Transcript ANTIARRHYTHMIC DRUGS - سایت جامع پرستاران

ANTIARRHYTHMIC DRUGS
 Arrhythmia or
dysrhythmia means an
abnormal or irregular
heart beat
 Arrhythmias may
originate in the atria, SA
node or AV node,
whereby they are
known as supraventricular arrhythmias
or in the ventricles
giving rise to the lifethreatening ventricular
arrhythmias
Causes of Arrhythmias
 Arteriosclerosis
 Coronary artery spasm
 Heart block (mostly AV
block)
 Myocardial ischemia
Mechnisms of Arrhythmogenesis
I. Abnormal Impulse
Generation
A. Automatic rhythms:
- Enhanced normal
automaticity
- Abnormal automaticity
B. Triggered rhythms
-Early after-depolarisation
- Delayed afterdepolarisation
II. Abnormal Impulse
Conduction
A. Conduction block
First-, second-, third–degree
block
B. Re-entry
- Circus movement
- Reflection
ANTIARRHYTHMIC DRUGS
 Most antiarrhythmic
drugs are proarrhythmic
 Only ß-blockers are
proved to reduce
mortality in postmyocardial infarction
patients
 They are classified
according to Vaughan
William into four
classes according to
their effects on the
cardiac action
potential
 1. Class I ANTIARRHYTHMIC
DRUGS:
 Drugs in this class are blockers of
voltage-operated Na+ channels in
the myocardial membrane
 They show (class IA & IB)
preferential selectivity to Na+
channels in the open or inactivated
closed states
 Hence, they have better degree of
blockade in tissues that are
frequently depolarized or usedependent or state-dependent
 They decrease conduction velocity in
non-nodal tissue (atrial and
ventricular muscle, purkinje
conducting system)
Class IA Drugs
 Quinidine is the prototype of
this class
 Class IA agents slow the
phase 0/reduction of Vmax of
the cardiac action potential
 They prolong muscle action
potential and increase
ventricular effective refractory
period
 They decrease the slope of
Phase 4 spontaneous
depolarization, tending to
suppress enhanced normal
automaticity-induced
arrhythmias
Class IA Drugs
 They possess intermediate rate of association
and dissociation with sodium channels
 Agents of Class IA:
 Quinidine
 Procainamide
 Disopyramide
 Uses:
 Class IA drugs are used in treatment of both
atrial and ventricular arrhytmias
Class IA Drugs Toxicity
Quinidine
 A-V block at higher plasma levels
 At toxic levels, ventricular
tachycardia and torsade de pointes
ventricular arrhythmia
 Increasing digoxin plasma
concentration by displacing digoxin
from binding sites in addition to
decreased digoxin renal clearance
 Cinchonism occurs at large dose
levels (blurred vision, tinnitus,
headache, psychosis and
gastrointestinal upset)
 Digoxin is administered before
quinidine to prevent the conversion
of atrial fibrillation or flutter into
paradoxical ventricular tachycardia.
Quinidine shortens of A-V nodal
refractoriness by atropine-like
effects
Procainamide
 1. At high levels, asystole or induction of
ventricular arrhythmias
 2. Hypersensitivity reactions including drug
fever and rarely agranulocytosis.
 3. Systemic lupus erythromatosus (SLE)like (arthralgia, fever & pleural-pericardial
inflammation)
 The SLE is dose- and time-dependent, and
usually disappears upon drug stop
 It is most common in patients with slow
hepatic acetylation resulting in higher
plasma level of the parent drug
Disopyramide
 1. Anticholinergic side-effects
 2. Induction of ventricular arrhythmias in
patients with prolonged QT interval
 3. Similar to quinidine, disopyramide may
induce ventricular arrhythmia if used alone in
the treatment of fibrillation
Class IB Drugs
 They shorten Phase 3
repolarisation and
decreases the duration of
the cardiac action potential
 They suppress arrhythmias
caused by abnormal
automaticity (c.f. quinidine
suppresses enhanced
normal automaticity-induced
arrhythmias)
 They show rapid
association &
dissociation with Na+
channels with appreciable
degree of use-dependence
Agents of Class IB
Lidocaine
 It should be used by
intravenous route because
of its extensive first-pass
metabolism
 Lidocaine is the drug of
choice in emergency
treatment of ventricular
arrhythmias
Mexiletine and tocainide
 These are the oral analogs of
lidocaine
 Mexiletine is used for
chronic treatment of
ventricular arrhythmias
associated with previous
myocardial infarction
 Tocainide is used for
ventricular tachyarrhythmias
but its use is limited by its
pulmonary toxicity that may
lead to pulmonary fibrosis
Uses
They are used in the treatment of ventricular arrhythmias arising during
myocardial ischemia or due to digoxin toxicity
They have little effect on atrial or AV junction arrhythmias
Class IC Drugs
 They markedly slow Phase 0 fast
depolarization
 They possess slow rate of
association and dissociation with
sodium channels
 They markedly slow conduction in
the myocardial tissue
 They only have minor effects on
duration of action potential and
refractoriness
 They reduce automaticity by
increasing the threshold potential
rather than decreasing the slope of
Phase 4 spontaneous
depolarization
Class IC Drugs
 Agents of Class IC: Flecainide & propafenone
 Uses:
 They are broad-spectrum but only approved for refractory
ventricular arrhythmias
 Flecainide is a particularly potent suppressant of premature
ventricular contractions
 Toxicity and Cautions for Class IC Drugs:
 They are severe proarrhythmic drugs causing severe
worsening of a preexisting arrhythmia or de novo
occurrence of life-threatening ventricular tachycardia
 In patients with frequent PVCs following MI, flecainide
increased mortality compared to placebo
Notice: Class 1C drugs are particularly of low safety
and have shown even to increase mortality when used
chronically after MI
Class II ANTIARRHYTHMIC DRUGS
(β-adrenergic blockers)
β-Adrenergic blockers
produce both negative
inotropic &
chronotropic effects
 They diminish phase 4
spontaneous
depolarization
suppressing
automaticity and
prolonging AV
conduction
Uses
 They are used in treatment
of increased sympathetic
activity-induced arrhythmias
such as stress- and exerciseinduced arrhythmias
 Treatment of atrial flutter and
fibrillation
 AV nodal tachycardia
Class II ANTIARRHYTHMIC DRUGS
 Propranolol: was proved to reduce the incidence
of sudden arrhythmatic death after myocardial
infarction
 Metoprolol & Pindolol
 Metoprolol and other selective β1-adrenergic
blockers reduce the risk of bronchospasm
 Pidolol, having additional partial agonistic activity,
may decrease the frequency of cardiac failure
 Esmolol:
 Esmolol is a very short-acting β1-adrenergic
blocker that is used in the by intravenous route in
acute arrhythmias occurring during surgery or
emergencies
Class III ANTIARRHYTHMIC DRUGS
Class III antiarrhythmic drugs prolong
phase 3 depolarization, without altering
phase 0 upstroke or the resting membrane
potential
They prolong both the duration of the action
potential and the effective refractory period
(ERP)
Their mechanism of action is still not clear
but it is thought that they block potassium
channels
Class III ANTIARRHYTHMIC DRUGS
Drugs of Class III:
Sotalol, bretylium, amiodarone, ibulitide
Uses:
They are used in the treatment of
ventricular arrhythmias, especially
ventricular fibrillation or tachycardia
Supra-ventricular tachycardia
Amiodarone usage is limited by its wide
range of side effects
Class III ANTIARRHYTHMIC DRUGS
Sotalol (Sotacor)
 Sotalol is a β-adrenergic blocker that also prolongs the
duration of action potential and refractoriness in all cardiac
tissues
 Sotalol suppresses Phase 4 spontaneous depolarization and
possibly producing severe sinus bradycardia
 The β-adrenergic blockade combined with prolonged action
potential duration may of special efficacy in prevention of
sustained ventricular tachycardia
 It may induce the polymorphic torsade de pointes ventricular
tachycardia
Bretylium
 It is generally administered parenteraly because of poor GIT
absorption
 Long-term oral use is associated with painful parotid
enlargement as well as severe postural hypotension
Class III ANTIARRHYTHMIC DRUGS
Amiodarone (Cordarone)
 Amiodarone is a drug of multiple actions and not well understood
 It is extensively taken up by tissues, especially fatty tissues, and has a halflife of up to 60 days
 Amiodarone antiarrhythmic effect is complex comprising class I, II, III,
and IV actions
• Prolongation of action potential duration and refractoriness is the main
• It slows cardiac conduction, works as Ca2+ channel blocker, and as a weak
β-adrenergic blocker
 Amiodarone Toxicity
 Amiodarone has wide-spectrum toxicity
 Most common include GI intolerance, tremors, ataxia, dizziness, hyper-or
hypothyrodism
 Corneal microdeposits may be accompanied with disturbed night vision
 Other common side effects include liver toxicity, photosensitivity, gray facial
discoloration, neuropathy, muscle weakness, and weight loss
 The most dangerous side effect is pulmonary fibrosis which occurs in 25% 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
They slow conduction in Ca2+ currentdependent tissues like AV node
Verapamil and diltiazem, but not nifedipine
(or the other dihydropyridine Ca2+
antagonists), are representative of this
class being more effective on the heart than
blood vessels
Class IV ANTIARRHYTHMIC DRUGS
 Verapamil and diltiazem bind only to open
depolarized voltage-operated Ca2+ channels,
and hence preventing re-polarization until the
drug dissociates from the channels.
 Therefore, they are use-dependent blocking
rapidly beating heart since in a normally-paced
heart, Ca2+ channels have enough time to
repolarize and the drug to dissociate from the
channel before the next conduction cycle
 Verapamil and diltiazem slow conduction and
prolong effective refractory period in Ca2+
current-dependent tissues like AV node
Class IV ANTIARRHYTHMIC DRUGS
Verapamil & diltiazem are more effective in
treatment of atrial than ventricular arrhythmias.
They are used in treatment of supra-ventricular
tachycardia preventing the occurrence of
ventricular arrhythmias
They are used in treatment of atrial flutter and
fibrillation
Both drugs are contraindicated patients with preexisting depressed heart function because of their
negative inotropic activity
Both drugs may cause bradycardia, and asystole
especially when given in combination with βadrenergic blockers
Miscellaneous Antiarrhythmic Drugs
Adenosine
 Adenosine activates A1-purinergic receptors
decreasing the SA nodal firing and automaticity,
reducing conduction velocity, prolonging
effective refractory period, and depressing AV
nodal conductivity
 It is the drug of choice in treatment of supraventricular tachycardia
 It is used only by intravenous route
 It has only low-profile toxicity being ultra-short
acting of 15 seconds duration
 Sodium-channel
blockade:
IC > IA > IB
 Increasing the ERP:
IA>IC>IB (lowered)