antiarrhythmic drugs

Question 1

What are the classes of antiarrhythmic drugs?

Answer 1

Class 1 (Na channel blockers), Class II (beta blockers), class III (Prolongation of phase 2), class IV (Ca channel blockers), unclassified drugs (ie. Adenosine)

Question 2

What do class I drugs do?

Answer 2

Block Na channels in fast response cells, and to a lesser extent they block L-type Ca channels in slow response cells. All class I drugs decrease conduction rate and increase refractory period

Question 3

What are examples of class Ia drugs?

Answer 3

quinidine, procainamide, disopyramide (quit procrastinating dis)

Question 4

What do class Ia drugs do?

Answer 4

slow the upstroke of the fast response (by blocking Na channels), and they also delay the onset of repolarization (by blocking K channels, a class III effect)

Question 5

How do Class Ia drugs prolong refractory period?

Answer 5

(i) via classic, use-dependent mechanism, similar to local anesthetics in action. (ii) because depolarization (phase 2 duration) is prolonged

Question 6

What other actions does Quinidine have that are not related to Na channel block?

Answer 6

Prolongs AP duration by blocking K channels, vagal inhibitor (anti-choliergic) and it is an alpha-adrenergic receptor antagonist

Question 7

Class Ib drug examples

Answer 7

lidocaine, mexiletine, phenytoin (little mexican phenytoin)

Question 8

Class Ib actions

Answer 8

Pure class I action. Like class Ia drugs, class Ib drugs are use-dependent blockers of voltage-gated Na+ channels (slows upstroke and prolongs refractory period). Unlike class Ia drugs, Ib drugs do NOT prolong phase 2 of AP

Question 9

Class Ic drug examples

Answer 9

propafenone, flecainide, encainide (probably forget encainide)

Question 10

Class Ic drug actions

Answer 10

Use-dependent blockers of Na channels, produce most pronounced slowing of upstroke and midly prolongs phase 2 (by blocking K channels), powerful prolongation of tissue refractory period

Question 11

What is use-dependence?

Answer 11

The block of Na+ channels by class I antiarrhythmic drugs is optimized so that Na+ channels in myocytes with abnormally high firing rates or abnormally depolarized membranes will be blocked to a greater degree than are Na+ channels in normal, healthy myocytes. Also important for class IV Ca channel blockers

Question 12

Explain the mechanism of use-dependence

Answer 12

The hydrophilic drug can only enter/exit the channel when the channel is open

Question 13

How do use dependent channel blockers prolong the refractory period?

Answer 13

These drugs block initially by entering the open channel, but they have a higher affinity for the inactivated state of the channel. That means they stabilize the inactivated state, thus prolonging the time the channel spends in the inactivated state

Question 14

What is another mechanism that some class I drugs use to prolong refractory period?

Answer 14

Class Ia drugs prolong phase 2 and delay repolarization via a class III action (blocks K channels). Prolonged phase 2 means myocyte is depolarized for longer and more Na channels become inactivated, making refractory period longer.

Question 15

How do Class I drugs suppress re-entrant arrhythmias?

Answer 15

1. slowing AP conduction velocity (reducing upstroke rate) 2. Prolonging refractory period

Question 16

Explain how slowed conduction velocity suppresses re-entry

Answer 16

Reduced upstroke results in slower conduction velocity and a slower AP is more likely to fail to propagate trhough a depressed region. This converts a uni-directional block into a bi-directional block

Question 17

Explain how prolonging refractory period suppresses re-entry

Answer 17

Refractory tissue will not generate an AP, so re-entry of excitation is prevented

Question 18

What are examples of Class II drugs?

Answer 18

propranolol, metoprolol, esmolol

Question 19

Class II drug actions

Answer 19

Beta-adrenergic receptor blockers reduce pacing rate (automaticity) and prolong refractory period in SA/AV nodes by reducing funny current, L-type Ca and Ks current. This reduces rate of diastolic depolarization, reduces upstroke rate, and slowes repolarization in AV node.

Question 20

What are class II drugs used for?

Answer 20

terminate arrhythmias that involve AV nodal re-entry, and in controlling ventricular rate during atrial fibrillation.

Question 21

Class III drug examples

Answer 21

ibutilide, dofetilide, amiodarone, sotalol, bretylium

Question 22

What do class III drugs do?

Answer 22

Block K channels (ibutilide and dofetilide specifically block Kr). This prolongs phase 2 in fast Aps and prolongs the refractory period.

Question 23

How do class III drugs prolong the refractory period?

Answer 23

Prolonged duration of phase 2 leads to increased inactivation of Na channels

Question 24

What other actions does amiodarone have (in addition to blocking K channels?)

Answer 24

reduces conduction velocity and increases refractory period by blocking Na+ channels. Also decreases rate of diastolic depolarization (phase 4) in automatic cells, thus reducing firing rate

Question 25

What other actions does Sotalol have (in addition to K blocking)?

Answer 25

Acts as a beta blocker

Question 26

Class IV drug examples

Answer 26

verapamil, diltiazem

Question 27

Class IV drug actions

Answer 27

Use-dependent blockers of L-type Ca2+ channels ( in nodal cells and fast response myocytes). Slow Ca-dependent upstroke in slow tissue, which slows conduction velocity. Prolongs refractory period (thus suppress re-entry)

Question 28

How does Adenosine work?

Answer 28

Increases K+ current, while also decreasing both L-type Ca2+ current (dihydropyridine-sensitive, slow inward current) and If in SA and AV nodes. This causes reduction in SA/AV firing rate and reduced conduction rate at AV node

Question 29

Antiarrhythmic drugs are primary therapy for what?

Answer 29

Atrial fibrillation only. Ablation or ICD is currently thought to be equal or superior in the management of all other arrhythmias.

Question 30

What specific therapeutics are used for Paroxysmal supraventricular tachycardia?

Answer 30

“Re-entry problem. For Acute, Adenosine. For,Chronic: AV nodal blockers [Class II (β-blockers), Class IV (Ca2+ channel blockers), Class III (amiodarone, sotalol), digoxin] and
catheter ablation of ectopic focus”

Question 31

What specific therapeutics are used for Atrial fibrillation?

Answer 31

re-entry problem. Acute: AV nodal blockers, electrical cardioversion. For Chronic: AV nodal blockers combined with long-term anticoagulation (warfarin), Cardioversion (electrical, ibutilide), and maintenance of sinus rhythm with drug therapy, Class III (amiodarone, sotalol, dofetilide) and Class Ic (propafenone, flecainide)

Question 32

What therapies are used for ventricular tachycardias/fibrillation?

Answer 32

“afterdepolarization and reentry problem. Acute: amiodarone, lidocaine, procainamide. Drug prevention of sudden cardiac death:proven benefit- β-blockers, angiotensin converting enzyme (ACE) inhibitors, aspirin, statins
Perhaps of benefit: amiodarone, digoxin
Potentially harmful: Class I drugs (Na+ channel blockers), Class IV drugs (Ca2+ channel blockers)”

Question 33

What are the half lives of Esmolol, Amiodarone and Adenosine?

Answer 33

Esmolol is 10 minutes, Amiodarone is 13-100 days, Adenosine is less than 10 seconds

Question 34

What are side effects of Amiodarone

Answer 34

Cardiac problems include bradycardia and heart block. Dose-related effects include: thyroid dysfunction, corneal deposits, pulmonary fibrosis and skin discoloration.