ANTIARRHYTHMIC AND CARDIOTONIC

OLEH:
DELINDA MARTI
1800010

College Teacher :
Novia Sinata, M.Si., Apt
 Definition
Cardiac arrhythmias are a common problem in clinical practice, occurring in
up to 25% of patients treated with digitalis, 50% of anesthetized patients, and
over 80% of patients with acute myocardial infarction. Arrhythmias may
require treatment because rhythms that are too rapid, too slow, or
asynchronous can reduce cardiac output. Some arrhythmias can precipitate
more serious or even lethal rhythm disturbances; for example, early premature
ventricular depolarizations can precipitate ventricular fibrillation. In such
patients, antiarrhythmic drugs may be lifesaving. On the other hand, the
hazards of antiarrhythmic drugs and in particular the fact that they can
precipitate lethal arrhythmias in some patients has led to a reevaluation of
their relative risks and benefits. In general, treatment of asymptomatic or
minimally symptomatic arrhythmias should be avoided for this reason.
 CLASSIFICATION OF ANTIARRHYTHMIC

1. Class 1 action is sodium channel blockade

2. Class 2 action is sympatholytic
3. Class 3 action manifests as prolongation of the APD
4. Class 4 calcium channel blocking
5. Miscellaneous antiarrhythmic agents
 Class 1 action is sodium channel blockade

Subclasses of this action reflect effects on the action potential

duration (APD) and the kinetics of sodium channel blockade. Drugs
with class 1A action prolong the APD and dissociate from the channel
with intermediate kinetics; drugs with class 1B action shorten the APD
in some tissues of the heart and dissociate from the channel with rapid
kinetics; and drugs with class 1C action have minimal effects on the
APD and dissociate from the channel with slow kinetics.
SODIUM CHANNEL-BLOCKING DRUGS (CLASS 1)
PROCAINAMIDE (SUBGROUP 1A)
By blocking sodium channels, procainamide slows the upstroke of the action
potential, slows conduction, and prolongs the QRS duration of the ECG.
Indications :
ventricular arrhythmias, especially after myocardial infarction, atrial tachycardia
Contra Indications :
heart block, heart failure, hypotension and breastfeeding.
Side Effects :
Nausea, diarrhea, skin rashes, fever, myocardial depression, heart failure,
syndromes such as SLE (systemic lupus erythematosus syndrome), agranulocytosis
after prolonged use; psychosis and angioedema.
 LIDOCAINE (SUBGROUP 1B)
Lidocaine blocks activated and inactivated sodium channels with rapid
kinetics.
Indications : ventricular arrhythmias, especially after myocardial infarction
Contra Indications : SA node disorders, all degrees of AV block, severe
myocardial depression; porphyria.
Side Effects : dizziness, tingling, or drowsiness (especially if the injection is
too fast); other CNS effects (confusion,
respiratory depression and convulsions); hypotension
and bradycardia (until cardiac arrest); hypersensitivity.
 PROPAFENONE (SUBGROUP 1C)
potent blocker of sodium and potassium channels with slow unblocking kinetics.
Indications : ventricular arithmetic, paroxysmal supraventricular tachyarrhythmias,
including paroxysmal atrial fluter or fibrillation and paroxysmal recurrent
tachycardia that are added to the AV node or added, which do not respond to
standard therapy or are contraindicated
Contra Indikations : heart failure, electrolyte balance disorders, severe pulmonary
obstruction, severe hypotension, myasthenia gravis, atrial conduction disorders
Side effects : nausea and vomiting, fatigue,
mouth feeling bitter,diarrhea, headache
and allergic skin reactions.
 BETA-ADRENOCEPTOR–BLOCKING DRUGS
(CLASS 2)
Propranolol and similar drugs have antiarrhythmic properties by virtue of
their β-receptor–blocking action and direct membrane effects. The relative
contributions of the β-blocking and direct membrane effects to the
antiarrhythmic effects of these drugs are not fully known. Although β blockers
are fairly well tolerated, their efficacy for suppression of ventricular ectopic
depolarizations is lower than that of sodium channel blockers. Esmolol is a
short-acting β blocker used primarily as an antiarrhythmic drug for
intraoperative and other acute arrhythmias. Sotalol is a nonselective β-
blocking drug that prolongs the action potential .
Indications : Treat high blood pressure, irregular heartbeat, tremor and other
conditions.
Side Effects : irregular heartbeat, dizzy head, fainted,swelling of the heel or
foot, nausea, upper abdominal pain, itching, loss of appetite
DRUGS THAT PROLONG EFFECTIVE REFRACTORY
PERIOD BY PROLONGING THE ACTION POTENTIAL
(CLASS 3)

These drugs prolong action potentials, usually by blocking

potassium channels in cardiac muscle or by enhancing inward
current, eg, through sodium channels.
Amiodarone
Amiodarone also significantly blocks inactivated sodium channels. Its
action potentialprolonging action reinforces this effect. Amiodarone also
has weak adrenergic and calcium channel-blocking actions. Consequences
of these actions include slowing of the heart rate and AV node conduction.
Indications : Used to treat certain types of arrhythmias (serious heart
rhythm disorders) that may be fatal (such as ventricular fibrillation /
persistent tachycardia).
Side Effects : Limp, No appetite, Constipation, Hypotension, Headache,
Dizzy, Memory loss
Brand Name : Lamda, Kendaron, Cordarone, Rexodrone, Amiodarone HCL,
Tiaryt, Cortifib, Cordarone.
 CALCIUM CHANNEL-BLOCKING DRUGS (CLASS 4)

These drugs, of which verapamil is the prototype, were first introduced

as antianginal agents. Verapamil and diltiazem also have antiarrhythmic
effect.
Verapamil AV nodal conduction time and effective refractory period are
consistently prolonged by therapeutic concentrations. Verapamil usually
slows the SA node by its direct action, but its hypotensive action may
occasionally result in a small reflex increase of SA rate.
 MISCELLANEOUS ANTIARRHYTHMIC
AGENTS
1. Adenosine
Its mechanism of action involves activation of an inward rectifier K + current
and inhibition of calcium current. The results of these actions are marked
hyperpolarization and suppression of calcium-dependent action potentials.
2. Magnesium
Originally used for patients with digitalis-induced arrhythmias who were
hypomagnesemic, magnesium infusion has been found to have antiarrhythmic
effects in some patients with normal serum magnesium levels. The mechanisms of
these effects are not known, but magnesium is recognized to influence Na + /K +
-ATPase, sodium channels, certain potassium channels, and calcium channels.
Cardiotonic
Definition

Cardiotonic drugs that strengthen the performance of the heart, used in disorders of cardiac decompensation, the type of
drug is individual. Then the replacement of drugs must be on the advice of a doctor. For example: (digitoxin, digoxin, folia
digitalis, lenatoside C)
Classification of drugs

1. Cardiac glycosides (digoxin, methyldigoxin and digitoxin)

2. Dopaminergika (dopamine, ibopamine, and dobutamine)
3. Phosphodiesterase inhibitors (amrinom and milrinone)
General Drug Used

Cardiac Glycosides
Digoxin
Fargoxin
Lanoxin
Dopamine
Dobutamine
Dopamine
Doburan
Phosphodiesterase inhibitors
Amrinone
Milrinone
Mecanism of action

1. Cardiac Glycosides
Cardiac glycosides bind reversibly to the cell membrane of heart cells. Therefore,
there is a barrier to (Na + / K +) -ATPase, which carries Na + ions out of cells and
K + ions into cells => resulting in an increase in intracellular Na = levels.

2. Dopamine
Stimulates adrenergic and dopamienergic receptors, lower doses primarily
stimulate dopaminenergic stimulation and produce renal and mesenteric
vasodilation, higher doses stimulate dopaminergic and beta 1-adrenergic
receptors and cause cardiac stimulation and renal vasodilation, large doses
stimulate alpha-adrenergic receptors.

3. Phosphodiesterase inhibitors
Inhibition of phosphodieterase which breaks down cAMP (phosphodieterase 3) in
heart muscle cells and vascular smooth muscle cells so that in myocardial cells:
increased intrasesular cAMP concentration => increased Ca2 + inlet flow => Ca2
+ intracellular liberation => effect positive inotropes and chronotopes => increase
in stroke volume and minute heart volume.
Side effect

1. Cardiac glycosides: stomach-intestinal disorders,

nausea, vomiting, diarrhea and abdominal pain.
2. Dopamine: Headache, rhythm disorders,
vomiting and tightness, heart palpitations,
tachycardia, stomach-intestinal disorders,
dizziness, hypotension and hypertension.
3. Phosphodieterase inhibitors: Stomach-intestinal
disorders, fever, Hypotension and arrhythmias
Digoxin

Uses
Digoxin is used to treat heart failure, usually along with other
medications. It is also used to treat certain types of irregular
heartbeat (such as chronic atrial fibrillation). Treating heart failure
may help maintain your ability to walk and exercise and may improve
the strength of your heart. Treating an irregular heartbeat can also
improve your ability to exercise.
Digoxin belongs to a class of medications called cardiac
glycosides. It works by affecting certain minerals (sodium and
potassium) inside heart cells. This reduces strain on the heart and
helps it maintain a normal, steady, and strong heartbeat.
Side effect
Nausea, vomiting, headache, dizziness, loss of appetite, and diarrhea may occur.

Contraindications
Hypersensitivity
Ventricular fibrillation
Indication
Dobutamine injection is indicated when parenteral
therapy is necessary for inotropic support in the
short-term treatment of adults with cardiac
decompensation due to depressed contractility
resulting either from organic heart disease or from
cardiac surgical procedures.

In patients who have atrial fibrillation with rapid

ventricular response, a digitalis preparation should be
used prior to institution of therapy with dobutamine
hydrochloride.
Side Effects
Increased Heart Rate, Blood Pressure, And Ventricular Ectopic Activity
A 10- to 20-mm increase in systolic blood pressure and an increase in heart rate of 5 to 15 beats/minute have been noted in most patients. Approximately 5% of patients have had increased premature ventricular beats during infusions. These effects are dose related.

Hypotension
Precipitous decreases in blood pressure have occasionally been described in association with dobutamine therapy. Decreasing the dose or discontinuing the infusion typically results in rapid return of blood pressure to baseline values. In rare cases, however, intervention may be
required and reversibility may not be immediate.
Interactions
Animal studies indicate that dobutamine may be ineffective if the patient
has recently received AY-blocking drug. In such a case, the peripheral
vascular resistance may increase.

Preliminary studies indicate that the concomitant use of dobutamine and

nitroprusside results in a higher cardiac output and, usually, a lower
pulmonary wedge pressure than when either drug is used alone.

There was no evidence of drug interactions in clinical studies in which

dobutamine was administered concurrently with other drugs, including
digitalis preparations, furosemide, spironolactone, lidocaine,
nitroglycerin, isosorbide dinitrate, morphine, atropine, heparin,
protamine, potassium chloride, folic acid, and acetaminophen.
Toxicity
Toxicity from dobutamine hydrochloride is usually due to excessive cardiac
β- receptor stimulation. The duration of action of dobutamine
hydrochloride is generally short (T½= 2 minutes) because it is rapidly
metabolized by catechol-0-methyltransferase. The symptoms of toxicity
may include anorexia, nausea, vomiting, tremor, anxiety, palpitations,
headache, shortness of breath, and anginal and nonspecific chest pain. The
positive inotropic and chronotropic effects of dobutamine on the
myocardium may cause hypertension, tachyarrhythmias, myocardial
ischemia, and ventricular fibrillation. Hypotension may result from
vasodilation.
Amrinone
Indications
Short-term management of severe CHF (not used long
term because of increased mortality, probably due to
heart failure).

Contraindications
Patients with aortic stenosis, hypertrophic cardiomyopathy, or
history of hypersensitivity to the drug.
Side effect
Thrombocytopenia is the most prominent and dose-related side effect, but it is transient and asymptomatic. Nausea, diarrhoea, hepatotoxicity, arrhythmias and fever are other adverse effects

Actions
Increases cardiac contractility, vasodilator. Acts by inhibiting the breakdown of both cAMP and cGMP by the phosphodiesterase (PDE3) enzyme. There is a long-standing controversy regarding
whether the drug actually increases cardiac contractility in diseased myocardium (and therefore whether it is of any clinical use)
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