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Dr Khulood Alsaraf

Definition
An arrhythmias : Is abnormality in the rate, regularity, or site of origin or a disturbance in conduction that disrupts the abnormal sequence of activation in the atria or ventricles.

Arrhythmias have a varying degree of severity & significance based on: Site of origin Symptoms Frequency Duration The clinical implications of disordered cardiac activation range from asymptomatic palpitations to lethal arrhythmias

Treatment Goals
Prevent morbidity and mortality associated with cardiac arrhythmias

Restore normal sinus rhythm in appropriate patients

Balance therapeutic benefits of antiarrhythmic therapies

with the potential for serious adverse effects

Classification Of Antiarrhythmic Drugs


Antiarrhythmic drugs are classified into four main groups, based on their predominant mechanism of action :

Class I drugs
These drugs act by blocking voltage-sensitive sodium channels via the same mechanism as local anesthetics.

Class Ia :

Quinidine Procainamide Disopyramide

Mechanism of action
Act by blocking the fast (sodium) channels & prevents sodium influx thus slowing the rapid upstrock during phase 0. It is also decreases the slope of phase 4 spontaneous depolarization. The direct action is a generalized slowing of both automaticity conduction velocity in the SA node, AV node, and His-Purkinje system. In addition, all three agents are negative inotropes via their sodium channel blockade.

Quinidine, Procainamide, Disopyramide


All 3 agents are used in the management of supraventricular tachyarrhythmias. Quinidine : used in treatment of a wide variety of arrhymias, largely replaced by other antiarrhymic drugs because of it is toxicity.

Therapeutic uses

Procainamide : It is a derivative of the local anesthetic procaine.


Class Ia agents are generally used as a second line agents. They are limited by their negative inotropic effects, Q-T interval prolongation , drug interactions (especially Quinidine), and extensive adverse effect profiles.

Class Ib : Lidocaine
Mexiletine Tocainide

These drugs act by blocking fast sodium channels, they exhibit fast on off characteristics as opposed to class Ia [intermediate] & class Ic [slow]. Thus, the action of class Ib agents are manifested when the cardiac cell is depolarized or firing rapidly.

Lidocaine

useful in tretment of ventricular tachyarrhythmias arising during myocardial ischemia. little effect on atrial or AV junction arrhythmias. drug of choice for emergency treatment of cardiac arrhythmias.

Mexiletine & Tocainide


They can be administered orally. Mexiletine : is used for chronic treatment of ventricular arrhythmias associated with previous myocardial infarction.

Tocainide : is used for treatment of ventricular

tachyarrhythmias . Tocainide has pulmonary toxicity, which may lead to pulmonary fibrosis

Class Ic : Propafenone Flecainide


These agents are characterized by their long binding to the fast (sodium) channels

Propafenone

indicated for documented life threatening ventricular

arrhythmias [e.g; sustained ventricular tachycardia] It is effective in supraventricular arrhythmias, & considered drug of choice in wolff parkinson white syndrome (WPW)

Flecainide
Used in treating refractory ventricular arrhythmias,& in suppressing premature ventricular contraction. Orally effective. Has a negative inotropic effect & can aggravate CHF.

Class II drugs

adrenergic antagonists [ blockers] are antiarrhythmic in addition to antagonize sympathetic activity, resulting in reduced automaticity in the sinus node & conduction velocity through the AV node. blockers : are most commonly used for rapid control of the ventricular rate during supraventricular tachycardia such as atrial fibrillation & atrial flutter.

Propranolol

: reduce the incidence of sudden arrhythmic death after myocardial infarction. Metoprolol : 1 specific drugs, used by IV administration mainly to reduce the risk of bronchospasm.

Esmolol

: is a very short acting blockers used for IV administration in acute arrhythmias that occur during surgery or emergency situation.

Class III drugs Amiodarone sotalol Dofetilide


These drugs block potassium channels &, thus, diminish the outward potassium current during repolarization of cardiac cells. These agents prolong the duration of action potential without altering phase 0 of depolarization or the resting membrane potential. Instead, they prolong the effective refractory period.

Contains iodine & is related structurally to thyroxine. -It has complex effects, showing class I, II, III, IV actions. -Its dominant effect is prolongation of the action potential duration & refractory period. -It has antianginal as well as antiarrhythmic activity. -Effective in the treatment of sever refractory supraventricular , ventricular tachyarrhythemias and atrial fibrillation. -Its the most commonly employed antiarrythmic.

Amiodarone

Sotalol
Has potent blockers activity. -Blocks a rapid outward potassium current, known as delayed rectifier, this blockade prolongs both repolarization & duration of the action potential, thus lengthening the effective refractory period. -Effective in the management of life threatening ventricular arrhythmias.

Class IV drugs

Are calcium channel blockers. They decrease the inward current carried by calcium, resulting in a decreased rate of phase 4 spontaneous depolarization, & slowing the conduction in AV node.

Verapamil & Diltiazem


Show greater action on the heart than on vascular smooth muscle. Bind only to open, depolarized channels, thus preventing repolarization until the drug dissociates from the channel. Slow conduction & prolong the effective refractory period in tissues that are dependent on calcium currents, such as AV node. More effective against atrial than ventricular dysrhymais. Used in treatment of reentrant supraventricular tachycardia.

Miscellaneous Antiarrhythmics Digoxin


-Shortens the refractory period in atrial & ventricular myocardial cells while prolonging the effective refractory period & diminishing conduction velocity in Purkinje fibers. -Used to control the ventricular response rate in atrial fibrillation & flutter. -At toxic conc. Digoxin cause ectopic ventricular beats that may result in ventricular tachycardia & fibrillation.

Miscellaneous Antiarrhythmics

Adenosine
Naturally occurring nucleoside, but at high doses, the drug decreases conduction velocity, prolongs the refractory period, & decreases automaticity in the AV node. IV adenosine is the drug of choice for abolishing acute supraventricular tachycardia. It has low toxicity very short duration of action (approximately 15 sec.)

Side effects of Antiarrhythmics drugs


The most common side effects are dry mouth and throat, diarrhea, and loss of appetite. Less common side effects, such as dizziness, blurred vision, dry eyes and nose, frequent urge to urinate, bloating, stomach pain, and decreased sexual ability, constipation. More serious side effects are not common: fever and chills difficult urination swollen or painful joints pain when breathing skin rash or itching

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