Atrial Fib Background and Drugs

Steps of the propagation of the action potential

1. SA nodal cells in the atria initiate contract

2. Impulse waves travel from the SA node through the atria

3. The impulse reaches the AV node

4. The impulse is then conducted through the Purkinje fibers

5. The impulse travels through the ventricular cardiomyocytes

6. Cardiomyocytes repolarize

What determines resting membrane potential

Ion concentration inside and outside of the cell

Ion concentration at normal resting potential

Large amount of sodium outside of the cell. Large amounts of potassium inside the cell. The sodium potassium pump is used to maintain the gradient.

Cardiomyocyte Action Potential

Phase 0: Sodium channels open in response to neighboring depolarization. Causes rapid influx of sodium.

Phase 1: Potassium channels open and K+ leaves the cell.

Phase 2: Calcium channels also open and calcium go into the cell. Sodium Channels close.

Phase 3: Calcium Channels close and potassium channels remain open to repolarize the cell.

Phase 4: channel close and are at reset resting membrane potential.

SA/AV node action potential

Phase 4: Slow influx of sodium ions “funny current”

Phase 0: Calcium channels open, large influx of calcium

Phase 3: Potassium channels open, potassium leaves the cell causing repolarization

P-wave

Atrial conduction

P-Q interval

Conduction between SA/AV nodes

QRS complex

Ventricular depolarization/contraction

QT interval

Time until ventricle is repolarized

T Wave

Repolarization of the myocardium

Open Channel

Activation causes opening

Closed chanel

Not open but can be activated

Inactivated channel

closed and unable to open because of inactivation gate

ARP

Absolute refractory period, impossible to fire

ERP

Effective refractor period, small but incomplete depolarizations may occur

RRP

relative refractory period, very strong stimuli can initiate propagating

What is automaticity

The intrinsic rate at which pacemaker cells fire. SA node can have pathological changes in automaticity. Non SA cells can gain automaticity disturbing conduction.

Triggered arrythmias

Caused by areas of the heart that initiate an errant beat that leads to additional unorganized electrical activity

EAD

Early afterdepolarization arrythmia that occurs while the AP is still occurring. Usually happens in phase 3

DAD

Delayed after depolarization arrythmia occurs after the AP has completed but premature to the normal rhythm. Often initiated by too much Calcium influx associated with damaged cells or altered signaling.

Atrial fibrallation

Most common arrythmia. Irregular and disordered electrical activity of the atria. Loss of P wave.

Atrial Flutter

Increased rate of atrial firing (automaticity). More organized than afib. Too fast to conduct through AV node and cause ventricular firing.

AFib and Remodeling

Fibrotic or ischemic tissue can have different electrical properties that impair normal propagation

What are the 4 classes of antiarrhythmic drugs

Class 1: Na+ Channel Blocker

Class 2: Beta Blockers

Class 3: K+ Channel Blockers

Class 4: Ca2+ Channel Blocker

Which classes of drugs are used of rhythm control

Class 1a: Na Channel Blockers

Class 3: K Channel Blockers

What drugs are class 1a sodium channel blockers

Quinidine, Procainamide, Disopyramide

What drugs are Class 1b sodium channel blockers

Lidocaine, tocainide, mexiletine

What drugs are class 1c sodium channel blockers

Flecainide, propafenone

What drugs are Class III potassium channel blockers

Amiodarone, Dronedarone, Sotalol

Effects of sodium Channel blockers

They decrease conduction velocity, increase duration of action potential, and increase refractory period

Class 1a and 1c bind to what kind of channels

Open state. They have a more pronounced effect on sodium currents but are slower on/off

Class 1b binds to what kind of channls

Inactivated channels. Have milder effect but faster on/off.

Effects of Class 1a Sodium Channel Blockers

Slow CV, Prolong refractoriness, Increase APD, Decrease automaticity

When are Class 1a Sodium channel blockers used

In atrial and ventricular arrythmia

Additional effects of class 1a Sodium Channel Blockers

Have K+ blocking activity that contribute to the prolongation of APD

Adverse effects of Class 1a sodium channel blockers

Can promote ventricular arrythmia

Effects of Class 1b sodium channel blockers

Slow conduction only at high heart rates

Are class 1b sodium channel blockers used for atrial fibrillation or flutter

no

Effects of class 1c sodium channel blockers

Slow CV, prolong phase 0. Slow on/off

Additional effects of flecainide

Some inhibition of RyR limiting calcium release. May decrease EAD and DAD caused by excess calcium.

Additional effects of propafenone

Beta blocking activity. Slows HR and limits calcium cycling.

Effects of K+ Channel Blockers

Prolong phase 3 of the action potential and increase refractory time. Increase APD, increases refractory period (limit reentrant arrythmia), increase QT interval

Properties of Amiodarone

Very lipophilic. Extremely long half-life. Inhibits automaticity, increases APD, prolongs ARS, lowers HR, slows conduction. Has properties of all 4 classes of drug.

Properties of Drondarone

Similar to amiodarone. Shorter half life. Less side effects.

Properties of Sotalol

Has beta blocking activity. Increases APD and slows HR. Prolongs refractoriness. Decreases automaticity and slows conduction.

Properties of Ibutilide and Dofetilide

Not as effective or potent as amiodaron for afib

Adverse effects associated with Amiodarone

Numerous drug interactions (CYP450). Pulmonary fibrosis, thyroid problems, ventricular tachycardia, bradycardia, AV block

Beta 1 Selective BB

Bisprolol, Metoprolol, Esmolol, Propranolol (Na+ inhibition), Sotalol (K+ inhibition), Esmolol (IV fast acting)

Why are BB used for arrythmias

Slow HR (rate control), Slow conduction, reduce calcium signaling to myocytes, reduce remodeling and fibrosis

Why are Non-DHPs used for arrythmias

Slow HR, slow conduction, increase AV node refractoriness

Adverse effects of Non-DHPS

AV block, bradycardia, hypotension

General: How do Class 1a Na Channel Blockers help rhythm control

Decrease conduction, prolong APD, and increase RP

General: How do Class 1b Na Channel Blockers help rhythm control

Slight decrease in conduction, decrease APD, RP

General: How do Class 1c Na Channel Blockers help rhythm control

Large decrease in conduction, no change to APD, RP

General: How do Beta Blockers help rate control

Decrease automaticity, decrease conduction, and increase RP of SA/AV node

General: How do Class III K+ channel blocker help rhythm control

No effect on conduction velocity (except amiodaron and dronedarone), Increase APD, increase RP

General: How do Class IV Ca Channel Blockers help rate control

Decrease automaticity (HR), decrease conduction velocity (SA/AV node), increase APD and RP (SA/AV node)