This document discusses various antiarrhythmic drugs, organized by class. It provides details on each drug's mechanisms of action, dosing, indications, efficacy, and side effects. The drugs discussed include quinidine, procainamide, disopyramide, ajmaline, lidocaine, mexiletine, phenytoin, flecainide, propafenone, and verapamil.

1. ANTIARRHYTHMICS - II
Dr Sunil Reddy

2. CLASS 1A
QUINIDINE
• Quinidine has a wide spectrum of activity against
reentrant and ectopic tachyarrhythmias.
• It slows conduction and increases refractoriness in
the retrograde fast pathway limb of AV nodal
tachycardias and over the accessory pathway
• Quinidine also slows the ventricular response to AF
in WPW syndrome
• Quinidine may show reverse use dependence
because of blockade of IKr (as well as enhancing late
Na current).

3. • Quinidine's effect on repolarization and overall
efficacy vary directly with left ventricular function
• The usual oral dose of quinidine sulfate for an adult
is 300 to 600 mg four times daily, which results in a
steady-state level within about 24 hours.
• A loading dose of 600 to 1000 mg produces an
earlier effective concentration
• Because it crosses the placenta, quinidine can be
used to treat arrhythmias in the fetus.

4. • The most common adverse effects of chronic oral
quinidine therapy are gastrointestinal (milder with
the gluconate form).
• Central nervous system toxicity includes tinnitus,
hearing loss, visual disturbances, confusion, delirium,
and psychosis (cinchonism).
• Allergic reactions may be manifested as rash, fever,
immune-mediated thrombocytopenia and hemolytic
anemia
• Quinidine can produce syncope in 0.5% to 2.0% of
patients, most often the result of a self-terminating
episode of torsades de pointes.

5. PROCAINAMIDE
• The cardiac actions of procainamide on automaticity,
conduction, excitability and membrane
responsiveness resemble those of quinidine.
• It predominantly blocks the inactivated state of INa
and it blocks IKr & IK.ATP as well
• NAPA (procainamide's major metabolite), a K+
channel blocker (IKr), exerts a class III action and
prolongs the APD of ventricular muscle and Purkinje
fibers in a dose-dependent manner
• In sustained VT, procainamide is more effective than
lidocaine at the cost of QRS and QT widening

6. • In VT , 25 to 50 mg can be given during a 1-minute
period and then repeated every 5 minutes until the
arrhythmia has been controlled, hypotension results,
or the QRS complex is prolonged more than 50%
• An oral loading dose of procainamide (1 gm) is
followed by upto 500 mg 3-hourly.
• The oral use is limited by a short half-life and the long-
term danger of the lupus syndrome
• The risk of lupus (likeliest in slow acetylators) is about
1/3rd in those pts treated for longer than 6 months and
is genetically influenced.
• Acetylation of procainamide to form NAPA appears to
block the SLE-inducing effect

7. • The development of symptoms or a positive anti-
DNA Ab indicates that drug should be discontinued
• Noncardiac adverse effects include rashes, myalgias,
digital vasculitis, and Raynaud phenomenon
• GI S/E are less frequent than with quinidine, and
adverse CNS S/E are less frequent than with lidocaine
• Arthralgia, fever, pleuropericarditis and hemorrhagic
pericardial effusion with tamponade have been
described in a SLE–like syndrome related to
procainamide administration

8. • Increasing age, CCF, and renal dysfunction
necessitate a reduced dosage
• Procainamide can block conduction in the accessory
pathway of patients with the WPW and may be used
in patients with atrial fibrillation and a rapid
ventricular response related to conduction over the
accessory pathway
• It has been used to facilitate VT induction at EPS
when the arrhythmia could not be initiated in the
baseline state

9. DISOPYRAMIDE
• Similar to Quinidine and Procainamide, Disopyramide
causes use-dependent block of INa and non–use-
dependent block of IKr.
• It does not affect calcium-dependent AP , except
possibly at very high concentrations
• Disopyramide is a muscarinic blocker and can
increase the sinus node discharge rate and shorten
AV nodal conduction time and refractoriness when
the nodes are under cholinergic (vagal) influences.

10. • The drug prolongs atrial and ventricular refractory
periods, but its effect on AV nodal conduction and
refractoriness is not consistent.
• Disopyramide prolongs His-Purkinje conduction time,
but infra-His block rarely occurs. It can be
administered safely to patients who have first-degree
AV delay and narrow QRS complexes.
• Doses are generally 100 to 200 mg orally every 6
hours, with a range of 400 to 1200 mg/day.
• A controlled-release preparation can be given as 200
to 300 mg every 12 hours.

11. • Disopyramide appears comparable to quinidine and
procainamide in reducing the frequency of PVCs and
effectively preventing recurrence of VT in selected
patients.
• Disopyramide helps prevent recurrence of atrial
fibrillation after successful cardioversion as
effectively as quinidine and may terminate atrial
flutter.
• Its negative inotropic effect is so marked that
disopyramide is also used in the therapy of HOCM
and neurocardiogenic syncope, presumably because
it interferes with excitation contraction coupling

12. • The most common adverse effects are related to the
drug's potent parasympatholytic properties and
include urinary hesitancy or retention, constipation,
blurred vision, closed-angle glaucoma, and dry
mouth
• Ventricular tachyarrhythmias that are commonly
associated with QT prolongation and torsades de
pointes.

13. AJMALINE
• Ajmaline, a rauwolfia derivative, has been used
extensively to treat patients with ventricular and
supraventricular arrhythmias in Europe and Asia
• Like other type IA drugs, ajmaline produces use-
dependent block of INa; it also weakly blocks IKr.
• The drug has mild anticholinergic activity and a
potent antiplatelet activity
• It mildly suppresses ventricular systolic performance
but does not affect peripheral resistance.
• The drug's use has evolved to that of a diagnostic
tool

14. • When it is administered IV at doses of 50 mg during 3 min,
or 10 mg/min, to a total dose of 1 mg/kg, ajmaline can
have the following effects:
1. Delta wave disappearance in pts with WPW (indicating an
AP anterograde ERP > 250 msecs)
2. ST-T abnormalities and IVCD in pts with occult chagasic
cardiomyopathy
3. Heart block in patients with BBB and syncope, but in
whom no rhythm disturbance had been discovered
4. Right precordial ST elevation in pts with suspected
Brugada syndrome with a normal resting ECG
It is in this last setting that ajmaline is used most frequently.

15. CLASS II B
LIDOCAINE
• Lidocaine blocks INa, predominantly in the open or
possibly inactivated state.
• It has rapid onset and offset kinetics
• It does not affect normal sinus node automaticity in
usual doses but does depress other normal and
abnormal forms of automaticity as well as EAD and
DAD in Purkinje fibers in vitro.

16. • Faster rates of stimulation, reduced pH, increased
extracellular K+ concentration, and reduced
membrane potential, all changes that can result from
ischemia, increase the ability of lidocaine to block INa.
• Lidocaine can convert areas of unidirectional block
into bidirectional block during ischemia and prevent
development of VF by preventing fragmentation of
organized large wave fronts into heterogeneous
wavelets.
• Lidocaine has little effect on atrial fibers and does
not affect conduction in accessory pathways.

18. • IV lidocaine is given as a bolus of 1 to 2 mg/kg b wt
@ 20 to 50 mg/min, with a second injection of half
the initial dose 20 to 40 minutes later
• If the initial bolus of lidocaine is ineffective, up to two
more boluses of 1 mg/kg may be administered at 5-
minute intervals.
• Maintenance infusion rates in the range of 1 to
4 mg/min produce steady-state plasma levels of 1 to
5 mg/mL in patients with uncomplicated myocardial
infarction

19. • Lidocaine acts preferentially on the ischemic
myocardium and is more effective in the presence of a
high external potassium concentration.
• Therefore hypokalemia must be corrected for
maximum efficacy
• The efficacy of lidocaine is relatively low (15%to 20%)
(procainamide-approximately 80%)
• It is generally ineffective against SVT s

20. • Lidocaine has been effective in pts after coronary
revascularization and in pts resuscitated from out-of-
hospital VF
• The most commonly reported adverse effects of
lidocaine are dose-related manifestations of CNS
toxicity: dizziness, paresthesias, confusion, delirium,
stupor, coma, and seizures.
• Occasional sinus node depression and His-Purkinje
block have been reported.
• Both lidocaine and procainamide can elevate
defibrillation thresholds.

21. MEXILETINE
• Mexiletine, a local anesthetic congener of lidocaine
with anticonvulsant properties, is used for the oral
treatment of patients with symptomatic ventricular
arrhythmias
• Mexiletine does not appear to affect human atrial
muscle. It does not affect the QT interval
• Mexiletine exerts no major hemodynamic effects on
ventricular contractile performance or peripheral
resistance.

22. • Mexiletine is a moderately effective antiarrhythmic
agent for treatment of patients with acute and
chronic ventricular tachyarrhythmias but not SVTs
• Mexiletine may be very useful in children with
congenital heart disease and serious ventricular
arrhythmias. In treating patients with a long QT
interval, mexiletine may be safer than drugs such as
quinidine that increase the QT interval further.
• Adverse effects include tremor, dysarthria, dizziness,
paresthesia, diplopia, nystagmus, mental confusion,
anxiety, nausea, vomiting, and dyspepsia.

23. PHENYTOIN
• Phenytoin effectively abolishes abnormal automaticity
caused by digitalis-induced DAD in cardiac Purkinje
fibers and suppresses certain digitalis-induced
arrhythmias in humans
• Some of phenytoin's antiarrhythmic effects may be
neurally mediated because it can modulate both
sympathetic and vagal efferent activity
• Orally, phenytoin is given as a loading dose of
1000 mg the first day, 500 mg on the second and third
days, and 300 to 400 mg daily thereafter

24. • To achieve a therapeutic plasma concentration
rapidly, 100 mg of phenytoin should be administered
intravenously every 5 minutes until the arrhythmia is
controlled, 1 g has been given, or side effects result.
• Therapeutic serum concentrations of phenytoin (10
to 20 mg/mL) are similar for treatment of cardiac
arrhythmias and epilepsy.
• Lower concentrations can suppress certain digitalis-
induced arrhythmias
• It is effective against the ventricular arrhythmias
occurring after congenital heart surgery.

25. • Phenytoin is an inducer of hepatic enzymes and
therefore alters the dose requirements of many
other drugs
• Phenytoin has concentration-dependent kinetics for
elimination that can cause unexpected toxicity
because disproportionately large changes in plasma
concentration can follow dose increases.
• The most common manifestations of phenytoin
toxicity are CNS effects of nystagmus, ataxia,
drowsiness, stupor, and coma and correlate with
increases in plasma drug concentration

26. CLASS I C
FLECAINIDE
• Flecainide exhibits marked use-dependent
depressant effects on the rapid sodium channel,
decreasing V max, with slow onset and offset
kinetics.
• Drug dissociation from the sodium channel is slow,
with time constants of 10 to 30 seconds (compared
with 4 to 8 seconds for quinidine and less than 1
second for lidocaine).

27. • Flecainide slows conduction in all cardiac fibers and, in
high concentrations, inhibits the slow Ca2+ channel
• Minimal increases in atrial or ventricular refractoriness
or in the QT interval result.
• Anterograde & retrograde refractoriness in AP pathways
can increase significantly in a use-dependent fashion.
• The starting dose is 100 mg every 12 hours, increased in
increments of 50 mg twice daily, no sooner than every 3
to 4 days, until efficacy is achieved or an adverse effect
is noted or to a maximum of 400 mg/day.

28. • Flecainide is indicated for the treatment of life-
threatening ventricular tachyarrhythmias, SVTs, and
paroxysmal atrial fibrillation (catecholaminergic
polymorphic VT also)
• Therapy should begin in the hospital with the ECG
monitoring because of the possibility of proarrhythmias
• Flecainide is particularly effective in almost totally
suppressing PVCs and short runs of nonsustained VT.
• Data from the CAST study have indicated increased
mortality in patients with coronary artery disease.

29. • Flecainide produces a use-dependent prolongation of
VT cycle length that can improve hemodynamic
tolerance
• Flecainide is also useful in various SVTs, such as atrial
tachycardia (AT), flutter, and atrial fibrillation
• Flecainide has been used to treat fetal arrhythmias
and arrhythmias in children
• Flecainide administration may produce ST elevation
in lead V1 characteristic of Brugada syndrome and
has been used as a diagnostic tool in these pts

30. • In the CAST study, pts treated with flecainide had
5.1% mortality or nonfatal cardiac arrest compared
with 2.3% in the placebo gp during 10 months.
• Mortality was highest in those with non–Q-wave
infarction, frequent PVCs, and faster heart rates,
raising the possibility of drug interaction with
ischemia and electrical instability.
• Exercise can amplify the conduction slowing in the
ventricle produced by flecainide and in some cases
can precipitate a proarrhythmic response. Therefore,
exercise testing has been recommended to screen
for proarrhythmia.

31. PROPAFENONE
• Propafenone blocks the fast sodium current in a use-
dependent manner in Purkinje fibers and to a lesser
degree in ventricular muscle.
• Effects are greater in ischemic than in normal tissue
and at reduced membrane potentials.
• Propafenone decreases excitability and suppresses
spontaneous automaticity and triggered activity.
• The drug is a weak blocker of IKr and beta-adrenergic
receptors.

32. • Although ventricular refractoriness increases,
conduction slowing is the major effect.
• In the CASH study, propafenone was withdrawn from
one arm because of increased lotal mortality and
cardiac arrest recurrence
• Propafenone is regarded as relatively safe in
suppressing supraventricular arrhythmias including
those of the WPW syndrome and recurrent atrial
fibrillation, always bearing in mind the need first to
eliminate structural heart disease

33. • Most patients respond to oral doses of 150 to 300 mg
every 8 hours, not exceeding 1200 mg/day
• Concomitant food administration increases
bioavailability , as does hepatic dysfunction.
• Propafenone is indicated for the treatment of
paroxysmal SVT, atrial fibrillation, and life-threatening
ventricular tachyarrhythmias and effectively
suppresses spontaneous PVCs and nonsustained and
sustained VT.
• It has been used effectively in the pediatric age group.

34. • Pill in the pocket approach – Propafenone 600 mg
orally is taken with the onset of a paroxysm, and
then 300mg 8 hours later ; most attacks are aborted
• Adverse effects - exacerbation of bronchospastic
lung disease can occur because of mild beta-blocking
effects.
• Cardiovascular side effects occur in 10% to 15% of
patients, including AV block, sinus node depression,
and worsening of heart failure.

35. CLASS IV - CCB
• By blocking ICa.L in all cardiac fibers, verapamil
reduces the plateau height of the action potential,
slightly shortens muscle action potential, and slightly
prolongs total Purkinje fiber action potential.
• Verapamil suppresses sustained triggered activity
• Verapamil and diltiazem suppress electrical activity in
the normal sinus and AV nodes.
• They prolong conduction time and refractory periods
of the AV node.

36. • The AV node blocking effects of verapamil and
diltiazem are more apparent at faster rates of
stimulation (use dependence) and in depolarized
fibers (voltage-dependence).
• Verapamil slows the activation and delays recovery
from inactivation of the slow channel
• Verapamil decreasing platelet adhesiveness or
reducing the extent of myocardial ischemia
• It inhibits vascular smooth muscle contraction and
causes marked vasodilation in coronary and other
peripheral vascular beds

37. • HR, CI, LV minute work, and mean PA pressure do not
change significantly.
• Thus, afterload reduction produced by verapamil
significantly counterbalances its negative inotropic
action, so that the cardiac index may not be reduced
• After a single oral doses, measurable prolongation of
AV nodal conduction time occurs in 30 min and lasts
4 to 6 hours.
• After intravenous administration, AV nodal
conduction delay occurs within 1 to 2 minutes

38. • For acute termination of SVT or rapid achievement of
ventricular rate control during atrial fibrillation, the
most commonly used intravenous dose of verapamil is
10 mg infused during 1 to 2 minutes while cardiac
rhythm and blood pressure are monitored.
• It is followed by a continuous infusion of the drug at a
rate of 5 mcg/kg/min.
• Diltiazem is given intravenously at a dose of
0.25 mg/kg as a bolus during 2 minutes
• Because it is generally better tolerated (less
hypotension) for long-term administration, such as for
control of ventricular rate during atrial fibrillation,
diltiazem is preferred to verapamil in this setting

39. • It is used for termination of sustained AV node
reentry or orthodromic AV reciprocating tachycardia
associated with an accessory pathway
• Verapamil and diltiazem terminate 60% to 90% or
more episodes of paroxysmal SVTs within several
minutes. Verapamil may also be of use in some fetal
SVTs.
• A general rule for avoiding complications, however, is
not to administer verapamil intravenously to any
patient with wide QRS tachycardia unless one is
absolutely certain of the nature of the tachycardia
and its likely response to verapamil.

40. THANK YOU