Anti-Arrythmia Drugs

Question 1

What are the 4 classes of anti-arrythmia drugs?

Answer 1

Class 1: Na+ Channel Blockers Class 2: Beta blockers Class 3: K+ Channel Blockers Class 4: Ca2+ Channel Blockers

Question 2

AP in cardiac muscle is slow/fast.

Answer 2

Fast

Question 3

Describe the AP in cardiac mucle

Answer 3

Phase 0: Na+ influx via VGNa+ channels. Here, VG L-Type Ca2+ channels open slowly, slowing Ca2+ to NTR.

Phase 1 (slight repolarization): K+ efflux

Phase 2 (plateau): Influx of Ca+ via slow VG L-type Ca+ channels offsets K+ efflux.

Phase 3 (repolarization): Ca2+ channels close and K+ continues to leave

Phase 4 (RMP): Controlled by Na/K ATPase and Na/Ca+ exchanger.

Question 4

Describe a pacemaker AP.

Answer 4

• Phase 4 (spontaneous depolarization): Na+/K influx via Funny Na+ channels and Ca2+ influx via slow T-type Ca2+ channels
• Phase 0 (upstroke of AP): slow, L-type Ca2+ channels cause influx of Ca2+
• Phase 3 (Repolarization): Ca+ channels inactivate and K + efflux

T-type Ca2+ channels = transient

L-type Ca2+ channels = long-acting

Question 5

What factors determine the firing rate (automaticity) of our pacemaker cells?

Answer 5

• 1. Rate of spontaneous depolization (incline of the slope)
• 2. Threshold potential
• 3. RMP

Question 6

If the slope in phase 4 is decreased, what does this tell us about our firing rate?

Answer 6

Decreased slope => decreased rate because we need more time to reach threshold

Question 7

What are the 3 states that the Na+ channel found on cardiac myocytes exists in and describe each?

Answer 7

• • Resting: the channel is closedbut ready to generate AP
    
    • m-gates closed
    • h-gates open
• • Activated state: threshold met=> depolarization opens m-gates; ↑ Na+ permeability
    
    • both gates open
• • Inactivated state (repolarization): h-gates are closed, inward Na+ flux is inhibited, the channl is not available for reactivation –> refractory period
    
    • m-gate open
    • h-gate is closed

Question 8

What are 3 cardiac AE’s associated with the class 1A antiarrhythmics, Procainamide and Quinidine?

Answer 8

• • QT interval prolongation
• • Induction of torsade de pointes arrhythmias and syncope
• • Excessive inhibition of conduction

Question 9

What is the triad of Cinchonism and what class 1A antiarrhythmic may cause this as an AE?

Answer 9

1. HA
2. Dizziness
3. Tinnitus

Quinidine

Question 10

Other SE of Quinidone

Answer 10

1. NVD

2. Cinochism triasm (dizziness, tinnitus, HA)

3. Thrombocytopenia

4. Hepatitus

Question 11

What are the cardiac AE’s of the class 1A antiarrhythmic, Quinidine?

Answer 11

QT interval prolongation –> induction of torsade de pointes arrhythmia

• Negative inotrope effect - may precipitate HF;

Question 12

What are some rare extra-cardiac and common AE’s associated with the class 1A antiarrhythmic, Procainamide?

Answer 12

1. Drug induced lupus

2. Agranulocytosis

3. Common: N/V/D, hypOtension

Question 13

The class 1C antiarrhythmic, Flecainide may be very effective in suppressing premature ventricular contractions, but pt’s with what cardiac status are at risk for AE’s and what are these effects?

Answer 13

Can worsen ventricular arrythmias when given to patients with

• 1. Pre-existing ventricular tacharrythmias
• 2. Previous MI
• 3. Ventricular ectopic rhythms

Question 14

______ was used Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multi center, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had a MI.

Answer 14

Fecainide

Question 15

What was the result of the CAST trial

Answer 15

Stopped early because flecainide and 1C drugs increased mortaility by 2.5 fold

Question 16

Propafenone

AE

Answer 16

1. Metallic taste

2. Worsen ventricular arrythmias

3. Constipation

Question 17

Clinical uses of

1. Flecainide

2. Propafenone

Answer 17

Flecainide: Patients with normal hearts who have supraventricular arrythmia

Propafenone: Patients who have supraventriculararrythmia without structural disease