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Flashcards in Antiarrhythmics Deck (47):

Increased Automaticity

With an arrhythmia from such a mechanism, the goal of the AAD is to lower the maximum frequency at which cardiac APs can occur by:
1. Reducing slope of spontaneous phase 4 depolarization.
2. Prolonging the effective refractory period by:
Making the diastolic potential more negative
Making the threshold potential less negative therefore increasing threshold



1. Increased automaticity of pacemaker and non-pacemaker cells
2. Reenterant pathways
3. Triggered activity

Antiarrythmic Drugs (AADs) work by interrupting
one or more of these mechanisms!


Re-Entrant Pathways

The time to complete the circuit must be greater than the effective refractory period otherwise the arrhythmia will not propagate

A: two pathways that flow down = normal situation
B: beta pathway is blocked/ unidirectional block; tries to go down beta pathway, but cannot so it goes back up and if alpha pathway is still in refractory period, it cannot form a reentry circuit
C: alpha pathway is blocked
D: If the beta pathway is slow it can allow enough time for the alpha pathway to repolarize and then it can propagate the arrhythmia


Re-Entrant Pathways: Mechanism

With an arrhythmia from such a mechanism, two conditions must be met:
Unidirectional block
An area of slowed conduction

AADs interrupt the arrhythmia by:
Prolonging the tissue refractory period
Further slowing of conduction within the already “slowed” area
Suppressing premature beats which initiate reentry


Triggered Activity

With an arrhythmia from such a mechanism, oscillations in the membrane voltage occur known as early afterdeopolarizations (EADs) and delayed afterdepolarizations (DADs).

AADs interrupt the arrhythmia by:
1. Suppression of EADs by shortening of the AP and increasing the period of repolarization which prolongs the QT interval
2. Suppression of DADs by correcting conditions of calcium overload


A Major Adverse Effect of Many AADs

Most are pro-arrhythmic
QT prolongation primarily by classes IA, IC, III

Prolongation of QT: AP is lengthening (phases 2 and 3); EADs trigger this disorder (Torsade de Pointes)


Vaughan-Williams Classification of Antiarrhythmic Drugs

Class I: (IA, IB, IC): Sodium-channel blockers
Class II: Beta-blockers
Class III: Potassium-channel blockers
Class IV: Calcium-channel blockers


Other Antiarrhythmic Drugs

Have no class specification


Class I

Block the fast Na channels
Thus primarily affect Phase 0 depolarization
Divided into 3 categories (IA, IB, IC) based on degree of Na channel blockade and effect on cell’s AP duration.

IB: Mild Na channel blockade, Shortened AP duration
IA: Moderate Na channel blockade, Prolonged AP duration
IC: Marked Na channel blockade, No change in AP duration

Na channel Blockade: IC > IA > IB (CAB)


Class I AP Changes

Class IC: slope is decreased and AP duration is not increased at all

Class IB: mild blockade with short AP duration increase

Class IA: prolongs AP, repolarization, and refractory period which doesn’t allow for the arrhythmias to propagate because the refractory period blocks any propagation


Class I A, B, and C Drugs

Class IA: Procainamide; Disopyramide; Quinidine

Class IB: Lidocaine; Mexiletine

Class IC: Flecainide; Propafenone


Class IA Mechanism

Slow phase 0 depolarization, prolong APs, and slow conduction

Mechanism: moderate fast Na Channel blockade, thus slows Phase 0 depolarization

Effect on Pacemaker Cells (like all Class I agents)
Decreases automaticity by :
Decreased slope of phase 4 depolarization
Raising the threshold potential

Effect on AP of Myocardial Cells:
Decreases reentry by prolongation of AP duration thus slows conduction (this is due to some K+ channel inhibition properties)


Class IA Clinical Use

Paroxysmal SVT
Atrial fibrillation/Atrial flutter
Ventricular tachycardia

Rarely prescribed anymore because of drug interactions



Class IA

Route: po, IV

Adverse effects:
Anti-cholinergic: dry mouth, constipation, urinary retention, exacerbation of glaucoma
QT Prolongation



Class IA

Route: po, IV, IM
Hypotension can occur with IV route

Adverse effects:
Fever, rash
GI: diarrhea
+ ANA in 80% of pts taking drug
30% develop drug induced lupus
QT prolongation, especially in rapid aceylators

Can be used for pregnant women


Procainamide Metabolites

Metabolite: NAPA (N-acetyl procainamide)
Formed in liver by acetylation.
Elevated levels with renal failure or those that are rapid aceylators.
NAPA has the ability to prolong AP duration, but does not affect the slope of phase 4 depolarization in pacemaker cells and does not affect the slope of phase 0 depolarization.



Class IA

Route: po
Excretion: Liver

QT prolongation
Increased mortality in Afib patients! - AVOID


Class IB Mechanism

Mild Fast Na Channel blockade
Not much effect on normal tissue, preferentially act on diseased or ischemic myocardium

Effect on Pacemaker Cells (like all class I agents)
Decreases automaticity by :
Decreased slope of phase 4 depolarization
Raising the threshold potential

Effect on AP of Myocardial Tissue:
Reduces slope of Phase 0 depolarization and slows conduction velocity, decreases reentry preferentially in diseased tissue
Shortening of Phase 3 repolarization, thus shortening of AP duration in normal myocardium. This may actually predispose to arrhythmias but decreases chance of QT prolongation.


Class IB Clinical Uses

Ventricular tachycardia
Little effect on atrial arrhythmias due to already short AP duration of atrial cells.



Class IB

Route: IV
Extensive hepatic, 1st pass metabolism
Administered as a continuous infusion (gtt)

Increased Levels with:
Advanced liver disease

Adverse effects:
CNS: Seizures, tremors, confusion, dizziness



Class IB

Route: po
Equivalent to an “oral Lidocaine”

Metabolism: Liver

Adverse effects:
CNS: Tremor, slurred speech, dizziness
GI: N/V, dyspepsia
Cardiac: Hypotension, bradycardia


Class IC

Marked Fast Na Channel blockade, thus slows phase 0 depolarization

Effect on Pacemaker Cells (like all Class I agents)
Decreases automaticity by :
Decreased slope of phase 4 depolarization
Raising the threshold potential

Effect on AP:
No change in AP duration of Purkinje Fibers
Prolongs AP duration in AV node and accessory pathways


Class IC Clinical Uses and Contraindications

Paroxysmal SVT
Atrial fibrillation/Atrial flutter
Ventricular tachycardia

Contraindicated with:
Ischemic heart disease (CAD, Hx MI)
CHF (especially systolic HF – depressed EF)



Class IC

Route: po
Metabolism: Liver and kidney

Adverse effects:
CNS: Dizziness, confusion, blurred vision
CHF exacerbation (especially with low EF)
Conduction abnormalities
QT prolongation
Can accelerate HR in Afib/Aflutter – give with AV nodal blocking agent

AV nodal blocking agent needed since effect of drug is to decrease atrial rate which may precipitate more AV conduction and thus higher ventricular rates.



Class IC

Route: po

Metabolism: Liver

Adverse effects:
Weak B-blocker: Asthma exacerbation, conduction abnormalities
CNS: Dizziness, blurred vision
GI: N/V, Taste disturbance - metallic
CHF exacerbation (especially with low EF)
QT prolongation


Mneumonic For Class I AADs

Police Department Questions Little Man For Pushing drugs



Class II AADs

Beta Blockers

Mechanism: antiarrhythmic properties attributed to inhibition of cardiac sympathetic activity

Decreased phase 4 slope and prolong repolarization of AV node and decreases re-entry


Class II Clinical Uses

Beta Blockers

Supraventricular arrhythmias
Ventricular arrhythmias, Long QT syndrome
Post-MI, decrease oxygen demand, decrease arrhythmias

1. Beta1 selective: highly selective for that receptor, which are highly concentrated in the myocardium and want to use them to decrease other side effects
2. Beta1 non-selective
3. Non B selective and alpha receptor blockers: help with BP as well because it acts on the alpha receptor too


Class II Adverse Effects and Contraindications

Beta Blockers

Adverse Effects: fatigue, cold hands, headache, upset stomach, constipation, diarrhea, dizziness, and shortness of breath.

High degree AV block (2nd degree Type II, 3rd Degree)
Active wheezing/Asthma Exacerbation- B1 selective may be OK, but use cautiously


Class II: Beta1 Selective, Non-Selective, and Combined Non-Selective/Alpha Receptor Blockers

Beta1 selective: metoprolol (most used), esmolol, bisoprolol, atenolol, and acebutolol

Beta1 non-selective: nadolol and propranolol

Non beta selective and alpha receptor blockers: carvedilol and labetalol


Class III AADs

K+ Channel Blockers

Most are structurally distinct from each other.

Common Mechanism in non-pacemaker cells:
Suppresses reentry by:
Blocking outward K+ current during phase 3 repolarization.
Causes prolongation of AP duration thus slowing conduction

Most dangerous group of medications
Lengthen phase 3 depolarization and AP and prolong AP and QT and set early off depolarizations leading to Torsade de pointes


Class III Clinical Uses

K+ Channel Blockers

Varies by drug, but uses may include:
Atiral fibrillation/Atiral flutter
Ventricular arryhthmias


Class III AADs List of Drugs

A Big D-Dog Is Scary

Bretylium – no longer available in US!


Amiodarone: Route, Metabolism, Mechanism, and Uses

Class III

Route: po, IV
Metabolism: liver with half-life: 25-60 days

Additional Mechanism: also has Class I, II, & IV Properties
Decreases phase 4 depolarization of pacemaker cells, thus decreasing automaticity

Uses: Most effective AAD for Atrial fibrillation, Ventricular tachycardia, and Ventricular fibrillation


Amiodarone: Interactions and Adverse Effects

Class III

Interactions: increases levels of digoxin, warfarin

Adverse effects:
GI: N/V, anorexia, Increased LFTs
Pulmonary: Pneumonitis, Pulmonary fibrosis
Optho: Corneal deposits, optic neuritis
Endo: Hypothyroidism, Hyperthyroidism
Derm: Bluish skin discoloration - "smurf syndrome"
Neuro: Tremors, Neuropathy, Ataxia
Bradycardia, QT prolongation

Side effects are related to dosage and duration of use
Longer the patient has been on this the more likely they will have side effects; same with higher dosage


Dofetilide: Route, Metabolism, Uses, and Adverse Effects

Class III

Route: po

Metabolism: renal

Uses: Atrial fibrillation/Atrial Flutter

Adverse effects: QT prolongation (must be loaded in hospital)


Dronedarone: Route, Metabolism, and Mechanism

Class III

Similar to Amiodarone, but iodine moiety is absent, thus less toxicity, and not used in ventricular arrhythmias; doesn't work as well though

Route: po

Metabolism: liver

Additional Mechanism: has class I, II and IV properties too



Class III

Route: IV

Metabolism: renal

Additional Mechanism: activation of a slow inward current that prolongs phase 2 of the AP.

Uses: acute conversion of Atrial fibrillation/Atrial flutter

Adverse effects: QT prolongation


Sotalol: Route, Metabolism, Mechanism, Uses, and Adverse Effects

Class III

Route: po, IV

Metabolism: renal

Additional Mechanism: class II properties too (non-selective b-blocker)

Uses: supraventricular and Ventricular arrhythmias

Adverse effects:
QT prolongation (load in the hospital)


Class IV AADs

Non-dihydropyridine Calcium Channel Blockers:

1. Blockade of slow L-type Ca2+ channels
2. Most potent in SA and AV nodes - elevates threshold potential, decreases rate of phase 0 depolarization, and lengthens the refractory period of the AV node
3. Clinically this results in decreased SA node rat, decreased impulse transmission through AV node, and possible termination of reentrant arrhythmias traversing the AV node


Class IV: Route, Uses, Adverse Reactions, and Contraindications

Route: po, IV

Uses: mainly supraventricular arrhythmias and some ventricular arrhythmias (fasicular VT)

Adverse reactions:
Caution with other AV nodal blockers

Contraindications: systolic heart failure


Adenosine: Mechanism

Binds to adenosine receptors, thus activating outward K+ channels, thus hyperpolarizing the membrane
Inhibits adenylate cyclase, thus decreasing inward pacemaker If current and Ca2+ current.
Suppresses spontaneous depolarization of the SA node and slow conduction through the AV node
Causes brief, complete AV block


Adenosine: Interactions and Method of Administration

Interactions: decreased effect with methylxanthines (caffeine, theophylline) and increased effect with dipyridamole

Central line: in jugular or subclavian because if given peripherally it will be broken down already due to short half life; put adenosine and flush it really quickly to get into the heart ASAP


Adenosine: Route, Adverse Reactions, and Use

Route/Half-life: IV; 9-10 seconds

Adverse Reactions: HA, CP, Flushing, Bronchoconstriction

Use: Paroxysmal SVT


Digitalis: Metabolism, Adverse Reactions

Extract of the foxglove plant and Monarch butterflies

Metabolism: renal

Adverse Reactions:
Various arrhythmias may be provoked at toxic levels
Visual disturbance


Digitalis Mechanisms

1. Inhibits Na+K+-ATPase pump
Intracellular Na+ rises, thus reduces Ca2+ extrusion through the Na+-Ca2+ exchanger
Thus more Ca2+ pumped into sarcoplasmic reticulum
Thus enhances force of contraction (positive inotrope)

2. Enhances vagal tone
Slows conduction through AV node (negative chronotrope)


Digitalis: Uses and Toxicity

Supraventricular arrhythmias
Inotropic agent in systolic heart failure

Narrow therapeutic window

Toxicity Results In:
Less negative resting potential, enhances the possibility of automaticity causing various arrhythmias
Calcium overload, predisposing to DADs – this may cause PVCs (ventricular bigeminy) or paroxysmal atrial tachycardia
Enhanced vagal stimulation – this causes sinus bradycardia and AV blocks