Procainamide

Procainamide is an antiarrhythmic Class 1 A agent belonging to a Sodium channel blocker.

Procainamide is used in the treatment of ventricular arrhythmias. It is also used in the treatment of Stable Ventricular Tachycardia, Ventricular Arrhythmia Associated with Myocardial Infarction, Atrial Fibrillation, and AV Junctional Tachycardia.

Procainamide is almost completely absorbed after oral administration, i.e., about 75 to 95% widely distributed throughout the body and crosses the placenta and enters breast milk with a Volume of distribution: of 2 L/kg and Plasma protein binding: of 15-20%. It gets Metabolised in the liver via acetylation to form the active metabolite N-acetyl procainamide (NAPA) and gets excreted mainly via urine (approx 30-60% as unchanged drug; 6-52% as NAPA); feces (<5% as unchanged drug with Elimination half-life: 2.5-4.7 hours (Procainamide); 6-8 hours (NAPA).

The common side effects are Drug-induced lupus erythematosus-like syndrome with prolonged use, conduction disturbances; proarrhythmic effects (e.g. QTc prolongation), increased A-V conduction leading to ventricular rate acceleration, etc.

Procainamide is available in the dosage forms such as Tablets, Capsules, and injections.

Procainamide is available in Switzerland, Europe, India, U.S

Procainamide is a sodium channel blocker. It stabilizes the neuronal membrane by inhibiting the ionic fluxes required for the initiation and conduction of impulses thereby affecting local anesthetic action

Procainamide is a class 1a antiarrhythmic. Through direct cardiac effects and an increased electrical stimulation threshold of the ventricle and His-Purkinje system, it causes reduced myocardial excitability and conduction velocity and possibly a decreased myocardial contractility.

The onset of Action of Procainamide was within 10 to 30 minutes.

The Duration of Action of Procainamide was within 2–4 h

The Tmax was about 15 to 60 minutes and Cmax was about 9 h, respectively

Procainamide is available in the dosage forms such as Tablets, Capsules, and injections.

Procainamide is used in the treatment of ventricular arrhythmias. It is also used in the treatment of Stable Ventricular Tachycardia, Ventricular Arrhythmia Associated with Myocardial Infarction, Atrial Fibrillation, and AV Junctional Tachycardia.

Procainamide is a class 1a antiarrhythmic. Through direct cardiac effects and an increased electrical stimulation threshold of the ventricle and His-Purkinje system, it causes reduced myocardial excitability and conduction velocity and possibly a decreased myocardial contractility.

Procainamide is used in the treatment of ventricular arrhythmias. It is also used in the treatment of Stable Ventricular Tachycardia, Ventricular Arrhythmia Associated with Myocardial Infarction, Atrial Fibrillation, and AV Junctional Tachycardia.

Intravenous

• Ventricular arrhythmias

Adult: In life-threatening cases: 100 mg every 5 minutes as a bolus inj given at a rate not exceeding 50 mg/min. Administer doses until the arrhythmia is controlled or until a total of 500 mg has been given; wait for approx 10 minutes before giving additional doses. Alternatively, a loading dose of 20 mg/mL may be given via infusion at a rate of 1 mL/min over 25-30 minutes to deliver 500-600 mg of Procainamide. Max: 1000 mg (given by either method). Maintenance to ensure therapeutic plasma concentrations: 2 mg/mL may be given at a rate of 1-3 mL/min; if total daily fluid intake must be decreased: 4 mg/mL may be given at a rate of 0.5-1.5 mL/min. Maintenance doses are adjusted according to clinical response, weight and age, and the general condition and CV status of the patient. Discontinue treatment if continuous conduction disturbances or hypotension occurs.

• Although not approved there has been certain off-label use documented for Procainamide which includes:
• Stable Ventricular Tachycardia

For patients who are stable with likely VT, IV antiarrhythmic drugs or elective cardioversion is the preferred treatment strategy. Procainamide can be administered at a rate of 20 to 50 mg/min until the arrhythmia is suppressed, hypotension ensues, QRS duration increases >50%, or the maximum dose of 17 mg/kg is given. Maintenance infusion is 1 to 4 mg/min. Procainamide should be avoided in patients with prolonged QT and congestive heart failure.

• Atrial Fibrillation

In patients with pre-excited AF and rapid ventricular response who are hemodynamically stable, IV procainamide (1 g over 30 minutes, followed by an infusion of 2 mg/minute over 1 hour) may be used to slow ventricular rate and convert to sinus rhythm.

The dosage and the duration of treatment should be as per the clinical judgment of the treating physician.

Procainamide is available in various dosage strengths of 250 mg; 375 mg; 500 mg; 100 mg/mL; 500 mg/mL; 750 mg; 1000 mg

Procainamide is available in the form of dosage forms such as Tablets, Capsules, and injections.

Procainamide is used in the treatment of ventricular arrhythmias. It is also used in the treatment of Stable Ventricular Tachycardia, Ventricular Arrhythmia Associated with Myocardial Infarction, Atrial Fibrillation, and AV Junctional Tachycardia.

Ventricular arrhythmias: Diets high in processed foods, such as fast food, and items high in added sugar, like soda and sugary baked goods, have been linked to increased heart disease risk.

Drinking too much alcohol can increase the risk of developing AFib.It may also trigger AFib episodes in people who already have AFib, especially if patients have existing cardiovascular disease or diabetes

Ventricular Tachycardia: High blood pressure can lead to an abnormally fast heartbeat. The DASH diet encourages the inclusion of fruits, vegetables, low-fat dairy, protein, and whole grains to keep your blood pressure at normal levels and reduce your risk of heart disease and stroke.

The dietary restriction should be individualized as per the patient's requirements.

Procainamide may be contraindicated in the following

• Use with caution in patients with heart failure, electrolyte imbalances (particularly hypokalemia and hypomagnesemia), myasthenia gravis patients, and hepatic or renal impairment. Procainamide also crosses the placenta and may be present in the milk of breastfeeding mothers, and as such, chronic use requires caution in this population.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows.

• Mortality

In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial (CAST), a long-term, multicentered, randomized, double-blind study in patients with asymptomatic non-life-threatening ventricular arrhythmias who had had myocardial infarctions more than six days but less than two years previously, excessive mortality or non-fatal cardiac arrest rate was seen in patients treated with encainide or flecainide (56/730) compared with that seen in patients assigned to matched placebo-treated groups (22/725). The average duration of treatment with encainide or flecainide in this study was ten months.

The applicability of these results to other populations (e.g., those without recent myocardial infarctions) or to other antiarrhythmic drugs is uncertain, but at present, it is prudent to consider any antiarrhythmic agent to have a significant risk in patients with structural heart disease.

• Blood Dyscrasias

Agranulocytosis, bone marrow depression, neutropenia, hypoplastic anemia and thrombocytopenia in patients receiving procainamide hydrochloride have been reported at a rate of approximately 0.5 percent. Most of these patients received Procainamide within the recommended dosage range. Fatalities have occurred (with approximately 20-25 percent mortality in reported cases of agranulocytosis). Since most of these events have been noted during the first 12 weeks of therapy, it is recommended that complete blood counts, including white cell, differential, and platelet counts be performed at weekly intervals for the first three months of therapy, and periodically thereafter. Complete blood counts should be performed promptly if the patient develops any signs of infection (such as fever, chills, sore throat, or stomatitis), bruising, or bleeding. If any of these hematologic disorders are identified, procainamide therapy should be discontinued. Blood counts usually return to normal within one month of discontinuation.

• Digitalis Intoxication

Caution should be exercised in the use of Procainamide in arrhythmias associated with digitalis intoxication. Procainamide can suppress digitalis-induced arrhythmias; however, if there is a concomitant marked disturbance of atrioventricular conduction, additional depression of conduction and ventricular asystole or fibrillation may result. Therefore, the use of Procainamide should be considered only if discontinuation of digitalis and therapy with potassium, lidocaine, or phenytoin are ineffective.

• First Degree Heart Block

Caution should be exercised also if the patient exhibits or develops first-degree heart block while taking Procainamide, and dosage reduction is advised in such cases. If the block persists despite dosage reduction, a continuation of Procainamide administration must be evaluated on the basis of current benefit versus the risk of increased heart block.

• Predigitalization for Atrial Flutter or Fibrillation

Patients with atrial flutter or fibrillation should be cardioverted or digitalized prior to Procainamide administration to avoid enhancement of A-V conduction which may result in ventricular rate acceleration beyond tolerable limits. Adequate digitalization reduces but does not eliminate the possibility of a sudden increase in ventricular rate as the atrial rate is slowed by Procainamide in these arrhythmias.

• Congestive Heart Failure

For patients with congestive heart failure, and those with acute ischemic heart disease or cardiomyopathy, caution should be used in Procainamide therapy, since even slight depression of myocardial contractility may further reduce the cardiac output of the damaged heart.

• Concurrent Other Antiarrhythmic Agents

Concurrent use of Procainamide with other Group 1A antiarrhythmic agents such as Procainamide or disopyramide may produce an enhanced prolongation of conduction or depression of contractility and hypotension, especially in patients with cardiac decompensation. Such use should be reserved for patients with serious arrhythmias unresponsive to a single drug and employed only if the close observation is possible.

• Renal insufficiency

Renal insufficiency may lead to the accumulation of high plasma levels from conventional oral doses of Procainamide, with effects similar to those of overdosage, unless the dosage is adjusted for the individual patient.

• Myasthenia Gravis

Patients with myasthenia gravis may show worsening symptoms from Procainamide due to its procaine-like effect on diminishing acetylcholine release at skeletal muscle motor nerve endings, so Procainamide administration may be hazardous without optimal adjustment of anticholinesterase medications and other precautions.

General

Immediately after initiation of Procainamide therapy, patients should be closely observed for possible hypersensitivity reactions, especially if procaine or local anesthetic sensitivity is suspected, and for muscular weakness, if myasthenia gravis is a possibility.

In the conversion of atrial fibrillation to normal sinus rhythm by any means, dislodgement of mural thrombi may lead to embolization, which should be kept in mind.

After a day or so, steady-state plasma Procainamide levels are produced following regular oral administration of a given dose of Procainamide at set intervals, with peak plasma concentrations at about 90 to 120 minutes after each dose. After achieving and maintaining therapeutic plasma concentrations and satisfactory electrocardiographic and clinical responses, continued frequent periodic monitoring of vital signs and electrocardiograms is advised.

If evidence of QRS widening of more than 25 percent or marked prolongation of the Q-T interval occurs, concern for overdosage is appropriate, and a reduction in dosage is advisable if a 50 percent increase occurs. Elevated serum creatinine or urea nitrogen, reduced creatinine clearance, or history of renal insufficiency, as well as use in older patients (over age 50), provide grounds to anticipate that less than the usual dosage and longer time intervals between doses may suffice, since the urinary elimination of PA and NAPA may be reduced, leading to gradual accumulation beyond normally predicted amounts. If facilities are available for measurement of plasma Procainamide and NAPA, or acetylation capability, individual dose adjustment for optimal therapeutic levels may be easier, but close observation of clinical effectiveness is the most important criterion.

Laboratory Tests

Laboratory tests such as complete blood count (CBC), electrocardiogram, and serum creatinine or urea nitrogen may be indicated, depending on the clinical situation, and periodic rechecking of the CBC and ANA may be helpful in the early detection of untoward reactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Long-term studies in animals have not been performed.

Teratogenic Effects: Pregnancy Category C

Animal reproduction studies have not been conducted with Procainamide. It also is not known whether Procainamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Procainamide should be given to a pregnant woman only if clearly needed.

Alcohol consumption with Procainamide may increase the risk of low blood pressure and cause adverse effects, such as Dizziness, fainting, light-headedness, or headache. Alcohol consumption with Procainamide may increase the risk of low blood pressure and cause adverse effects, such as Dizziness, fainting, light-headedness, or headache.

Procainamide use in breastfeeding patients is not recommended.

Pregnancy Category C

Animal reproduction studies have not been conducted with Procainamide. It also is not known whether Procainamide can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Procainamide should be given to a pregnant woman only if clearly needed.

Tobacco: Using tobacco may interfere with the action of Procainamide and as a result, this may alter the effectiveness of the drug.

The adverse reactions related to the molecule Procainamide can be categorized as

• Common Adverse effects:

Diarrhea, Hardening or thickening of the skin where the needle is placed, Loss of appetite

• Less Common adverse effects:

Fever and chills, Joint pain or swelling, Pains with breathing, Skin rash or itching

• Rare adverse effects:

Bleeding, blistering, burning, coldness, discoloration of the skin, feeling of pressure, hives, infection, inflammation, itching, lumps, numbness, pain, rash, redness, scarring, soreness, stinging, swelling, tenderness, tingling, or warmth at the injection site, Confusion, Fever or sore mouth, gums, or throat, Hallucinations (seeing, hearing, or feeling things that are not there), Mental depression, Unusual bleeding or bruising, Unusual tiredness or weakness.

The clinically relevant drug interactions of Procainamide is briefly summarized here.

• May cause a potentiated prolongation of conduction or diminished contractility and hypotension with another group IA antiarrhythmic agents (e.g. Procainamide, disopyramide).
• May cause additive antiviral effects on A-V nodal conduction with anticholinergic agents.
• May enhance the therapeutic efficacy of neuromuscular blocking agents.
• Cimetidine or trimethoprim may increase the plasma concentration of Procainamide.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

Geriatric Use

No overall differences in safety or effectiveness have been observed between elderly and younger patients.

Symptoms:

Hypotension, oliguria, lethargy, nausea, vomiting, confusion; continuous widening of the QRS complex, prolonged Q-T and P-R intervals, lowering of the R and T waves; increasing AV block, ventricular extrasystoles, ventricular tachycardia or fibrillation; delayed intraventricular conduction.

Management:

Symptomatic and supportive treatment. Monitor ECG, blood pressure, and vital signs. Administer vasopressors after adequate fluid volume replacement. Ensure mechanical cardiorespiratory support. May perform hemodialysis to remove from the circulation.

Pharmacodynamics:

• Procainamide is an agent indicated for the production of local or regional anesthesia and in the treatment of ventricular tachycardia occurring during cardiac manipulation, such as surgery or catheterization, or which may occur during acute myocardial infarction, digitalis toxicity, or other cardiac diseases. The mode of action of the antiarrhythmic effect of Procainamide appears to be similar to that of procaine and Procainamide. Ventricular excitability is depressed and the stimulation threshold of the ventricle is increased during diastole. The sinoatrial node is, however, unaffected.

Pharmacokinetics:

• Absorption:

Procainamide is almost completely absorbed after oral administration, and peak plasma concentrations are generally reached within 1 to 2 hours. Upon intravenous administration, there is a rapid initial distribution phase, which is completed after about 30 minutes.

• Distribution:

Widely distributed throughout the body. Crosses the placenta and enters breast milk. The volume of distribution: 2 L/kg. Plasma protein binding: 15-20%.

• Metabolism:

Metabolized in the liver via acetylation to form the active metabolite N-acetyl Procainamide (NAPA).

• Excretion:

Mainly via urine (approx 30-60% as unchanged drug; 6-52% as NAPA); feces (<5% as unchanged drug). Elimination half-life: 2.5-4.7 hours (procainamide); 6-8 hours (NAPA).

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