AP and Antiarrhythmics

Question 1

What is the process of electrical conduction in the heart?

Answer 1

1. SA node fires
2. Excitation spreads through atrial myocardium
3. AV node fires
4. Excitation spreads down AV bundle
5. Purkinje fibers distribute excitation through ventricular myocardium

Question 2

What do pacemaker cells have?

Answer 2

Automaticity

Question 3

What are the channels in the sodium channels?

Answer 3

Voltage gated, Nav1.5

Question 4

What are the channels in the calcium channels?

Answer 4

N type Cav2.2, t type Cav3.x

Question 5

What are the channels in the potassium channels?

Answer 5

Kir, Kv

Question 6

What are the channels in the HCN channels?

Answer 6

HCN1, HCN4

Question 7

What is the channel to avoid when developing new drugs?

Answer 7

hERG

Question 8

What are pacemaker cells?

Answer 8

• Specialized, non-contractile cells
• Physiologically depolarized
• High automaticity
• Ca dependent spikes

Question 9

What are ventricular myocytes?

Answer 9

• Contractile cells
• Hyperpolarized
• Low automaticity
• Na dependent spikes

Question 10

What drugs are in the class 2 beta adrenergic antagonists?

Answer 10

Esmolol, Acebutolol, Propranolol

Question 11

What are the clinical uses of class 2 beta adrenergic antagonists?

Answer 11

• Arrhythmias involving catecholamines
• Atrial arrhythmias (protect ventricular rate)
• Post MI prevention of ventricular arrhythmias
• Prophylaxis in long QT syndrome

Question 12

Specifics of esmolol:

Answer 12

• Cardioselective (b1 AR)
• 9 min half life due to plasma esterase hydrolysis
• Given IV

Question 13

Specifics of acebutolol:

Answer 13

• Cardioselective
• Weak partial agonist at b1 AR (sympathomimetic)
• Weak Na channel blockade

Question 14

Specifics of propranolol:

Answer 14

• Non selective
• Weak Na channel blockade

Question 15

What drugs are in the class 4 Ca channel blockers?

Answer 15

Verapamil, Diltiazem

Question 16

Specifics of verapamil:

Answer 16

• Frequency dependent block of Ca1.2 channels
• Selective block for channels opening more frequently
• Accumulation of blockade in rapidly depolarizing tissue (ie tachycardia)

Question 17

Specifics of diltiazem:

Answer 17

• Block re-entrant arrhythmias involving AV node
• Protect ventricular rate in atrial flutter and afib

Question 18

What is the drugs in class 1A Na channel blockers?

Answer 18

Quinidine, Procainamide, Disopyramide

Question 19

What is the drugs in class 1B Na channel blockers?

Answer 19

Lidocaine, mexiletine

Question 20

What is the drugs in class 1C Na channel blockers?

Answer 20

Flecainide, Propafenone

Question 21

What are the effects of class 1A drugs on action potential?

Answer 21

• Mixed block: Na and K channels
• Blocks open state
• Moderate, incomplete dissociation
• Widen QRS
• Prolonged QT

Question 22

What are the effects of class 1B drugs on action potential?

Answer 22

• Na channel block
• Blocks open and inactivated state
• Rapid, complete dissociation
• Slight narrowing of action potential
• No clinically sig effect on ECG

Question 23

What are the effects of class 1C drugs on action potential?

Answer 23

• Strong Na channel block
• Blocks open state
• Very slow, incomplete dissocation
• Widen QRS

Question 24

What is the MOA of class 3 K channel blockers?

Answer 24

• Block Ikr, prolong action potential duration and QT interval
• Increases effective refractory period
• IN re-entrant circuit, increased ERP above conduction time around circuit will terminate re-entry