Antiarrhymic Agents

Question 1

Cardiac electrical conduction pathway

Answer 1

SA node generates action potential and delivers it to atria and AV node
AV node delivers impulse to purkinje fibers
Purkinje fibers conduct impulse to ventricles

SA -> atrial contraction -> AV node -> ventricular contraction

Question 2

Sodium/potassium channels

Answer 2

Fast conducting, driven by ATP

Atrial tissue, ventricular tissue, purkinje fiber of action potential

No automaticity

Phase 0: fast upstroke - Na+ influx cells less negative (positive vertical slope)
Phase 1 repolarization - due to rapid efflux of K+ (graph comes to a point)
Phase 2: plateau due to Ca + influx - slower conducting (2 is more horizontal)
Phase 3: repolarization - K+ efflux (negative vertical slope)
Phase 4: resting membrane potential

No automaticity because phase 4 is flat

Question 3

Calcium channels

Answer 3

Slow conducting - SA (pacemaker) and Av node, action potential

Phase 4: pacemaker potential - Na+ influx and K + efflux and Ca+ influx until cell reaches threshold then turns to phase 0
Phase 0: upstroke - Ca + influx
Phase 3: repolarization due to K+efflux

Automaticity as slope is never 0 - pacemaker (autonomic cells) have an unstable membrane potential so they can generate AP spontaneously

Question 4

Supraventricular arrythmia

Answer 4

Originated above AV node

Not immediately life threatening unless prolong and affecting the ventricular rate and cardiac output

Sinus tachycardia
Afib/flutter
Paroxysmal supraventricular arrhythmias

Question 5

Ventricular arrythmia

Answer 5

Below AV node

Can be acutely life threatening -> directly lead to worsening CO and possibly hypotension

Incidence is unknown, usually occurs in patients with underlying cardiac diseases

Premature ventricular tachycardia
Non-sustained ventricular tachycardia
Sustained ventricular tachycardia - Torsades de Pointe
cardiac arrest (vfib, sudden cardiac death, asystole)

Question 6

Signs/symptoms related to arrhythmias

Answer 6

Released to decrease in CO and hypotension

Palpitation
Dizziness/syncope
Shortness of breath
HF
Cardiac arrest

Question 7

Management of Afib

Answer 7

1. Control ventricular rate - slow down AV node
   Beta blockers - SNS control
   CCBs/ K channel blockers - work on AV node
   Digoxin - enchanted PNS and slow down HR
2. To stop fibrillation -> restore NSR (Rhythm control)
   Class I or III - work on atrium and ventricles

Question 8

Management of ventricular arrhythmias

Answer 8

Class I or Class III - work on atrium and ventricles

Question 9

Class I (Is)

Answer 9

MOA: Na channel blockers - work on atrium and ventricles (directly on AV node)

Uses: restoring NSR in Afib involving SA or AV node, supraventricular arrythmia
Increase QRS, QT

Drug subclass:

1a- moderate Na channel blockage “double quarter pounder”

Drugs w ADRs:
Disopryamide - anticholinergic effects, strong negative ionotropes
Quinidine - elevated LFTs, Diarrhea
Procainamide - Nausea, lupus

Do not use in patients with gross cardiac abnormalities (ex: fibrosis, HF, valve disease)
High rate of recurrent arrhythmias
K channel blockade

Question 10

Class I (Ib)

Answer 10

MOA: Na channel blockers - work on atrium and ventricles (directly on AV node)
Inhibit Na channel when body is acedodic (decrease QT)

Uses: restoring NSR in Afib involving SA or AV node
Good for ventricular arrythmia due to ischemia - NOT supraventricular arrythmia such as afib

Ib - weak rate and pH dependent
Faster rate -> stronger Na channel blockade effect
Lower pH -> stronger Na channel blockade

Drug examples: “Lettuce and mayo”
Lidocaine
Mexiletine

ADRs: CNS related (tinnitus and seizure)

Question 11

Class I (Ic)

Answer 11

Na channel blocker - Most potent

Drug examples; “fries please”
Flecanide
Propafenone

ADRS:
negative ionotropes - not feasible in HF patients,
Contraindicated in asthma patients - affect bronchodilation of lung
Do not use in patients with gross cardiac abnormalities (fibrosis, post MI, HF, valve disease)
Beta blockade

Question 12

Class II

Answer 12

MOA: Beta blocker - blocking sympathetic activity in SA and AV node -
works on nodes and myocardium

Drug examples: metropolol, atenolol

Uses:
ventricular arrythmia
Control rate in patients with supraventricular arrhythmias
Preventing ventricular arrythmia post MI or HF patients

ADR:
Hypotension
Bradycardia
Exercise intolerance 
Sexual dysfunction
Negative ionotropic effect 

DO NOT USE in patients with severe asthma

Question 13

Class III

Answer 13

MOA: K blockers - delay repolarization and increase refractory period - proarrythmic and most notably increase Torsades

Amioderone
Dronedarone
Sorta lol
Dofetillide
Ibutillide

Question 14

Amioderone

Dronedarone

Answer 14

Class III ( K channel blockers)

MOA: all 4 classses of effect Na, K, Ca, beta-blocker, broad spectrum
Most effective - minimum negative ionotropic effects (good for HF)
Long 1/2 life and large volume of distribution

Uses: restore NSR, ventricular arrythmia

Amioderone - large VOD and half life, least proarrythmic - good for HF patients with low EF
Dronedarone- less proarrythmic then other class III -
Contraindicated increase mortality in HF patients and patients with chronic AFIB

Drug interactions:
Digoxin -> decrease dose by 50%
Warfarin -> decrease dose by 30-50%
Simvastatin -> max dose 20mg daily

Question 15

Sotalol

Dofetillde

Answer 15

Class III (K blockers)

Sotalol- same as beta-blockers, proarrythmic, K channel and Beta-blocker
Dofetillide - proarrythmic - K channel blocker - minimal negative ionotropic effects - OK in HF patients

Renal dosing

Use: monitor QT intervals in hospital

Question 16

Ibutilide

Answer 16

MOA: Class III (K blockers)

Uses: IV only - treatment of acute afib

Considerations: high risk of torsade

Question 17

Class IV

Answer 17

MOA: Ca blockers (nonDHPs)
Slows conduction in AV node by blocking Ca channels - control ventricular rate

Negative ionotropes -> exacerbation of HF

drug examples: verpamil and diltiazem

Uses: control ventricular rate

ADR: constipation, hypotension, bradycardia

Drug interactions:
Statins
Digoxin

Question 18

Digoxin

Answer 18

MOA: enhance PNS - slow HR,
Inhibit Na/K ATPase pump - positive ionotrope effects

Use: control ventricular rate

ADR: nausea, vomiting, yellow-green visual halo, arrythmia

Drug interactions: renal dosing
Quinidine
Amiodarone
Verapamil

Question 19

Adenosine (IV)

Answer 19

MOA: delay AV node conduction by binding to adenosine receptor

IV only - short duration of action - no chronic use

Uses: control ventricular rate

ADR:
vasodilation (flushing + hypotension)
angina (chest pain)
dyspnea - adenosine receptor in lung

Question 20

AADs for patients with structural heart disease

Answer 20

Increase risk of proarrythmia or cannot tolerate negative ionotropic effects
Highest risk for developing arrhythmias

Post MI: contraindicated class Ic
HF: can tolerate amioderone, dofetillide, digoxin, select beta blockers (Carvediol, metropolol)

Question 21

Efficacy for rhythm control

Answer 21

Class III better then class Ic and class Ib -> Ib only works in ischemic situation

Amiodarone is MOST effective - side effect on every organ system except for kidney

AADs that have K channel blockade (Class Is, Ic, III) increase refractory period and increase risk of Torsades -> prolong QT interval

Question 22

AADs for HF patients

Answer 22

HF patients cannot handle negatives ionotropic effects:

all AADs (class I-IV) have negative ionotropic effects except:

amioderone
dofetillide
deronedarone
class Ib -lidocaine, mexiletine

Question 23

Renal dosing

Answer 23

Most AADS metabolized in liver EXCEPT:

Dofetilide
Sotalol
Digoxin

Dose according to kidney function!