Types of Arrhythmia

Supraventricular Arrhythmias
 Sinus Tachycardia: high sinus rate of 100-180 beats/min,
occurs during exercise or other conditions that lead to
increased SA nodal firing rate
 Atrial Tachycardia: a series of 3 or more consecutive
atrial premature beats occurring at a frequency >100/min
 Paroxysmal Atrial Tachycardia (PAT): tachycardia which
begins and ends in acute manner
 Atrial Flutter: sinus rate of 250-350 beats/min.
 Atrial Fibrillation: uncoordinated atrial depolarizations.
AV blocks
A conduction block within the AV node , occasionally in the
bundle of His, that impairs impulse conduction from the
atria to the ventricles.
 ventricular Arrhythmias
 Ventricular Premature Beats (VPBs): caused by ectopic
ventricular foci; characterized by widened QRS.
 Ventricular Tachycardia (VT): high ventricular rate
caused by abnormal ventricular automaticity or by
intraventricular reentry; can be sustained or non-
sustained (paroxysmal); characterized by widened QRS;
rates of 100 to 200 beats/min; life-threatening.
 Ventricular Flutter - ventricular depolarizations >200/min.
 Ventricular Fibrillation - uncoordinated ventricular
depolarizations
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
 Antyarrhythmic drugs
• Most antiarrhythmic drugs are pro-arrhythmic (promote arrhythmia)
• They are classified according to Vaughan William into four classes according to their
effects on the cardiac action potential
class mechanism action notes
Can abolish
Change the slope of tachyarrhythmia
I Na+ channel blocker
phase 0 caused by reentry
circuit

II β blocker
↓heart rate and Can indirectly alter K
conduction velocity and Ca conductance

1. ↑action potential
duration (APD) or
Inhibit reentry
III K+ channel blocker effective refractory
tachycardia
period (ERP).
2. Delay repolarization.

Slowing the rate of rise ↓conduction

IV Ca++ channel blocker in phase 4 of SA velocity in SA and
node(slide 12) AV node
 Class I drugs
Have moderate K+
channel blockade

↓
They conduction velocity in non-nodal
They act on open tissues (atria, ventricles, and purkinje fibers)
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
Slowing of the rate of rise in
↓
phase 0  conduction
velocity
↓ of Vmax of the cardiac
action potential
They prolong muscle action
potential & ventricular (ERP)
↓
They the slope of Phase 4
spontaneous depolarization
(SA node)  decrease
enhanced normal They make the
slope more
automaticity horizontal
Class IA Drugs
They possess intermediate rate of association and
dissociation (moderate effect) with sodium channels.
Pharmacokinetics:
Class IA Drugs Uses
Supraventricular and ventricular arrhythmias
Quinidine is rarely used for supraventricular
arrhythmias
Oral quinidine/procainamide are used with class III
drugs in refractory ventricular tachycardia patients
with implantable defibrillator
IV procainamide used for hemodynamically stable
ventricular tachycardia
IV procainamide is used for acute conversion of
atrial fibrillation including Wolff-Parkinson-White
Syndrome (WPWS)

defibrillator
Class IA Drugs Toxicity

Systemic lupus erythromatosus (SLE)-like

symptoms: arthralgia, fever, pleural-
pericardial inflammation.

Symptoms are dose and time dependent

Common in patients with slow hepatic

acetylation
 Class II ANTIARRHYTHMIC DRUGS
(β-adrenergic blockers)
Uses
Mechanism of action
Treatment of increased
Negative inotropic sympathetic activity-induced
and chronotropic arrhythmias such as stress-
action. and exercise-induced
Prolong AV arrhythmias
conduction (delay) Atrial flutter and fibrillation.
Diminish phase 4 AV nodal tachycardia.
depolarization  Reduce mortality in post-
suppressing myocardial infarction
automaticity(of patients
ectopic focus) Protection against sudden
cardiac death
Class II ANTIARRHYTHMIC DRUGS

Propranolol (nonselective): was proved to reduce

the incidence of sudden arrhythmatic death after
myocardial infarction
Metoprolol
 reduce the risk of bronchospasm selective
Esmolol:
 Esmolol is a very short-acting β1-adrenergic
blocker that is used by intravenous route in acute
arrhythmias occurring during surgery or
emergencies
 Class III ANTIARRHYTHMIC DRUGS
K+ blockers

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
Their mechanism of action is
still not clear but it is thought
that they block potassium
channels
 Uses:
 Ventricular arrhythmias, especially ventricular
fibrillation or tachycardia
 Supra-ventricular tachycardia
 Amiodarone usage is limited due to its wide
range of side effects
 Amiodarone (Cordarone)
Amiodarone is a drug of multiple actions and is still not well understood
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
• Dominant effect: Prolongation of action potential duration and
refractoriness
• It slows cardiac conduction, works as Ca2+ channel blocker, and as a weak
β-adrenergic blocker
Toxicity
 Most common include GI intolerance, tremors, ataxia, dizziness, and hyper-
or hypothyrodism
 Corneal microdeposits may be accompanied with disturbed night vision
 Others: liver toxicity, photosensitivity, gray facial discoloration, neuropathy,
muscle weakness, and weight loss
 The most dangerous side effect is pulmonary fibrosis which occurs in
2-5% of the patients
 Class IV ANTIARRHYTHMIC DRUGS
(Calcium Channel Blockers)
 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
 Mechanism of action
They bind only to depolarized (open) channels  prevention of repolarization

So they act only in cases of arrhythmia because many Ca2+

channels are depolarized while in normal rhythm many of them
are at rest

They prolong ERP of AV node 

ventricles
↓conduction of impulses from the atria to the

Uses
More effective in treatment of atrial than ventricular arrhythmias.
Treatment of supra-ventricular tachycardia preventing the
occurrence of ventricular arrhythmias
Treatment of atrial flutter and fibrillation
 contraindication
 Contraindicated in patients with pre-existing
depressed heart function because of their negative
inotropic activity

Adverse effects
 Cause bradycardia, and asystole especially when
given in combination with β-adrenergic blockers
Miscellaneous Antiarrhythmic Drugs

Adenosine
o Adenosine activates A1-purinergic receptors
decreasing the SA nodal firing and automaticity,
reducing conduction velocity, prolonging
effective refractory period, and depressing AV
nodal conductivity
o It is the drug of choice in the treatment of
paroxysmal supra-ventricular tachycardia
o It is used only by slow intravenous bolus
o It only has a low-profile toxicity (lead to
bronchospasm) being extremly short acting for
15 seconds only