Comprehensive Pharmacology of Anti-Arrhythmic Drugs in Cardiovascular Therapy

Comprehensive Pharmacology of Anti-Arrhythmic Drugs in Cardiovascular Therapy

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  PHARMACOLOGY OF DRUGSACTING ON THE CARDIOVASCULAR SYSTEM ANTI-ARRHYTHMIC DRUGS Introduction Cardiac arrhythmias are disturbances in the normal rhythm, rate, or conduction of the heartbeat resulting from abnormalities in impulse generation or impulse conduction. They may occur due to enhanced automaticity, triggered activity, or re-entry mechanisms. Anti-arrhythmic drugs are agents that restore and maintain normal sinus rhythm by modifying the electrical activity of the myocardium. The primary objectives of anti-arrhythmic therapy are to: Restore normal cardiac rhythm. Prevent recurrence of arrhythmias. Improve cardiac output. Reduce symptoms such as palpitations and syncope (temporary loss of consciousness when blood flow to the brain drops) Prevent sudden cardiac death.
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  Classification of Anti-arrhythmicDrugs (Vaughan Williams Classification) Class Mechanism Drugs Class I Sodium channel blockers Quinidine, Procainamide, Disopyramide, Lidocaine, Mexiletine, Propafenone IA Moderate Na+ block; prolong AP Quinidine, Procainamide, Disopyramide IB Mild Na+ block; shorten AP Lidocaine, Mexiletine IC Strong Na+ block Flecainide, Propafenone Class II β-adrenergic blockers Propranolol, Metoprolol, Esmolol, Atenolol Class III Potassium channel blockers Amiodarone, Sotalol, Dofetilide, Ibutilide, Dronedarone Class IV Calcium channel blockers Verapamil, Diltiazem Miscellaneous Other mechanisms Adenosine, Digoxin, Magnesium sulfate, Atropine
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  Pathophysiology of Arrhythmia RiskFactors ↓ Disturbance in Cardiac Electrical Activity ↓ Abnormal Impulse Formation (Increased Automaticity / Triggered Activity) OR Abnormal Impulse Conduction (Re-entry / Conduction Block) ↓ Abnormal Cardiac Rhythm ↓ Tachyarrhythmia or Bradyarrhythmia ↓ Reduced Cardiac Output ↓ Palpitations • Syncope • Hypotension ↓ Heart Failure / Stroke / Sudden Cardiac Death
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  CLASS I -ANTI-ARRHYTHMIC DRUGS Sodium Channel Blockers •These drugs inhibit fast sodium channels responsible for phase 0 depolarization in atrial and ventricular muscle Class IA Drugs Drugs:- Quinidine, Procainamide, Disopyramide Mechanism of Action Administration ↓ Blocks fast Na+ channels ↓ Slows Phase 0 depolarization ↓ ↓ Conduction velocity ↓ Blocks K+ channels ↓ Prolongs Action Potential Duration ↓ ↑ Effective Refractory Period ↓ Suppresses Re-entry Circuits ↓ Restoration of Normal Cardiac Rhythm
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  •Therapeutic Effects •Decreases myocardialexcitability. •Slows conduction velocity. •Prolongs refractory period. •Prevents re-entry arrhythmias. •Clinical Uses •Atrial fibrillation (a common type of irregular heart rhythm (arrhythmia) where the upper chambers of the heart (the atria) beat chaotically and out of sync with the lower chambers (the ventricles).) •Atrial flutter (a type of fast heart rhythm) •Supraventricular tachycardia •Ventricular tachycardia •Adverse Effects •Quinidine •Cinchonism (tinnitus, headache, dizziness) •Diarrhea •QT prolongation •Hypotension
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  •Procainamide •Drug-induced lupus (rednessof skin) •Agranulocytosis (the bone marrow stops making enough neutrophils, a vital type of white blood cell that fights bacterial and fungal infections.) •Hypotension •Disopyramide •Dry mouth •Urinary retention •Constipation •Heart failure •Contraindications •Complete heart block •Long QT syndrome •Severe hypotension •Heart failure
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  •Class IB Drugs •Drugs:Lidocaine, Mexiletine •Mechanism of Action Drug Administration ↓ Blocks Na+ channels in ischemic myocardium ↓ Shortens Action Potential Duration ↓ Suppresses abnormal automaticity ↓ Decreases ventricular ectopic activity (extra or early heartbeats) ↓ Controls Ventricular Arrhythmias
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  •Therapeutic Effects •Reduces ventricularexcitability •Suppresses ectopic pacemakers. •Minimal effect on normal myocardium. •Clinical Uses •Acute ventricular tachycardia •Ventricular arrhythmias after myocardial infarction •Digitalis-induced ventricular arrhythmias •Adverse Effects •Tremor (an involuntary, rhythmic shaking movement) •Drowsiness •Confusion •Convulsions (body muscles contract and relax fast and repeatedly) •Contraindications •Severe SA block •AV block •Hypersensitivity
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  •Class IC Drugs •Drugs:-Flecainide, Propafenone •Mechanism of Action Administration ↓ Marked Na+ Channel Block ↓ Marked slowing of conduction ↓ Suppresses ectopic impulses ↓ Terminates Re-entry ↓ Maintains Sinus Rhythm
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  •Therapeutic Effects •Markedly slowsimpulse conduction. •Suppresses premature ventricular contractions. •Prevents atrial fibrillation recurrence. •Clinical Uses •Resistant supraventricular arrhythmias •Atrial fibrillation •Ventricular arrhythmias (selected patients) •Adverse Effects •Pro-arrhythmia •Heart failure •Blurred vision •Dizziness •Contraindications •Structural heart disease •Previous myocardial infarction •Heart failure •AV block
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  •CLASS II •Beta-Adrenergic Blockers •Drugs:Propranolol, Metoprolol, Atenolol, Esmolol •Mechanism of Action β1 Receptor Blockade ↓ ↓ cAMP ↓ ↓ Ca2+ Entry ↓ Reduced SA Node Automaticity ↓ Slowed AV Conduction ↓ Increased AV Refractory Period ↓ Suppression of Tachyarrhythmias
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  •Therapeutic Effects •Reduces heartrate. •Decreases myocardial oxygen demand. •Prevents catecholamine-induced arrhythmias. •Clinical Uses •Atrial fibrillation •Atrial flutter •Ventricular arrhythmias after myocardial infarction •Long QT syndrome •Adverse Effects •Bradycardia •Hypotension •Fatigue •Bronchospasm •Depression •Erectile dysfunction •Contraindications •Asthma •COPD (non-selective agents) •Severe bradycardia •Cardiogenic shock •Second- or third-degree AV block
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  •CLASS III •Potassium ChannelBlockers Drugs: Amiodarone, Sotalol, Dofetilide, Ibutilide, Dronedarone Mechanism of Action Blocks K+ Channels ↓ Delayed Repolarization ↓ Prolonged Action Potential ↓ ↑ Effective Refractory Period ↓ Interrupts Re-entry Circuits ↓ Prevents Arrhythmias
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  •Therapeutic Effects •Prolongs refractoryperiod. •Suppresses ventricular and supraventricular arrhythmias. •Reduces recurrence of atrial fibrillation. •Clinical Uses •Amiodarone •Ventricular tachycardia •Ventricular fibrillation •Atrial fibrillation •Atrial flutter •Sotalol •Ventricular tachycardia •Atrial fibrillation •Ibutilide •Pharmacological cardioversion of atrial flutter and atrial fibrillation •Adverse Effects •Amiodarone •Pulmonary fibrosis •Photosensitivity •Blue-gray skin discoloration •Thyroid dysfunction •Hepatotoxicity •Bradycardia •Sotalol •Bradycardia •Contraindications •Severe sinus bradycardia •AV block •Cardiogenic shock •Pregnancy (relative) •Severe thyroid disease (amiodarone)
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  •CLASS IV •Calcium ChannelBlockers Drugs: Verapamil, Diltiazem Mechanism of Action Blocks L-type Ca2+ Channels ↓ Reduced Ca2+ Entry ↓ Slower AV Node Conduction ↓ Longer AV Refractory Period ↓ Terminates AV Nodal Re-entry ↓ Normal Sinus Rhythm
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  •Therapeutic Effects •Slows ventricularrate. •Controls supraventricular tachycardia ( fast heart rate where heart beats 150- 220 times a min) •Reduces myocardial oxygen demand. •Clinical Uses •Paroxysmal supraventricular tachycardia •Atrial flutter •Atrial fibrillation •Adverse Effects •Constipation (verapamil) •Bradycardia •Hypotension •Heart block •Peripheral edema •Contraindications •Heart failure with reduced ejection fraction •Sick sinus syndrome •Severe hypotension •AV block (without pacemaker)
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  •Miscellaneous Anti-arrhythmic Drugs •Adenosine Mechanism A1Receptor Activation ↓ ↑ K+ Efflux ↓ Ca2+ Influx ↓ Transient AV Node Block ↓ Terminates AV Nodal Re-entry
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  •Uses •Acute paroxysmal supraventriculartachycardia (PSVT) •Adverse Effects •Flushing •Chest pain •Dyspnea •Transient asystole •Contraindications •Second- or third-degree AV block •Sick sinus syndrome (without pacemaker) •Severe asthma
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  •Digoxin •Mechanism •Increases vagal tone,thereby slowing AV nodal conduction and prolonging AV nodal refractory period. •Uses •Atrial fibrillation with heart failure •Atrial flutter •Adverse Effects •Digitalis toxicity •Arrhythmias •Nausea •Vomiting •Visual disturbances (yellow vision) •Contraindications •Ventricular fibrillation •Hypertrophic obstructive cardiomyopathy •Digitalis toxicity
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  •Magnesium Sulfate •Mechanism •Stabilizes cardiaccell membranes and suppresses early after-depolarizations by correcting magnesium deficiency. •Uses •Torsades de Pointes •Digoxin-induced arrhythmias •Hypomagnesemia-associated arrhythmias •Adverse Effects •Hypotension •Flushing •Muscle weakness •Contraindications •Hypermagnesemia •Severe renal failure (use cautiously)