Five Phases: cardiac action potential associated with HIS-purkinje fibers or ventricular muscle
and ionic and electrophysiological
changes are associated with normal cardiac rhythm
Resting
membrane potential and conduction velocity
beta-adrenergic receptor blockers (propranolol
(Inderal)),
and
digitalis glycosides.
Treatment of atrial
fibrillation: Verapamil (Isoptin, Calan) & Diltiazem (Cardiazem)
Blocks cardiac
calcium channels in slow response tissues, such
as the sinus and AV nodes.
Useful in treating AV
reentrant tachyarrhythmias and in management of
high ventricular rates secondary to atrial
flutter or fibrillation.
Major
adverse effect (i.v. administration) is
hypotension. Heart block or sinus bradycardia can
also occur.
Treatment of atrial
fibrillation: Propranolol (Inderal)
Antiarrhythmic effects are due mainly
to beta-adrenergic receptor blockade.
Normally,
sympathetic drive results in increased in Ca2+
,K+ ,and Cl-
currents.
Increased sympathetic tone also
increases phase 4 depolarization (heart rate goes
up), and increases DAD (delayed
afterdepolarizations) and EAD (early
afterdepolarization) mediated arrhythmias.
These
effects are blocked by beta-adrenergic receptor
blockers.
Beta-adrenergic receptor blockers
increase AV conduction time (takes longer) and increase AV nodal
refractoriness, thereby helping to terminate
nodal reentrant arrhythmias.
Beta-adrenergic receptor blockade can
also help reduce ventricular following rates in
atrial flutter and fibrillation, again by acting
at the AV node.
Adverse effects of beta blocker
therapy can lead to fatigue, bronchospasm,
depression, impotence, and attenuation of
hypoglycemic symptoms in diabetic patients and
worsening of congestive heart failure.
Drugs assist in restoring
and maintaining normal sinus rhythm include quinidine and
procainamide.
Blocks cardiac
calcium channels in slow response tissues, such
as the sinus and AV nodes.
Useful in treating AV
reentrant tachyarrhythmias and in management of
high ventricular rates secondary to atrial
flutter or fibrillation.
Major
adverse effect (i.v. administration) is hypotension. Heart block or sinus bradycardia can
also occur.
Esmolol (Brevibloc)
Esmolol
is a very short acting, cardioselective beta-adrenergic
receptor antagonist.
i.v. administration is used for
rapid beta-receptor blockade in treatment of atrial
fibrillation with high ventricular following rates.
Antiarrhythmic
effects are due mainly to beta-adrenergic receptor
blockade. Normally, sympathetic drive results in
increased in Ca2+ ,K+and Cl-
currents.
Increased sympathetic tone also increases phase 4
depolarization (heart rate goes up), and increases
DAD (delayed afterdepolarizations) and EAD (early
afterdepolarization) mediated arrhythmias. These
effects are blocked by beta-adrenergic receptor
blockers.
Beta-adrenergic receptor blockers
increase AV conduction time
increase AV nodal
refractoriness, thereby helping to terminate
nodal reentrant arrhythmias.
Three
mechanisms have been associated with many tachyarrhythmias
Enhanced Automaticity
Triggered Automaticity
Reentry
ENHANCED AUTOMATICITY: An increase in the
slope of phase 4 depolarization results in
As a result of the increase
in phase 4 slope the cell reaches
threshold more often per minute resulting
in higher heart rate.
Factors that increase
automaticity include
mechanical stretch
beta-adrenergic
stimulation
hypokalemia
Ischemia can induce abnormal automaticity, i.e. automaticity that occurs in
cells not typically exhibiting pacemaker
activity.
TRIGGERED AUTOMATICITY: occurs when a second
depolarization occurs prematurely.
One type of triggered
automaticity is a delayed
afterdepolarization (DAD).
If this
late depolarization reaches
threshold (a) second beat(s) may
occur.
Factors that predispose to
delayed afterdepolarizations include
excessive adrenergic
activity
digitalis toxicity
high intracellular Ca2+
A
second type of triggered automaticity is
Early Afterdepolarization (EAD) which is
associated with significant prolongation of
the action potential duration.
In
this case, during a prolonged phase 3
repolarization, the repolarization is
interrupted by a second depolarization.
Factors that predispose to
Early Afterdepolarizations include
Prolongation
of cardiac repolarization (prolonged Q-T
interval)
Possibly
induced by early afterdepolarizations.
The
antiarrhythmic drug quinidine gluconate
(Quinaglute, Quinalan) can cause this arrhythmia. Many other
drugs can also cause this effect.
REENTRY is the most
common cardiac conduction abnormality leading to
arrhythmias.
PF:
Branched Purkinje Fiber terminating on
ventricular muscle (VM).
Shaded Area: Depolarized region with unidirectional
(one-way) block (Decremental conduction, impulse
slowly dies out)
slowed conduction may be
due to depression of Na +
or Ca2+
currents (e.g. AV node)
Retrograde impulses
(wavy line) propagate slow
enough such that cells in branch 1 are no longer
refractory and can be activated by the re-entry
potential.
Drugs that terminate
reentry may further depress conduction,
converting the "unidirectional" block
to a "bidirectional" block
A
reentrant circuit involves a pathway that
bifurcates into two branches.
One
pathway is blocked to anterograde
conduction, but can be excited in a
retrograde manner by the impulse that
traversed the unblocked path.
Retrograde
conduction occurs until excitation of now
non-refractory tissue re-initiates the
process.
Although for
a given arrhythmia in a patient the mechanism may
not be known, there are certain general
explanations for the action of anti-arrhythmic
agents. Anti-arrhythmic drugs may work by:
(a) Suppressing initiation
site (automaticity/after-depolarizations)
and/or
(b) Preventing early or
delayed afterdepolarizations and/or
(c) By disrupting a
re-entrant pathway.
(a) Automaticity: Automaticity
may be diminished by:
(1) increasing the maximum
diastolic membrane potential
(2) decreasing the slope of
phase 4 depolarization
(3) increasing action
potential duration
(4) raising the threshold
potential
All of these
factors make it take longer or make it more
difficult for the membrane potential to reach
threshold.
(1) The diastolic membrane
potential may be increased by adenosine
and acetylcholine.
(2) The slope of phase 4
depolarization may be decreased by beta
receptor blockers
(3) The duration of the
action potential may be prolonged by
drugs that block cardiac K+
channels
(4) The membrane threshold
potential may be altered by drugs that
block Na+ or Ca2+
channels.
(b) Delayed or
Early Afterdepolarizations:
Delayed or early
afterdepolarizations may be blocked by
factors that
(1)
prevent the conditions that lead
to afterdepolarizations.
(2)
directly interfere with the
inward currents (Na+,
Ca2+)
that cause afterdepolarizations.
(c) Reentry
For anatomically-determined
re-entry such as Wolf-Parkinson-White
syndrome (WPW) drugs the arrhythmia can
be resolved by blocking action potential
(AP) propagation. (In WPW syndrome, an accessory
conduction pathway, linking atria and ventricles and bypassing the atrioventricular node, is the
structure responsible for the arrhythmia)
In WPW-based arrhythmias,
blocking conduction through the AV node may be clinically effective.
Drugs
that prolong nodal
refractoriness and slow
conduction include: Ca2+
channel blockers, beta-adrenergic
blockers, or digitalis
glycosides.
For
functional (non-anatomical)
reentrant circuits, prolongation
of refractoriness is the
electrophysiological change most
likely to terminate the reentry
arrhythmia.
Prolongation
of tissue refractoriness can be accomplished by
those antiarrhythmic drugs that block Na+
channels.
Sodium channel blockers
reduces the percentage of recovered
channels (following inactivation by
depolarization) at any given membrane
potential.
Examples of antiarrhythmic
drugs classified as sodium channel
blockers include lidocaine, quinidine,
and tocainide.
"Although any type of arrhythmia can occur in a patient with WPW, the two most common are CMTs
(circus
movement tachycardias) and atrial fibrillation (AFib). CMT is the more common arrhythmia of the two
Treatment of CMTs associated with WPW is similar to treating PSVT
In a stable patient, adenosine (6 mg rapid IV push; if unsuccessful, 12 mg rapid IV push) should be the first-line treatment in any regular
tachycardia, regardless of whether the complex is wide or
narrow
Treatment of AFib associated with WPW is necessarily different than for a patient with a normal heart. AFib is an irregular rhythm as opposed to the regular rhythm seen in
CMTs.
The basic treatment principle in WPW AFib is to prolong the anterograde refractory period of the accessory pathway relative to the AV node.
This slows the rate of impulse transmission through the accessory pathway and, thus, the ventricular rate.
If AFib were treated in the conventional manner by drugs that prolong the refractory period of the AV node
(eg, calcium channel blockers, beta-blockers, digoxin), the rate of transmission through the accessory pathway likely would increase, with a corresponding increase in ventricular
rate. This could have disastrous consequences, possibly causing the arrhythmia to deteriorate into V fib.
Procainamide (17 mg/kg IV infusion, not to exceed 50 mg/min; hold for hypotension or 50% QRS widening) blocks the accessory pathway, but it has the added effect of increasing transmission through the AV node. Thus, although procainamide may control the AFib rate through the accessory pathway, it may create a potentially dangerous conventional AFib that may require treatment with other medications. Prompt cardioversion of patients with WPW and AFib is recommended.
Medical management may be a viable option in some patients, but it may have unpredictable results. Note that cardioversion is always the treatment of choice in unstable patients."
*From emedicine
Authored by Mel Herbert, MD, MBBS, Assistant Professor of Medicine and Nursing, Department of Emergency Medicine, Olive View-University of
California at Los Angeles Medical Center