Antiarrhythmics Drugs PDF

‫بسم هللا الرحمن الرحيم‬ Antiarrhythmics (Antidysrhythmic drugs)  Cardiac arrhythmias  Arrhythmias may require treatment because rhythms that are too rapid, too slow, or asynchronous can reduce cardiac output.  Arrhythmias can be treated with drugs and with non-pharma...

‫بسم هللا الرحمن الرحيم‬ Antiarrhythmics (Antidysrhythmic drugs)  Cardiac arrhythmias  Arrhythmias may require treatment because rhythms that are too rapid, too slow, or asynchronous can reduce cardiac output.  Arrhythmias can be treated with drugs and with non-pharmacologic therapies such as pacemakers, cardioversion, catheter ablation, and surgery.  Clinically, dysrhythmias are divided: 1. According to their site of origin (supraventricular and ventricular). 2. According to whether the heart rate is increased or decreased (tachycardia or bradycardia).  Causes of arrhythmias  All arrhythmias result from: 1. Disturbances in impulse formation (abnormal automaticity). 2. Disturbances in impulse conduction. .g. Reentry: Most common cause of arrhythmias  Reentry results in reexcitation causing ventricular arrhythmia 3. Both.  Antiarrhythmic drugs  Most of the antiarrhythmic agents:  Suppress automaticity:  by blocking either Na+ or Ca+2 channels  Suppress abnormalities in impulse conduction:  E.g. Reentry  Antiarrhythmic drugs can be classified according to their predominant effects on the action potential. (many antiarrhythmic drugs are proarrhythmic). 4 6  Antiarrhythmic agents  There are four classes:  Class I: drugs that block voltage-sensitive sodium channels. They are subdivided: Ia, Ib and Ic.  Class II: β-adrenoceptor antagonists.  Class III: drugs that substantially prolong the cardiac action potential.  Class IV: Calcium antagonists. 8  Antiarrhythmic drugs  Class IA antiarrhythmic drugs:  Quinidine, procainamide and disopyramide.  Quinidine is the prototype 9  Class IA antiarrhythmic drugs  Class IA antiarrhythmic drugs:  Therapeutic uses:  Quinidine:  For atrial, AV junctional, and ventricular tachyarrhythmias  Adverse effects: Quinidine (high dose): cinchonism: Blurred vision, tinnitus, headache  Disorientation and psychosis  Class IA antiarrhythmic drugs  Class IA antiarrhythmic drugs:  Therapeutic uses:  Procainamide:  As IV only  For acute atrial and ventricular arrhythmias  Disopyramide is used in the treatment of ventricular arrhythmias as an alternative to procainamide or quinidine and may also be used for maintenance of sinus rhythm in atrial fibrillation or flutter.  Class IB antiarrhythmic drugs  Class IB antiarrhythmic drugs:  Lidocaine, mexiletine and Phenytoin.  For ventricular arrhythmias  Therapeutic uses:  Amiodarone has replaced lidocaine for ventricular fibrillation.  Lidocaine: combined with amiodarone for VT (ventricular tachycardia) storm.  Class IB antiarrhythmic drugs  Class IB antiarrhythmic drugs:  Lidocaine adverse effects: CNS effects include nystagmus (early indicator of toxicity), drowsiness, slurred speech, paresthesia, agitation, confusion, and convulsions, which often limit the duration of continuous infusions.  Mexiletine has a narrow therapeutic index and caution should be used when administering the drug with inhibitors of CYP2D6.  Class IC antiarrhythmic drugs  Class IC antiarrhythmic drugs:  Flecainide and propafenone:  Several studies have cast serious doubts on the safety of this class. They were found increase the incidence of sudden death associated with ventricular fibrillation after myocardial infarction, so they are no longer used in this setting.  Class IC antiarrhythmic drugs  Class IC antiarrhythmic drugs:  Therapeutic uses:  Flecainide:  For refractory ventricular arrhythmias  Has a - ve inotropic effect:  Can aggravate CHF  Use of propafenone is restricted mostly to atrial arrhythmias (fibrillation or flutter).  Class II antiarrhythmic drugs  Class II antiarrhythmic drugs (β-blockers):  Examples: Propranolol, Esmolol, Sotalol, Metoprolol and atenolol.  They depress automaticity, prolong AV conduction, decrease HR and FC.  Sotalol is a nonselective β -blocking drug that prolongs the action potential (class 3 action).  For atrial flutter and atrial fibrillation.  Prevent life-threatening ventricular arrhythmia following a MI.  Class II antiarrhythmic drugs  Clinical uses: 1. To reduce mortality following myocardial infarction. 2. To prevent recurrence of tachyarrhythmias (e.g. paroxysmal atrial fibrillation) provoked by increased sympathetic activity.  Adverse effects: The most important being: 1. Bronchospasm in patients with asthma or other forms of obstructive airways disease. 2. A negative inotropic effect. 3. Increased fatigue.  Class III antiarrhythmic drugs  Class III antiarrhythmic drugs  E.g. Amiodarone and Sotalol (Non-selective BB)  They are K+ Channel blockers.  Prolong repolarization  Prolong refractory period  Therapeutic uses:  For severe refractory supraventricular and ventricular tachyarrhythmias  Class III antiarrhythmic drugs  Clinical use of sotalol: 1. Sotalol is approved for the treatment of life- threatening ventricular arrhythmias and the maintenance of sinus rhythm in patients with atrial fibrillation. 2. It is also approved for treatment of supraventricular and ventricular arrhythmias in the pediatric age group.  Class III antiarrhythmic drugs  Adverse effects: Amiodarone  Pulmonary fibrosis, hepatotoxicity, optic neuritis, blue-gray skin.  Hypo - or hyperthyroidism:  Amiodarone: Contains iodine (thyroid activity)  Use of low doses: reduce toxicity.  Class IV antiarrhythmic drugs  They are the nondihydropyridine calcium channel blockers: verapamil and diltiazem.  Class IV drugs slow conduction in the SA and AV nodes where action potential propagation depends on slow inward Ca2+ current, slowing the heart and terminating SVT by causing partial AV block.  They shorten the plateau of the action potential and reduce the force of contraction.  Class IV antiarrhythmic drugs  Verapamil and diltiazem :  They are more effective against atrial than against ventricular arrhythmias  They are useful in treating reentrant supraventricular tachycardia and in reducing the ventricular rate in atrial flutter and fibrillation.  Both drugs are metabolized in the liver by CYP3A4. Dosage adjustments may be needed in patients with hepatic dysfunction.  Both agents are also inhibitors of CYP3A4, so they are subject to many drug interactions.  Other antiarrhythmic drugs Digoxin  Digoxin inhibits the Na+/K+-ATPase pump, ultimately shortening the refractory period in atrial and ventricular myocardial cells while prolonging the effective refractory period and diminishing conduction velocity in the AV node.  It used to control ventricular response rate in atrial fibrillation and flutter.  At toxic concentrations, digoxin causes ectopic ventricular beats that may result in VT and fibrillation.  Other antiarrhythmic drugs Adenosine  Adenosine is a naturally occurring nucleoside, but at high doses, the drug decreases conduction velocity, prolongs the refractory period, and decreases automaticity in the AV node.  I.V adenosine is the drug of choice for abolishing acute supraventricular tachycardia.  It has an extremely short duration of action (approximately 10 to 15 seconds) due to rapid uptake by erythrocytes and endothelial cells.  Other antiarrhythmic drugs Magnesium sulfate  Magnesium is necessary for the transport of Na, Ca, and K across cell membranes.  It slows the rate of SA node impulse formation and prolongs conduction time along the myocardial tissue.  I. V magnesium sulfate is the salt used to treat arrhythmias (oral is not effective in arrhythmia).  Magnesium is the drug of choice for treating the potentially fatal arrhythmia torsades de pointes and digoxin-induced arrhythmias.