RX412 PDA2 E4: Antiarrhythmics 1

What are the therapeutic targets of Antiarrhythmics?

Sodium, potassium, and calcium.

What are 5 of the common causes of cardiac arrhythmias?

Acute MI

Anesthesia

Digoxin use

Electrolyte imbalances

Suffered trauma

What is the major effect of cardiac arrhythmias?

Decrease cardiac output

What is the normal range of heart rate?

60-100

What is a heartbeat below average (assuming not athletic)?

<60bpm

What is a heartbeat above average (at rest)?

>100bpm

What are the origins of site for bradycardia?

Sinus bradycardia

AV / heart block

What are the sites of origins for AT (Atrial tachycardia)?

Sinus tachycardia

Atrial flutter (AFI)

Atrial fibrillation (AF(ib))

What are the sites of origin for VT (Ventricular tachycardia)?

SVT and PVST6

What are the 5 phases of action potentials in the heart?

P wave

PR interval

QRS complex

T wave

QT interval

What is the P wave?

Atrial depolarization

What is the PR interval?

From initial depolarization of atria to initial depolarization of ventricles.

What is the QRT complex?

Ventricular depolarization

What is the T wave?

Ventricular repolarization

What is the QT interval?

Covers ventricular depolarization and repolarization

Describe the stages of action potentials

SA node generates action potentials

Myocytes see them and goes down the nerves (Causes delay)

AV nodes get the signal and sends it to the perkinji cells

Perkinji cells send the alert to ventricles

Which components of the heart have spontaneous depolarization? what phase would you see that in?

SA node and AV nodes to some extent. You’ll see it in phase 4

What tissues in the heart normally have automaticity?

Pacemaker cells

• SA-native pacemakers

• AV-latent pacemakers

Latent pacemakers

• Conductive tissue (Bundle of histamine and purkinje fibers)

When would the heart use AV-latent pacemakers?

If the SA-native pacemakers aren’t working

What heart rate is associated with SA-native pacemakers? (Generally)

60-80bpm

What heart rate is associated with AV-latent pacemakers? (Generally)

50-60bpm

When would the heart use latent pacemakers?

When both SA-native and AV-latent pacemakers are not working

What heart rate is associated with latent pacemakers?

30-40bpm

What tissues in the heart lack automaticity?

Ventricular myocytes

Atrial myocytes

What type of tissue are atrial and ventricular myocytes?

Muscle fibers

What are ventricular and atrial myocytes in charge of in the heart?

Contract and pump blood

What ions move across the plasma membrane during action potentials?

sodium, potassium, and calcium.

What is going on in phase 0 of SA and AV node action potential

Calcium influx through L-type calcium channels

What is going on in Phase 3 of SA and AV node action potential?

efflux of potassium through Na/K pumps to repolarize the cell

What is going on in phase 4 of SA and AV node action potential?

Gradual sodium influx through funny sodium channels to depolarize cell to threshold

How does Tachyarrhythmia happen?

Re-entry of conduction at the AV node

What is it called when there is a re-entrant circuit within/near the AV node?

Supraventricular tachycardia (SVT)

What phase of the action potential do L-type calcium channel blockers target?

Phase 0

What happens in phase 1 of an action potential?

Brief potassium efflux

What cell is phase 1 unique to?

Purkinje

What phase is contraction linked to?

Phase 2

What channels allow a sloped phase 4?

Leaky channels (1 calcium and 1 sodium entry for every potassium exit)

What is the mechanism of tachyarrhythmia? (Not SVT)

Enhanced automaticity due to increased phase 4 slope-diastolic “Leaky” channels

What is the mechanical stretch of cardiac muscle and how do leaky channels cause it?

Hypertrophy → Cells become big because more sodium and calcium entry than potassium exit

What is the result of mechanical stretch of cardiac muscle cells?

HPN

Heart failure

Valvular heart disease

How do leaky channels lead to hypokalemia?

Decrease potassium in the blood and cell

What cells are leaky channels found in?

Purkinje and myocytes

What causes beta stimulation in Purkinje and myocytes?

Increased inward leak of sodium in phase 4 due to leaky channels

What is the result of hypoxia / ischemia in phase 4 of purkinje cells?

Decrease of Na / K ATPase pump activity → Increase calcium returned to cell

What are the 4 mechanisms of enhanced / abnormal automaticity of myocytes / Purkinje cells (Increased phase 4 slope)?

Mechanical stretch of cardiac muscle cells

Hypokalemia

Beta stimulation

Hypoxia / ischemia

What are 3 ways to reduce rate of spontaneous discharge / enhanced automaticity?

Decrease phase 4 slope

Increase threshold potential

Increase action potential duration

What is DAD?

Delayed after-depolarizations

what is the pathophysiology of DAD?

Intracellular calcium overload

What a possible causes of DAD?

Myocardial ischemia

Adrenergic stress

DIGOXIN TOXICITY

Hypercalcemia

What is this an example of?

DAD

What is EAD?

Early afterdepolarizations

What is the pathophysiology of EAD?

Inward movement of sodium or calcium during phase 3 repolarization

What are the causes of EAD?

Phase 3 prolongation

• Slowed repolarization

• Long QT interval

What is this an example of?

EAD

What are the 3 treatments for DAD?

Calcium channel blockers

Sodium channel blockers

Beta-adrenergic blockers

What are the 2 treatments for EAD?

Calcium channel blockers

Beta-Adrenergic blockers

What are the 3 treatments for Sodium channel dependent reentry?

Sodium blockers

Potassium channel blockers

Amiodarone

What 2 drugs induce sinus bradycardia?

Digoxin and verapamil

How does Digoxin cause sinus bradycardia?

Increase vagal tone

How do you treat Digoxin induced Sinus Bradycardia?

Anti-digoxin Abs

What drug induces Atrial tachycardia with AV block?

Digoxin

How does Digoxin cause Atrial tachycardia with AV block?

DAD-related triggered activity with or without increased vagal tone

How do you treat digoxin-induced atrial tachycardia with AV block?

Anti-digoxin Abs

What drug induces AV block?

Diltiazem

How do you treat Diltiazem induced AV block

Temporary pacing

How do you treat Verapamil induced Sinus Bradycardia?

Calcium

How does Verapamil cause Sinus bradycardia?

Calcium channel blocking

What drug induces ventricular fibrillation?

Inappropriate use of IV verapamil

How does IV verapamil induce ventricular fibrillation?

Severe hypotension and/or myocardial ischemia

What is the treatment for verapamil induced ventricular fibrillation?

Cardiac resuscitation

What drug induces Torsade’s de pointes?

Dofetilide (Used in atrial fibrillation)

How does dofetilide cause TDP?

EAD-related triggered activity

How do you treat dofetilide induced TDP?

Isoproterenol

What are atrial fibrillations?

Atriums contract irregularly and rapidly