8/3/2019 Wesam R Kadhum
1/31
Antiarrhythmics
Wesam Radhi Kadhum
8/3/2019 Wesam R Kadhum
2/31
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.
8/3/2019 Wesam R Kadhum
3/31
8/3/2019 Wesam R Kadhum
4/31
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.
8/3/2019 Wesam R Kadhum
5/31
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.
8/3/2019 Wesam R Kadhum
6/31
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.
8/3/2019 Wesam R Kadhum
7/31
8/3/2019 Wesam R Kadhum
8/31
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.
8/3/2019 Wesam R Kadhum
9/31
8/3/2019 Wesam R Kadhum
10/31
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
8/3/2019 Wesam R Kadhum
11/31
A. Causes of arrhythmias
Most arrhythmias arise either from
aberrations in impulse generation (abnormal
automaticity) or from a defect in impulse
conduction.
8/3/2019 Wesam R Kadhum
12/31
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.
8/3/2019 Wesam R Kadhum
13/31
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.
8/3/2019 Wesam R Kadhum
14/31
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.
8/3/2019 Wesam R Kadhum
15/31
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.
8/3/2019 Wesam R Kadhum
16/31
B. Antiarrhythmic drugs
Home Work
8/3/2019 Wesam R Kadhum
17/31
III. Class I Antiarrhythmic Drugs
8/3/2019 Wesam R Kadhum
18/31
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.
8/3/2019 Wesam R Kadhum
19/31
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).
8/3/2019 Wesam R Kadhum
20/31
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.
8/3/2019 Wesam R Kadhum
21/31
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.
8/3/2019 Wesam R Kadhum
22/31
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.
8/3/2019 Wesam R Kadhum
23/31
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.
8/3/2019 Wesam R Kadhum
24/31
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.
8/3/2019 Wesam R Kadhum
25/31
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.
8/3/2019 Wesam R Kadhum
26/31
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.
8/3/2019 Wesam R Kadhum
27/31
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.
8/3/2019 Wesam R Kadhum
28/31
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.
8/3/2019 Wesam R Kadhum
29/31
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.
8/3/2019 Wesam R Kadhum
30/31
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).
8/3/2019 Wesam R Kadhum
31/31
END