Pharmaceutical Drug Article

Antiarrhythmic Drug

• Antiarrhythmic agents are used to treat abnormal electrical activity of the heart.

• There are seven classes: I, IA, IB, IC, II, III, and IV.

• In general, antiarrhythmic agents are used to treat,

suppress, or prevent three major mechanisms of arrhythmias:

Increased automaticity
Decreased conductivity
Reentry.

• When used in combination, antiarrhythmic agents may have a more powerful effect.

ADENOSINE

Adenosine (Adenocard) is a naturally occurring nucleoside indicated to convert paroxysmal supraventricular tachyarrhythmia (PSVT) to sinus rhythm. It can be used in the treatment of PSVT associated with accessory bypass tracts (Wolff-Parkinson-White [WPW] syndrome).

Action

• Adenosine acts on the AV node to slow conduction and inhibit

reentry pathways.

Dosage

• Give 6 mg I.V. by rapid bolus injection (over 1 to 3 seconds),

followed by NSS bolus of 20 ml

• Give 12 mg I .V. if arrhythmia isn’t eliminate d in 1 t o 2 minutes

• Give a third dose of 12 mg I.V. if necessary

Special considerations

Transient arrhythmias may occur after rapid I.V. push. The patient may report feeling:

flushed
lightheaded
nauseous

Adenosine can interact with other medications.
Use cautiously with carbamazepine because higher degrees of heart block may occur with concurrent use.
Dipyridamole may potentiate effects of drug; smaller doses may be needed.
Methylxanthines antagonize effects of adenosine.
Patients receiving theophylline may need higher doses or may not respond to adenosine therapy. Likewise, caffeine may antagonize effects of adenosine and higher doses may be needed, or the patient may not have any response at all.
Drug is contraindicated with second- or third-degree heart block unless an artificial pacemaker is present.
Adverse reactions include hypotension. Because half-life of adenosine is less than10 seconds, adverse effects of overdose usually dissipate rapidly and are self-limiting.

AMIODARONE HYDROCHLORIDE

Amiodarone hydrochloride (Cordarone) is a ventricular and supraventricular antiarrhythmic used in :

Recurrent VF,
Unstable VT,
Supraventricular arrhythmias,
Rapid atrial fibrillation (A-fib),
Angina
Hypertrophic cardiomyopathy.

It’s recommended as the first -line drug for shock refractory VF or pulseless VT.

Action:

Amiodarone has mixed class IC and III antiarrhythmic considered aclass III drug.
It increases the action potential duration (repolarization With prolonged therapy, amiodarone slows AV node and prolongs the refractory period.
Its vasodilating effect decreases cardiac workload oxygen consumption.
It affects sodium, potassium, and calcium channels and beta-adrenergic blocking properties.

Dosage

For cardiac arrest: Give 300 mg I.V. push; repeat with 150 mg I.V. push in 3 to 5 minutes.
Maximum cumulative dose: 2.2 g I.V./24 hours.
For wide complex tachycardia (stable): Give rapid infusion of 150 mg I.V. over first 10 minutes (15 mg/minute) and repeat every 10 minutes as needed; follow with a slow infusion of 360 mg I.V. over 6 hours (1 mg/minute)
Maintenance infusion: 540 mg I.V. over 18 hours (0.5 mg/minute)

Special considerations

Watch for hypersens itivity to drug. Don’t us e in patients with severe sinoatrial (SA) node disease resulting in preexisting bradycardia.
Unless an artificial pacemaker is present, drug is also contraindicated with second-or third-degree AV block and in those with syncope caused by bradycardia.
Concomitant use with beta-adrenergic blockers or calcium channel blockers may cause sinus bradycardia, sinus arrest, and AV block. Use together cautiously.
Adverse reactions to drug are more prevalent with high doses, but usually resolve within about 4 months after drug therapy stops.
Amiodarone I.V. infusions exceeding 2 hours must be administered in glass or polyolefin bottles containing D5W.
Amiodarone can’t be removed by dialysis.
Bradycardia, hypotension, arrhythmias, heart failure, heart block, or sinus arrest can occur with drug’s use.
Drug half-life is up to 40 days.

ATROPINE SULFATE

Atropine sulfate is an antiarrhythmic indicated for symptomatic bradycardia and Bradyarrhythmia (junctional or escape rhythm). It’s also indicated after epinephrine for asystole or bradycardic PEA.

Action

Atropine is an anticholinergic (parasympatholytic) that blocks the effects of acetylcholine on the SA and AV nodes, thereby increasing SA and AV node conduction velocity.
It also increases sinus node discharge rate and decreases the effective refractory period of the AV node. The result is an increased heart rate.

Dosage

If asystole or PEA is present: 1 mg by I.V. push; repeat every 3 to 5 minutes to maximum of 0.03 to 0.04 mg/kg
To treat bradycardia: 0.5 to 1 mg I.V. every 3 to 5 minutes as needed, not to exceed total dose of 0.04 mg/kg; shorter dosing interval of 3 minutes and a higher dose (0.04 mg/kg) may be used in severe clinical condition
ET administration: Dilute in 10-ml NSS.
Effects on heart rate peak within 2 to 4 minutes after I.V. administration.

Special considerations:

With I.V. administration, drug may cause paradoxical initial bradycardia, which usually disappears within 2 minutes.
Use drug with caution in myocardial ischemia and hypoxia, because myocardial oxygen demand is increased with atropine.
Avoid atropine’s use in hypothermic bradycardia.
Drug is ineffective for infranodal (type II) AV block and new third-degree block with wide QRS complex; paradoxical slowing may occur.
Other anticholinergics and drugs with anticholinergic effects produce additive effects; avoid concurrent use.
Signs of atropine overdose reflect excessive cardiovascular and CNS stimulation ; treat with physostigmine administration.
Tachycardia may occur after higher doses of drug.

DISOPYRAMIDE AND DISOPYRAMIDE PHOSPHATE

Disopyramide (Rythmodan) and disopyramide phosphate (Norpace) are class IA antiarrhythmics indicated for treatment of VT and other ventricular arrhythmias believed to be life-threatening. This medicine isn’t approved for I.V. use in the United State s.

Action

Disopyramide depolarizes phase 0 and prolongs action potential.
It has membrane stabilizing effects and also prolongs effective refractory period similar to procainamide.

Dosage

Give 2 mg/kg I.V. over 10 minutes, followed with a continuous infusion of 0.4 mg/kg/hour.

Special considerations

Infuse slowly, because these drugs have potent anticholinergic, negative inotropic, and hypotensive effects.
They may cause

Heart failure
Hypotension
Heart block
Arrhythmias.

Discontinue use if heart block develops, QRS widens by greater than 25%, or if QT interval lengthens by greater than 25% above baseline.
NSS or D5W can be used as compatible solutions to dilute disopyramide.

DOFETILIDE

Dofetilide (Tikosyn) is an antiarrhythmic indicated to treat A-fib.

Action

Dofetilide blocks potassium channels, thereby prolonging the cardiac action potential. •

Dosage

Give I.V. single infusion of 8 mcg/kg over 30 minutes.
I.V. administration not approved for use in the United States

Special considerations

Adverse reactions to drug include QT prolongation, which may be associated with torsades de pointes.
Patients with a history of heart failure may be more likely to have adverse reactions to drug.
Drug has limited use due to its required slow infusion.

FLECAINIDE ACETATE

Flecainide (Tambocor) is a class IC antiarrhythmic indicated to treat ventricular arrhythmias and supraventricular arrhythmias in patients without coronary artery disease.
It’s also used to terminate A -fib, atrial flutter (A-flutter), ectopic atrial tachycardia, AV nodal reentrant tachycardia, and supraventricular tachycardia (SVT) associated with an accessory pathway.

Action

Flecainide decreases excitability, conduction velocity, and automaticity due to slowed atrial, AV node, His-Purkinje system, and intraventricular conduction.
It causes a slight but significant prolongation of refractory periods in these tissues.

Dosage

Must be infused slowly.
Infuse 2 mg/kg body weight at 10 mg/minute I.V.; mix only with D5W
I.V. administration not approved for use in United States

Special considerations

Avoid use of drug in patients with impaired left ventricular function because of significant negative inotropic effects.
Adverse reactions to drug include bradycardia, worsened arrhythmias, heart failure, cardiac arrest, hypotension, and neurologic symptoms (oral paresthesia and visual blurring).
Drug may increase plasma digoxin levels by 15% to 25%.
Flecainide’s negative inotropic properties may be additive with disopyramide and verapamil. Propranolol and other beta-adrenergic blockers may cause increased toxicity to drug.
Drug can alter endocardial-pacing thresholds in patients with pacemakers.
Hypokalemia and hyperkalem ia may alter the drug’s eff ect.

IBUTILIDE FUMARATE

Ibutilide (Corvert) is used for supraventricular arrhythmias, most effectively for the conversion of new onset A-fib or A-flutter.

Action

Ibutilide prolongs action potential in isolated cardiac myocytes and increases atrial and ventricular refractoriness, namely class III electrophysiologic effects.

Dosage

Adults weighing 132 lb (60 kg) or more: Give 1 mg I.V. over 10 minutes, diluted or undiluted; a second dose may be repeated after 10 minutes.
Adults weighing less than 60 kg: Give 0.01 mg/kg I.V. over 10 minutes.

Special considerations

Drug may cause AV block, bradycardia, bundle-branch block (BBB), hypotension, nonsustained monomorphic and polymorphic VT, palpitations, prolonged QT segment, sustained polymorphic VT, tachycardia, and ventricular extrasystoles.
Monitor ECG continuously for 4 to 6 hours after administration.
Class IA and class III antiarrhythmics can cause prolonged refractoriness when used with ibutilide; don’t use within 4 hours after infusion.
In addition, drugs that prolong the QT interval, phenothiazine, TCAs and tetracyclic antidepressants, andcertain antihistamines, such as H1-receptor antagonists, may cause arrhythmiaswhen used with drug.
Polymorphic VT, including torsades de pointes, develops in 2% to 5% of patientswith ibutilide.
Patients with A-fib that lasts more than 2 to 3 days must be adequately anticoagulated, generally for at least 2 weeks, before drug is administered.
Monitor ECG continuously during drug administration and for at least 4 hours afterward or until QT returns to baseline.
Drug can worsen ventricular arrhythmias. Make sure that a cardiac monitor, intracardiac pacing, a cardioverter or a defibrillator, and medication for sustained VT is available.

LIDOCAINE

Lidocaine is a ventricular antiarrhythmic indicated for cardiac arrest from VF or VT, stable VT, wide-complex tachycardia of uncertain type, and wide-complex PSVT.

Action

As a class IB antiarrhythmic, lidocaine suppresses automaticity and shortens the effective refractory period and action potential duration of His-Purkinje fibers.
It also suppresses spontaneous ventricular depolarization during diastole. The drug seems to act preferentially on diseased or ischemic myocardial tissue.
By exerting its effects on the conduction system, it inhibits reentry mechanisms and halts ventricular arrhythmias.

Dosage

A single dose of 1.5 mg/kg I.V. may suffice as treatment in cardiac arrest.
ET administration: 2 to 4 mg/kg.
Maintenance infusion: 1 to 4 mg/minute (30 to 50 mcg/kg/minute)
For cardiac arrest: Give 50 to 100 mg (1 to 1.5 mg/kg) I.V. dose initially; in refractory VF, may give additional 0.5 to 0.75 mg/kg I.V. push and repeat in 5 to 10 minutes; maximum dose 3 mg/kg
In perfusing arrhythmia with stable VT, wide-complex tachycardia of uncertain type, or significant ectopy: Dose ranging from 0.5 to 0.75 mg/kg and up to 1.5 mg/kg I.V. push; repeat 0.5 to 0.75 mg/kg every 5 to 10 minutes with a maximum total dose of 3 mg/kg.

Special considerations

Drug is contraindicated in patients with hypersensitivity to amidetype local anesthetics, and in those with Stokes-Adams syndrome, WPW syndrome, and severe degrees of SA, AV, or intraventricular block in absence of artificial pacemaker.
Beta-adrenergic blockers and cimetidine may cause lidocaine toxicity from reduced hepatic clearance. Other antiarrhythmics (such as phenytoin, procainamide, propranolol, and quinidine) may cause additive or antagonist effects and additive toxicity with drug.
Use infusion pump or micro drip system and timer to monitor lidocaine infusion precisely. Never exceed infusion rate of 4 mg/minute, if possible. A faster rategreatly increases risk of toxicity.
Therapeutic serum levels of drug range from 2 to 5 mg/ml.
Effects of lidocaine overdose include signs and symptoms of CNS toxicity, such as seizures or respiratory depression, and cardiovascular toxicity (as indicated by hypotension).
Watch for signs of excessive depression of cardiac conductivity (such as sinus node dysfunction, PR-interval prolongation, QRSinterval widening, and appearance or exacerbation of arrhythmias). If they occur, reduce dosage or stop drug.

PROCAINAMIDE HYDROCHLORIDE

Procainamide (Pronestyl) is a ventricular antiarrhythmic and supraventricular antiarrhythmic.
It’s indicated for a wide variety of arrhythmias including PSVT, stable wide-complex tachycardia, and A-fib with rapid ventricular rate in the presence of WPW syndrome.
In cardiac arrest, procainamide is recommended for VF or pulseless VT that recurs after periods of non-VF rhythms during the arrest scenario.
In all instances, procainamide must be given as a slow I.V. infusion.

Action

As a class IA antiarrhythmic, procainamide depresses phase 0 of the action potential.
It’s considered a myocardial depressa nt beca use it decrease s myocardial excitability and conduction velocity and may depress myocardial contractility.
Procainamide also possesses anticholinergic activity, which may modify direct myocardial effects.
In therapeutic doses, the drug reduces conduction velocity in the atria, ventricles, and His-Purkinje system.
It controls atrial tachyarrhythmias by prolonging the effective refractory period and increasing the action potential duration in the atria, ventricles, and His-Purkinje system; the tissue remains refractory even after returning to resting membrane potential.
Procainamide shortens the effective refractory period of the AV node.
The drug’s anticholinergic action may also increase AV node conductivity.
Suppression of automaticity in the His-Purkinje system and ectopic pacem akers accounts for procainamide’s effec tiveness intreating ventricular premature beats.
At therapeutic doses, procainamide prolongs the PR and QT intervals.
Procainamide exerts a peripheral vasodilatory effect; with I.V. administration, it may cause hypotension.

Dosage

For cardiac arrest and for arrhythmia suppression: Give 20 mg/minute I.V. infusion with a maximum total dose of 17 mg/kg.
Maintenance infusion: 1 to 4 mg/minute.

Special considerations

Drug is contraindicated in patients with hypersensitivity to procaine and related drugs; complete, second-, or third-degree heart block in the absence of an artificial pacemaker; myasthenia gravis; systemic lupus erythematosus; and atypical VT (torsades de pointes).
Drug’s use with antihypertensives may cause additive hypotensive effects.
Other antiarrhythmics may cause additive or antagonistic cardiac effects; possible additive toxic effects.
Infusion pump or micro drip system and timer should be used to monitor procainamide infusion precisely.
Drug toxicity may cause severe hypotension, widening QRS complex, junctional tachycardia, intraventricular conduction delay, VF, oliguria, and confusion.
Watch for prolonged QT and QRS intervals (50% or greater widening), heart block, or increased arrhythmias. When these ECG signs appear, stop drug and monitor patient closely.

PROPAFENONE HYDROCHLORIDE

Propafenone (Rythmol) is a sodium channel antagonist that functions as an antiarrhythmic.
It’s used for suppression of ventricular and supra ventricular arrhythmias.
In the United States, only the oral form is used.

Action

Propafenone is a class 1C antiarrhythmic that reduces the inward sodium current in myocardial cells and Purkinje fibers.
It has weak beta-adrenergic blocking effects and slows the upstroke velocity of the action potential (phase 0 of the depolarization cycle).
Propafenone slows conduction in the AV node, His-Purkinje system, and intraventricular conduction system, as well as prolonging the refractory period in the AV node.

Special considerations

Drug is contraindicated in patients with severe or uncontrolled heart failure; cardiogenic shock; SA, AV, or intraventricular disorders of impulse conduction in the absence of a pacemaker; bradycardia; marked hypotension; or electrolyte imbalance.
Propafenone causes dose-related increase in plasma digoxin levels. Quinidine competitively inhibits one of the metabolic pathways for propafenone, increasing its half-life; don’t give together.
Adverse reactions to drug include A-fib, bradycardia, BBB, angina, chest pain, edema, first-degree AV block, hypotension, increased QRS complex duration, intraventricular conduction delay, palpitations, heart failure, and proarrhythmic events (VT, premature ventricular contractions [PVCs], VF).

SOTALOL

Action

Sotalol (Betapace) is a beta-adrenergic blocker used as an antiarrhythmic; it’s indicated for documented, lif e -threatening ventricular arrhythmias. Only the oral form is used in the United States.

Special considerations

It’s contraindicated in patients with se vere sinus node dysfunction, sinus bradycardia, second- and third-degree AV block in the absenceof an artificial pacemaker, congenital or acquired long QT syndrome, cardiogenicshock, uncontrolled heart failure, or bronchial asthma.
Drug should be avoided in patients with poor perfusion because of significant negative inotropic effects.
Drug given with calcium channel antagonists may result in enhanced myocardial depression. In addition, use it cautiously with drugs that prolong QT interval (procainamide, amiodarone).
Drug may cause increased blood glucose levels and mask symptoms of hypoglycemia in diabetics.
The most common signs and symptoms of sotalol overdose are bradycardia, heart failure, hypotension, bronchospasm, and hypoglycemia. If overdose occurs, stop drug and observe patient closely.
Patients given drug should be carefully observed until QT intervals are normalized.

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