Pharm II- CV Drugs/Antiarrhythmic

Question 1

Is a Class 1A antiarrhythmics, which block open Na+ channels and delay their recovery from inactivation

Answer 1

What is the mechanism of action of Quinidine, Procainamide, and Disopyramide

Question 2

Which cardiac ion channels are blocked by quinidine?

Answer 2

Na+ channels, K+ channels, and L-type Ca++ channels at high doses

Question 3

Describe major effects of quinidine on the action potential and the ECG.

Answer 3

1. By blocking Na+ channels—Reduces the dv/dt of phase 0 (wide QRS)
2. By blocking K+ channels—Prolong APD (ERP)—wide QT
3. Variable effects on PR interval—anti-muscarinic effects shorten PR while direct effects prolong it

Question 4

List major cardiac toxicities of Class Ia antiarrhythmics.

Answer 4

1. Vagolytic actions of Class 1A drugs can cause tachycardia and increase ventricular rate during AF/AFl
2. Quinidine blocks ⍺-1 receptors and can cause hypotension
3. Blockade of L-type Ca++ channels depresses myocardial contractility
4. Prolonged ERP can predispose to torsade de pointes
5. Heart block is seen at toxic doses due to direct effects on the AV node

Question 5

This drug has narrow therapeutic index and is displaced by quinidine from its binding site, which increases its toxicity that include green halos.

Answer 5

What is digoxin?

Question 6

It causes cinchonism at toxic doses, characterized by ringing ears, deafness, vertigo, headaches, visual disturbances, and delirium.

Answer 6

What is quinidine?

Question 7

More common in slow acetylators, this Class 1A drug causes lupus like reaction and positive antinuclear antibodies in 20% of patients given this drug.

Answer 7

What is procainamide?

Question 8

List major clinical uses of Class 1A antiarrhythmics.

Answer 8

1. Chronic management of AF/AFl—rhythm control
2. Ventricular tachycardias

Question 9

List major electrophysiological effects of lidocaine.

Answer 9

• Lidocaine binds to inactive Na channels and blocks them—duration of block is short lived. Thus, preferentially binds depolarized tissue.
• Lidocaine opens inward rectifier K+ channels and hyperpolarizes the cells—improves conduction velocity
• Lidocaine raises the threshold for Na+ channel opening

Question 10

List two, key class 1B drugs

Answer 10

1. Lidocaine
2. Mexiletine

Question 11

What are the effects of lidocaine on the ECG?

Answer 11

Little to no effect

Question 12

Only used I.V., this drug is effective in reducing premature ventricular depolarizations after an MI or those caused by digoxin toxicity.

Answer 12

What is lidocaine?

Question 13

List major Class 1C antiarrhythmics.

Answer 13

Flecainide, Propafenone

Question 14

List major contraindications for use of Class 1A drugs.

Answer 14

• Heart failure
• Prolonged QT interval
• Sick sinus syndrome
• Narrow angle glaucoma (disopyramide)

Question 15

List electrophysiological effects of Class 1C antiarrhythmics.

Answer 15

1. Most potent blockers of Na channels—bind open Na channels with long duration of block. This severely depresses cardiac conduction velocity
2. Blocks outward K+ currents and prolongs APD. This effect is less than Class 1A drugs
3. Slows AV conduction

Question 16

What are some of the effects of Class 1C drugs on the ECG?

Answer 16

1. Prolong PR interval—due to slow AV conduction
2. Wide QRS (a lot)—due to reduced conduction velocity
3. Wide QT—due to K+ channel block

Question 17

List major electrophysiological effects of β-blockers when used in the management of cardiac arrhythmias.

Answer 17

1. Reduce AV conduction by blocking L-type Ca++ channels
2. Reduce automaticity by decreasing the dv/dt of phase 4 depolarizations
3. Prolong ERP (APD) by deactivating K+ currents
4. Reduce SA node depolarizations and HR

Question 18

What is the predominant effect of β-blockers on the ECG?

Answer 18

Prolongation of the P-R interval

Question 19

List major uses of Class II antiarrhythmics.

Answer 19

1. Ventricular rate control in supra-ventricular arrhythmias
2. Reduce ventricular extra systoles caused by exercise or stress
3. Prevent reentry arrhythmias after an MI

Question 20

List major Class III antiarrhythmics.

Answer 20

1. Amiodarone
2. Sotalol
3. Ibutilide

Question 21

List principal electrophysiological effects of amiodarone.

Answer 21

1. Blocks K+ channels—prolongs APD
2. Blocks Na+ channels—rate of channel recovery is somewhere between lidocaine and quinidine
3. Blocks Ca++ channels—delays AV conduction
4. Prolongs refractoriness in all cardiac tissue

Question 22

What are the effects of amiodarone on the ECG?

Answer 22

Prolongs P-R, QRS and Q-T

Question 23

List major adverse effects of amiodarone.

Answer 23

1. Depresses myocardial contractility and causes hypotension—effects due to its β-blocking properties
2. Reversible corneal micro deposits
3. Pulmonary fibrosis—irreversible
4. Hypothyroidism

Question 24

List major electrophysiological effects and uses of adenosine.

Answer 24

Adenosine activates ACh-sensitive K+ channels and hyper polarizes the atria and the nodes.

Slows AV conduction

Mainly used in the rapid termination of PSVTs

Question 25

List major electrophysiological effects of digoxin when used as an anti arrhythmic agent.

Answer 25

At low doses, digoxin is a parasympathomimetic and has effects similar to adenosine—

1. Hyper-polarize the atria and the nodes
2. Slow AV conduction

Digoxin also slows conduction velocity. This is due to partial depolarization, which inactivates Na+ channels (recall, conduction velocity is dependent on speed and readiness of Na+ to open).

Digoxin also ↓ERP. This is mainly due to it’s effects on K+ channels.

Question 26

List some common clinical uses of digoxin in the management of cardiac arrhythmias?

Answer 26

Digoxin is primarily used for rate control in supra-ventricular tachy-arrhythmias (mainly due to vagomimetic effects)—

1. PSVT
2. Atrial fibrillation

Question 27

List predominant ECG effects of digoxin, in therapeutic doses.

Answer 27

1. Slows AV conduction—prolonged PR interval
2. ↓ERP—shorter QT

Question 28

What arrhythmias are caused by digoxin toxicity?

Answer 28

1. AV block
2. Premature ventricular complexes—partially depolarized cells become “automatic” and lead to ectopic beats.
3. Delayed afterdepolarizations in Ca++ loaded cells
4. Reentry arrhythmias due to ↓conduction velocity and ↓ERP, mainly atrial fibrillations

* it is noteworthy that digoxin can cause the very same arrhythmias its used to treat.

Question 29

List some “classical” non-cardiac signs and symptoms of digoxin toxicity.

Answer 29

Anorexia, nausea, fatigue, confusion, altered vision with green-yellow halos.

Question 30

Briefly, list management strategies for digoxin toxicity.

Answer 30

1. Prevent and treat hypokalemia—low [K]o accentuates digoxin binding to the Na-K-ATPase and ↑ toxicity
2. Lidocaine for dioxin-induced reentry arrhythmias
3. Digibind—antibody against digoxin

Question 31

List common adverse effects of adenosine.

Answer 31

Nausea, headache, flushing, chest pain, bronchospasm (contraindicated if asthma)

Question 32

This class 1A drug has most potent anticholinergic effects, causes urinary retention, constipation and is contraindicated in narrow angle glaucoma.

Answer 32

What is disopyramide?

Question 33

Used in the management of cardiac arrhythmias for ventricular rate control, these drugs causes fatigue, depression, bronchospasm and impotence as side effects.

Answer 33

What are β-blockers?

Question 34

Used for cardiac rate control, this drug causes constipation and peripheral edema. Its main effect is to decreases dv/dt of phase 0 of the nodes.

Answer 34

What is verapamil or diltiazem?

Question 35

This adverse effect is observed in patients treated with quinidine, sotalol, and ibutilide; Not in patients treated with amiodarone.

Answer 35

What is long QT syndrome or torsade de pointes?

Question 36

Name two preferred drugs to rapidly terminate AV conduction for control of ventricular rate in AVRT/AVNRT

Answer 36

1. Adenosine
2. Amiodarone

Question 37

What is the strategy for management of acute atrial fibrillation?

Answer 37

IV rate-control drugs are the treatment of choice. These include—

1. Esmolol
2. Verapamil
3. Metoprolol
4. Diltiazem

Question 38

Discuss Long-term management strategies for atrial fibrillation.

Answer 38

1. Achieve adequate anticoagulation (warfarin)
2. For rate control—β-blockers, Ca++ channel blockers or digoxin
3. Rhythm control—Class 1A drugs or Class 3 drugs (amiodarone is the t/t of choice)