Arrhythmia MedChem

SA node

• "natural pacemaker”

• electrical impulse originates

• triggers atrial contraction

AV node

• delays SA node signal before sending to ventricles

• allows time for atria to contract and fill ventricle

Bundle of His

• high speed transmission cells branching off AV node

• send signal between atria and ventricle

• end in Purkinje Fibers

Purkinje Fibers

• connect with myocytes

• initiates depolarization of muscle cells

Main electrolyes in cardiac contraction

• Na

• K

• Ca

• (Cl bc of gradient, not voltage gated channels)

Inward currents (voltage gated ion channels)

• Na

• Ca

Outward currents (voltage gated ion channels)

• K

P wave

atrial depolarization (contraction)

QRS wave

ventricular depolarization (contraction) and atrial repolarization

T wave

ventricular repolarization

PR interval

time from atrial depolarization to ventricular depolarization

conduction time through AV node

QT interval

duration of ventricular action potential

time it takes for ventricles to contract and fully relax

ST segment

period during which ventricles are depolarized

plateau phase of action potential

Phase 0 of AP

depolarization

Na+ influx

Phase 1 of AP

Fast repolarization

K+ OUT

Phase 2 of AP

Plateau

Ca2+ IN, K+ OUT

Phase 3 of AP

Terminal repolarization

K+ OUT

Phase 4 of AP

diastolic depolarization and resting membrane potential

Na/K ATPase maintain ion gradient (push 3 Na OUT, 2 K IN)

Voltage-gated Sodium Channel

• activated when membrane potential increases

• Na enters

• Na cannot enter when resting or inactivated → unavailable right after activation

Early AfterDepolarization

transient membrane depolarizations that occur during repolarization

bradycardia dependent

Delayed afterdepolarization

transient membrane depolarization that occur after repolarization but prior to phase 4

tachycardia dependent

Sinus tachycardia

• automatic/normal mechanism

• sinus node origin

Atrial fibrillation

• mechanism: reentry, automatic, triggered activity

• origin: atria, thoracic veins, pulmonary veins, and superior vena cava

Atrial flutter

• mech: reentry

• origin: right and left atria

Atrial tachycardia

• mech: reentry, automatic, triggered activity

• origin:atria

AV nodal reentry tachycardia

• mech: reentry

• origin: AV junction

AV reentry tachycardia

• mech: reentry

• origin: circuit includes accessory AV connection, atria, AV node, His-Purkinje system, ventricles

Ventricular tachycardia

• mech: reentry, atuomatic, triggered

• origin: ventricles

Torsades de Pointes

• mech: reentry, triggered activity

• origin: ventricles

Vaughan-Williams classification

classify antiarrhythmic drugs based on electrophysiologic actions

Class 1

• sodium channel blockers

• increase his-ventricle interval

• increase QRS

• oldest antiarrhythmis drugs

Class 1a

• sodium channel blocker (also potassium channel blocker)

• prolong action potential (upstroke)

• prolong QRS

• intermediate dissociation

• quinidine, procainamide, disopyramide

Class 1B

• sodium channel blocker (both activated and inactivated)

• shorten action potential

• rapid dissociation

• used in ventricular tachycardia, ventricular fibrillation

• lidocaine, mexiletine

Class 1C

• sodium channel blocker

• minimal effect on action potential

• slow dissociation

• used in supraventricular arrhythmias

• do NOT use post-MI

• flecainide, propafenone

Class 2

• beta blockers

• prolong action potential

• increase PR, atria-His interval

• slow SA and AV node, decrease HR

• used in atrial arrhythmias

Class 3

• potassium channel blockers

• prolong action potential and QT interval

• slow heart rate and AV node

• increase effective refractory period for atria and ventricle

• used in ventricular arrhythmias, supraventricular arrythmias, atrial fibrillation

• amiodarone, dofetilide, dronedarone, sotalol, ibutilide

Class 4

• calcium channel blocker

• slow conduction in SA and AV nodes

• increase PR, decrease HR

• decrease cardiac contractility

• reduce BP

• used in supraventricular tachycardia

• verapamil, diltiazem

Adenosine

• activate inward K channel, block Calcium channel

• causes brief AV blockade

• used in paroxymal supraventricular tachycardia

• IV only

Magnesium

• interact with Na/K-ATPase, K, and Ca channels

• normalizes or increases plasma Mg

• used in torsades de pointes

• IV

Potassium

• increases K permeability, K curents

• slows ectopic pacemakers, slows conduction velocity

• used in digitalis induced arrhythmias