This document discusses antiarrhythmic drugs, their mechanisms of action, indications, and side effects. It covers the Vaughan-Williams classification system for antiarrhythmic drugs (Classes I-IV) and describes examples from each class such as quinidine, amiodarone, beta blockers, calcium channel blockers, and others. The mechanisms by which these drugs treat arrhythmias include blocking sodium, potassium, or calcium channels or suppressing automaticity. Adverse effects and considerations for use are also outlined.

1. Antiarrhythmic drugs
Dr. KAZI ALAM NOWAZ
MD FINAL PART STUDENT CARDIOLOGY
NHFH & RI

2. Normal conduction pathway:
1- SA node generates
action potential and
delivers it to the atria
and the AV node
2- The AV node delivers
the impulse to purkinje
fibers
3- purkinje fibers
conduct the impulse to
the ventricles
Other types of
conduction that occurs
between myocardial
cells:
When a cell is
depolarized 
adjacent cell
depolarizes along

3. Phases of action potential of
non pacemaker cells

4. +30 mV
0 mV
-80 mV
-90 mV
OUTSIDE
MEMBRANE
INSIDE
Na+
0
4
3
2
1
K+
Ca++ K+
Atp
K+
Na+
K+
Ca++
Na+
K+
Na+
Resting
open
Inactivated
Phase zero
depolarization
Due to Na+ influx
Early repolarization
Due to rapid efflux of K+
Plateau phase Due to Ca++ influx
Rapid Repolarization
phase Due to K+
efflux
Phase 4
depolarization

5. Pacemaker AP
Phase 4: pacemaker
potential
Na influx and K efflux and
Ca influx until the cell
reaches threshold and
then turns into phase 0
Phase 0: upstroke:
Due to Ca++ influx
Phase 3:
repolarization:
Due to K+ efflux
Pacemaker cells (automatic cells) have
unstable membrane potential so they can
generate AP spontaneously

6. Refractory period

7. Cardiac arrhythmias
• A cardiac arrhythmia is defined as a disturbance of the electrical
rhythm of the heart.
• Cardiac arrhythmias are often a manifestation of structural heart
disease but may also occur because of abnormal conduction or
depolarisation in an otherwise healthy heart.

8. Factors that precipitate arrhythmia:
• Cardiac ischemia,
• Structural heart disease,
• Hypoxia,
• Acidosis, alkalosis
• Electrolyte disturbances
• Excessive catecholamine exposure
• Exposure to toxic substances
• Unknown etiology

9. Why should we treat arrhythmia?
Arrhythmias can cause serious
complications like-
1. Heart failure.
2. Sudden cardiac death
3. Syncope.
4. Stroke.

10. ARRHYTHMIAS
Sinus arrythmia
Atrial arrhythmia
Nodal arrhythmia
(junctional)
Ventricular arrhytmia
SVT

11. Mechanisms of cardiac arrythmia
• Abnormal impulse generation:
Depressed automaticity
Enhanced automaticity
• Triggered activity (after depolarization):
Delayed after depolarization
 Early after depolarization
• Abnormal impulse conduction:
 Conduction block
 Re-entry phenomenon
 Accessory tract pathways

12. Pharmacologic Rationale & Goals
 The ultimate goal of antiarrhythmic drug therapy:
o Restore normal sinus rhythm and conduction
o Prevent more serious and possibly lethal arrhythmias
from occurring.
 Antiarrhythmic drugs are used to:
 decrease conduction velocity
 change the duration of the effective refractory period
(ERP)
 suppress abnormal automaticity

14. class mechanism action notes
I Na+ channel blocker
Change the slope of
phase 0
Can abolish
tachyarrhythmia
caused by reentry
circuit
II β blocker
↓heart rate and
conduction velocity
Can indirectly alter K
and Ca conductance
III K+ channel blocker
1. ↑action potential
duration (APD) or
effective refractory
period (ERP).
2. Delay repolarization.
Inhibit reentry
tachycardia
IV Ca++ channel blocker
Slowing the rate of rise in
phase 4 of SA node(slide
12)
↓conduction velocity
in SA and AV node
VAUGHAN-WILLIAMS CLASSIFICATION

15. Class I
IA IB IC
They ↓ conduction velocity in non-nodal tissues
(atria, ventricles, and purkinje fibers)They act on open Na+
channels or
inactivated only
So they are used when
many Na+ channels are
opened or inactivated
(in tachycardia only)
because in normal
rhythm the channels
will be at rest state so
the drugs won’t work
Class I drugs
Have moderate K+ channel
blockade

16. • Slowing the rate of rise in phase 0
• Have moderate K+ channel blockade
• They prolong action potential & ERP
• ↓ the slope of Phase 4 spontaneous depolarization
• ↑ QRS & QT interval
IA
Quinidine Procainamide Disopyramide

17. QUINIDINE
• Antimalarial, antipyretic, skeletal muscle relaxant and atropine like
action.
• 1st antiarrhythmic used, treat both atrial and ventricular arrhythmias,
increases refractory period
• Oral drug
• Blocks activated Na+ channel: ↓slope of phase 0 and 4
• Inhibit K+ current:↑phase 3
• Associated with increase mortality

18. Quinidine-adverse effects
Cardiac Adverse effects:
• torsade depoints (↑QT interval) twisting of peak in ECG
• Proarrhythmogenic effects, AV block or asystole (toxic
dose)
Extracardiac Adverse effects:
• GIT: Diarrhoea,Nausea,Vomiting
• Cinchonism: headache, dizziness, confusion, tinnitus,
deafness, blurring of vision
• Quinidine syncope because of VA (↑QT);
light headedness and fainting

19. Procainamide
• Intravenous drugs
• Slows conduction in accessory pathways (WPW syndrome)
• Used in arrhythmia associated with bypass tract
• Associated with Systemic lupus erythromatosus (SLE)-like symptoms:
arthralgia, fever, pleural-pericardial inflammation
• ANA can be positive
• Resolves on stopping drugs

20. • They shorten Phase 3 repolarization
• ↓ the duration of the cardiac action potential
• They suppress arrhythmias caused by abnormal automaticity
They show rapid association & dissociation (weak effect) with Na+
channels with appreciable degree of use-dependence
No effect on conduction velocity
Class IB
lidocaine mexiletine tocainide

21. • Lidocaine (also acts as local anesthetic) – blocks Na+
channels mostly in ventricular cells, also good for digitalis-
associated arrhythmias.
• Mexiletine - oral lidocaine derivative, similar activity.
• Phenytoin – anticonvulsant that also works as
antiarrhythmic similar to lidocaine.

22. Lidocaine
• t1/2 1-1.5 hr given by I.V loading dose followed by I.V
infusion
• Block both activated & inactivated Na+ channel
• ↓The slope of phase 0 & 4
• Dose: Bolus 50–100 mg, 4 mg/min for 30 mins, then 2
mg/min for 2 hrs, then 1 mg/min for 24 hrs
Main uses:
• Ventricular Arrhythmia following MI.

23. Why After MI?
• In ischaemic myocardium with reduced membrane potential, voltage
and time dependent recovery of sodium channel from inactivation is
delayed. As Ib drugs bind with inactivated sodium channel, binding is
significantly increased.

24. Why less effective in atrial arrhythmia?
• Atrial repolarization is faster compared with the ventricles and is
associated with rapid transition of the atrial sodium channel in
activated to resting state. Therefore, Ib drug play little role in atrial
arrhythmia.

25. Lidocaine adverse effects
CNS:
drowsiness,
numbness,
parathesia,
slurred speeches,
difficulty of swallowing,
convulsions,
nystagmus,
tremor,
Diplopia
Heart:
• AV block
• ↓contractility

26. • Blocks open Na+ channel
• Very slow unbinding
• Results QRS can markedly prolong
• Limited use due to concern toxicity specially proarrythmic effects
• Only used patients with structurally normal heart
• Effective in reducing recurrence of atrial fibrillation
Class IC
flecainide propafenone

27. Flecainide
• Initially developed as a local anesthetic
• Potent blocker of Na+ shorten AP
• Potent blocker of K+ prolong AP
• Net result no change
• Slows conduction in all parts of heart,
• Also inhibits abnormal automaticity
• Proarrhytmogenic : reserved for life threatening SVA & VA in pts
without myocardial structural abnormalities

28. Propafenone
• Has some structural similarities to propranolol
• Weak β – blocker
• Also some Ca2+ channel blockade
• Also slows conduction
• VA & SVA: its spectrum of action similar to that flecainide
• AE: metallic taste & constipation
• Dose:150 mg 3 times daily for 1 week, then 300 mg twice
daily

29. USE DEPENDENCE
• Na+ channels fluctuate between 3 different states: Resting, Open,
Inactivated
• Drugs bind more in certain state
• Class I drugs bind best in open/ inactivate state
• These drug exhibit use dependence
• So, more binding in fast heart rates
• Seen most frequently in class Ic drugs, so toxicity (QRS prolongation) at
high heart rates
• This is thought to be responsible for the increased efficacy of the class Ic
antiarrhythmic drugs in slowing and converting tachycardia with minimal
effects at normal sinus rates.

30. Class III
sotalol amiodarone ibutilide
 Prolongation of phase 3 repolarization without altering phase 0
upstroke or the resting membrane potential
 They prolong both the duration of the action potential and ERP
 K+ channel blockers
 Prolong QT & PR

31. Amiodarone
• Structurally related to thyroid hormone.
• Effective in most types of arrhythmias & is most efficacious
of all antiarrhythmic, because of toxicities, mainly used in
arrhythmias that are resistant to other drugs.
• Blocks Na+, Ca+2 & K+ channels and α-& β-receptors
• Marked prolongs the QT interval & QRS duration, it
increases Atrial, AV and Ventricular refractory period
• It is extensively taken up by tissues, especially fatty tissues
(extensive distribution)
• t1/2 = 60 days
• Potent P450 inhibitor
• Amiodarone antiarrhythmic effect is complex comprising
class I, II, III, and IV actions

32. Amiodarone: main clinical use
• It’s a unique wide spectrum anti-arrhythmic drug.
• Pts with AF where rapid rhythm control is needed.
• Recurrent ventricular fibrillation.
• Recurrent haemodynamically unstable ventricular tachycardia.

33. Dose:
• IV 5 mg/kg over 20–120 mins, then up to 15
mg/kg/24 hrs
• Oral Initially 600–1200 mg/day, then 100–400 mg
daily
• Hepatic metabolism; lipid soluble with extensive
distribution in body.

34. Amiodarone-adverse effects
• Toxicity due to accumulation
• Cardiac: heart block , QT prolongation, bradycardia, cardiac
failure, hypotension
• Hepatic, pulmonary fibrosis.
• Blocks peripheral conversion of T4to T3 can cause
hypothyroidism or hyperthyroidism
• Bluish discoloration of skin
• Peripheral neuropathy
• Corneal deposits
• ↑Digoxin level
• Development of new arrhythmia.

35. Sotalol
Racemate of d & l isomers.
Both exhibit antiarrhythmic action via blocking Ikr.
In addition l isomers also exhibit nonselective beta blocking activity.
USE: To prevent recurrence of AF & VT (particularly in OMI)
CONTRAINDICATION: Long QT syndrome, AV block, severe asthma
ELIMINATION: kidney ( unchanged)
HALF LIFE: 10- 16 hours
Dose IV 10–20 mg slowly, Oral 40–160 mg twice daily

36. Dofetilide, Ibutilide
• – Selective K+ channel blocker, less adverse events
• – use in AF to convert or maintain sinus rhythm
• – May cause QT prolongation

37. Newer class III drugs: Dronedarone
• It is an analog of amiodarone but is a noniodinated benzofuran derivative
with the most significant molecular modification being removal of iodine
and the addition of a methane sulfonyl group.
• It is used for the prevention of recurrent atrial fibrillation and flutter.
• its efficacy in suppressing cardiac arrhythmias is inferior to amiodarone
• It is not associated with thyroid, neurologic, ocular, or pulmonary toxicity
• The most common adverse effects of dronedarone are gastrointestinal,
including nausea, vomiting, and diarrhea
• It prolongs the R-R and QTc intervals and may also mildly increase QRS
duration.

38. Reverse use dependence
• K+ channels also fluctuate between 3 different states
• Class III drugs bind best in resting state
• These drugs exhibit reverse use dependence
• These drugs more bind on slow heart rates
• Most of the class III drugs demonstrate reverse use dependence, with
their maximal effect on repolarization at slower heart rates, which
may be counterproductive for effective arrhythmia termination.

39. Class II ANTIARRHYTHMIC DRUGS
(β-adrenergic blockers)
Mechanism of action
 Negative inotropic and chronotropic action.
 Prolong AV conduction (delay)
 Diminish phase 4 depolarization  suppressing automaticity(of
ectopic focus)

40. Indication
 Treatment of increased sympathetic activity-induced arrhythmias
such as stress- and exercise-induced arrhythmias
 Atrial flutter and fibrillation.
 AV nodal tachycardia.
 Reduce mortality in post-myocardial infarction patients
 Protection against sudden cardiac death

41. Calcium channel blockers (Class IV)
 Calcium channel blockers decrease inward Ca2+ currents resulting in a
decrease of phase 4 spontaneous depolarization (SA node)
 They slow conductance in Ca2+ current-dependent tissues like AV
node.
 Examples: verapamil & diltiazem
 Because they act on the heart only and not on blood vessels.
 Dihydropyridine family are not used because they only act on blood vessels

42. • Verapamil
• Stronger action on heart than smooth muscle
• Used in supraventricular arrhythmia
• 80-120mg three times a day
• A/E – ankle oedema, constipation
• C/I – AV block, LVF, hypotention & WPW
• Diltiazem
• Mixed action
• Oral dose 30-90mg 6hourly

43. Other antiarrhythmics

44. Adenosine
• Naturally occurring nucleoside
• Receptors in many locations (AV nodal tissue, Vascular smooth muscle
• In AV nodal cells activate K+ channels & drives K+ out of cells, thus
hyperpolarize cells, makes longer to depolarize
• IV suppresses automaticity, AV conduction and dilates coronaries
• Used in Reentry circuit, PSVTs & SVT
• Ultra short t1/2 (10-20 sec)
• A/E – facial flushing, short breath, bronchospasm, metallic taste
• Rapid IV push (6 mg over 1-2 sec)
• When using IV line, flush with saline
• If no effect after 1-2 min, give 12 mg; may repeat 12 mg dose once

45. Digoxin
• It augments vagal tone, leading to the prolongation of the AV node
effective refractory period and a decrease in sinus rate and AV
conduction
• It is used to control the ventricular rate in atrial fibrillation/flutter or
to prevent relapse of supraventricular arrhythmias using the AV node
•Half-life: 36 hours or longer,Primarily renal elimination
• A/E – Dysrhythmias, anorexia, nausea, headache, halo vision, visual
scotomas, and altered color perception.
• Hypokalemia enhances digoxin toxicity

46. Magnesium
• Acute management of torsade de pointes
• Mg blocks influx of Ca into cells
• Ca influx leads to early after depolarization
• Dose: 8 mmol over 15 mins, then 72 mmol over 24 hrs

47. Ranolazine
• Ranolazine is approved for treatment of chronic angina. However, this
drug has potent antiarrhythmic activity
• It inhibits IKr, IKs, late INa, ICa, and INa-Ca
• It appears to be useful for treatment of both atrial fibrillation and
ischemia-induced ventricular arrhythmias
• Adverse effects include constipation, headache, dizziness, nausea,
bradycardia, orthostatic hypotension, palpitations & QT prolongation
may be present

48. Ivabradine
• It is approved for treatment of stable symptomatic heart failure, specifically
in patients with decreased systolic function who are in sinus rhythm with a
heart rate of 70 bpm of greater
• Its utilization has also been explored in management of inappropriate sinus
tachycardia and postural tachycardia syndrome (POTS)
• It works by blocking the (HCN) channel causing a decrease in the
spontaneous pacemaker activity of the sinus node through inhibition of the
“f-current” (If).
• It is contraindicated in patients with severe liver dysfunction.
• Adverse reactions include bradycardia, hypertension, atrial fibrillation, and
visual disturbances.

49. Vernakalant
• It is a novel intravenous antiarrhythmic that rapidly terminate acute-
onset atrial fibrillation.
• It blocks of sodium channels and early activation of potassium
channels.
• It also has an atrial selective potassium channel blocking effect.
• Its elimination half-life is approximately two hours.
• It is predominantly cleared by the liver, and likely requires dose
adjustments in advanced liver disease
• Prior studies reveal an approximate 50% conversion rate from atrial
fibrillation to sinus rhythm within 90 minutes from initial infusion

50. PROARRHYTHMIA
• Antiarrhythmic drugs intended to suppress arrhythmias may
potentially worsen a preexisting arrhythmia or cause a new
arrhythmia
• It may divided into atrial & ventricular Proarrhythmia
• Class Ic antiarrhythmic drugs are used for the treatment of SVT, they
can cause atrial flutter, often with slower rates (~200 bpm)
• Adenosine and digitalis occasionally promote the development of
atrial fibrillation by shortening the atrial effective refractory period.
• Class Ia and class III antiarrhythmic drugs that block IKr and/or
increase late INa may facilitate the development of TdP

51. DRUG-DEVICE INTERACTIONS
• Patients with devices may require concomitant drug therapy for a variety of
reasons, the most common being to reduce arrhythmia frequency.
• An antiarrhythmic drug can cause excessive rate slowing that mandates
placement of a permanent pacemaker.
• Drugs can also have an impact on the pacing threshold and the thresholds
for arrhythmia termination
• Drugs that reduce the sodium current should be expected to raise pacing
and defibrillation thresholds, whereas potassium channel blockers reduce
the defibrillation threshold
• Slowing of ventricular tachycardia may be beneficial in improving
hemodynamic stability and decreasing risk of degeneration to ventricular
fibrillation, but may also lead to underdetection by the device.

52. Acute pharmacologic Management of
hemodynamic stable AF:
Rhythm control
Severe HFrEF,
significant
aortic stenosis
CAD,
moderate HFrEF or
HFmrEF/HFpEF,
abnormal LVH
No relevant
structural
heart disease
Intravenous
Amiodarone
(IA)
Intravenous
Vernakalant
(IIb)
Amiodarone
(IA)
Intravenous
Flecainide (IA)
Ibutilide (IIa)
Propafenone
(IA)
Vernakalant
(IA)
Pill in the
pocket
Flecainide
(IIa)
Propafenone
(IIaB)
Acute rate
control
LVEF <40% or
signs of
congestive heart
failure
LVEF ≥40%
beta-blocker
If not control
then add
digoxin
Beta-blocker
or CCB
If not control
then add
digoxin
2016 ESC AF GUIDELINE

53. Acute pharmacologic Management of
hemodynamic stable SVT:
AVNRT
Adenosine
IV BB, IV CCB
Oral BB, Oral CCB
IV Amiodarone
Maintainance
Oral CCB,BB
Flecainide or propafenone
Sotalol,
Dofetilide,Amiodarone,Digoxin
• Symptomatic Manifest or Concealed
Accessory Pathways
IV Adenosine, Ibutilide,
procainamide
IV BB
Maintainance
Oral BB
Flecainide or propafenone
Sotalol, Dofetilide,Amiodarone,
I
IIa
IIb
IIb
I
IIb
I
IIa
IIb
I
IIa
IIb
2015 AHA SVT GUIDELINE

54. • Acute pharmacologic Management of hemodynamic stable VT:
Amiodarone (Ia), Lidocaine(Ib),Procainamide(Ib),Sotalol (Ib)
• For Management of torsade de pointes (Tdp):
Magnesium

55. Conclusion
• All antiarrythmatic drugs are proarrythmatic, So, we should use them
causiously
• Class Ic drugs are very effective in preventing atrial arrythmia with
structurally normal heart
• Amiodarone has efficacy in preventing most of tacchyarrythmia
• Among antiarrythmic drugs only beta blockers have mortality benefit
and less side effects

56. Thanks to All