Lecture 12: Anti-Arrhythmic Drugs (Part II)

Question 1

What three drugs make up the Class 1A Anti-Arrythmic Class?

Answer 1

Quinidine, Procainamide, Disopyramide

Question 2

How do Class 1A Anti-Arrythmics raise the threshold for AP and slow rate of depolarization in cardiac muscles?
(hint: what channels do they block?)

Answer 2

Block Na+ channels (preference for open channels)

Question 3

How do Class 1A Anti-Arrythmics affect phase 0 upstroke? myocardial conduction velocity?

Answer 3

Class 1A Anti-Arrythmics
- Phase 0 upstroke: decrease
- Myocardial conduction velocity: decrease

Question 4

True or False: Class 1A Anti-Arrythmics block Na and K channels

Answer 4

True

Question 5

How do Class 1A Anti-Arrythmics affect outward K+ current, which is responsible for repolarization of membrane?

Answer 5

• Decrease outward K current

Question 6

How do Class 1A Anti-Arrythmics affect ERP and AP duration?

Answer 6

Class 1A Anti-Arrythmics
- ERP: Increase
- AP duration: Increase

Question 7

Quinidine, a Class 1A Anti-Arrythmic, increases conduction velocity in the nodes. Why is this?

Answer 7

Has a strong ANTI-CHOLINERGIC effect (in addition to Na+ blocking effect)

Question 8

Contraindications for Quinidine?
Contraindications fro Disopyramide?

Answer 8

Quinidine: atrial flutter
Disopyramide: glaucoma, uropathy

Question 9

DDI for Quinidine?

Answer 9

Quinidine and Digoxin (can lead to Digoxin toxicity)

Question 10

True or False: Both quinidine and disopyramide have anti-cholinergic effects, but the latter is more severe

Answer 10

True

Question 11

Of the three Class 1A Anti-Arrythmic drugs (Quinidine, Procainamide, Disopyramide) - which has the FEWEST anticholinergic effects and does NOT have a DDI with Digoxin?

Answer 11

Procainamide

Question 12

All Class 1A agents are contraindicated in patients with _____ or with drugs that predispose patients to QT prolongation, leading to TdP

Answer 12

QT prolongation

Question 13

True or False: Class 1B Anti-Arrythmics bind to both open and inactivated Na+ Channels

Answer 13

True

Question 14

Binding perference for Class 1A Anti-Arrythmics vs. Class 1B Anti-Arrythmics?

Answer 14

Class 1A: Open
Class 1B: Inactive

Question 15

How do Class 1B Anti-Arrythmics act on Na+ channels?

Answer 15

Block open and inactivated Na+ channels

Question 16

What are the three drugs part of the Class 1B Anti-Arrythmics?

Answer 16

1) Lidocaine
2) Mexiletine
3) Phenytoin

Question 17

Why can Class 1B Anti-Arrythmics lead to seizures or dizzyness?

Answer 17

Can cross BBB

Question 18

True or False: Mexiletine is an analogue of lidocaine and has a negligible influence on QT interval compared to lidocaine, has less vagolytic affects

Answer 18

True

Question 19

True or False: Phenytoin can be used as an anti-epileptic medication

Answer 19

True

Question 20

Which class of anti-arrythmic drugs has the most potent Na+ channel blockers

Answer 20

Class 1C

Question 21

How do Class 1B Anti-Arrythmics affect ERP and AP duration?

Answer 21

ERP: Decreased
AP Duration: Decreased

Question 22

How do Class 1C Anti-Arrythmics affect phase 0 of ventricular cells?

Answer 22

Decrease phase 0 of ventricular cells
(as a result, suppresses pre-mature ventricular contraction)

Question 23

Do Class 1C Anti-Arrythmics bind to open/active Na+ channel or closed/inactive Na+ channel?

Answer 23

Open/Active Na+ channel

Question 24

What are the three Class 1C anti-arrythmics?

Answer 24

1) Flecainide
2) Encainide
3) Propafenone

Question 25

True or False: Class 1B Anti-arrythmics can worsen a pre-existing arrythmia. Therefore: only approved for life-threatening situations, such as: paroxysmal supraventricular arrythmia

Answer 25

False - this is the case for class 1C anti-arrythima drugs

Question 26

How do Class 1C Anti-arrythmics affect AP duration and ERP?

Answer 26

Normal - do not change

Question 27

What two class 1C drugs can lead to developing cardiac arrest/mortality, as per NHLBI study?

Answer 27

Encainide Flexainide

Question 28

True or False: Propafenone can cause mortality

Answer 28

True

Question 29

Order the anti-arrythmic drug class from strongest to weakest Na+ channel blocking ability

Answer 29

Na+ Blocking Ability Class 1C > Class 1A > Class 1B

Question 30

In the SA Node, the beta1 receptor triggers an increase in pacemaker activity via _____

Answer 30

Funny current/HCN

Question 31

Typically, beta 1 receptors lead to increase SA nodal firing, which increases the phase ___ depolarization rate in pacemaker cells

Answer 31

phase 4

Question 32

True or False: In the AV Node - beta 1 receptors increase calcium current, resulting in enhanced conduction velocity and decreased refractory period

Answer 32

True

Question 33

Beta blockers belong to which class of anti-arrythmic drugs?

Answer 33

Class II anti-arrythmia drug

Question 34

Beta 1 blockers act on both __ and ___ nodes to decrease phase ___ in pacemaker cells. How does this effect ERP and rate of automaticity?

Answer 34

Beta 1 blockers act on: SA/AV Nodes to decrease phase 4 in pacemaker cells - Prolongs ERP, decreases rate of automaticity

Question 35

True or False: Non-specific beta blockers (propranolol, sotalol) come with warning of life threatening pro-arrythmia

Answer 35

True

Question 36

What type of beta blockers are labetolol and carvediolol? Atenolol and metoprolol?

Answer 36

Beta and alpha 1 receptor blockers Specific beta 1 blockers

Question 37

AE of non-specific beta blockers? AE of beta blockers?

Answer 37

Bronchospasm (due to blocking B2) Negative inotropic effect, bradycardia, block

Question 38

What four drugs belong to the class III anti-arrythmic drug class?

Answer 38

1) Amiodarone 2) Dronedarone 3) Ibutilide 4) Dofetilide

Question 39

____ channels play a major role in regulating plateau phase, specifically outward delayed rectifying K+ currents (K efflux)

Answer 39

K+ channels

Question 40

Which class of Anti-Arrythmia drugs are K+ channel blockers?

Answer 40

Class III

Question 41

How do K+ channel blockers (Class III) affect K+ efflux? Plateau phase, repolarization, and ERP?

Answer 41

K+ blockers prevent K+ efflux - Longer plateau phase and re-polarization - Increased ERP

Question 42

____ shows K+ blocking activity and is considered to be a mixed class II and class III drug

Answer 42

Sotalol

Question 43

AE associated with use of Class III drugs?

Answer 43

- Prolongation of plateau duration can give rise to EAD - Can result in TdP

Question 44

What is the metabolite of Amiodarone, a K+ channel blocker?

Answer 44

Des-ethyl Amiodarone

Question 45

___ is a benzofuran compounds with 37% iodine that has HIGH affinity for thyroid cells and is toxic to thyroid follicular cells, ultimately leads to destruction of thyroid gland and hypothyroidism

Answer 45

Amiodarone

Question 46

True or False: Amiodarone is known to inhibit 5-deiodinase activity, thereby decreasing conversion of T4 to T3; also known to be depositied in eyes, skin, and liver

Answer 46

True

Question 47

True of False: Dronedarone is known to cause optic neuropathy, corneal deposits, and keratopathy with long-term use

Answer 47

False - Amiodarone

Question 48

What anti-arrythmic drugs are associated with ocular toxicity?

Answer 48

Amiodarone Quinidine and Disopyramide (Class 1A)

Question 49

What drug and its metabolite are known to decrease dose of UV radiation known to cause erythema? Cause?

Answer 49

Amiodarone - Induction of ROS and DNA damage by amiodarone and DEA (metabolite) by cutaneous tissue

Question 50

What is a substitute for Amiodarone, with reduced toxic effects? Why is this substitute less toxic?

Answer 50

Dronedarone (or Ibutilide or Dofetilide) - Sulfonamide moiety, results in less iodide toxicity and decreased 1/2 life

Question 51

Calcium channel blockers belong to which type of anti-arrythmia drugs? A. Class II B. Class I C. Class III D. Class IV

Answer 51

D. Class IV

Question 52

Calcium channel blockers primarily cat on which tissues?

Answer 52

SA and AV Nodal Tissues (these effects are more prominent than atrial and ventricular muscles)

Question 53

How do Ca2+ blockers affect AP and conduction of impulses in nodal tissues?

Answer 53

Slows down AP and impulse conduction

Question 54

True or False: The mechanism used by Ca channel blockers could be helpful in regulating AV Node mediated re-entry phenomenon

Answer 54

True

Question 55

What two drugs belong to Class IV Anti-arrythmia drugs?

Answer 55

Verapamil and Diltiazem

Question 56

Which class of Anti-Arrythmic drugs can cause AV nodal block?

Answer 56

Class IV

Question 57

Class IV Anti-Arrythmia drugs - contraindications?

Answer 57

With beta-blockers, can precipitate HF

Question 58

True or False: If Digoxin is co-admin with Verapamil or Diltiazem, could result in enhanced Digoxin toxicity

Answer 58

True

Question 59

How does Ivabradine affect Na+ entry?

Answer 59

Inhibits Na entry and funny current through HCN in the SA Node

Question 60

What can Ivabradine (Class 0) treat?

Answer 60

Arrythmias due to SA nodal origin (e.g sinus tacchycardiacs)

Question 61

What drug can treat A fib / Paroxysmal Supraventricular Tachy?

Answer 61

Digoxin

Question 62

Which drug inhibits M3 receptors in SA and AV Nodes to normalize sinus rhythm and reverse AV Nodal block? CI?

Answer 62

Atropine - Glaucoma

Question 63

True or False: Afib can lead to stroke

Answer 63

True

Question 64

What drugs can be given as anti-coags to prevent stroke?

Answer 64

1) Dabigatran; Rivaroxaban; Apixaban - ban/tran

Question 65

Treatment for A-fib induced stroke?

Answer 65

1) Heart rate controlling meds - Beta or Ca2+ blockers 2) Heart rhythm controlling meds - Na/K+ channel blockers