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8/3/2019 Wesam R Kadhum

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Antiarrhythmics

Wesam Radhi Kadhum


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Arrhythmia

An arrhythmia is a problem with the rate or

rhythm of the heartbeat (irregular heartbeat) .

During an arrhythmia, the heart can beat too

fast, too slow, or with an irregular rhythm.

A heartbeat that is too fast is called

tachycardia. A heartbeat that is too slow is

called bradycardia.


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All the wave of electrical activity across the

heart muscles can be measured by the

electrocardiogram (ECG).

Function of this conduction system is to keepthe heart beating in regular and synchronized

manner thus maintaining cardiac output.


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Diagnosis Patients must have ECG

Symptoms dizziness, weakness, decreased exercise

tolerance, shortness of breath, fainting, palpitation or

report of skipped heartbeat.

Some have minor effects on heart, some fatal.

Risk factors men, age, Inherited gene defects,

Obesity, Medications and Hypertension.


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In contrast to skeletal muscle, which contracts

only when it receives a stimulus, the heart

contains specialized cells that exhibit

automaticity; that is, they can intrinsically

generate rhythmic action potentials in the

absence of external stimuli. These pacemakercells differ from other

myocardial cells in showing a slow,

spontaneous depolarization during diastole(Phase 4), caused by an inward positive

current carried by sodium- and calcium-ion

flows.


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The heart cavity from which the arrhythmia

originates gives the name to the arrhythmiaatrial tachycardia for a rapid arrhythmia

originating in the atria.

Impulses originating from sites other than theSA node, or impulses traveling along accessory

(extra) pathways that lead to deviant

depolarizations (AV reentry, Wolff-Parkinson-

White syndrome), may also trigger

arrhythmias.


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Dysrhythmias Types

Type Description

Premature atrial contractions,

Premature ventricular contractions

An extra beat, not originating from SA node.

Not serious unless high frequency

Atrial tachycardia,

Ventricular tachycardia

Heartbeat > 150/min. Ventricular more

serious

Atrial flutter and/or fibrillation

Ventricular flutter and/or fibrillation

Very rapid, uncoordinated beats. Ventricular

requires immediate treatment

Sinus bradycardia Heartbeat < 50/min. May require pacemaker

Heart blockArea of nonconduction in myocardium. Partial

or complete


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A. Causes of arrhythmias

Most arrhythmias arise either from

aberrations in impulse generation (abnormal

automaticity) or from a defect in impulse

conduction.


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1. Abnormal automaticity:

The SA node shows the fastest rate of Phase 4depolarization and, therefore, exhibits a higherrate of discharge than that occurring in otherpacemaker cells exhibiting automaticity.

Abnormal automaticity may also occur if themyocardial cells are damaged (for example, byhypoxia or potassium imbalance).

These cells may remain partially depolarized

during diastole and, therefore, can reach thefiring threshold earlier than normal cells.Abnormal automatic discharges may thus beinduced.


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2. Effect of drugs on automaticity: Most of the

antiarrhythmic agents suppress automaticityby blocking either Na+ or Ca2+ channels to

reduce the ratio of these ions to K+.

This decreases the slope of Phase 4 (diastolic)

depolarization and/or raises the threshold of

discharge to a less negative voltage.

Such drugs cause the frequency of discharge

to decrease an effect that is morepronounced in cells with ectopic pacemaker

activity than in normal cells.


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3. Abnormalities in impulse conduction:

Impulses from higher pacemakercenters are normally conducted downpathways that bifurcate to activate theentire ventricular surface.

A phenomenon called reentry canoccur if a unidirectional block caused bymyocardial injury or a prolongedrefractory period results in an abnormalconduction pathway.

Reentry is the most common cause ofarrhythmias, and it can occur at any

level of the cardiac conduction system.


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4. Effects of drugs on conduction

abnormalities:

Antiarrhythmic agents prevent reentry

by slowing conduction and/or

increasing the refractory period,thereby converting a unidirectional

block into a bidirectional block.


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B. Antiarrhythmic drugs

Home Work


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III. Class I Antiarrhythmic Drugs


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Quinidine IA Therapeutic uses: Quinidine is used

in the treatment of a wide variety ofarrhythmias, including atrial, AV-

junctional, and ventriculartachyarrhythmias. Quinidine is usedto maintain sinus rhythm after

direct-current cardioversion of atrialflutter or fibrillation and to preventfrequent ventricular tachycardia.

Pharmacokinetics: Quinidine sulfateis rapidly and almost completelyabsorbed after oral administration.It undergoes extensive metabolismby the hepatic cytochrome P450enzymes, forming activemetabolites.


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Adverse effects

Quinidine may cause SA and AV block orasystole.

At toxic levels, the drug may induce

ventricular tachycardia. Cardiotoxic effects areexacerbated by hyperkalemia.

Nausea, vomiting, and diarrhea are commonlyobserved.

Large doses of quinidine may induce thesymptoms ofcinchonism (for example, blurredvision, tinnitus, headache, disorientation, andpsychosis).


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Mexiletine and

Tocainide IB

These Class IB drugs have actionssimilar to those of lidocaine, andthey can be administered orally.Mexiletine is used for chronic

treatment of ventriculararrhythmias associated withprevious myocardial infarction.Tocainide is used for treatment ofventricular tachyarrhythmias.

Tocainide has pulmonary toxicity,which may lead to pulmonaryfibrosis.


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H. Flecainide IC Therapeutic uses: Flecainide is useful in

treating refractory ventriculararrhythmias. It is particularly useful insuppressing premature ventricularcontraction. Flecainide has a negativeinotropic effect and can aggravatecongestive heart failure.

Pharmacokinetics: Flecainide is absorbedorally, undergoes minimalbiotransformation, and has a half-life of16 to 20 hours.

Adverse effects: Flecainide can causedizziness, blurred vision, headache, and

nausea. Like other Class IC drugs,flecainide can aggravate preexistingarrhythmias or induce life-threateningventricular tachycardia that is resistant totreatment.


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Class II Antiarrhythmic Drugs

Class II agents are -adrenergic antagonists. Thesedrugs diminish Phase 4 depolarization, thus depressingautomaticity, prolonging AV conduction, anddecreasing heart rate and contractility.

Class II agents are useful in treating tachyarrhythmiascaused by increased sympathetic activity. They are alsoused for atrial flutter and fibrillation and for AV-nodalreentrant tachycardia.

In contrast to the sodium-channel blockers, -blockers

and Class III compounds, such as sotalol andamiodarone, are increasing in use.


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A. Propranolol

Propranolol reduces the incidence of sudden

arrhythmic death after myocardial infarction (the mostcommon cause of death in this group of patients). Themortality rate in the first year after a heart attack issignificantly reduced by propranolol, partly because ofits ability to prevent ventricular arrhythmias.

B. MetoprololMetoprolol is the -adrenergic antagonist most widelyused in the treatment of cardiac arrhythmias.Compared to propranolol, it reduces the risk ofbronchospasm.

C. EsmololEsmolol is a very short-acting -blocker used forintravenous administration in acute arrhythmias thatoccur during surgery or emergency situations.


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Amiodarone III

Therapeutic uses: Amiodarone iseffective in the treatment of severerefractory supraventricular andventricular tachyarrhythmias. Despite itsside-effect profile, amiodarone is the

most commonly employedantiarrhythmic.

Pharmacokinetics: Amiodarone isincompletely absorbed after oraladministration. The drug is unusual inhaving a prolonged half-life of several

weeks, and it distributes extensively inadipose issue. Full clinical effects may notbe achieved until 6 weeks after initiationof treatment.


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Adverse effects

Amiodarone shows a variety of toxic effects. Afterlong-term use, more than half of patientsreceiving the drug show side effects that aresevere enough to prompt its discontinuation.

Some of the more common effects includeinterstitial pulmonary fibrosis, gastrointestinaltract intolerance, tremor, ataxia, dizziness, hyper-or hypothyroidism, liver toxicity, photosensitivity,

neuropathy, muscle weakness, and blue skindiscoloration caused by iodine accumulation inthe skin.


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Dofetilide III

Dofetilide can be used as afirst-line antiarrhythmic agent inpatients with persistent atrial fibrillation and heart failure

or in those with coronary artery disease with impaired leftventricular function.

Because of the risk of proarrhythmia, dofetilide initiation islimited to the inpatient setting and is restricted toprescribers who have completed a specific manufacturer'straining session. Along with amiodarone and -blockers,dofetilide is the only antiarrhythmic drug that isrecommended by experts for the treatment of atrialfibrillation in a wide range of patients.

The half-life is 10 hours. Excretion is in the urine, with 80percent as unchanged drug and 20 percent as inactive orminimally active metabolites.


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Verapamil and diltiazem (IV)

Therapeutic uses: Verapamil anddiltiazem are more effective againstatrial than against ventriculararrhythmias. They are useful intreating reentrant supraventriculartachycardia and in reducing the

ventricular rate in atrial flutter andfibrillation. In addition, these drugsare used to treat hypertension andangina.

Pharmacokinetics: Verapamil anddiltiazem are absorbed after oraladministration. Verapamil isextensively metabolized by the liver;thus, care should be taken whenadministering this drug to patientswith hepatic dysfunction.


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Adverse effects:

Verapamil and diltiazem have negative

inotropic properties and, therefore, may be

contraindicated in patients with preexisting

depressed cardiac function. Both drugs can

also produce a decrease in blood pressure

because of peripheral vasodilation an effect

that is actually beneficial in treatinghypertension.


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Other Antiarrhythmic Drugs

Digoxin shortens the refractory period in atrialand ventricular myocardial cells while prolongingthe effective refractory period and diminishing

conduction velocity in the AV node.Digoxin is used to control the ventricularresponse rate in atrial fibrillation and flutter.

At toxic concentrations, digoxin causes ectopic

ventricular beats that may result in ventriculartachycardia and fibrillation.


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Adenosine is a naturally occurring nucleoside,

but at high doses, the drug decreasesconduction velocity, prolongs the refractory

period, and decreases automaticity in the AV

node. Intravenous adenosine is the drug of

choice for abolishing acute supraventricular

tachycardia. It has low toxicity but causes

flushing, chest pain, and hypotension.

Adenosine has an extremely short duration ofaction (approximately 15 seconds).


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END

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