Anti-Arrhythmia Drugs

Question 1

Broadly, what do all class I drugs do?

Answer 1

Block fast sodium channel
Slow the rate of rise of phase 0 of active potential
Decrease excitability and conduction velocity
Block channels in tachycardic, and ischemic cardiomyocytes more effectively than channels in normal tissues
Use-dependent or state-dependent phenomena

Question 2

Class IA mechanism

Answer 2

Intermediately bind to activated Na channels and block K channels
Decreases phase 0
Inhibits phase 3

Question 3

Class IA effect

Answer 3

Decrease Vmax
Prolong APD
Prolong QRS and QT

Question 4

Class IB mechanism

Answer 4

Binds to inactivated Na channel, blocking the Na window current
Binds and releases rapidly

Question 5

Class IB effect

Answer 5

No effect on Vmax

Decreased APD

Question 6

Class IC mechanism

Answer 6

Binds to activated Na channels
Bind and release is slow
Reduces phase 0 of action potential

Question 7

Class IC effect

Answer 7

Largely decreased Vmax
No effect on APD
Prolong QRS
Normal QT

Question 8

Use of class IA drug quinidine

Answer 8

Treatment for atrial, AV junctional and ventricular tachy arrhythmias
When used for a-fib, digoxin must be used first to slow A-V conduction

Question 9

Explain the tachycardia side effect of quinidine

Answer 9

Block muscarinic receptor: may increase HR and A-V conduction
Block α1 receptor: may cause postural hypotension and reflex tachycardia

Question 10

How do P450 inducers and inhibitors affect quinidine?

Answer 10

Quinidine effect is decreased by P450 inducers, and is enhanced by P450 inhibitors.

Question 11

ADR of quinidine

Answer 11

Large doses may result in cinchonism (blurred vision, tinnitus, headache, disorientation and psychosis)
Severe anticholinergic side effects.
Hypotension
Prolong Q-T interval associated with torsades de point

Question 12

What is the benefit of using procainamide over other class IA drugs?

Answer 12

No anti-muscarinic or anti-alpha effects

Question 13

How is procainamide metabolized?

Answer 13

Via acetyltransferase it is metabolized to N-acetyl procainamide, which prolongs the duration of the action potential

Question 14

ADR of procainamide

Answer 14

Reversible lupus erythematous like syndrome
Torsades de point, asystole or ventricular arrhythmias (due to prolonged QT)
Depression, hallucination, psychosis (high doses)

Question 15

When is disopyramide (class IA) used?

Answer 15

Ventricular arrhythmias

Question 16

ADR of disopyramide

Answer 16

Anticholinergic effects (stronger than quinidine)
Negative inotropic effects (decreased myocardial contractility)

Question 17

Disopyramide is contraindicated in:

Answer 17

Heart failure

Question 18

MOA of lidocaine

Answer 18

Blocks sodium channel at inactivated state, but bind and release so quickly, no effect to Vmax. Lidocaine exerts greater effects in depolarized (e.g., ischemic) cardiocytes, to decrease excitation and abolishes ventricular reentry.
Is not useful in atrial arrhythmias possibly because atrial action potentials are so short that the Na+ channel is in the inactivated state only briefly.
Shortens phase 3 repolarization and decreases APD due to inhibiting the slow Na+ “window” current.

Question 19

Use of lidocaine

Answer 19

Local anesthetic

Treatment of ventricular arrhythmias (including post MI, digoxin toxicity-induced)

Question 20

ADR of lidocaine

Answer 20

Drowsiness, slurred speech, paresthesia, agitation, confusion
Convulsions
May precipitate arrhythmias

Question 21

Mexiletine

Answer 21

Oral class IB drug, similar to lidocaine

Question 22

Phenytoin

Answer 22

Class IB drug

Mainly used as an anti-convulsant

Question 23

What are class IC drugs used to treat?

Answer 23

Flecainide, propafenone

Supraventricular arrhythmia with normal heart

Question 24

What is the concern with class IC drugs?

Answer 24

Safety - pro-arrhythmogenic and increase mortality after MI when using for prophylaxis for ventricular tachycardia

Question 25

MOA of class II drugs (BBs)?

Answer 25

Decrease cAMP --> Na+, Ca2+ and K+ channels are dephosphorylated --> Na+, Ca2+ channels close and K+ channel opens --> phase 4 is slowed Diminish phase 4 depolarization in SA and AV nodes, prolonging conduction and decreasing HR

Question 26

When are class II drugs used?

Answer 26

Tachyarrhythmias caused by increased sympathetic activity (e.g. hyperthyroidism) Atrial flutter and fibrillation and AV nodal reentry tachycardia

Question 27

What is esmolol used specifically for?

Answer 27

Acute supra ventricular tachycardia (SVT)

Question 28

MOA of class III drugs

Answer 28

Block K+ channels during phase 3 | Prolonged APD

Question 29

Which class actions does amiodarone possess?

Answer 29

Class IA, II, III and some IV | Blocks K+ channel and prolongs ADP and ERP

Question 30

Uses of amiodarone

Answer 30

Refractory SVT and VT (all arrhythmia)

Question 31

How long does it take amiodarone to take full effect?

Answer 31

6 weeks

Question 32

ADR of amiodarone

Answer 32

Interstitial pulmonary fibrosis in 1% of patients Monitor thyroid function (hyper or hypo) Corneal microdeposit Neuropathy: ataxia, tremor, dizziness Blue skin discoloration (because of iodine accumulation) Photosensitivity Liver damage GI intolerance

Question 33

How does amiodarone affect P450?

Answer 33

Casues p450 inhibition (digoxin, warfarin, statin, quinidine, theophylline, etc.)

Question 34

What are ibutilide and dofetilide used for?

Answer 34

Class III drugs | Used for conversion of a-fib to normal sinus rhythm

Question 35

What is sotalol used for?

Answer 35

Class III drug Potent beta blocking activity Used for long term therapy to decrease the rate of sudden death following an MI Strong anti fibrillary effects in ischemic myocardium

Question 36

MOA of class IV drugs (CCBs)

Answer 36

Calcium channel blockers - verapamil and diltiazem | Block stage 0 and stage 4 in SA and AV nodes

Question 37

Use of class IV drugs (CCBs)

Answer 37

Atrial arrhythmias Reenterent supraventricular tachycardia IV use in paroxysmal supraventricular tachycardia

Question 38

ADR of class IV drugs (CCBs)

Answer 38

Constipation AV block Heart failure (especially verapamil)

Question 39

How can digoxin be used as an anti arrhythmic?

Answer 39

Inhibits Na+/K+ ATPase, increasing Ca2+ in the cytosol, causing increased release of Ach --> prolongs ERP and decreases SA and AV conduction Useful to control a-fib and flutter

Question 40

MOA of adenosine

Answer 40

Stimulates adenosine receptors (Gi) Decreases AV node conduction velocity Prolongs AV node refractory period Less effect in SA node

Question 41

What is the drug of choice in paroxysmal supraventricular tachycardia and AV nodal arrhythmias?

Answer 41

Adenosine | Half life is less than 30s --> IV bolus push

Question 42

ADR of adenosine

Answer 42

Flushing, sedation, dyspnea

Question 43

What can you do physically to help paroxysmal supraventricular tachycardia?

Answer 43

Unilaterally press the eye ball or carotid sinus | Valsava maneuver

Question 44

Which drugs can cause torsades de point?

Answer 44

Quinidine (IA) K+ channel blockers (III) Thioridazine TCA

Question 45

What is used to help in torsades de point?

Answer 45

``` Magnesium Interferes with Na+/K+ ATPase, Na+, K+ and Ca2+ channels (exact mechanism unknown) Given slow (IV) ```

Question 46

Which drug treats sinus bradycardia?

Answer 46

Atropine