Transcript Antiarrythmic drugs

Antiarrhythmic
Drugs
Learning outcomes:At the end of the lectures students should be
able to:
1-Classify antiarrhythmic drugs
2-Identify the general characteristics of each
class
3-To elaborate on clinical uses , adverse
effects and drug –drug interactions of
selected drugs
1- What is cardiac arrhythmia?
2-What causes cardiac arrhythmias?
3-Why do we treat cardiac arrhythmias?
4-When to treat?
5-What are the goals of therapy?
CLASSIFICATION
OF
ANTIARRHYTHMIC DRUGS
According to Vaughan-Williams
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Miscellaneous
 Adenosine
 Electrolyte supplement ( magnesium,
potassium)
 Digitalis
 Atropine
CLASS 1
Bind & block the fast sodium
channels that are responsible for
rapid depolarization ( phase 0).
These drugs decrease the slope
of phase 0, thus causing
decrease in the amplitude of
action potential.
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This type of action potential is found in
non-nodal cardiomyocytes ( atria,
ventricles, purkinje tissues which are
depending on sodium to start
depolarization )
CLASS 1
At high concentration they have
local anaesthetic
-Ve inotropic effect
( cardiac depression )
CLASS 1
SUBCLASSIFIED INTO :
Class(1A)
 Slow phase 0 depolarization
Decrease conduction velocity
( sodium channel blocking effect )
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Prolong action potential duration
Prolong Effective refractory period
(ERP)
{ Potassium channel blocking effect
Prolong QT interval in ECG
Other actions of class 1A
Anticholinergic effect :
- Increase conduction through the
A.V. node
May lead to increase ventricular rate in
atrial flutter. Can be prevented by
administration of a drug that slow A.V.
conduction such as : digoxin, β blocker
calcium channel blockers.
 Negative inotropic effect
Clinical uses of Class 1A
Atrial flutter, Atrial fibrillation
Supraventricular , ventricular
tachyarrhythmias
Examples of Class 1A :
{1}
Qunidine
Actions of quinidine
 Cause α-adrenergic blocking effect
cause vasodilatation and reflex sinus
tachycardia
This effect is seen more after I.V. I
Adverse effects of quinidine
 GIT:
anorexia, nausea, vomiting, diarrhea
 CARDIAC:
quinidine syncope:
(fainting attack)
- (due to torsades de pointes developing at
therapeutic plasma levels )
- may terminate spontaneously or lead to
fatal ventricular fibrillation
Torsades de pointes
Adverse effects ( continue)

Anticholinergic adverse effects
 Cinchonism:
( tinnitus , headache & dizziness)
Hypotension
Adverse effects ( continue)
- At toxic concentrations, can
precipitate arrhythmia and produce
asystole ( cardiac arrest ) if serum
concentrations exceed 5 µg/ml
QUINIDINE
Drug interactions:
- Increase serum concentration of digoxin:
- Displacement from plasma proteins
- Inhibition of digoxin renal clearance
GIVEN ORALLY ....rarely given I.V. because of
toxicity .
{2} PROCAINAMIDE
As compared to quinidine
 less toxic on the heart...
can be given I.V. ( common route)
 more effective in ventricular than in
atrial arrhythmias
 less depressant on cardiac contractility
 Weak anticholinergic or α-blocking
actions
PROCAINAMIDE
-Second choice ( after lidocaine ) in
ventricular tachycardia after acute
myocardial infarction
ADVERSE EFFECTS
In long term therapy it cause reversible
lupus erythematosus-like syndrome
Hypotension
Torsades de pointes
Hallucination & psychosis
CLASS 1 B
Shorten action potential duration
and refractory period of
ventricles
lidocaine
mexiletine
LIDOCAINE
USES :
Drug of choice for treatment of ventricular
tachycardia in
emergency ..e.g.
cardiac surgery , acute myocardial infarction
- NOT effective orally (3% bioavailability)
- GIVEN I.V. bolus or slow infusion
ADVERSE EFFECTS :
 hypotension
 neurological such as:
paresthesia, tremor, dysarthria
(slurred speech), convulsions
T1/2
(2hrs)
MEXILETINE
- Given ORALLY
USES :
 Chronic treatment of ventricular arrhythmia
 digitalis-induced arrhythmias
 chronic pain e.g. diabetic neuropathy and
nerve injury
ADVERSE EFFECTS :
 nausea , vomiting
 neurological
 hypotension
t1/2 ( 10 hr)
CLASS 1C
have no or little effect on action
potential duration
flecainide
propafenone
Clinical uses of class 1C
Life –threatening supraventricular ( SVT)
And ventricular tachyarrhythmias
FLECAINIDE
It is a proarrhythmic drug
Can induce life-threatening ventricular
arrhythmias
-
ADVERSE EFFECTS :
CNS : dizziness, tremor, blurred
vision, abnormal taste sensations,
paraesthesia
 arrhythmias
 heart failure due to -ve inotropic effect
PROPAFENONE:
- has weak beta-blocking action
- cause metallic taste and constipation
CLASS 11 DRUGS
β- ADRENOCEPTOR BLOCKERS
PHARMACOLOGICAL ACTIONS :
blocking β1- receptors in the heart → reduce
the sympathetic effect on the heart
causing :
- decrease automaticity of S.A. node and
ectopic pacemakers
- slow conduction of the A.V node
CLINICAL USES :
1- atrial arrhythmias associated with emotion,
exercise and thyrotoxicosis
2- digitalis-induced arrhythmias
3- Prophylactic or treatment of choice for
post myocardial infarction arrhythmias
( Decrease the incidence of sudden death
e.g. Propranolol
Q1
1-What are the therapeutic effects of
nonster . At this stage, would you initia
.
Q2
1-What are the therapeutic effects of
nonster . At this stage, would you initia
.
Class III
Potassium channels blocking drugs
Prolong the action potential duration &
effective refractory period .
(Prolong phase 3 )
CLASS III
AMIODARONE
PHARMACOLOGICAL ACTIONS :
 Main effect is to prolong action potential
duration and refractory period

Additional actions of classes : 1, 2 & 4
 vasodilating effects
( due to α- and β-adrenoceptor blocking
effects and calcium channel blocking
effects )
Clinical uses of amiodarone
Broad spectrum antiarrhythmic
o
serious resistant ventricular arrhythmias
o maintenance of sinus rhythm after D.C.
cardioversion of atrial flutter and
fibrillation
o resistant supraventricular arrhythmias
o Re-entry arrhythmia
ADVERSE EFFECTS
1-bradycardia & heart block, heart failure
2- pulmonary fibrosis
3- hyper- or hypothyroidism
- 4- Skin deposits causes photodermatitis ,
patients should avoid exposure to the sun.
may cause bluish discoloration of the skin
(CONTiNUE)
5- tremor, headache, ataxia, paresthesia
6- constipation
7- corneal microdeposits
8- hepatocellular necrosis
9- peripheral neuropathy
AMIODARONE
Pharmacokinetics:
extremely long t1/2 = 13 - 103 DAYS
Drug Interactions:
reduce renal clearance of several drugs e.g.
quinidine, warfarin, procaiamide,
flecainide
Ibutilide
Given by a rapid I.V. infusion
Used for the acute conversion of atrial
flutter or atrial fibrillation to normal
sinus rhythm.
Causes QT interval prolongation , so it
precipitates torsades de pointes.
Class 1V calcium channel
blockers
Verapamil,
Diltiazem
Site of action is A.V.N & S.A.N .
L-type calcium channels play important
role in pacemaker currents & in phase 0
of A.P.
Clinical uses of calcium channel blockers
Related to their ability to decrease conduction
velocity& prolong repolarization mainly at A.V. N
 atrial arrhythmias
 re-entry supraventricular arrhythmias
NOT effective in ventricular arrhythmias
Miscellaneous Group
ADENOSINE
ADENOSINE
- naturally occurring nucleoside
-half-life= less than 10 sec.
Mechanism: In cardiac tissues
Binds to type 1 (A1) receptors which are
coupled to Gi- proteins , activation of this
pathway causing :
 Opening of potassium channels
(hyperpolarization)
 Decrease cAMP which inhibits L-type
calcium channels ( calcium influx ) causing
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decrease in conduction velocity (
negative dromotropic effect )mainly at
AVN.
In cardiac pacemaker cells ( SAN) ,
inhibits pacemaker current, which  the
slope of phase 4 of pacemaker action
potential (  spontaneous firing rate
{negative chronotropic effect})
ADENOSINE
■ drug of choice for acute management
of:
paroxysmal supraventricular tachycardia
■ given 6 mg I.V. bolus followed by 12 mg if
necessary
Adverse effects
■ flushing & headache
■ shortness of breath and chest burning in
10% of patients ( bronchospasm)
■ Hypotension
Contraindicated in 2 nd , or 3rd degree AV block
BRADYARRHYTHMIAS
ATROPINE
■ can be used in sinus bradycardia after
myocardial infarction and in heart
block
■ in emergency heart block isoprenaline
may be combined with atropine
NONPHARMACOLOGIC THERAPY OF
ARRHYTHMIAS (CONT’D):
Implantable Cardiac Defibrillator (ICD)
can automatically detect and treat fatal
arrhythmias such as ventricular fibrillation
A 69-year-old retired teacher presents with a 1-month
history of palpitations, intermittent shortness of
breath, and fatigue. She has a history of
hypertension. An ECG shows atrial fibrillation with a
ventricular response of 122 bpm and signs of left
ventricular hypertrophy. She is anticoagulated
with warfarin and started on sustainedrelease propranolol l60 mg/d. After 7 days, her
rhythm reverts to normal sinus spontaneously.
However, over the ensuing month, she continues to
have intermittent palpitations and fatigue. Continuous
ECG recording over a 48-hour period documents
paroxysms of atrial fibrillation with heart rates of 88–
114 bpm. An echocardiogram shows a left ventricular
ejection fraction of 38% with no localized wall motion
abnormality
Q
1-What are the therapeutic effects of
nonster . At this stage, would you initia
. At
this stage, would you initiate
treatment with an antiarrhythmic
drug to maintain normal sinus
rhythm, and if so, what drug
would you choose?
Thank you