Disopyramide
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| Trade names | Norpace |
| AHFS/Drugs.com | Monograph |
| MedlinePlus | a682408 |
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| Routes of administration |
Oral, intravenous |
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| Pharmacokinetic data | |
| Bioavailability | High |
| Protein binding | 50% to 65% (concentration-dependent) |
| Metabolism | Hepatic (CYP3A4-mediated) |
| Biological half-life | 6.7 hours (range 4 to 10 hours) |
| Excretion | Renal (80%) |
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| ECHA InfoCard | 100.021.010 |
| Chemical and physical data | |
| Formula | C21H29N3O |
| Molar mass | 339.475 g/mol |
| 3D model (Jmol) | |
| Melting point | 94.5 to 95 °C (202.1 to 203.0 °F) |
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Disopyramide (INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication used in the treatment of ventricular tachycardia. It is a sodium channel blocker and therefore classified as a Class 1a anti-arrhythmic agent. Disopyramide has a negative inotropic effect on the ventricular myocardium, significantly decreasing the contractility. Disopyramide also has an anticholinergic effect on the heart which accounts for many adverse side effects. Disopyramide is available in both oral and intravenous forms, and has a low degree of toxicity.
Disopyramide’s Class 1a activity is similar to that of quinidine in that 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.
Levites proposed a possible secondary mode of action for disopyramide, against reentrant arrhythmias after an ischemic insult. Disopyramide decreases the inhomogeneity between infarcted and normal myocardium refractory periods; in addition to lengthening the refractory period. This decreases the chance of re-entry depolarization, because signals are more likely to encounter tissue in a refractory state which cannot be excited. This provides a possible treatment for atrial and ventricular fibrillation, as it restores pacemaker control of the tissue to the SA and AV nodes.
Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease, occurring in 1:500 individuals in the general population. It is estimated that there are 600,000 individuals in the United States with hypertrophic cardiomyopathy. The most common variant of HCM presents with left ventricular (LV) intracavitary obstruction due to systolic anterior motion of the mitral valve, and mitral-septal contact, diagnosed readily with echocardiography. Pharmacologic treatment with negative inotropic drugs is first-line therapy. Beta-blockers are used first, and while they improve symptoms of shortness of breath, chest pain and exercise intolerance, they do not reduce resting LV intraventricular pressure gradients and often are inadequate to control symptoms. Many investigators and clinicians believe that disopyramide controlled release is the most potent agent available for reducing resting pressure gradients and improving symptoms. Disopyramide has been actively used for more than 30 years. Disopyramide administration for obstructive HCM has a IIa recommendation in the 2011 American Heart Association/American College of Cardiology Foundation guidelines for treatment of obstructive HCM. A IIa treatment recommendation indicates that benefits outweigh risk, and that it is reasonable to administer treatment.
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