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Cardiovascular agents. Anti-arrhythmic Drugs. Cardiac arrhythmia (also dysrhythmia ) is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart . The heart beat may be too fast or too slow, and may be regular or irregular.

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cardiovascular agents

Cardiovascular agents

Anti-arrhythmic Drugs

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Cardiac arrhythmia (also dysrhythmia) is a term for any of a large and heterogeneous group of conditions in which there is abnormal electrical activity in the heart. The heart beat may be too fast or too slow, and may be regular or irregular.

Cardiac arrhythmias are caused by a disturbance in the conduction of the impulse through the myocardial tissue , by disorders of impulse formation , or by a combination of these factors

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Classes of anti-arrhythmic drugs :

Class ( I ) Membrane-stabilizing drugs :

A ) : Quinidine, procainamide, disopyramide.

Mode of action : Lengthens refractory period .

B ) : Lidocaine , phenytoin , tocainide , mexiletine .

Mode of action : Shortens duration of action potential .

C ) : Ecainide , flecainide , lorcainide .

Mode of action : Slows conduction .

Class ( II ) : b-adrenergic blockers ( e.g. propranolol ).

Mode of action : Slows AV conduction time , suppresses

automaticity .

Class ( III ) :Amiodarone , bretylium tosylate .

Mode of action: Prolongs refractoriness.

Class ( IV ) : Verapamil , diltiazem .

Mode of action : Blocks slow inward calcium channel

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Class ( I ) : Membrane-stabilizing drugs

Anti-arrhythmic drugs that have membrane-stabilizing properties ( i. e. , shift membrane to more negative potentials ) . Drugs in this class act on the fast Na+ channels and interfere with the process by which the depolarizing charge is transferred across the membrane.

Class ( I ) anti-arrhythmic drugs can be subdivided on the basis of the relative ease with which they dissociate from Na+ ion channel to (A,B,C )

Class I (A ) :

Includes quinidine , procainamide , and disopyramide, which are drugs that have an intermediate rate of dissociation from Na+ channel and lengthen the refractory period of cardiac tissue to cause cessation of arrhythmias .

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Procainamide hydrochlorid

P-Amino-N-( 2-( diethylamino ) ethyl ) benzamide monohydrochloride

Procainamide is the nitrogen isoster of procaine, which had limited effect as an anti-arrhythmic agent because of its central nervous system side effects and short-lived action resulting from the rapid hydrolysis of its ester linkage by plasma esterases .

Metabolism of procainamide occurs through the action of N-acetyltranseferase.

Procainamide is used mainly for ventricular tachycardias .

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Disopyramide phosphate

( 2( Diisopropylamino ) ethyl )- -phenyl-2-pyridineacetamide phosphate

It is used clinically in the treatment of refractory, life-threating ventricular tachyarrhythmia

Disopyramide commonly exhibits side effects of dry mouth, constipation, urinary retention, and other cholinergic-blocking actions because of its structural similarity to anti-cholinergic drugs.

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Class I (B ) :

Includes lidocaine, phenytoin, tocainide, and mexiletine. Class IB have the property of rapidly dissociating from the Na+ channels. These drugs shorten the action potential duration .

Lidocaine hydrochloride

2-( Diethylamino )-2', 6'-acetoxylidide monohydrochloride

Lidocaine is used intravenously as a standard parenteral agent for suppression of arrhythmias associated with acute myocardial infarction and with cardiac surgery.

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Phenytoin sodium

5, 5-Diphenyl-2, 4-imidazolidinedione

used in the treatment of digitalis-induced arrhythmias.

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Mexiletine hydrochloride

1-Methyl-2- ( 2, 6-xylyloxy )ethylamine hydrochloride

Mexiletine is metabolized by oxidative and reductive processes in the liver to p-hydroxymexiletine and hydroxymethylmexiletine which are not active as anti-arrhythmic agents

Mexiletine is used for long-term oral prophylaxis of ventricular tachycardia.

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Tocainide hydrochloride

2- (amino )-2',6' –propionoxylidide hydrochloride

Tocainide is used orally to prevent or treat ventricular ectopy and tachycardia.

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Class I (C ) :

Includes Encainide , Flecainide , and Lorcainide. These drugs are slowly dissociated from Na+ channel causing a slowing down of the conduction time of the impulse through the heart .

Encainide hydrochloride

4-Methoxy- N- ( 2-(2-(1-methyl-2-piperidinyl ) ethyl ) phenyl ) benzamide monohydrochloride .

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Encainide is one of the more recent anti-arrhythmic agents . It is a benzanilide derivative that has local anesthetic properties in addition to its class IC anti-arrhythmic action . The drug is extensively metabolized , producing products that also have anti-arrhythmic properties

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Flecainide acetate

N-( 2-Piperidinylmethyl )-2 , 5 –bis ( 2, 2, 2 –trifluoroethoxy) benzamide monoacetate .

Flecainide is given orally to suppress chronic ventricular ectopy and ventricular tachycardia. The drug has some limitations because of central nervous system side effects .

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Lorcainide hydrochloride

N-(4-chlorophenyl)-N-(1-isopropylpiperidin-4-yl)-2-phenylacetamide

Lorcainide is a local anesthetic-type anti-arrhythmic agent. It is used to suppress chronic ventricular ectopy

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Class ( II ) : B-Adrenergic Blocking Agents

B-adrenergic blocking agents , ( cardio selective B-blockers ) ,have the property of causing membrane-stabilizing or depressant effects on myocardial tissue . However, their anti-arrhythmic properties are considered to be principally due to inhibition of adrenergic stimutation of the heart , such that the heart rate decreases , and ectopic tachycardia are either slowed down or converted to sinus rhythm. This group includes:

Propranolol, Pindolol, Atenolol, Esmolol, and Metoprolol

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Class ( III ) : Repolarization prolongators

Drugs in this class (e. g. , amiodarone , bretylium tosylate ) cause a homogenous prolongation of the duration of the membrane action potential. This resulted in an increase of the effective refractory period . The drugs of class III have a high efficacy

In the treatment of "refractory" cardiac arrhythmias.

Amiodarone

2-Butyl-3-benzofuranyl 4-( 2-(diethylamino ) ethoxy )-3, 5-diiodophenyl ketone

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Amiodarone lengthens the effective refractory period by prolonging the action potential duration

Bretylium Tosylate

( o-Bromobenzyl ) ethyl dimethylammonium p-toluenesulfonate

Bretylium Tosylate is reserved for use in ventricular arrhythmias that are resistant to other therapy. It prolongs the effective refratory period relative to the action potential duration but doesn't affect conduction time

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Class ( IV ) : Cardio selective calcium channel blockers :

some members of this class of anti-arrhythmic drugs (Verapamil and Diltiazem ) block the slow inward current of calcium ions during phase 2 of the membrane action potential in cardiac cells . For example , Verapamil , selectively blocks entry of calcium ions into the myocardial cell and serves to depress AV conduction as well as block excitation-contraction coupling .These drugs are used in controlling atrial and paroxysmal tachycardia