This document discusses antiarrhythmic drugs, which are used to treat and prevent cardiac arrhythmias. It defines arrhythmias and describes their various causes, including abnormal automaticity, impaired conduction, ischemia, electrolyte imbalances, and other factors. The document then explains the mechanisms of different types of arrhythmias such as enhanced pacemaker activity, afterdepolarizations, reentry, fractionated impulses, and conduction block. It proceeds to classify antiarrhythmic drugs into five classes based on their mechanisms of action, such as blocking sodium, potassium, calcium, or beta-adrenergic channels. For each class, specific drugs are discussed along with their indications, mechanisms, effects, interactions and adverse

1. ANTIARRHYTHMIC
DRUGS
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2. Arrhythmia is a any abnormality in heart rate,
regularity, or site of origin, or a disturbance in
conduction that disrupts the normal sequence of
activation in atria or ventricle.
It may cause:
Heart to beat too slowly(sinus bradycardia)
Heart to beat too rapidly (sinus or ventricular tachychardia, atrial or
ventricular premature depolarisation, atrial flutter)
To respond to impulses originating from sites other than the SA node
To respond to impulses travelling along accessory (extra) pathways
that lead to deviant depolarisations (A-V reentry, Wolff-Parkinson White
Syndrome)
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3. Antiarrhythmics are drugs used to prevent or treat
irregularities of cardiac rhythm.
CAUSES OF ARRHYTHMIAS
Abnormal automaticity or impaired conduction or
both .
Ischemia
Electrolyte and pH imbalance
Mechanical injury
Stretching
Neurogenic and drug influences.
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5. PATHOPHYSIOLOGY
a) Enhanced/ ectopic pacemaker activity
Slope of phase-4 depolarisation may be increased
sinus tachycardia, atrial & ventricular extrasystoles (ES), or
tachycardias, atrial flutter.
 Ectopic pacemaker activity may result from current of injury
 Myocardial cells damaged by ischemia become partially
depolarised: a current may flow between these and normally
polarised fibres & initiate an impulse
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6. b) After-depolarisations
These are secondary depolarisations accompanying a normal or
premature action potential
 Early after-depolarisation
• Repolarisation during phase-3 is interrupted, membrane potential
oscillates.
• If amplitude is sufficiently large , neighbouring tissue is activated & a series
of impulses are propagated.
 Delayed after-depolarisation
• After attaining RMP a secondary deflection occurs , reach threshold
potential & initiate a single premature AP
• Generally result from Ca2+ overload (digitalis toxicity, ischemia-reperfusion)
 Because an AP is needed to trigger after-depolarisations, arrhythmias
based on these are called “TRIGGERED ARRHYTHMIAS”
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7. c) Reentry
Due primarily to abnormality of conduction, an impulse may recirculate
in the heart & cause repetitive activation without the need for any new
impulse to be generated. These are called “REENTRANT
ARRHYTHMIAS”.
i) Circus movement type
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8. ii) Microreentry circuit
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9. d) Fractionation of impulse
When atrial ERP is brief & inhomogeneous , an impulse generated
early in diastole gets conducted irregularly over the atrium
Ie., it moves rapidly through fibres with short ERP
( which have completely recovered)
Slowly through fibres with longer ERP (partially recovered)
& not at all through those still refractory
Thus, asynchronus activation of atrial fibres occurs & atrial
fibrillation(AF)
e) Conduction block
Under physiological conditions, conduction through SA & A-V nodes is
tardy.
It may be further slowed by ischemia etc. Causing partial to complete A-
V block.
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10. DIAGNOSIS
• ECG
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ANTIARRHYTHMIC DRUGS
1) CLASS I ( Na+ CHANNEL BLOCKERS )
Disopyramide
Flecainide
Lidocaine
Mexiletine
Procainamide
Propafenone
Quinidine
Tocainide
2) CLASS II (Beta- adrenoreceptor blockers )
Esmolol
Metoprolol & Pindolol
Propanolol
3) CLASS III (K+ Channel blockers )
Amiodarone
Bretylium
Sotalol
4) CLASS IV ( Ca++ Channel blockers )
Diltiazem
Verapamil
5) OTHER ANTI-ARRHYTHMIC DRUGS
Adenosine
Digoxin

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POSSIBLE MECHANISMS OF ANTIARRHYTHMIC
DRUGS
1. Suppressing the automaticity
- decrease the rate of phase 0
- decrease slope of phase 0
- duration of ERP increases
- resting membrane potential more negative
2. Abolishing reentry
- slow conduction
- increase ERP

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PHARMACOLOGICAL GOAL OF DRUG
THERAPY
 The ultimate goal of antiarrhythmic drug therapy:
• Restore normal sinus rhythm
• Prevent more serious and possibly lethal arrhythmias
from occuring
 Antiarrhythmic drugs are used to:
• Decrease conduction velocity
• Change the duration of the effective refractory period
(ERP)
• Suppress abnormal automaticity

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1) CLASS I ANTIARRHYTHMIC DRUGS
 Sodium channel blocker
IA Slows phase 0 depolarisation
IB Shortens phase 3 repolarisation
IC Markedly slows phase 0 depolarisation
Use dependance : These drugs bind more rapidly to
open/ inactivated sodium channels. Therefore, these
drugs show a greater degree of blockade in tissues that
are frequently depolarising.

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a) CLASS IA DRUGS
• Slow the rate of rise of the
action potential, thus slowing
conduction
• Prolong the action
potential and increase the
ventricular effective refractory
period.
• Have an intermediate speed of
association with activated/
inactivated Na channels.

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i) QUINIDINE
MOA:
 Quinidine binds to open and inactivated Na channels and prevent
Na influx, thus slowing the rapid upstroke during phase 0.
 Also decreases the slope of phase 4 spontaneous depolarisation.
Pharmacological actions:
o Inhibits ectopic arrhythmias & ventricular arrhythmias
o Prevents reentry arrhythmias.
Adverse effects:
o Exacerbation of arrhythmia
o SA & AV block or asystole
o At high dose ventricular tachycardia
o Nausea, vomiting, diarrhoea
o Cinchonism- blurred vision, tinnitus, headache, disorientation &
psychosis.
Drug interactions:
o Quinidine increase steady state conc. Of digoxin.

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ii) PROCAINAMIDE
• Procaine derivative, quinidine like action
Adverse effects:
oHypotension
oHypersensitivity reactions
Uses:
oPremature atrial contractions
oParoxysmal atrial tachycardia
Drug interactions:
oCimetidine inhibit metabolism of procainamide.

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III) DISOPYRAMIDE
MOA:
Produces a negative ionotropic effect that is greater than the weak
effect exerted by quinidine & procainamide.
Unlike others it causes peripheral vasoconstriction
Adverse effects:
o Urinary retension
o Blurred vision
o Constipation
Uses:
o Ventricular tachycardia
o AF
Drug interactions:
o Phenytoin increases the metabolism of disopyramide, increased
accumulation of its metabolite, thereby increasing probability of
anticholinergic effects.

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b) Class IB drugs
• Little effect on the rate of
depolarisation
• Decrease the duration of the
action potential by shortening
repolarisation.
• Rapidly interact with Na
channels

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i) LIDOCAINE
MOA:
 Shortens phase 3 repolarisation and decreases the duration of
action potential
Uses:
o Ventricular arrhythmia
Adverse effects:
o Drowsiness
o Slurred speech
o Confusion
o Convulsion
Drug interactions:
o Propanolol increases its toxicity
o The myocardial depressant effect of lidocaine is enhanced by
phenytoin

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c) CLASS IC DRUGS
• Markedly depress the rate of rise of the membrane action
potential.
• They cause marked conduction slowing but have little
effect on the duration of the membrane action potential or the
ventricular effective refractory period.
• Bind slowly to sodium channels.

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i) FLECAINIDE
MOA:
 Suppresses phase 0 upstroke in Purkinje and myocardial fibers
 This causes marked slowing of conduction in all cardiac tissue,
with a minor effect on the duration of the action potential.
 Automaticity is reduced by an increase in the threshold
potential rather than a decrease in the slope of phase 4
depolarisation
Uses:
o Refractory ventricular arrhythmia
Adverse effects:
o Dizziness, blurred vision, headache and nausea

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2) CLASS II ANTIARRHYTHMIC DRUGS
Beta adrenoreceptor blocker
These drugs diminish phase 4 depolarisation, thus
depressing automaticity, prolonging AV conduction, and
decreasing heart rate and contractility.
Useful in treating tachyarrhythmias caused by increased
sympathetic activity.
Also used for atrial flutter and fibrillation and for AV nodal
reentrant tachycardia.

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i) Propanolol
Uses:
o MI
o AF
Adverse effects:
o Bronchoconstriction
o Sexual impairment
o Hypoglycemia
Drug interactions:
o Drugs that interfere with the metabolism of propanolol, such as
Cimetidine, furosemide ,may potentiate its antihypertensive effects.
ii) Metoprolol and pindolol
iii) esmolol

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3) CLASS III ANTYARRHYTHMIC DRUGS
K+ channel blocker
These agents block K+ channels and thus diminish the
outward potassium current during repolarisation of cardiac
cells.
Prolong the duration of action potential without altering
phase 0 of depolarisation or the resting membrane
potential.

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i) Sotalol
Has both class II and class III actions.
MOA:
Sotalol blocks a rapid outward current of potassium.
This blockade prolongs both repolarisation & the
duration of the action potential, thus lengthening the
effective refractory period.
Uses:
o Decrease the rate of sudden death following an acute
myocardial infraction

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ii) Amiodarone

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4) CLASS IV ANTIARRHYTHMIC DRUGS
Calcium channel blockers
They decrease the inward current carried by calcium,
resulting in a decrease in the rate of phase 4 spontaneous
depolarisation and slowed conduction in tissues dependent
on calcium currents, such as AV node.

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i) VERAPAMIL & DILTIAZEM
 Verapamil shows greater action on the heart than on
vascular smooth muscle. Diltiazem is intermediate in
its actions
Uses:
o ventricular arrhythmias
o Ventricular flutter & fibrillation
Adverse effects:
o Contraindicated in patients with pre-existing
depressed cardiac function

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