ANTIARRHYTHMIC DRUGS

AMIODARONE

Chairperson:
Dr. M. A. Bari
Assistant professor
Department of Cardiology, MMCH

Speaker:
Dr. Nure Alam Siddique
AR, Cardiology Department
MMCH
 Antiarrythmic drugs are used either to
alleviate significant symptoms or to
prolong survival. There are four
established classes of antiarrhythmic
action. The vaughn williams
classification is a crude system, but is
convenient for describing mode of
action of antiarrhythmic drugs.
Antiarrhythmic drugs can also be more
acutely catagorised by referring to the
cardiac ion channels and receptors on
which they act.
 The vaughn williams classification.
Class-l: class l is divided into three
Class Drugs M/A
Class-la Quinidine Block na+channel and
Disopyramide prolong action potential.
procainamide
Class-lb Lidocaine Block na+ channel and
Mexilatine shorten action potential.
Tocainide
Class-lc Flecanide Block na+ channel with no
Propafenone effect on action potential.
 Cont’d
Class-ll Beta B-blocking drugs have
blockers complex action . This
Atenolol includes, inhibition of
spontaneous
Bisoprolol
depolarization(phase-4) and
Metoprolol indirect closure of calcium
i-sotalol channel.
Propanolol
Acebutalol
 Cont’d
Class-lll Amiodaron These agents block the
e outwards potassium
D-sotalol channels and prolong
the action potential.
Ibutilide
dofetilide
Class-lV Verapamil Inward calcium current
deltiazem which is more
prominent in nodal
tissue, particularly in
AV node.
 Other antiarrhythmic drugs are-
1. Atropine
2. Adenosine
3. Digoxin
AMIODARONE
 Amiodarone is the principal drug in the class-lll. It is
a unique wide-spectrum antiarrhythmic agent chiefly
class-lll but also with powerful class-l, ll & lV activity.
This drugs is increasingly used in life threatening
arrhythmias and in low dose for AF. Its established
antiarrhythmic benefit and potential for mortality
reduction need to be balanced against several
problems.
 First, the slow onset of action of oral therapy may
require large oral loading doses.
 Second, the many serious side effect dictate that
there must be fine balance between the maximum
antiarrhythmic effect of the drug and the potential for
the side effects.
 Third, the half life is extremely long.
 Fourth, there are a large number of potentially
serious drug interaction. Some of which
predispose torsades de pointes which is rear
when amiodarone is used alone.
 Electrophysiology
 Amiodarone blocks the outward potassium
channel thus lengthens the effective
refractory period by prolonging the action
potential duration in all cardiac tissue
including the bypass tracts.
 It decreases the phase “O” of the rapid
depolarization of the action potential.
 Amiodarone noncompetitively blocks the a
& b adrenergic receptors .
 It inhibits the inwards calcium channel
which is most prominent in nodal tissue.
 Pharmacokinetics
 It is a highly lipid soluble drug markedly differ from
other cardiovascular agents. Only30-50% slowly
absorbed in gastrointestinal tract and very slowly
eliminated with a very long half life. It takes nine
months before amiodarone is expelled completely from
the body. The onset of action after oral administration
is delayed and steady state drug effect may not be
established for several months unless large loading
dose are used. The electrophysiolic effect of IV
amiodarone differ from oral amiodarone . IV
amiodarone is effective within 1-12hours. It undergoes
extensive hepatic metabolism to the pharmacologically
active metabolite desethylamiodarone. Amiodarone is
almost protein bound and excreted by lacrimal gland,
skin and biliary tract.
 Dose
 Rapid control of an urgent arrhythmia:
The initial loading regimen is upto 1600mg daily
in 2-4 divided doses usually given for 7-14 days,
which is then reduce to 400 to 800mg/day for a
further 1-3wks. By using a loading dose,
sustained VT can be controlled after a mean
interval of five days. Practice varies widely,
however with loading dose of as low as
600mg/day is being used in less urgent settings.
Maintenance dose vary, but for high dose therapy
400mg or more is employed.
 For prevention of recurrent AF:
The loading dose is 600-800mg/day in 2-3
divided doses 2-4wks followed by a maintenance
dose of 200-400mg/day and lowered at 3-
6months to 100-300mg/day.
 Intravenous amiodarone:
Intravenous amiodarone may be used for
intractable arrhythmia. Start with
150mg/10mins, then 360mg over the next 6
hours, then 540mg over the remaining 24hours
to give a total 1000mg over 24 hours.
 For AF after AMI or after cardiac surgery:
5mg/kg over 20mins, 500 to 1000 over 24 hours
then orally.
 In patient with VF, who do not respond to
electrical counter shock:
5mg/kg to a maximum of 300mg/kg is given
rapidly into p[eripheral vein.
 Indications
 Recurrent VF
 Haemodynamically unstable VT after
adequate doses of other ventricular
anti arrhythmic have been tested or
are not tolerated.
 Prophylactic control of life threatening
of ventricular tachyarrhythmia.
 Preventing recurrence of paroxysmal
AF or atrial flutter.
 Contraindications
 Severe sinus node dysfunction with
marked bradycardia or syncope.
 Second or third degree heart block.
 Known hypersensitivity.
 Cardiogenic shock
 Severe chronic lung disease.
 Adverse effects
 Sinus bradycardia
 QT prolongation
 Torsades de pointes
 Optic neuropathy(1-2%)
 blue- gray skin discoloration (4-9%)
 Photosensitivity
 Hypothyroidism(6%)
 Hyperthyroidism(.9-2%)
 Pulmonary fibrosis(10-17%)
 Elevated liver enzymes, cirrhosis, hepatitis
 Peripheral neuropathy
 Headache, ataxia, tremor, bad dreams
 Corneal micro deposits
 Recommended preventive action
 Baseline & every six month thyroid
function test
 Test for the liver enzymes
 Yearly ECG & chest radiograph
 Physical examination of skin, eye &
peripheral nerves
 Drug interaction
 The most serious interaction is an additive
proarrhythmic effect with other drugs prolonging
the QT interval such as phenothiazines, TCA,
thiazide diuretics and sotalol.
 FDA alert against the use of combined
amiodarone with high dose simvastatin, because
of reports of myopathy and rhabdomyolysis.
 amiodarone prolongs the prothombin time and
may cause bleeding in patient on warfarin.
 Amiodarone increases the plasma degoxin
concentration predisposing to digitalis toxic
effect.