Antiarrhythmic agents are a group of drugs used to treat abnormal heart rhythms. There are 5 main classes of antiarrhythmic agents:
Class I agents block sodium channels. Class II agents are beta blockers. Class III agents affect potassium channels. Class IV agents affect calcium channels and the AV node. Class V agents have unknown mechanisms.
Common antiarrhythmic drugs include quinidine, procainamide, disopyramide (Class IA), lidocaine (Class IB), beta blockers (Class II), sotalol and amiodarone (Class III). These drugs work by blocking ion channels or receptors to normalize electrical signaling in the heart and restore normal rhythm. Side effects vary
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Antiarrhythmic drugs. I.Ponnilavarasan, Professor,KMCH College of Pharmacy
1. Antiarrhythmic agents
Antiarrhythmic agents are a group of drugs that are used to suppress abnormal
rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter,
ventricular tachycardia, and ventricular fibrillation.
There are five main classes
• Class I agents interfere with the sodium (Na+
) channel.
• Class II agents are anti-sympathetic nervous system agents. Most agents in this
class are beta blockers.
• Class III agents affect potassium (K+
) efflux.
• Class IV agents affect calcium channels and the AV node.
• Class V agents work by other or unknown mechanism
Or
Class I: Fast sodium (Na) channel blockers
• I a -Quinidine, procainamide, disopyramide (depress phase 0, prolonging
repolarization)
• I b -Lidocaine, phenytoin, mexiletine (depress phase 0 selectively in
abnormal/ischemic tissue, shorten repolarization)
• I c -Flecainide, propafenone, moricizine (markedly depress phase 0, minimal
effect on repolarization)
Class II: Beta blockers (partial list)
• Propranolol (decreases slope of phase 4)
• Esmolol (decreases slope of phase 4)
• Timolol (decreases slope of phase 4)
• Metoprolol (decreases slope of phase 4)
2. • Atenolol (decreases slope of phase 4)
Class III: Potassium (K) channel blockers
• Amiodarone (prolongs phase 3; also acts on phases 1, 2, and 4)
• Sotalol (prolongs phase 3, decreases slope of phase 4)
• Ibutilide (prolongs phase 3)
• Dofetilide (prolongs phase 3)
Class IV: Slow calcium (Ca) channel blockers
• Verapamil (prolongs phase 2)
• Diltiazem (prolongs phase 2)
Class V: Variable mechanism
• Adenosine
• Digoxin
• Magnesium sulfate
Normally, the heart beats at a steady, even pace. The pace is controlled by electrical sig
nalsthat begin in one part of the heart and quickly spread through the whole heart. If so
mething goeswrong with this control system, the result may be an irregular heartbeat, or
an arrhythmia.Antiarrhythmic drugs correct irregular heartbeats, restoring the normal rhy
thm. If the heart isbeating too fast, these drugs will slow it down. By correcting these pro
blems, antiarrhythmicdrugs help the heart work more efficiently.
3. QUINIDINE
An optical isomer of quinine, extracted from the bark of the CHINCHONA tree and similar plant
species. This alkaloid dampens the excitability of cardiac and skeletal muscles by blocking
sodium and potassium currents across cellular membranes. It prolongs cellular ACTION
POTENTIALS, and decreases automaticity.
Quinidine also blocks muscarinic and alpha-adrenergic neurotransmission.
Drug mechanism
Quinidine is an antiarrhythmic medication that is used to correct disturbances in the rhythm of
the heart (antiarrhythmic). Other antiarrhythmic drugs within the same class include
procainamide (for example, Pronestyl) and disopyramide (for example,Norpace). This class of
antiarrhythmics is specifically called "Class I" antiarrhythmics, and they differ from other
antiarrhythmic drugs because they work by interfering with the sodium channel in the
membranes of cells. The sodium channel is part of the membrane (wall) surrounding every cell
that allows sodium to pass through into the cell, making the cells (for example, muscle and
nerve cells) excitable and, in the case of muscle cells, able to contract. Thus, the flow of sodium
through these channels is necessary for the muscle cells of the heart to be stimulated to
contract, and Class I antiarrhythmics decrease the electrical stimulation of the muscle cells.
There are three actions that are responsible for quinidine's ability to stop arrhythmias and
prevent their recurrence. Quinidine decreases the speed of the electrical current that travels
through the heart muscle that causes the heart muscle cells to contract. It also prolongs the
period during which heart muscle cells can become electrically stimulated to contract and
prolongs the recovery period after contraction during which the heart muscle cells cannot be
stimulated to contract.
4. Uses
A combination of dextromethorphan and quinidine has been shown to alleviate symptoms of
easy laughing and crying (pseudobulbar affect) in patients with amyotrophic lateral
sclerosis and multiple sclerosis. This drug is marketed as Nuedexta in the United States.
Intravenous quinidine is also indicated for treatment of Plasmodium falciparum malaria
However, quinidine is not considered the first-line therapy for P. falciparum. The recommended
treatments for P. falciparum malaria, according to the Toronto Notes 2008, are a combination of
either quinine and doxycycline or atovaquone and proguanil (Malarone).
Quinidine sulfate is used in the treatment of atrial fibrillation in horses.
Usual Adult Dose for Arrhythmias
Tablet (sulfate):100 to 600 mg/dose orally every 4 to 6 hours; begin at 200 mg/dose and titrate
to desired effect (maximum daily dose: 3 to 4 g).
Extended Release: 324 to 648 mg (gluconate) orally every 8 to 12 hours or 300 to 600 mg
(sulfate) orally every 8 to 12 hours.
IV: 800 mg of quinidine gluconate diluted to 50 mL and given at a rate not to exceed 1 mL/min.
Usual Adult Dose for Malaria
Test Dose: 200 mg quinidine sulfate tablet or quinidine gluconate IM injection to determine
possibility of idiosyncratic reaction.
Side effects
The adverse reactions most frequently reported have consistently been gastrointestinal,
including diarrhea, nausea, vomiting, and heart–burn/esophagitis. Vomiting and diarrhea can
occur as isolated reactions to therapeutic levels of Quinidine, but they may also be the first
signs of cinchonism, a syndrome that may also include tinnitus, reversible high–frequency
hearing loss, deafness, vertigo, blurred vision, diplopia, photophobia, headache, confusion, and
delirium. Cinchonism is most often a sign of chronic Quinidine toxicity, but it may appear in
sensitive patients after a single moderate dose
.
5. PROCAINAMIDE
PRONESTYL (procainamide hydrochloride)
Trade names: Pronestyl®, Pronestyl-SR®, Procan®, Procanbid®, Procapan®
Group 1A cardiac antiarrhythmic drug, is p-amino-N-{2-(diethyl amino) ethyl}-benzamide
monohydrochloride (OR) 4-amino-N-(2-diethylaminoethyl) benzamide.
Mechanism of action: Procainamide is a Class IA antiarrhythmic agent, which means it is a
quinidine-like sodium channel blocker, slowing the conduction of sodium ions through
transmembrane fast sodium channels. During an action potential, voltage-gated sodium
channels open, allowing sodium ions to diffuse across the membrane down their
electrochemical gradient, further depolarizing the membrane of the cell. Blocking these
channels slows conductivity and thereby prolongs the action potential and the refractory period.
This results in an increase in the refractory period and a decrease in excitability and impulse
conduction velocity of the atria and ventricles, relieving symptoms of arrhythmia and
tachycardia. Procainamide also has weak vagolytic activity, which can result in an increased
heart rate and other side effects.
Uses
This medication is used to treat a certain serious, life-threatening irregular heartbeat (ventricular
tachycardia). It is used to restore normal heart rhythm and to keep a regular, steady heartbeat.
Administration: Procainamide can be administered orally as tablets or by intravenous or
intramuscular injection.
• Procaine can be administered intravenously at a controlled rate with an infusion pump to
avoid hypotension. A diluted solution (1 g procainamide, diluted to 50 mL with 5%
dextrose solution) is administered at 1 mL/min for 25 to 30 min, with the patient’s heart
rate and blood pressure being consistently monitored, until the arrhythmia is
suppressed. The total dose given should not exceed 1 g. A maintenance dose of 4-6
mg/min should then be given.
6. • Intramuscular administration can be used in patients with nausea and vomiting, or
patients who are receiving nothing by mouth. The daily dose is about 50 mg/kg, divided
into one-quarter to one-eighth fractions and injected every 3 to 6 hours.
• Oral procainamide can be used for long-term maintenance therapy after initial
intravenous or intramuscular therapy. Dosage can depend on factors including age,
weight and renal function, and can range from 250 mg every 3 hours to 1.25 g every 6
hours.
SIDE EFFECTS
Fever and chills
Joint pain or swelling
Pains with breathing
Skin rash or itching
Diarrhea
Hardening or thickening of the skin where the needle is placed
Loss of appetite
DISOPYRAMIDE PHOSPHATE
(RS)-4-(Diisopropylamino)-2-phenyl-2-(pyridin-2-yl) butanamide
Norpace®
(disopyramide phosphate) Capsules
7. Norpace®CR
(disopyramide phosphate) Extended-Release Capsules
Rythmodan
(disopyramide capsules, BP, 100 mg and 150 mg)
MECHANISM OF ACTION
Disopyramide is Class 1a antiarrhythmic agent; it targets sodium channels to inhibit conduction.
Disopyramide depresses the increase in sodium permeability of the cardiac Myocyte during
Phase 0 of the cardiac action potential, in turn decreasing the inward sodium current. This
results in an increased threshold for excitation and a decreased upstroke velocity. Disopyramide
prolongs the PR interval by lengthening both the QRS and P wave duration. This effect is
particularly well suited in the treatment of ventricular tachycardia as it slows the action potential
propagation through the atria to the ventricles. Disopyramide does not act as a blocking agent
for beta or alpha adrenergic receptors, but does have a significant negative inotropic effect on
the ventricular myocardium. As a result, the use of disopyramide may reduce contractile force
up to 42% at low doses and up to 100% in higher doses leading to heart failure.
USUAL ADULT DOSE FOR ARRHYTHMIAS
400-800 mg/day. The recommended dose for most adults is 600 mg/day. Patients < 50
kg may be given 400 mg/day.
Immediate-release form: The dose is divided and administered every 6 hours.
Extended-release form: The dose is divided and administered every 12 hours.
USES
This medication is used to treat certain types of serious (possibly fatal) irregular heartbeat, such
as persistent ventricular tachycardia. It is used to restore normal heart rhythm and maintain a
regular, steady heartbeat.
It works by blocking certain electrical signals in the heart that can cause an irregular heartbeat.
Treating an irregular heartbeat can decrease the risk for blood clots, and this effect can reduce
your risk of heart attack or stroke.
SIDE EFFECTS
• Dizziness, feeling of faintness
• fainting
• heartbeat sensations
• shortness of breath
8. • unusual tiredness
LIDOCAINE
Lidocaine is chemically designated as acetamide, 2-(diethyl amino)-N-(2, 6-dimethylphenyl)
Brand Name: Xylocaine- MPF, Anestacaine , Dilocaine , Nervocaine
Lidocaine, also known as xylocaine and lignocaine
MECHANISM OF ACTION
Antiarrhythmic—Lidocaine decreases the depolarization, automaticity, and excitability in the
ventricles during the diastolic phase by a direct action on the tissues, especially the Purkinje
network, without involvement of the autonomic system. Neither contractility, systolic arterial
blood pressure, atrioventricular (AV) conduction velocity, nor absolute refractory period is
altered by usual therapeutic doses. In the Vaughan Williams classification of antiarrhythmics,
lidocaine is a class IB agent.
USES
Lidocaine is a local anesthetic .Lidocaine topical (for use on the skin) is used to reduce pain or
discomfort caused by skin irritations such as sunburn, insect bites, poison ivy, poison oak,
poison sumac, and minor cuts, scratches, or burns. Lidocaine topical is also used to treat rectal
discomfort caused by hemorrhoids.
Lidocaine is used as alternative medicine to other antiarrhythmic drugs (e.g., amiodarone,
procainamide, sotalol) for the acute treatment of hemodynamically compromising ventricular
ectopy (e.g., VPCs) that occurs following myocardial ischemia or infarction or during cardiac
manipulative procedures such as cardiac surgery or cardiac catheterization.
It is the drug of choice in the acute management of ventricular arrhythmias, such as those
resulting from acute myocardial infarction, digitalis toxicity, cardiac surgery, or cardiac
catheterization.
9. Ventricular arrhythmias from MI, cardiac manipulation, or cardiac glycosides
Adults: 50 to 100 mg I.V. bolus given at 25 to 50 mg/ minute. If no clinical response, repeat
bolus after 5 minutes. Don’t exceed 300-mg total bolus during a 1-hour period. Simultaneously,
begin continuous infusion of 1 to 4 mg/ minute. If single bolus has been given, repeat smaller
bolus (usually one-half initial bolus) 5 to 10 minutes after start of infusion to maintain therapeutic
serum level. After 24 hours of continuous infusion, decrease rate by one half.
Elderly patients: Give a reduced bolus amount and use slower infusion rate.
Dosage adjustment. A reduction in amount of bolus dosage may be needed in patients with
heart failure or hepatic disease. Use slower infusion rate. For I.M. administration in all adults,
300 mg (4.3 mg/kg) in deltoid muscle has been used in early stages of acute MI. If needed, may
be repeated in 60 to 90 minutes.
Children: 0.5 to 1 mg/kg by I.V. bolus; may repeat bolus if needed, not to exceed 3 to 5 mg/kg,
followed by infusion of 10 to 50 mcg/kg/minute. In advanced cardiac life support, 1 mg/kg I.V.
bolus, followed by an infusion of 20 to 50 mcg/kg/minute if needed after defibrillation or
cardioversion.
DOSAGE FORMS
• Injected local anesthetic (sometimes combined with epinephrine to reduce bleeding)
• Dermal patch (sometimes combined with prilocaine)
• Intravenous injection
• Intravenous infusion
• Intraosseous infusion
• Nasal instillation/spray (combined with phenylephrine)
• Oral gel (often referred to as "viscous lidocaine" or abbreviated "lidocaine visc" or
"lidocaine HCl visc" in pharmacology; used as teething gel)
• Oral liquid
• Oral and topical ointments, with and without flavoring, respectively
• Topical gel (as with aloe vera gels that include lidocaine)
• Topical liquid
10. • Lidocaine HCl 2% jelly, combined with hypromellose, to anesthetize and lubricate the
urethra, etc., for inserting a catheter or instrument
• Topical patch (lidocaine 5%)
• Topical ointment (lidocaine 5%) as a temporary reliever of discomfort associated with
anorectal disorders, such as hemorrhoids,
• Topical aerosol spray
• Inhaled by nebulizer
• Ophthalmic solution