140 Antiarrhythmic Drug Therapy

Question 1

Mechanisms/Classifications of Bradyarrhythmias

Answer 1

1. Diminished automaticity
2. Block

Question 2

Mechanisms of Tachyarrhythmias

Answer 2

1. Enhanced automaticity
   
   1. Increased phase 4 depol
   2. Make threshold more negative
2. Renentry
3. Triggered activity
   
   1. Early after depols
      
      1. •During Phase 2, 3 of AP

• Ca2+ current Dependent
• Occurs in setting of prolonged APD (prolonged QT interval)
  2. Delayed afterdepols
     
     1. During Phase 4 of AP

Associated with high Ca2+ (eg digoxin toxicity)

Question 3

Supraventricular tachyarrhythmias list

Answer 3

oSinus Tachycardia

oAtrial Premature Beats

oParoxysmal Supraventricular Tachycardia

(aka Supraventricular Tachycardia aka SVT)

oAtrioventricular Nodal Reentrant Tachycardia (AVNRT)

oAtrioventricular Reentrant Tachycardia (AVRT)

oEctopic Atrial Tachycardia

oAtrial Flutter

oAtrial Fibrillation

oMultifocal Atrial Tachycardia

Question 4

Ventricular tachyarrhythmias list

Answer 4

Question 5

AV Nodal Reentrant Tachycardia (AVNRT)

Answer 5

Question 6

Atrioventricular Reentrant Tachycardia (AVRT)

Answer 6

Question 7

Atrial Flutter

Answer 7

Question 8

Atrial Fibrillation

Answer 8

Question 9

Ventricular Tachycardia

Answer 9

Question 10

Polymorphic Ventricular Tachycardia

Answer 10

Question 11

Ventricular Fibrillation

Answer 11

Question 12

Treating Enhanced Automaticity (theory)

Answer 12

1. •Make maximum diastolic potential more negative
2. •Reduce slope of phase 4 depolarization
3. •Make the threshold potential more positive

Question 13

Treating Reentry (theory)

Answer 13

Disrupt the Balance

• e.g. slow the “slow conduction” even more so it blocks
• supress premature beats which often set up slow conduction

Question 14

Treating Triggered Activity (theory)

Answer 14

Question 15

Rate Control vs. Rhythm Control in Atrial Fibrillation

Answer 15

Question 16

Vaughan-Williams Classification

Answer 16

Question 17

Na+-Channel Blockers Mechanism

Answer 17

Question 18

Na+-Channel Blockers: Effect on Phase 0

Na+-Channel Blockers: Effect on Action Potential Duration

Answer 18

Question 19

Procainamide

Answer 19

Class 1A

•Drug-induced Lupus: arthralgia, pleuritis, pericarditis with PO (not clinically available)

•Torsades de Pointes:

N-acetylprocainamide a first pass

metabolite with strong K+ channel

activity

Question 20

Quinidine

Answer 20

Class 1A

•Additional vagolytic effects

–eg urinary retention, constipation, blurred vision, dry mouth

•Cinchonism: CNS toxicity – tinnitus, psychosis

•Torsades de Pointes: K+ blocking activity

Question 21

Disopyramide

Answer 21

Class 1A

• Additional stronger vagolytic effects
• Additional negative inotropic effects

•Antimuscarinic: urinary retention, constipation, blurred vision, dry mouth

•Torsades de Pointes: K+ blocking activity

Question 22

Lidocaine

Answer 22

Class 1B

•CNS Toxicity:

confusion, delerium, grand mal seizures

good for post MI

Question 23

Mexelitine

Answer 23

Class 1B

•CNS Toxicity:

confusion, delerium, grand mal seizures

Question 24

Flecainide

Answer 24

Class 1C

• Potent negative inotropic effects
• Propafenone: beta-blocking effects
• Slows conduction (because of potent Na+ blocking)

•Contraindicated in LV systolic dysfunction and heart block

Question 25

Propafenone

Answer 25

Class 1C * Potent negative inotropic effects * Propafenone: beta-blocking effects * Slows conduction (because of potent Na+ blocking) * Contraindicated in LV systolic dysfunction and heart block

Question 26

β-Blockers Mechanism Side effects

Answer 26

* Hypotension * Bradycardia * Depression, Bronchospasm, Cognitive Impairment, Sexual Dysfunction

Question 27

Esmolol

Answer 27

Beta blocker, Class 2 ## Footnote * Hypotension * Bradycardia * Depression, Bronchospasm, Cognitive Impairment, Sexual Dysfunction GIven IV

Question 28

Metoprolol

Answer 28

Beta blocker, Class 2 * Hypotension * Bradycardia * Depression, Bronchospasm, Cognitive Impairment, Sexual Dysfunction GIven PO Side effect: oClass II (eg Metoprolol) -- Depression, Bronchospasm, Cognitive Impairment, Sexual Dysfunction

Question 29

K+-Channel Blockers Mechanism

Answer 29

Question 30

Amiodarone

Answer 30

Question 31

Sotalol

Answer 31

Class 3 antiarrhythmic, K+ blocker * B-blocking effects * PO * •Prolong QT-interval à Torsades de Pointes * should be avoided in renal failure.

Question 32

Dofetilide

Answer 32

Class 3 Antiarrhthmic, K+ blocker * PO * requires renal dose adjustment * •Prolong QT-interval à Torsades de Pointes

Question 33

Ibutilide

Answer 33

Class 3 antiarrhtymic, K+ channel blocker * IV * •Prolong QT-interval à Torsades de Pointes

Question 34

Ca2+-Channel Blockers Mechanism

Answer 34

Question 35

Verapamil

Answer 35

Question 36

Diltiazem

Answer 36

Side Effect: oClass IV (eg Diltiazem) – Constipation, Peripheral Edema

Question 37

Adenosine

Answer 37

non classified antiarrythmic * Transient Elective Heart Block * Treatment of AVNRT, AVRT * – reentrant rhythms that depend on the AV node * Diagnosis of Supraventricular Tachyarrhythmias * --gets rid of QRS complexes * --see underlying Atrial Fibrillation or Atrial Flutter

Question 38

Digoxin

Answer 38

Unclassified antiarrythmic drug ## Footnote * Narrow Therapeutic Window * Toxicity: nausea, diarrhea, yellow vision * Proarrhythmic Effects: –almost anything •Treatment of severe toxicity: anti-digoxin Fab fragments Side effect: nausea, diarrhea, yellow vision

Question 39

Tx Disrupting AVNRT, AVRT

Answer 39

* Acute: Adenosine – rapidly acting * Chronic: Beta Blockers, Calcium Channel Blockers, perhaps Digoxin

Question 40

Tx AFib, AFlutter: Rate Control

Answer 40

•Beta Blockers (Class II) –slows conduction through AV node •Calcium Channel Blockers (Class IV) –slows conduction through AV node •Digoxin –slows conduction through the AV node

Question 41

Tx AFib, AFlutter: Rhythm Control

Answer 41

•Class Ic Agents: **Flecainide, Propafenone** –Probably Interferes with Reentry by slowing conduction •Class III Agents: **Amiodarone, Sotalol, Dofetilide, Ibutilide** –Probably Interferes with Reentry by prolonging repolarization _•Class Ia Agents_ –obsolete for this indication

Question 42

Tx Suppress VT and Symptomatic PVCs

Answer 42

•Class II Agents : beta-blockers –Can slow conduction in sick tissue •Class III Agents : Sotalol and Amiodarone –Interferes with Reentry by prolonging repolarization •Class Ib Agents –Interferes with Reentry by slowing conduction •Class Ia Agents –almost obsolete for this indication –Procainamide occasionally used in ischemic VT –Disopyramide occasionally used in Hypertrophic Cardiomyopathy (negative inotropic effects)

Question 43

Tx ## Footnote Suppress VT and Symptomatic PVCs Special Case: In setting of Myocardial Infarction

Answer 43

•Class II Agents : beta-blockers –Can slow conduction in sick tissue * Class III Agent: Amiodarone * Class Ib Agents –Interferes with Reentry by slowing conduction •Class Ia Agents –almost obsolete for this indication –Procainamide occasionally used in ischemic VT –Disopyramide occasionally used in Hypertrophic Cardiomyopathy (negative inotropic effects)

Question 44

Tx ## Footnote Suppress VT and Symptomatic PVCs Special Case: Treatment of Torsades de Pointes

Answer 44

* Magnesium * Phenytoin * Isoproterenol * Overdrive Pacing * Shock

Question 45

Pacemaker cells APs (vagus, b-adrenergic, SA node)

Answer 45

Question 46

Wolff-Parkinson-White

Answer 46

* oWolff-Parkinson-White pattern * oECG finding only of a delta wave * oWolff-Parkinson-White syndrome * oECG finding of a delta wave * oECG evidence also of arrhythmia using accessory pathway * oAVRT – orthodromic vs. antidromic * oYou could also have Atrial Fibrillation, Atrial Flutter, or even AVNRT

Question 47

Tx AVRT

Answer 47