Na channel blockers (Class 1 antiarrhythmic drugs)

Question 1

Which group of drugs is class I antiarrhythmics?

Answer 1

Na channel blokcers

Question 2

Na channel blockers - MOA

Answer 2

Bind to open and inactivated sodium channels. Dissociate during resting stage. More pronounced effect on rapidly firing cardiac tissue.

Question 3

Use-dependent blockade: what does it mean?

Answer 3

Na channels in rapidly firing cardiac tissue spend more time open and inactivated. Since this is when the Na channel blockers bind to the channels, they suppress conduction more in e.g. tachycardia than in normal rhythm.

Question 4

Na channel blockers - subdivisions (3) and their drugs (3, 2, 2)

Answer 4

Class IA: Quinidine, disopyramide, procainamide.
Class IB: Lidocaine, mexiletine.
Class IC: Flecainide, propafenone.

Question 5

Main differences between the classes of Na channel blockers

Answer 5

Class IA: Open>inactivated Na channels. Slow dissociation.
Class IB: Inactivated>open Na channels. Rapid dissociation.
Class IC: Open>inactivated Na channels. Very slow dissociation.

Question 6

Class IA - affinity for which channels and effects.

Answer 6

Fast Na channels and delayed K channels.
Decreased conduction velocity. Prolonged ventricular action potential and refractory period. (Prolonged QRS and QT intervals. Suppress ectopic automaticity without suppressing SA node automaticity.
Antimuscarinic activity - inhibit vagal effects on SA and AV nodes.

Question 7

Degree of antimuscarinic activity of the class IA Na channel blockers

Answer 7

Disopyamidine - highest
Quinidine - intermediate
Procainamide - least

Question 8

Quinidine - indications

Answer 8

Malaria and fever. Suppress supraventricular and ventricular arrhythmias.

Question 9

Quinidine - adverse effects

Answer 9

Diarrhea.
Torsade de pointes. Reduced cardiac output causing syncope.
Thrombocytopenia.
High doses: tinnitus, dizziness, blurred vision

Question 10

Procainamide - Adverse effects

Answer 10

Long-term: Reversible lupus like syndrome (arthralgia, butterfly rash)

Question 11

Administration of Class I antiarrhythmics

Answer 11

All orally except lidocaine (parenteral)

Question 12

Procainamide - indications

Answer 12

Acute ventricular arrhythmia

Question 13

Disopyramide - indications

Answer 13

Life-threatening ventricular arrhythmias (sustained VT)

Question 14

Disopyramide - contraindications

Answer 14

Asymptomatic ventricular premature contractions. Heart failure and elderly patients.

Question 15

Lidocaine - effects

Answer 15

Has more pronounced suppression of conduction in ischemic tissue than normal tissue. (little effect on normal tissue)

Question 16

Lidocaine - adverse effects

Answer 16

High serum level: nervousness, tremor, paresthesia.

Toxic doses: cardiac arrest.

Question 17

Lidocaine - interactions

Answer 17

Metabolized by cytochrome P450 enzymes.

Question 18

Lidocaine - indications

Answer 18

Local anesthesia. Refractory VT or ventricular arrhythmias associated with cardiac surgery.

Question 19

Mexiletine - indications

Answer 19

Long-term suppression of life-threatening ventricular arrhythmias.

Question 20

Class IC antiarrhythmic drugs - benefits

Answer 20

Do not prolong QT interval substantially.

Question 21

Flecainide - indications

Answer 21

Supraventricular arrhythmias, documented life-threatening ventricular arrhythmias.

Question 22

Flecainide - contraindications

Answer 22

MI

Question 23

Flecainide - adverse effects

Answer 23

Reenterant VT, bronchospasm, leukopenia, thrombocytopenia, seizures.

Question 24

Propafenone - indications

Answer 24

Long-term suppression of supraventricular tachycardia and atrial fibrillation. Life-threatening ventricular arrhythmias (sustained ventricular tachycardia).

Question 25

Propafenone - adverse effects

Answer 25

Ventricular arrhythmias, agranulocytosis, anemia, thrombocytopenia.