Transcript Drugs for treating arrhythmias

Drugs for Arrhythmias
A. Pathophysiology of arrhythmias
• Arrhythmias are a group of conditions in
which the muscle contraction of the heart
is irregular, and they occur in both healthy
and diseased hearts.
• Many arrhythmias are associated with
other cardiovascular conditions: CAD, HT,
and MI.
B. Arrhythmia therapy
• Antiarrhythmic drugs do not cure the
underlying causes of an arrhythmia.
Instead, they attempt to restore the normal
cardiac rhythm.
• Drugs are classified according to the
phase of the action potential that they
affect.
1. Class I antiarrhythmic drugs (Na1+
channel blockers)
• This class of drugs reduces the excitability
of the heart by slowing the spread of
impulse conduction across the heart.
• Sodium channel blockers are similar in
structure and action to the local
anesthetics.
• This is the largest class of antiarrhythmic
drugs.
• They are subclassified according to the
effects they have on the cardiac action
potential.
Phase 4: The resting membrane potential, when
the cell is not being stimulated (represented by
baseline on the ECG).
Phase 0: This is the rapid depolarization phase
and occurs with the opening of the Na1+ channels
and the rapid influx of Na1+ into the cell.
Phase 1: This phase of the action potential occurs with the closure of
the Na1+ channels. There is a transient net outward current due to the
movement of K1+ and Cl1- ions. Phase 0 and 1 together correspond to
the QRS complex of the ECG.
Phase 2: This is the plateau phase of the action potential and occurs
because of the balanced inward movement of Ca2+ ions through
calcium channels, and outward movement of K1+ ions through
potassium channels. It corresponds to the ST segment of the ECG.
Phase 3: In this phase of the action potential, the K1+ channel is still
open, allowing more K1+ to leave the cell, resulting in a net loss of
positive charge, which causes the cell to repolarize. Phase 3
corresponds to the T wave of the ECG.
a. Class IA
They slow the rate of rise of phase 0 and lengthen the
action potential and are indicated for managing a variety of
atrial and ventricular arrhythmias.
• Quinidine, procainamide and disopyramide
are drugs in this subclass.
quinidine gluconate (62% quinidine):
• Quinidine is indicated for a wide variety of
both atrial and ventricular arrhythmias.
The off label use of this is the treatment of
malaria.
• Dosage:
• IV: infuse at 16 mg/min until arrhythmia is
resolved;
• PO: 325 – 650 mg every 6 hours.
quinidine sulfate (83% quinidine):
• Dosage: PO: 400 – 600 mg every 2 – 3
hours until arrhythmia is resolved, for
supraventricular tachycardia;
• 200 mg every 2 – 3 hours for 5 – 8 doses
for atrial fibrillation
• Quinidine is related to quinine, originally
derived from the bark of the cinchona tree.
• It’s side effects include a syndrome called
"cinchonism" consisting of various sound
and visual disturbances (hallucinations,
ringing in the ears), salivation, GI
disturbances, weakness, fatigue, rashes,
headache, and confusion.
• It can cause/aggravate Torsades de
pointes (an uncommon variant of
ventricular tachycardia), as can all class IA
drugs
procainamide (Procanbid,
Promine, Pronestyl)
• procainamide first approved for use in the
United States in 1950, is indicated for a
wide variety of both atrial and ventricular
arrhythmias.
• Dosage: IV: 100 mg every 5 minutes until
arrhythmia is resolved, or 500 – 600 mg
every 25 – 30 minutes followed by
maintenance infusion of 2 – 6 mg/min.
• It’s most serious adverse effects include
seizures, asystole, heart block, ventricular
arrhythmias and agranulocytosis.
• It’s most common adverse effects are GI
disturbances. Some individuals experience
lupus-like symptoms (rash, muscle pain).
disopyramide (Norpace, Rythmodan)
• disopyramide is usually only used after
quinidine and procainamide have been
ruled out as possibilities. It is indicated for
the treatment of ventricular tachycardia.
• Dosage: PO: 150 mg every 6 hours, not to
exceed 800 mg/day
• Disopyramide can aggravate or precipitate
severe CHF.
• Other adverse effects associated with
disopyramide include dry mouth, blurred
vision, urinary retention, and constipation.
b. Class IB
They shorten the action potential and are indicated for the
treatment of ventricular tachycardia and prevention of
ventricular fibrillation
• Lidocaine and mexilitine are drugs in this
subclass.
lidocaine (Xylocaine)
• lidocaine is indicated for the treatment of
ventricular arrhythmias.
• Dosage: IV: 50 – 100 mg bolus over 2
minutes, then 1 – 4 mg/min infusion
• It’s most serious adverse effects include
cardiac arrest, anaphylaxis, and seizures.
It’s most common adverse effects include
agitation, confusion, slurred speech,
tremors and drowsiness.
mexiletine (Mexitil)
• mexiletine (Mexitil) is structurally similar
to lidocaine, except it can be administered
orally.
• Mexiletine is usually the class IB agent
used when there is a history of MI.
• Dosage mexiletine:
• PO: 400 mg loading dose, then 200 mg
more in 8 hours, then 200 – 400 mg every
8 hours
c. Class IC
They have no effect on the length of the action potential, but reduce the
rate of rise of phase 0. These drugs are indicated for the treatment of
ventricular tachycardia and supraventricular tachycardia.
• Flecainide and propafenone are drugs in
this class
flecainide (Tambocor)
• flecainide (Tambocor) is used in the
treatment of supraventricular tachycardia.
• Dosage:
• PO: 100 mg every 12 hours, increased by
50 mg bid until arrhythmia is resolved
(maximum daily dose of 400 mg).
• It’s most serious adverse effects are CHF
and arrhythmias (V-tach).
• It’s most common adverse effects are
dizziness and blurred vision.
propafenone (Rythmol)
• propafenone (Rythmol) is used in the
treatment of both ventricular tachycardia
and supraventricular tachycardia
• Dosage:
• PO: 150 mg every 8 hours, may be
increased up to 300 mg every 8 – 12
hours.
• It’s most serious adverse effects are the
events that it is indicated for, ventricular
tachycardia and supraventricular
tachycardia
• It’s most common adverse effects include
dizziness, altered taste, nausea, vomiting
and constipation.
2. Class II antiarrhythmic drugs (beta
blockers)
• This class of drugs are the beta blockers
which block the effects of catecholamines
at the β receptors, thereby decreasing
sympathetic activity and resulting in a
decrease in the heart rate.
• They are indicated for the treatment of
atrial fibrillation and atrial flutter.
• These class II drugs include acebutolol,
esmolol, propanolol, and sotalol.
3. Class III antiarrhythmic drugs (K1+
channel blockers)
• By blocking K1+ channels, these drugs
lengthen the action potential (by
lengthening the refractory period/resting
stage).
• This tends to decrease the frequency of
arrhythmias. They are indicated for the
treatment of atrial fibrillation, atrial flutter,
• as well as V-tach, and V-fib.
• amiodarone, dofetilide and ibutilide are
drugs in this class.
amiodarone (Cordarone, Pacerone)
• amiodarone is indicated for the treatment
of life threatening ventricular arrhythmias,
but only when the patient is unresponsive
to less toxic agents (i.e. dofetilide or
ibutilide)
• Dosage:
• PO: 800 – 1600 mg/day in 1 – 2 doses for
1 – 3 weeks, then 600 – 800 mg/day in 1 –
2 doses for 1 month, then 400 mg/day for
maintenance
• IV: 150 mg over 10 minutes, then 360 mg
over 6 hours, then 540 mg over 18 hours.
Maintenance infusion of 0.5 mg/minute
until PO therapy is initiated.
• Amiodarone has a very large number of
adverse effects, affecting almost every
part of the body:
• ARDS
• pulmonary fibrosis
• CHF
• worsening of arrhythmias
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inflammation of the liver
nausea
vomiting
constipation
dizziness
fatigue
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thyroid dysfunction
photosensitivity
involuntary movement
tremors
bradycardia
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hypotension
visual problems
discoloration of the skin
decreased libido
dofetilide (Tikosyn)
• dofetilide (Tikosyn) is indicated for the
conversion of atrial fibrillation and atrial
flutter to normal sinus rhythm
• Dosage:
• PO: Initial dose is 500 μg bid;
maintenance dose is 250 μg bid
• It’s most serious adverse effects are
ventricular arrhythmias. It’s most common
adverse effects are dizziness, headache
and chest pain.
ibutilide (Corvert)
• ibutilide is indicated for the conversion of
atrial fibrillation and atrial flutter to normal
sinus rhythm, especially within 1 week of
bypass surgery.
• Dosage: 1 mg infusion, that may be
repeated every 10 minute
• Dosage after cardiac surgery: 0.5 mg
infusion, may be repeated once.
• It’s most serious adverse effects are
ventricular arrhythmias. It’s most common
adverse effects are headache and nausea.
4. Class IV antiarrhythmic drugs
• These drugs prevent the movement of
calcium into myocardial cells which slows
depolarization and decreases the heart
rate.
• In addition, these drugs decrease the force
of myocardial contractions (they would not
be recommended in patients with CHF).
• ALL CCB’s produce vasodilation, however,
only verapamil and diltiazem have direct
actions on the heart.
• These drugs are effective in treating a
variety of arrhythmias including atrial
flutter, atrial fibrillation and
supraventricular tachycardia
• Verapamil (Calan, Verelan, Isoptin)
• Diltiazem (Cardizem, Dilacor, Tiazac)
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Adverse effects include:
headache
Dizziness
GI disturbances
orthostatic hypotension