Pharmacology 4
Dr. Khalil Makki
Antiarrhythmic
Drugs
Arrhythmias
• Abnormalities in impulse formation and conduction
in the myocardium. They are common:
• MI(80%), anesthesia(50%),Digitalis(25%).
• should be treated if cause poor circulation or
threatened to do so.
• All antiarrhythmic drugs are pro-arrhythmic in some
circumstances.
• Electrical tt of arrhythmia is becoming more
commonly used.
• AF is the most common type, with high risk of
stroke, AC TT is essential.
Types of Cardiac tissues
• i.Ordinary myocardial muscle – contraction and
pumping action.
• ii.Specialized conducting tissue – cardiac impulse
initiation and determines the order in which the
muscle cells contract.
• Automaticity: the capacity of cells to initiate an
impulse without an external stimulus – a feature of
certain parts of conducting tissue as SAN, AVN & His
– purkinje system.
• These pacemaker cells show slow, spontaneous
depolarization during diastole Phase 4, (Ca & Na
inflow).
Classification of Arrhythmia
• According to:
 site of origin of abnormality:
Atrial, Junctional or Ventricular.
 Rate:
Tachicardia or bradicardia.
Their diagnosis depends on surface ECG.
Precipitating Factors
• Ischemia, Hypoxia, Acid base and Electrolytes
disturbancies.
• Autonomic effects.
• Drug toxicities as digitalis and even antiarrhythmic
drugs.
• Overstretching of cardiac fibers or presence of
scarred or diseased tissues.
• However all arrhythmias result from disturbance in
impulse formation and/or conduction.
Re-entry Phenomenum
• Normal conduction: the impulse dies out after
activation of the myocardium(?).
It is surrounded by refractory tissues.
• Re-entry : the impulse re-excites
regions of the myocardium after
the refractory period has subsided,
causing continuous circulation of APs.
• It can result from myocardial damage(IHD) or
congenital anamolies.
• It is a common cause of many types of arrhytmias.
Classification of Antiarrhythmic Drugs
Vaughan-Williams Classification(1970)
Class
Mechanism
Example
Ia
Ib
Ic
II
Na channel blockers
Intermediate dissociation
fast dissociation
Slow dissociation
Beta Blockers
Disoperamide
Lidocaine
Flecanide
Propranolol
III
K channel blockers
IV
Ca channel blockers
Other Digoxin, Adenosine,CaCl,
V
MgCl,Atropine,Epinephrine
Amiodarone &
Sotalol
Verapamil
&Isoprenaline
Class I Drugs,Na-blockers(memb.
Stabilizing)
• Slow phase 0 depolarization, prolong AP and slow
conduction.
• They produce Use dependent channel block i.e.
They bind strongly to the open and refractory
channels and less strongly to the resting channels.
This means, the more frequently the channels are
activated, the greater the degree of block produced.
• They block the high frequency excitation of the
myocardium with out preventing the heart from
beating at normal frequency.
Clinical Uses and ADRs
• Ia, Disopyramide (oral): VA, prevention of recurrent
paroxysmal AF.
Has atropine like effects.
• Ib, Lidocaine (IV): tt and prevention of VT &VF
during or after MI.
CNS ADRs and convulsion.
• Ic, Flecainide (oral):prevention of paroxysmal AF
and recurrent tachyarrhythmia.
can produce life threatening resistant VT.
Class II drugs
• β- Blockers: Propranolol, Timolol, Atenolol
• Inhibit phase 4 depolarization i.e. the pace maker
potential  Inhibiting automaticty and prolonging
AV conduction & decreasing the HR and
contractility.
• Clinical uses and ADRs:
1. Reduce mortality after MI.
2. Prevent recurrence of tachyarrhythmias as
paroxysmal AF provoked by sympathetic over
activity.
β- Blockers ADRs
•
•
•
•
•
Increase bronchospasm – asthma.
- ve inotropic effect.
Bradycardia and fatigue.
Sexual dysfunction.
Cold extrimities.
Class III Drugs
• Block K channels, decreasing K out flow during
repolarization (phase 3).
• Prolong the duration of AP and the ERP.
• Amiodarone: contains I2 ,has a dominant class III
effect and minor I,II and IV effects
• Also has antianginal effect.
• Sotalol: Class III effect and non selective β- Blocker.
Clinical Uses and ADRs
• Amiodarone : In many SV & V tachyarrhythmias
,which are severe and refractory.
• ADRs: GIT upset , pulmonary fibrosis, tremor,
ataxia, diziness, hypo and hyper thyroidism,
photosensitivity , hepatotoxicity and blue skin
discoloration.
• Satolol: Paroxysmal SVT & V T and V ectopics.
• ADRs: very low ,may prolong QT.
Class IV Drugs
• Ca channel blockers:
• Verapamil and Diltiazem, oral.
• Slow phase 2 “plateau” ,slow conduction and
prolonging ERP.
• They show use dependent block.
• Used to:1. Prevent recurrence of paroxysmal SVT
and 2. Reduce ventricular rate in pts with AF and
flutter.
3. Hypertension and angina.
Adenosine
• Naturally occurring nucleoside.
• At high doses:
a. Decreases conduction velocity.
b. Prolongs RP.
c. Decreases the automaticity in AV node
Adenosine
• Very rapid onset of action .
• Short half- life (seconds)
• Given as a rapid I.V. bolus injection
For the acute termination of
re-entrant
supraventricular tachycardia ( paroxysmal attack)
First choice.
ADRs and #s
•
•
•
•
•
•
Bronchospasm, Chest pain.
Shortness of breath.
Flushing of the face.
A-V block.
Hypotension.
#s :Bronchial asthma and A-V block
Others
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Mg Cl2: Used in:Digitalis induced arrhythmias and
Sinus tachycardia
KCl: Digitalis induced arrhythmias.
Ca Cl2 :Ventricular tachycardia due to hyperkalemia.
Atropine: Sinus bradycardia.
Epinephrine : Cardiac arrest.
Isoprenaline: Heart block.