A discussion of mechanisms of Arrhythmia.

1. Basic Critical Care Course
Antiarrhythmia Therapy
"
Frank W. Meissner, MD, FACP, FACC, FCCP, CPHIMS
"

3. LAD
"
Circumflex
"
L-Main
"
RCA
"
AV NODE
"
HIS
BUNDLE
"
LPF
"
RBB
"
LAF
"
Conduction & Vascular System "
3-D Spatial Inter- Relationships"

4. Nerves of the Heart"

5. Sympathetic & Parasympathetic Nervous Cardiac Nervous System"

6. Phases of Action Potential"

7. A
c
t
I
o
n
P
o
t
e
n
t
i
a
l
s

8. Cellular Channels & Action Potentials"

9. Mechanisms of
Arrhythmiogenesis "
 Re-entry"
• PSVT"
• Vtach"
• Atrial Fib/Flutter"
 Self-sustaining "
 Premature beat initiates "
 Can be terminated by overdrive pacing"

10.  Altered automaticity"
• Can not be terminated or initiated by
pacing"
• Accelerated rhythms"
• Associated with metabolic abnormalities or
drug toxicity's "
• Hyperthyroidism"
• Incessant Atrial tachycardia"
Mechanisms of
Arrhythmiogenesis"

11.  Triggered Activity"
• EP Laboratory"
• Exercise induced V-tach"
• Digitalis intoxication"
• Torsades de Pointes "
Mechanisms of
Arrhythmiogenesis"

12. Re-entry Mechanism"

13. Re-entry Mechanism II"

14. Re-entry Mechanism III"

15. Re-entry Mechanism IV"

16. Classification Of Antiarrhythmic Drugs
Class I Drugs that reduce maximal velocity of phase of depolarization (Vmax) due to block of inward Na+
current in tissue with fast response action potentials
A ⇓ Vmax at all heart rates and ⇑ action potential duration, e.g., quinidine, procainamide, disopyramide
B Little effect at slow rates on Vmax in normal tissue; ⇓ Vmax in partially depolarized cells with fast
response action potentials
Effects increased at faster rates
No change or ⇓ in action potential duration, e.g., lidocaine, phenytoin, tocainide, mexiletine
C ⇓ Vmax at normal rates in normal tissue
Minimal effect on action potential duration, e.g., flecainide, propafenone, moricizine
Class II Antisympathetic agents, e.g., propranolol and other beta-adrenergic blockers: ⇓ SA nodal automaticity, ⇑
AV nodal refractoriness, and ⇓ AV nodal conduction velocity
Class III
Agents that prolong action potential duration in tissue with fast-response action potentials, e.g.,
bretylium, amiodarone, sotalol
Class IV Calcium (slow) channel blocking agents: ⇓ conduction velocity and ⇑ refractoriness in tissue with slow-
response action potentials, e.g., verapamil, diltiazem
Drugs that cannot be classified by this schema:
Digitalis
Adenosine

17. Drug SA Node Atrium and
Ventricle
AV Node His-Purkinje
System
AV
Bypass
Tract
Digoxin ⇔,SSS exit block Controversial ⇑ERP,⇓conduction
velocity
⇔ ⇔ or⇓
ERP
Adenosine ⇓automaticity Atrium ⇓ ERP
Ventricle ⇔,
⇓conduction velocity
Quinidine
(1A)
⇔,SSS exit block ⇑ERP, ⇓conduction
velocity
⇔ or⇓ERP,
⇓conduction velocity
⇓automaticity,
⇓conduction
velocity, ⇑ERP
⇑ERP,
may
abolish all
condution
Procanamide ⇔ ⇑ERP,⇓conduction
velocity
⇔ or⇓ERP, ⇓ or
⇔ conduction
velocity
⇓automaticity,
⇑ERP,⇓condu
ction velocity
⇑ERP,
may
abolish all
condution
Disopyramide ⇔ ⇑ERP,⇓conduction
velocity
⇔ or⇓ERP, ⇓ or
⇔ conduction
velocity
⇓automaticity,
⇑ERP,⇓condu
ction velocity
⇑ERP,
may
abolish all
condution
Electrophysiological Effects of Antiarrhythmic Drugs"

18. Drug SA Node Atrium and
Ventricle
AV Node His-Purkinje
System
AV Bypass
Tract
Lidocaine
(1B)
⇔ ⇔ ERP ⇔ or⇓ERP ⇔ or⇓ERP ⇔ or⇓ or ⇑
ERP
Phenytoin
(1B)
⇔ ⇔ ERP ⇔or⇓ERP,
⇔ or ⇑conduction
velocity
⇓ERP,
⇓automaticity
Tocainide
(1)
⇔ ⇔ ⇔ ⇔,
⇓automaticity
⇑ERP
Mexiletine
(1B)
⇔,SSS exit block ⇔ variable and
inconsistent effects
on conduction and
refractoriness
⇑ERP,⇔ or
⇓conduction
velocity
Flecanide
(1C)
⇔,SSS exit block ⇑ERP,
⇓conduction velocity
⇑ERP, ⇓conduction
velocity
⇓conduction
velocity
⇓conduction
velocity,
⇑ERP, may
abolish all
condution
Electrophysiological Effects of Antiarrhythmic Drugs"

19. Drug SA Node Atrium and
Ventricle
AV Node His-Purkinje
System
AV Bypass
Tract
Propafenone
(1C)
⇔ ⇓ conduction
velocity,⇑ERP
⇓ conduction
velocity,⇑ERP
⇓ conduction
velocity,⇑ERP
⇑ERP
Propranolol,
atenolol,
metoprolol
(II)
⇓ sinus
rate,⇑sinus node
recovery time
⇔ ⇓ conduction
velocity,⇑ERP
⇔ ⇔
Bretylium
(III)
initial⇑ sinus
ratefollowed by⇓
⇑ERP ⇔ ⇔ ⇔
Amiodarone
(III)
⇓ sinus rate ⇑ERP ⇑ERP, ⇓conduction
velocity
⇑ERP,
⇓conduction
velocity
⇑ERP
Sotalol
(III)
⇓ sinus rate ⇑ERP ⇑ERP, ⇓conduction
velocity
⇑ERP,
⇓conduction
velocity
⇑ERP
Verapamil,
Diltiazem
(IV)
⇓ sinus rate ⇔ ⇑ERP, ⇓conduction
velocity
⇔ ⇔
Electrophysiological Effects of Antiarrhythmic Drugs"

20. Drug Clinical Effects/Indications Adverse Reactions
Digoxin Slowing of Vent rate in AF, Aflutter, other atrial
arrythmias in absence of pre-excitation; slowing,
termination &/or prevention of SVT due to AV
nodal re-entry
Atrial tachycardia, VT, AV nodal
block, accelerated junctional rhythm,
anorexia, nausea, vomiting,
acceleration of ventricular rate in the
presence of pre-excitation
Adenosine Acute termination of PSVT Transient atrial standstill &
hypotension
Quinidine Atrial & ventricular extrasystoles; atrial and
ventricular tachyarrythmias, all types of SVT;
control of ventricular rate in patients with
preexcitation and AF & flutter
Anorexia, nausea, vomiting, confusion,
hearing and visual changes, hemolytic
anemia, diarrhea, cinchonism, tinnitus,
thrombocytopenia, elevation of digoxin
levels, QT prolongation with torsades
de pointes, acceleration of Atrial
Fib/flutter, drug-drug interactions
Procainamide Same as quinidine Anorexia, nausea, vomiting, confusion,
hallucinations, agranuloctyosis, drug-
induced lupus, QT prolongation with
torsades de pointes, acceleration of
Atrial Fib/flutter, drug-drug
interactions
Disopyramide Same as quinidine Anticholinergic actions (dry mouth,
blurred vision, urinary retention,
hesitancy, constipation), narrow-angle
glaucoma, CHF, QT prolongation with
torsades de pointes
Lidiocaine VT & VF esp during acute ischemia or AMI Dizziness, parasthesias, confusion,
delirium, seizures, coma, decreased
sinus node function in patients with
preexisting sinus node dysfunction,
CHF or liver Dz increase likelyhood of
adverse events

21. Drug Clinical Effects/Indications Adverse Reactions
Phenytoin Tachyarrhythmias induced by digitalis; occasionally
effective for V-tachyarrythmias not induced by
digoxin, alone or in combination with other agents;
polymorphic V-tach in association with prolonged
QT intervals
Gingival hypertrophy, rash, blood
dyscrasias, nystagmus, ataxia, stupor,
coma, SLE, lymph node hyperplasia,
peripheral neuropathy, hypocalcemia,
hyperglycemia, phlebitis, hypotension
during IV administration
Tocainide VT, VF, freq VPC's Ataxia, tremor, parasthesias, light-
headness, nausea, rash, SLE,
pulmonary fibrosis, bone marrow
suppression, exacerbated CHF
Mexiletine Refractory atrial & tachyarrythmias;SVT due to AV
nodal reentry and AV bypass tracts
Nausea, vomting, ataxia, tremor, gait
disturbances, rash
Flecainide Refractory atrial & tachyarrythmias;SVT due to AV
nodal reentry and AV bypass tracts
Refractory polymorphic VT without
increased QT if dose is increased too
rapidly or in patients with abnormal
conduction system; sinus arrest in
patients with normal sinus node
function, nausea, dizziness, precipitate
CHF
Propanolol,
atenolol,
metoprolol
Slowing of ventricular rate during AF, flutter, and
other atrial arrythmias in the absence of
preexcitation, SVT due to AV nodal reentry, reentry
utilizing bypass tracts; arrythmias induced by
exercise; arrythmias occurring due to
hyperthyroidism; polymorphic VT in association
with congenital long QT syndrome
Sinus bradycardia, AV nodal block,
CHF, bronchospasm, masking of
symptoms of hypoglycemia

22. Drug Clinical Effects/Indications Adverse Reactions
Bretylium Refractory VT & VF especially due to acute
ischemia
Initially transient hypertension with
subsequent hypotension increased in
the upright position; hypotensive effect
can by prevented by tricyclic drugs;
nausea, vomiting
Amiodarone Refractory atrial and ventricular
tachyarrhthmias;refractory SVT due to AV nodal
reentry and AV renentry utilizing bypass tracts; not
approved by FDA atrial arrythymias;atrial and
ventricular extrasystoles and tachyarrhtmias
Marked sinus bradycardia, complete
heart block, IV administration can be
associated with hypotension, increased
QT with torsades;increased T4;hypo-
and hyperthyrodism;peripheral
neuropathy; proximal myopathy;
pulmonary fibrosis; increased liver
enzymes and hepatitis; blue-gray
discoloration of the skin; corneal micro
deposits;elevated digoxin levels;
potentiation of coumadin effect;
exacerbated CHF
Sotalol Atrial and ventricular arrhythmias (not FDA
approved for atrial arrythmias)
May exacerbate ventricular
tachycardia, dizziness, nausea
Verapamil,
Diltiazem
Slowing of ventricular rate during atrial fibrillation,
atrial flutter, and other atrial tachycardias in the
absence of preexcitation;SVT due to AV nodal
reentry, reentry utilizing bypass tracts; idiopathic
left ventricular tachycardia
Sinus bradycardia, AV node block,
CHF, constipation, peripheral edema,
drug interactions