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Flashcards in Antiarrhythmics Deck (47)
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1

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

2

Tachyarrhythmias

Mechanisms:
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!

3

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

4

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

5

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

6

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)

7

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

8

Other Antiarrhythmic Drugs

Have no class specification
Adenosine
Digitalis
Magnesium

9

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)

10

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

11

Class I A, B, and C Drugs

Class IA: Procainamide; Disopyramide; Quinidine

Class IB: Lidocaine; Mexiletine

Class IC: Flecainide; Propafenone

12

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)

13

Class IA Clinical Use

Uses:
Paroxysmal SVT
Atrial fibrillation/Atrial flutter
Ventricular tachycardia

Rarely prescribed anymore because of drug interactions

14

Disopyramide

Class IA

Route: po, IV

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

15

Procainamide

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

16

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.

17

Quinidine

Class IA

Route: po
Excretion: Liver

QT prolongation
Increased mortality in Afib patients! - AVOID

18

Class IB Mechanism

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.

19

Class IB Clinical Uses

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

20

Lidocaine

Class IB

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

Increased Levels with:
CHF
Advanced liver disease

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

21

Mexiletine

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

22

Class IC

Mechanism:
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

23

Class IC Clinical Uses and Contraindications

Uses:
Paroxysmal SVT
Atrial fibrillation/Atrial flutter
Ventricular tachycardia

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

24

Flecainide

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.

25

Propafenone

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

26

Mneumonic For Class I AADs

Police Department Questions Little Man For Pushing drugs

Procainamide
Disopyramide
Quinidine
Lidocaine
Mexiletine
Flecainide
Propafenone

27

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

28

Class II Clinical Uses

Beta Blockers

Use:
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

29

Class II Adverse Effects and Contraindications

Beta Blockers

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

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

30

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