atrial tachycardia)
◦ Treatment of some ventricular ectopy/arrhythmias
– Rare use

} Side effects
◦ Bradycardia
◦ Hypotension
◦ AV block
◦ CNS side effects (headache, fatigue, anxiety)



} Adenosine
◦ Slows automaticity
◦ Hyperpolarizes cardiocytes
– Activates potassium channels
◦ Decreases cAMP by inhibiting adenylate cyclase
◦ Primary effect on AV node
– Induces AV block
◦ Short half life (10 seconds)

◦ Indication: Termination of nodal dependent reentrant



} Digoxin

◦ Cardiac glycoside used primarily for heart failure

◦ Has properties that causes slowing of conduction through the AV node
– Rate control for atrial fibrillation, flutter, SVT

◦ Enhances vagal tone and reduces sympathetic activity
– Easily overcome by increases in sympathetic tone

◦ Very small therapeutic window

◦ Renal clearance

◦ Toxicity can cause life threatening arrhythmias
– Increase in resting potential
– Decreased action potential duration
– Increased cellular automaticity
– Increased intracellular calcium

} Digoxin toxicity can lead to:
◦ Sinus bradycardia/sinoatrial block
◦ AV block
◦ APC’s/VPC’s
◦ Accelerated junctional rhythm
◦ Ventricular tachycardia