Disopyramide heart failure with

Disopyramide directly depresses myocardial contractility. The negative inotropic effect may be detrimental in patients with compromised cardiac function. Some patients develop overt congestive heart failure. At usual therapeutic doses, depression of myocardial function is not a problem in most patients with normal ventricular function. 

Toxic concentrations of disopyramide can precipitate all of the electrophysiologic disturbances described under quinidine. As a result of its negative inotropic effect, disopyramide may precipitate heart failure de novo or in patients with preexisting depression of left ventricular function. Because of this effect, disopyramide is not used as a first-line antiarrhythmic agent in the USA. It should not be used in patients with heart failure. 

In the USA, disopyramide is only available for oral use. The typical oral dosage of disopyramide is 150 mg three times a day, but up to 1 g/d has been used. In patients with renal impairment, dosage must be reduced. Because of the danger of precipitating heart failure, loading doses are not recommended. 

DISOPYRAMIDE CALCIUM CHANNEL BLOCKERS Risk of myocardial depression and asystole when disopyramide is co administered with verapamil, particularly in the presence of heart failure Disopyramide is a myocardial depressant like verapamil and can cause ventricular tachycardia, ventricular fibrillation or torsades de pointes Avoid co administering verapamil with disopyramide if possible. If single-agent therapy is ineffective, monitor PR, BP and ECG closely watch for heart failure... 

Liver damage was reported in 22 (0.35%) of 6294 patients given disopyramide, with jaundice in 6 (0.09%) (17). Liver damage due to disopyramide can be associated with direct hepatocellular damage (18) and intrahepatic cholestasis (19,20). However, it can also occur indirectly, because of heart failure and hepatic congestion (21). Thus, the incidence of direct liver damage quoted above may be an overestimate. 

Quinidine may be associated with a syndrome called cinchonism, which is characterized by headache, vertigo, and tinnitus. Procainamide may result in hypotension or a reversible syndrome similar to lupus erythematosus. Patients may develop positive antinuclear antibody (ANA) titers and complain of rash, arthralgia, and arthritis. Disopyramide is poorly tolerated due to its anticholinergic effects (urinary retention, dry mouth, blurred vision), and its use should be avoided in patients with congestive heart failure (CHF) due to negative inotropic effects. 

Disopyramide should be avoided in patients with heart failure due to negative inotropic properties. ... 

Atenolol 100 mg daily has been shown to increase the serum disopyramide steady-state levels from 3.46 to 4.25 micrograms/mL and reduce the clearance of disopyramide by 16% in healthy subjects and patients with ischaemic heart disease. None of the subjects developed any adverse reactions or symptoms of heart failure, apart from one of the subjects who had transient frrst degree heart block. ... 

On the basis of this report, and on reports of studies in animals and from the known risks associated with the concurrent use of beta blockers (see Disopyramide -i- Beta blockers , p.252), the UK manufacturer warns about combining disopyramide and other drugs [such as verapamil] that may have additive negative inotropic effects. However, they do point out that in some specific circumstances combinations of antiarrhythmie drugs (they specifically name digoxin, beta blockers and verapamil for the control of atrial fibrillation) may be beneficial. They note that severe hypotension caused by disopyramide has usually been associated with cardiomyopathy or uncompensated congestive heart failure. However, the US manufacturer advises that until more data is available, disopyramide should not be given within 48 hours before or 24 hours after verapamil. ... 

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