Antiarrhythmic Drugs

Question 1

What are the classes of anti-arrhythmic?

Answer 1

• I - Sodium channel Blockers
  
  • Ia - Moderate phase 0 depression and slowed conduction (2+), prolong repolarization
  • Ib - Minimal phase 0 depression and slow conduction (0-1+); shorten repolarization
  • Ic - Marked phase 0 depression and slow conduction (4+); little effect on repolarization
• II - Beta-Adrenergic Blockers
• III - Potassium Channel Blockers (prolong repolarization)
• IV - Calcium Channel Blockers

Question 2

What is the mechanism of Class I drugs?

Answer 2

• Act on fast response cells
• Reduce membrane responsiveness
• Increase threshold for AP firing Reducing Vmax (depress conduction velocity)
• Prolong effective refractory period (ERP)

Question 3

What is a Class 1A Drug? What are its direct effects? What are its indirect effects? What are its indications?

Answer 3

Qunidine

• Direct: Increase AP threshold, ERP; Decrease Vmax
• Indirect effects: Blocks K channels leading to early afterdepolarizations (EADs), vagolytic effect
• Use: A-Flutter/fib, Prevention of V-Tach/Fib

Question 4

What are Quinidne’s side effects? Where is it metabolised? Can it be used with renal failure?

Answer 4

• SE: GI effects - Diarrhea, cramps; Vagolytic in heart, P450 inhibition, Proarrythmic for other arrythmias, reduces renal clearance of digitalis
• Liver metabolism
• Tolerated in patients with renal failure

Question 5

What is a Class 1B Drug? What are its direct effects? What are its SE? What are its indications?

Answer 5

Lidocaine

• Direct: Increase AP threshold; Decreases Vmax/Na channel activity at high HR, AP duration, ERP SE: Dizziness, seizures
• Use: V-Tach, Digitalis inudced arrhythmias, Safe with long QT patinets

Question 6

What is a Class 1C Drug? What are its direct effects? What is its major SE? What is its indication?

Answer 6

Flecainide

• Direct: Increase AP threshold; decrease Vmax/conduction velocity; variable effects on ERP; Slow Na channel dissociation
• SE: Pro-arrhythmic
• Use: Life-threatening situations where supraventricular and ventricular arrhythmias are resistant to other drugs

Question 7

What are some class II drugs and their specific kinetics? What is their mechanism? Which part of the action potential do they affect?

Answer 7

• Drugs: Propranolol - Long acting, oral Esmolol - Short acting, IV
• Mechanism: Competitive inhibitor of catecholamines for the beta-adrengergic receptors of cardiac cells
• Affects phase 4 (diastolic) depolarization in the presence of catecholamines

Question 8

What are the indications for beta-blockers? What are the major side effects?

Answer 8

• All atrial arrhythmias, V-Tach/Fib when there are high levels of catecholamines
• Most useful antiarrhythmic drugs due to safety and wide clinical applications
• Safe for long QT syndrome patients because they do not prolong repolarization in ventricular tissues
• Major side effects - Negative inotropic effect, heart block, bradycardia, bronchospasm

Question 9

What are some class III drugs? What is the general mechanism? What is the most common target? What is the main common effect?

Answer 9

Amiodarone, Sotalol

• Main mechanism: K+ Channel Block, prolongs AP repolarization; reverse use-dependence
• Target: IKr (hERG channel)
• Effect: Increased ERP

Question 10

What are the channel actions of amiodarone? What are its effects? What are its indications? What are its major side effects?

Answer 10

• Potent K+ channel blockers, modest Na+, Modest Ca2+, Modest Beta-blocker
• Effect: Potent K+ channel blocker, Increased AP duration, ERP
• Use: V-Tach/Fib, prevention of recurrent paroxysmal A-Fib/Flutter SE: Triggered arrhythmias (EADs), rarely Torsades de Pointes; Altered thyroid function/hypothyroidism, pulmonary fibrosis often irreversible

Question 11

What are the actions of Sotalol? What are the indications of Sotalol? What is the most serious side effect?

Answer 11

• Actions: Main: IKr block, Beta-blocking secondary actions
• Uses: V-Tach/Fib. Supraventricular tach, A-Fib
• Side effect: Triggered arrhythmias, Torsades de Pointes

Question 12

What is this?

Answer 12

Torsade de Pointes

Question 13

What are some Class IV drugs and the family they belong to?
What is their primary mechanism?
What are the major effects?
What are the indications?

Answer 13

Diltiazem (Benzothiazepines), Verapamil (Phenylalkylamines)
Mechanism: Acts primarily on slow response cells (SA & AV node), dependent on Ca2+ influx for depolarization
Increase threshold for AP firing in nodal cells, nodal cell refractory period; depress conduction velocity in the SA and AV nodes
Uses: A-Tach (Paroxysmal supraventricular tachycardia); Rarely for V-Tach

Question 14

Why are 1,4-DHPs not generally used for arrythmias?

Answer 14

They target vascular instead of cardiac cells; instead prescribed for treatment of angina to releieve arterial spasms

Question 15

What are the major side effects of Ca2+ blockers?
Common
Specific (Nifedipine, Verapamil, Diltiazem)

Answer 15

Common: Negative chronotropic effect - decreases SA node automaticity (bradycardia)
Negative inotropic effect - decreases Ca2+ influx during plateau of ventricular AP
Hypotension - Decreases Ca2+ influx into vascular smooth muscle cells

Peripheral edema (N-type mostly)
Constipation (V especially)
With digitalis to slow AV node leading to heart block (V&D)
Increase plasma digitalis levels by competiting for renal excretion (V&D)

Question 16

What is the mechanism of adenosine?
What is the indication?

Answer 16

• Mechanism: Very rapidly activates K+ channels to slow phase 4 depolarization at AV node (Half-life of 10 seconds)
• Blocks cAMP-enhanced Ca2+ channel activity in AV node
• Use: Supraventricular Tachycardia - Slows AV conduction and heart rate

Question 17

What is digoxin?
What is its mechanism?
What is its indication?

Answer 17

Digitalis Glycoside
Mech: Enhances vagal parasympathetic activity to slow conduction at the AV node
Use: A-Fib, Supraventricular Tachycardia to control ventricular response rate

Question 18

What ECG pattern is this?

Answer 18

Normal Sinus Rhythm

Question 19

What ECG pattern is this?

Answer 19

Sinus Tachycardia

Question 20

What ECG pattern is this?

Answer 20

Atrial Fibrilation

Question 21

What ECG pattern is this?

Answer 21

Ventricular Tachycardia

Question 22

What ECG pattern is this?

Answer 22

Ventricular Fibrillation

Question 23

What ECG pattern is this?

Answer 23

Ventricular Asystole (Flat line)

Question 24

What are the three main mechanisms of arrhythmias?

Answer 24

Increased automaticity (Inappropriately excitable cells)
Triggered automaticity (Normal AP is interrupted or followed by an abnormal depolarization; afterdepolarizations)
Re-entry (Abnormal impulse conduction)

Question 25

What changes can occur in increased automaticity?

Answer 25

Slope of phase 4 is increased
Threshold potential is more negative
Maximum diastolic potential (MDP) is more positive

Question 26

What is Early Afterdepolarization (EAD)?
What exacerbates it?
What can it result in?

Answer 26

Depolarization that interrupts repolarization
Exacerbated by slow rate/long QT syndrome
Torsades de Pointes results

Question 27

What is Delayed Afterdepolarization?
What exacerbates it?

Answer 27

Depolarization after repolarization
Exacerbated by fast rates, high intracellular Ca 2+, digitalis toxicity, catecholamines, ischemia

Question 28

What is re-entry?
What causes functionally defined re-entry?
Where can anatomic re-entry occur?

Answer 28

Re-excitation of a localized region of tissue from the same impulse (Current goes backwards)
Functionally defined: Ischemia and hypoxia
Anatomic: AV node