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CH 52: antidysrhythmic drugs

Heart Properties 

  • Dysrhythmia: an abnormality in the rhythm of the heart beat; caused by impulse formation disturbances

  • Caused by disturbances of automaticity (any part of the heart)

  • Caused by disturbances of conduction (AV block/reentry)

  • Reentry: heart impulse keeps circulating instead of dying 

  • SA node: pacemaker of the heart

  • Fast potentials: Occur in the fibers of the his-purkinje system and in the atrial and ventricular muscle in 5 phases 

  • Phase 0: depolarization

  • Phase 1: partial repolarization

  • Phase 2: plateau 

  • Phase 3: repolarization

  • Phase 4: stable potential 

  • Slow potentials: Occur in the SA node and AV node ventricular muscle; 3 important phases 

  • Phase 0: slow depolarization (mediated by calcium influx)

  • Phase 1, 2, 3

  • Phase 4: depolarization

  • Electrocardiogram: representation of cardiac electrical activity

  • P wave : depolarization of the atria

  • QRS complex: depolarization of the ventricles

  • T wave: repolarization of the ventricles


Common dysrhythmias and Drugs

  • Supraventricular: impulse arises from above the ventricle                                       Examples: atrial fibrillation/ atrial flutter

  • Ventricular: impulse arises from the ventricle 

Examples: sustained ventricular fibrillation, torsades de pointes, digoxin induced ventricular dysrhythmias 

Class 1: Sodium Channel Blockers

  • Quindine (class 1a)

Overall effects and MOA of Quindine

  • Slows impulse conduction

  • Delays repolarization

  • Blocks vagal input to the heart 

  • Widens the QRS complex

  • Prolongs the QT interval

Therapeutic uses Quindine

  • Supraventricular and ventricular dysrhythmias 

Adverse effects of Quindine

  • Diarrheas

  • Cinchonism (quinidine toxicity)

  • Cardiotoxicity 

  • Arterial embolism 

  • Alpha-adrenergic blockade, resulting in hypotension

  • Hypersensitivity reactions 

Drug interactions with Quindine

  • Digoxin

  • Procainamide [procanbid] (class 1a)

Overall effects and MOA of procainamide

  • Similar to quinidine 

  • Adverse effects:symptoms of lupus syndrome 

  • Lidocaine [xylocaine](class 1b)

Overall effects and MOA of Lidocaine

  • Slows conduction in atria, ventricles. And his-purkinje system

  • Reduces automaticity in the ventricles and his-purkinje system

  • Accelerates repolarization 

Adverse effects of Lidocaine

  • CNS effects

  • Drowsiness

  • Confusion 

  • Parethesias  

  • Phenytoin (class 1b)

Overall effects and MOA of Phenytoin

  • Antiseizure medication used to treat digoxin induced dysrhythmias 

  • Mexiletine (class 1b)

Overall effects and MOA of Phenytoin

  • Oral analog of lidocaine 

  • Used for symptomatic ventricular arrhythmias

  • class 1c agents 

Overall effects of class 1C agents 

  • Delays ventricular repolarization 

  • Can exacerbate existing arrhythmias and create new ones 

  • Examples: flecainide 

  • Propafenone 

Class 2: Beta Blockers

  • Propranolol [inderal] 

Overall effects and MOA of Propranolol

  • Decreased automaticity of SA node 

  • Decreased velocity of conduction through AV node 

  • Decreased myocardial contractility 

Therapeutic uses Propranolol

  • dysrhythmias caused by excessive sympathetic stimulation

  • Supraventricular tachydysrhythmias 

Adverse effects of Propranolol

  • Heart block 

  • Heart failure 

  • AV block 

  • Sinus arrest 

  • Hypotension

  • Bronchospasm (in asthma patients)

Class 3: Potassium channel Blockers

  • Amiodarone [Cordarone, Pacerone]

Overall effects of class Amiodarone

  • Reduced automaticity of SA node 

  • Reduced conduction velocity 

  • Reduced contractility

  • QRS widening 

  • Prolongation of the PR and QT intervals 

Therapeutic uses Amiodarone

  • Life threatening Ventricular dysrhythmias 

  • Recurrent ventricular fibrillation

  • Recurrent hemodynamically unstable ventricular tachycardia  

Adverse effects of Potassium Channel Blockers

  • Prolonged half life 

  • Pulmonary toxicity

  • Cardiotoxicity 

  • Toxicity in pregnancy and breast feeding 

  • Corneal microdeposits 

  • Optic neuropathy

Drug interactions with Potassium Channel Blockers 

  • Quinidine 

  • Diltiazem 

  • Cyclosporin 

  • Digoxin 

  • Procainamide 

  • Phenytoin 

  • Warfarin 

  • Lovastatin, simvastatin, atorvastatin 

  • Liver toxicity 

  • grapefruit juice and CYP3A4 inhibitors (can Increase Amiodarone levels)

  • Cholestyramine (decreases Amiodarone absorption)

  • Diuretics (increase risk of severe dysrhythmias because they reduce levels of potassium and magnesium) 

Class 4: Calcium channel Blockers

  • Verapamil [Calan, covera, verelan] and diltiazem [cardizem]

Overall effects of class Calcium Channel Blockers

  • Reduced automaticity of SA node 

  • Delay AV nodal conduction 

  • Reduced myocardial contractility

Therapeutic uses Calcium Channel Blockers

  • Slow Ventricular rate 

  • Terminate supraventricular tachycardia caused by an AV nodal reentrant circuit   

Adverse effects of Calcium Channel Blockers

  • Bradycardia

  • Hypotension 

  • AV block

  • Heart failure 

  • Peripheral Edema 

  • Constipation 

  • Elevate digoxin levels 

  • Adenosine [Adenocard]

Overall effects of Adenosine

  • Decreased automaticity of SA node

  • slows AV nodal conduction

  • Prolongs PR interval 

Therapeutic uses of adenosine 

  • Termination of paroxysmal SVT 

Adverse effects of Adenosine

  • Sinus Bradycardia

  • Dyspnea 

  • Hypotension 

  • Facial flushing 

  • Chest discomfort 

Drug interactions with Adenosine

  • Methylaxanthines 

  • Dipyridamole 

  • Digoxin [Lanoxin]

Overall effects of Digoxin

  • Primary indication is Heart failure 

  • Decreases conduction of AV node 

  • Decreased automaticity of SA node

Therapeutic uses of Digoxin

  • Treat supraventricular arrhythmias

  • Ventricular arrhythmias   

Adverse effects of Adenosine

  • Cardiotoxicity (risk increased by hypokalemia)