Yang Yang AP and Antiarrhythmics

Question 1

Important ion channels in the heart

Answer 1

-Sodium channels
-Calcium channels
-Potassium channels
-HCN channels
-hERG channels (avoid targeting when developing new drugs)

Question 2

Potassium concentration outside the cell

Answer 2

5 mM

Question 3

Sodium concentration outside the cell

Answer 3

142 mM

Question 4

Calcium concentration outside the cell

Answer 4

5 mM

Question 5

Chloride concentration outside the cell

Answer 5

103 mM

Question 6

Potassium concentration inside the cell

Answer 6

148 mM

Question 7

Sodium concentration inside the cell

Answer 7

10 mM

Question 8

Calcium concentration inside the cell

Answer 8

<1 uM

Question 9

Chloride concentration inside the cell

Answer 9

4 mM

Question 10

Voltage value inside the cell

Answer 10

-70 mV

Question 11

Voltage value outside the cell

Answer 11

0 mV

Question 12

What are pacemaker cells?

Answer 12

-Specialized, non-contractile cells
-Physiologically depolarized
-High automaticity
-Ca2+-dependent spikes

Question 13

What are ventricular myocytes?

Answer 13

-Contractile cells
-Hyperpolarized
-Low automaticity
-Na+-dependent spikes

Question 14

Common arrhtyhmias

Answer 14

-Atrial sinus arrhythmia
-Re-entry arrhythmias
-Atrial fibrillation
-Wolf-Parkinson White
-Monomorphic ventricular tachycardia
-AV nodal re-entrant tachycardia
-Premature ventricular complexes

Question 15

Re-entry arrhythmia requirements

Answer 15

-Multiple parallel pathways
-Unidirectional block
-Conduction time greater than ERP (effective refractory period)

Question 16

What are class 1 antiarrhythmic drugs?

Answer 16

Na+ channel blockers

Question 17

What are class 2 antiarrhythmic drugs?

Answer 17

Beta-adrenergic antagonists

Question 18

What are class 3 antiarrhythmic drugs?

Answer 18

Agents that prolong refractory period (K+ channel blockers)

Question 19

What are class 4 antiarrhythmic drugs?

Answer 19

Ca2+ channel blockers

Question 20

Class 2 antiarrhythmic drug mechanism of action

Answer 20

-Beta adrenergic blockers
-Slows pacemaker and Ca2+ currents in SA, AV node
-Increase refractoriness of SA, AV node
-Increase P-R interval
-Arrhythmias involving catecholamines (epinephrine, norepinephrine, etc . . .)

Question 21

Class 4 antiarrhythmic drug mechanism of action

Answer 21

-Ca2+ channel blockers
-Frequency-dependent block
-Increase refractoriness of AV node and P-R interval
-Protect ventricular rate from atrial tachycardia

Question 22

Beta blockers used as antiarrhythmics

Answer 22

-Esmolol
-Acebutolol
-Propranolol

Question 23

Beta blocker clinical use as antiarrhythmics

Answer 23

-Arrhythmias involving catecholamines
-Atrial arrhythmias (protect ventricular rate)
-Post-MI prevention of ventricular arrhythmias
-Prophylaxis in Long QT syndrome (catechol.-sens)

Question 24

Calcium channel blockers used as antiarrhythmics

Answer 24

-Verapamil
-Diltiazem

Question 25

Calcium channel blocker clinical use as antiarrhythmics

Answer 25

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

Question 26

Class 1A antiarrhythmic effect on action potential

Answer 26

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

Question 27

Class 1B antiarrhythmic effect on action potential

Answer 27

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

Question 28

Class 1C antiarrhythmic effect on action potential

Answer 28

-Strong Na+ channel block -Blocks open state -Very slow, incomplete dissociation -Widen QRS

Question 29

Class 1A antiarrhythmic drugs

Answer 29

-Quinidine -Procainamide -Disopyramide

Question 30

Class 1B antiarrhythmic drugs

Answer 30

-Lidocaine -Mexiletine -Tocainide -Phenytoin

Question 31

Class 1C antiarrhythmic drugs

Answer 31

-Flecainide -Propafenone -Moricizine

Question 32

Quinidine clinical pearls

Answer 32

-2-8% risk of torsades de pointes -Aniti-muscarinic activity

Question 33

Procainamide clinical pearls

Answer 33

-Lupus-like syndrome -Ganglionic blocker

Question 34

Disopyramide clinical pearls

Answer 34

-Anti-muscarinic activity

Question 35

Lidocaine clinical pearls

Answer 35

-IV only; not effective orally -Among top choices for rapid control of ventricular arrhythmias -Only ventricular, not atrial

Question 36

Mexiletine clinical pearls

Answer 36

-Orally available, similar to lidocaine in efficacy

Question 37

Flecainide clinical pearls

Answer 37

-Ventricular and supraventricular -Orally available

Question 38

Propafenone clinical pearls

Answer 38

-Ventricular and supraventricular -Beta receptor blocking activity -Orally available

Question 39

Class 3 antiarrhythmics mechanism of action

Answer 39

-Block IKr, prolong action potential duration and Q-T interval -Increases effective refractory period -In re-entrant circuit, increased ERP above conduction time around circuit will terminate re-entry

Question 40

Why can class 3 antiarrhythmics cause TDP?

Answer 40

-IKr block induces EADs and triggered upstrokes -Multifocal/polymorphic ventricular tachycardia -Can degenerate into ventricular fibrillation

Question 41

Class 3 antiarrhythmic drugs

Answer 41

-Amiodarone -Dronedarone -Ibutilide -Sotalol -Dofetilide

Question 42

Amiodarone clinical use

Answer 42

-Top choice for rate control in A-fib, suppression of post-MI ventricular arrhythmias

Question 43

Dronedarone clinical use

Answer 43

A-fib

Question 44

Sotalol clinical use

Answer 44

Prevent A-fib re-occurrence

Question 45

Ibutilide clinical use

Answer 45

Convert A-fib to sinus rhythm