1. Drugs used in the treatment of arrhythmia I
Dr. Asmaa Fady PhD., MSC., M.B, B.Ch
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8/2/2019

2. Learning Objectives: By the end of the lecture, the student should,
understand the cardiac action potential and pathophysiology of arrhythmia.
Recognize and categorize different antiarrhythmic drugs According to mechanism of action
Describe the mechanism of action of antiarrhythmic drugs and their effects on action potential & ECG reading
Identify the clinical uses of antiarrhythmic drugs
Identify side effects & toxicity of antiarrhythmic drugs that limit their clinical usefulness
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3. Cardiac conductive system
AV bundle
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4. Phases Of Cardiac Action Potential:
Non- Pacemaker cells
Phase 4
Pacemaker cells:
SAN
AVN
Purkinji fibers
8/2/2019

5. Phases Of Cardiac Action Potential:
Phase (0): (excitability& conductivity)
Normal muscle fiber: influx of Na+ through activated Na Channels (Rapid Na+ Influx: Depolarization = Excitability & Conductivity ).
SAN: Activation of Na & Ca + Channels (Rapid Ca+ Influx: Depolarization)
Phase (1): Inactivation of Na+ channels. Start of K+ Efflux.
Phase(2):Activation of Slow Ca + Channels( Slow Ca Influx: Plateau.)
Phase (3): Inactivation of Ca2+ Channels. Full activation of K+ Channels
: Rapid K+ Efflux : Rapid Repolarization.
Phase (4):
a- Normal Cardiac muscle fiber : Resting potential. (Inactivated ALL channels).
Due to Activation of Na+ / K+ ATPase ( Na/K Pump) Restore electrolyte balance.
b- Slope phase 4: (automaticity) S.A.N., Conductive tissue & Ectopic Focus (still Slow Na+ & Ca2+ Influx ) due to Opening of inactivated Na & Ca channels.
Action Potential Duration
(A.P.D) =
Effective Refractory Period
(E.R.P)
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6. Pathophysiology of Cardiac Dysrhythmia
Dysrhythmia (Arrhythmia) means any abnormality in Rate, Regularity, Origin or Conduction of an Impulse.
All arrhythmias result from:
• Disturbances in impulse formation:
Nodal abnormality (rate): SAN
Ectopic Focus Formation: Any cell with Automaticity faster than S.AN.
• Disturbances in impulse conduction (AVN- accessory pathways)
• Disturbance in impulse formation and conduction
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7. Antiarrhythmic Drugs Blocking ion Channels:
1- Block of Activated Na+ channels Slow Phase (0) Slow Excitability & Conductivity.
2- Block of Inactivated Na+ channels Slow Phase (4) Slow Automaticity.
3- Block of Slow Ca2+ Channel Short Phase (2) of cardiac muscle fiber. & Slow Automaticity (phase 0) of Ectopic focus.
4- Block of K+ channel Delay Repolarization Long Phase (3) Long A.P.D. & long E.R.P.
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8. Goals of Antiarrhythmic Drugs
• To maintain normal rhythm and conduction in the heart • Decrease conduction velocity • Increase the duration of the refractory period • Suppress abnormal automaticity
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9. Vaughn William Classification Of Anti-arrythmic Drugs:
Anti- arrhythmias
Class I (Na channel blockers) A B C
Class II (Beta blockers)
Class III (K channel blockers)
Class IV (Ca channel blockers)
Others
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10. 8/2/2019
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11. 1)Class I (Na Channel blockers): (Membrane stabilizers)
Mechanism:
Block activated Na channels slow (phase 0): excitability & conductivity.
Block inactivated Na channels Moderate Slow (phase 4): automaticity.
Class I A : Action Potential Duration. (moderate channel blocker)
Class I B: APD (weak channel blocker)
Class I C: no effect on Action Potential Duration. (strong channel blocker)
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12. Class I: Na+ Channel blockers = Membrane Stabilizers
A) Group A: Block BOTH types of Na+ & K+ Channels: Moderate block of Activated Na+ channel Moderate Slow of Phase(0) Moderate slow Excitability & Conductivity 2- Moderate Block Inactivated Na+ Channel Slow Phase (4) Slow Automaticity 3- Block K+ Channel Delay repolarization Long Phase (3) Long A.P.D., & E.R.P. Examples: Quinidine, Procainamide & Disopyramide. B) Group B: 4 1- Minimal Block of Activated Na+ channel Minimal effect on conductivity & Excitability 2- Block MAINLY Inactivated Na+ Channel Slow Phase (4) Slow Automaticity. 3- Activate K+ Channel Rapid repolarization Short Phase (3) Short APD & ERP Examples: Lidocaine & Mexiletine C) Group C: 0 1- Block MAINLY Activated Na+ Channels Marked Slow Phase (0) Marked Slow Excitability & Conductivity Examples: Flecainide, Encainide & Propafenone.
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13. Cardiac effect of class I anti-arrthymic drugs
Action potential duration APD no effect on APD
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14. Class I A Na channel blockers Quinidine, Disopyramide & procainamide.
Mechanism Of Action: all drugs in this class: a- Moderate block of Activated Na+ channel Moderate slow of phase (0) Moderate Slow of Excitability & Conductivity b- Block K+ channel Delay repolarization Long Phase (3) Long Action potential duration (APD) & Effective Refractory Period (ERP) c- moderate Block Inactivated Na+ channel Slow Phase (4) Slow Automaticity Stop Ectopic focus. 2- Quinidine blocks Vagal tone = Anti-Vagal = Vagolytic = Atropine-like effect. 3- procainamide is ganglion blocker.
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15. Class I A Na channel blockers Quinidine, Disopyramide & procainamide
Quinidine & Disopyramide are Rarely used
Cardioversion or defibrillation and amiodarone have mostly replaced procainamide in clinical use.
Therapeutic uses:
Atrial fibrillation, flutter, supraventricular tachy-arrhythmias.
Ventricular tachy-arrhythmias when other measure fail (last choice)
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16. Class I A Na channel blockers Toxicity
Quinidine
Disopyramide
Procainamide
Non-Cardiac
Toxicity
GI (N, V, D) in 1/3 patients
• Anticholinergic effect
• Cinchonism
•Profound anticholinergic effect
• Negative inotropic
• Drug-induced lupus
syndrome
• Hypotension (IV).
*ganglion blocker
Metabolism by liver acetylation. Into active (NAPA), excreted by kidneys
Therapeutic
Consideration
• Quinidine induced
Digoxin toxicity
•Caution in LV systolic dysfunction patients
•Lupus-like syndrome in slow acetylators
- Baseline & periodic
determination of (N-acetyl procainamide)
Cardiac
prolonge QT wave ⇒ torsades de pointes !!! Stop the drug immediately
Cinchonism such as: blurred vision, tinnitus, headache, disorientation, and psychosis
Anticholinergic effects such as: dry mouth, urinary retention, blurred vision, and constipation
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17. Class IB Na channel blockers:
Lidocaine (IV): oral form undergo extensive first pass hepatic effect
Mechanism of action:
1)anti-arrythmic drug:
2- Block MAINLY Inactivated Na+ Channel Slow Phase (4) Slow Automaticity.
3- Opens K+ Channel Rapid repolarization Short Phase (3) Short APD & ERP
2) In Therapeutic Dose on Normal Heart: NO Atropine-like effect
& NO Effect on S.A.N., A.V.N., Contractility or Blood pressure
3) Local Surface anesthetic.
Therapeutic Uses: IV ( Emergency VF or pulseless VT if amiodarone is unavailable
Toxicity: C.N.S. Stimulation & Allergy
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18. Class IB Na+ channel blockers:
Mexiletine: Orally active analog of lidocaine.
Therapeutic Uses: in combination with other anti-arrhythmic such as amiodarone for chronic treatment of ventricular arrthymia.
Observe: class I B has NO efficacy against atrial fibrillation, flutter; supraventricular tachy-arrhythmias
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19. Class IC Na+ channel blockers: Flecainide & Propafenone.
Mechanism of action:
Potent Block Activated Na+ channel Slow Phase “0” Slow Excitability & Conductivity, Especially in Atria, Ventricles & Purkinje fibers.
Propafenone has also B-Blocking effect
Therpuetic uses:
A. fibrillation, A. flutter, Paroxysmal Supra Ventricular Tachycardia, SVT in patients without structural heart diseases (left ventricular hypertrophy, heart failure, atherosclerotic heart disease).
Ventricular tachycardia.
Contraindicated in coronary artery disease or post-M. Infacrction
Also used as “Pill-in-the-pocket”
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20. Flecainide Propafenone
Class IC Na+ channel blockers: Flecainide & Propafenone (adverse effects)
Flecainide
Propafenone
Non-Cardiac
Toxicity
- Blurred vision (dose related)
- CNS (dizziness, headache, tremor)
- GI adverse effects
- Bronchospasm (B blockade)
Cardiac Toxicity
• Significant negative inotropic (bring on new or worsen CHF)
• Sinus bradycardia (B blockade)
Therapeutic
Consideration
Avoid in patients with underlying heart abnormalities – CAD, ventricular dysfunction – can precipitates heart failure
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21. 2) Class II: B-Blockers Metoprolol, Propranolol & Esmolol
antagonize sympathetic stimulation of β1- adrenergic receptors in SAN and AV node cells slow automaticity and slow rate (decrease all cardiac properties)
8/2/2019
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22. Class II: B-Blockers Propranolol
Mechanism of Action:
a- Small Dose Blocks ONLY B-Adrenergic receptors
b- Large Dose, It blocks also:
Na+ channel = Class “I” Activity = Membrane stabilizer = Quinidine-like
Slow Ca2+ channels = Class “IV” activity.
Decrease K current:
⇒ increase refractory period of impulse
ECG: PR prolongation
BB: HR, conduction velocity, contractility
SAN & AVN
Phase 4
(AVN) prolongs phase 3
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23. Class II: B-Blockers Propranolol, Therapeutic uses:
As Anti-Arrhythmic: a- Sympathetic-induced arrhythmia (Use Small Dose of Propranolol) b- Non-Sympathetic induced arrhythmia (Use Large Dose of Propranolol ) c- Particularly effective in Supra-ventricular arrhythmia Propranolol (decreases A-V conduction & Protects the ventricles)
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24. Class II: B-Blockers Propranolol toxicity
Non-cardiac toxicity: • Bronchospasm Cardiac toxicity: • Excessive negative inotropic effects, heart block • Hypotension •Sinus Tachycardia and/or hypertension upon sudden drug withdrawal Therapeutic considerations: • Taper drug withdrawal over 4-7 days
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25. Beta blockers contraindications
Beta blockers are contraindicated in cases of WPW syndrome. Because it slows the conduction via AV node and favors the accessory pathway conduction which my ppt. ventricular arrthymia and death
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26. اسم ورقم المقرر – Course Name and No.
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