Seven 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
afterdepolarizations
} 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
potential
} Tend to be related to bradycardia
} Common mechanism to arrhythmia in Long QT
syndromes
Delayed Afterdepolarization (DAD’s)
} Occur during phase 4 of the cardiac action
potential
} 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
REQUIREMENTS
◦ 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
Beta-blockers
} 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
Quinidine
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
Procainamide
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
dose
◦ 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)
Disopyramide
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
vision)
} Serious side effects include worsening of CHF,
proarrhythmia
} Rarely used due to side effect profile
◦ Never use in patients with history of CHF or BPH
} Renal Clearance
Lidocaine
} 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)
Mexelitine
} 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?
