Cardiovascular agents

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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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Metabolism of lidocaine
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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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Metabolism
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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