Disopyramide

Disopyramide is a class 1A antiarrhythmic agent belonging to sodium channel blocker class.

Disopyramide is a sodium channel blocker used in the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening.

Disopyramide is used in the treatment of ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias.

The common side effects are Oedema, chest pain, bradycardia, sinus block, ventricular fibrillation, ventricular tachycardia. GI: Dry mouth, abdominal pain, nausea, vomiting, anorexia, diarrhoea, constipation., etc.

Disopyramide is available in the form of a dosage form such as oral capsules.

Disopyramide is available in Switzerland, Europe, India, Japan, U.S

Disopyramide inhibits the fast sodium channels. Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors.

The Duration of Action of Disopyramidewas within 12-13 hrs

The Tmax was about 6-8 hr and Cmax was about 1-2 h, respectively

Disopyramide is available in the form of Capsules.

Disopyramide is used in the treatment of ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias .

Disopyramide are one that interferes directly with the depolarization of the cardiac membrane and thus serves as a membrane-stabilizing agent with a depressant action on the heart similar to that of guanidine. It also possesses some anticholinergic and local anesthetic properties

Disopyramide is used in the treatment of ventricular arrhythmias, such as sustained ventricular tachycardia, ventricular pre-excitation and cardiac dysrhythmias.

• Treatment of Ventricular arrhythmias

It inhibits the fast sodium channels. In animal studies Disopyramide decreases the rate of diastolic depolarization (phase 4) in cells with augmented automaticity, decreases the upstroke velocity (phase 0) and increases the action potential duration of normal cardiac cells, decreases the disparity in refractoriness between infarcted and adjacent normally perfused myocardium, and has no effect on alpha- or beta-adrenergic receptors

• Dosing

The dosage of Disopyramide must be individualized for each patient on the basis of response and tolerance. The usual adult dosage is 400 to 800 mg per day given in divided doses. The recommended dosage for most adults is 600 mg/day given in divided doses (either 150 mg every 6 hours for immediate-release or 300 mg every 12 hours for Controlled Release). For patients whose body weight is less than 110 pounds (50 kg), the recommended dosage is 400 mg/day given in divided doses (either 100 mg every 6 hours for immediate-release or 200 mg every 12 hours for Controlled release).

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

Disopyramide is available in immediate and controlled release capsules with 100 and 150 mg doses.

Disopyramide is available in the form of Capsules in strength of 100 and 150 mg.

Disopyramide is a sodium channel blocker used in the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening.

Ventricular Arrhythmia: 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.

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

Disopyramide may be contraindicated in the following

• Cardiogenic shock
• preexisting second-or third-degree AV block
• congenital Q-T prolongation
• Hypersensitivity

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

• Proarrhythmic Effects

Like many other drugs (including all other Class la antiarrhythmics), Disopyramideprolongs the QT c interval, and this can lead to torsades de pointes , a life-threatening ventricular arrhythmia . The risk of torsades is increased by bradycardia, hypokalemia, hypomagnesemia, or high serum levels of quinidine, but it may appear in the absence of any of these risk factors. The best predictor of this arrhythmia appears to be the length of the QT c interval, and Disopyramideshould be used with extreme care in patients who have preexisting long-QT syndromes, who have histories of torsades de pointes of any cause, or who have previously responded to Disopyramide(or other drugs that prolong ventricular repolarization) with marked lengthening of the QT c interval. Estimation of the incidence of torsades in patients with therapeutic levels of Disopyramideis not possible from the available data, resulting ventricular rate may be very high (greater than 200 beats per minute) and poorly tolerated. This hazard may be decreased if partial atrioventricular block is achieved prior to initiation of Disopyramidetherapy, using conduction-reducing drugs such as digitalis, verapamil, diltiazem, or a (beta)-receptor blocking agent.

• Exacerbated Bradycardia in Sick Sinus Syndrome

In patients with the sick sinus syndrome, Disopyramide has been associated with marked sinus node depression and bradycardia.

Vagolysis

Because Disopyramideopposes the atrial and A-V nodal effects of vagal stimulation, physical or pharmacological vagal maneuvers undertaken to terminate paroxysmal supraventricular tachycardia may be ineffective in patients receiving quinidine.

Precautions

• General

All the precautions applying to regular Disopyramidetherapy apply to this product. Hypersensitivity or anaphylactoid reactions to quinidine, although rare, should be considered, especially during the first weeks of therapy. Hospitalization for close clinical observation, electrocardiographic monitoring, and determination of serum Disopyramidelevels are indicated when large doses of Disopyramideare used or with patients who present an increased risk.

• Laboratory Tests

Periodic blood counts and liver and kidney function tests should be performed during long-term therapy; the drug should be discontinued if blood dyscrasias or evidence of hepatic or renal dysfunction occurs.

• Heart Block

In patients without implanted pacemakers who are at high risk of complete atrioventricular block (e.g., those with digitalis intoxication, second-degree atrioventricular block, or severe intraventricular conduction defects), Disopyramideshould be used only with caution.

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

Disopyramide use in breastfeeding patients is not recommended.

Pregnancy Category X

Risk Summary

Disopyramide may cause fetal harm when administered to a pregnant woman and is contraindicated during pregnancy.

Disopyramide was teratogenic and embryotoxic in rats at doses with exposures to an unbound drug that were approximately 8 Times and 2 times, respectively, the human exposure. In rabbits, Disopyramide led to abortions at 4 times the human exposure and fetal toxicity with exposures approximately 13 times the human exposure. If Disopyramide is used in pregnancy, or if the

Patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus.

Absorption was unaffected by food.

Avoid smoking tobacco while taking Disopyramide. Disopyramide doses higher than 2.5 mg three times a day may be considered to match the exposure seen in nonsmoking patients. In patients who smoke tobacco, plasma concentrations of Disopyramide are reduced by 50% to 60% compared to nonsmokers.

Decreased serum concentration with St. John’s wort.

The adverse reactions related to molecule Disopyramidecan be categorized as

• Common Adverse effects:

Hemodynamic compromise, Dizziness, peripheral ischemia, dry mouth,asthenia, and somnolence.

• Less Common adverse effects:

Asymptomatic and symptomatic hypotension, burning, crawling, itching, numbness.

• Rare adverse effects:

Bradycardia, decompensated heart failure, cardiac arrest, and heart block.

The clinically relevant drug interactions of Disopyramideis briefly summarized here.

• 1,2-Benzodiazepine may increase the central nervous system depressant (CNS depressant) activities of Disopyramide.
• Disopyramide may decrease the excretion rate of Abacavir which could result in a higher serum level.
• Disopyramide may increase the bradycardic activities of Acebutolol.
• Aceclofenac may decrease the excretion rate of Disopyramide which could result in a higher serum level.
• The metabolism of Acetaminophen can be decreased when combined with Disopyramide
• Decreased serum concentration with antacids, PPI, CYP3A4 inducers (e.g., phenytoin, rifampicin).
• Increased plasma concentration with CYP1A1 (e.g. erlotinib), CYP3A4 inhibitors (e.g., clarithromycin), potent P-GP/BCRP inhibitors (e.g. ciclosporin, azole antifungals, protease inhibitors).

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:

Resp depression or distress, ataxia, apnoea, severe hypotension, syncope, diarrhoea, vomiting, anuria, absence of P waves, PR and QT interval, and QRS complex broadening, extrasystoles, ventricular arrhythmias, heart block, heart failure, coma, irritability, lethargy, thrashing, hallucinations, twitching, paraesthesia, generalised seizures, signs of cinchonism.

Management:

Symptomatic treatment. Monitor ECG and BP. Perform gastric lavage, induce emesis, or administer activated charcoal for recent ingestion. May require artificial resp or other supportive measures.

Pharmacodynamics:

• Disopyramide is an anti-arrhythmic drug indicated for the treatment of documented ventricular arrhythmias, such as sustained ventricular tachycardia that are life-threatening. At therapeutic plasma levels, disopyramide shortens the sinus node recovery time, lengthens the effective refractory period of the atrium, and has a minimal effect on the effective refractory period of the AV node. Little effect has been shown on AV-nodal and His-Purkinje conduction times or QRS duration. However, prolongation of conduction in accessory pathways occurs.

Pharmacokinetics:

Absorption:

Nearly complete with no proper data available on its absorption and distribution in the body.

Metabolism:

Disopyramide is mainly metabolized in the liver by cytochrome P450 enzymes, specifically CYP3A4.

Excretion:

In healthy men, about 50% of a given dose of disopyramide is excreted in the urine as the unchanged drug, about 20% as the mono-N-dealkylated metabolite and 10% as the other metabolites.

1. https://pubmed.ncbi.nlm.nih.gov/95482/
2. https://clinicaltrials.gov/ct2/show/NCT02917395

1. https://www.pfizermedicalinformation.com/en-us/norpace/clinical-pharmacology
2. https://reference.medscape.com/drug/norpace-cr-disopyramide-342299
3. https://go.drugbank.com/drugs/DB00280