arrhythmia and its types, pathophysiology, classification and the pharmacology

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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