Disopyramide adverse effects

In the presence of phenytoin, the metabolism of disopyramide is increased (reducing its effective concentration) and the accumulation of its metabolites is also increased, thereby increasing the probability of anticholinergic adverse effects. Rifampin also stimulates the hepatic metaboUsm of disopyramide, reducing its plasma concentration. 

Disopyramide s atropine-like activity accounts for most of its symptomatic adverse effects urinary retention (most often, but not exclusively, in male patients with prostatic hyperplasia), dry mouth, blurred vision, constipation, and worsening of preexisting glaucoma. These effects may require discontinuation of the drug. 

Adverse effects Disopyramide shows effects of anticholinergic activity, for example, dry mouth, urinary retention, blurred vision, and constipation. 

The use, clinical pharmacology, and adverse effects of disopyramide have been reviewed thoroughly (1,2). 

Through its anticholinergic effects disopyramide causes dry mouth and blurred vision and can occasionally cause serious adverse effects, including glaucoma and acute urinary retention (1). 

Some of the macrolide antibiotics have been reported to inhibit the clearance of disopyramide (SEDA-21, 200) (SEDA-22, 207), resulting in serious dysrhythmias or hypoglycemia. The mechanism of this interaction is presumed to be inhibition of dealkylation of disopyramide to its major metabolite, mono-A-dealkyldisopyramide. For example, in human liver microsomes the macrolide antibiotic troleandomycin significantly inhibited the mono-A-dealkylation of disopyramide enantiomers by inhibition of CYP3A4 (34). This interaction can result in serious dysrhythmias or other adverse effects of disopyramide. 

Ellrodt G, Singh BN. Adverse effects of disopyramide (Norpace) toxic interactions with other antiarrhythmic agents. Heart Lung 1980 9(3) 469-74. 

Disopyramide (Norpace, others) exerts electrophysiologi-cal effects very similar to those of quinidine, but the drugs have different adverse effect profiles. Disopyramide is used to maintain sinus rhythm in patients with atrial flutter or atrial... 

Disopyramide phosphate is used orally for the treatment of certain ventricular and atrial arrhythmias. Despite its structural dissimilarity to procainamide (Fig. 26.10), its cardiac effects are very similar. Disopyramide is rapidly and completely absorbed from the gastrointestinal tract. Peak plasma level is usually reached within 1 to 3 hours, and a plasma half-life of 5 to 7 hours is common. Approximately half of an oral dose is excreted unchanged in the urine. The remaining drug undergoes hepatic metabolism, principally to the corresponding N-dealkylated form. This metabolite retains approximately half the antiarrhythmic activity of disopyramide and also is subject to renal excretion. Adverse effects of disopyramide frequently are observed. These effects are primarily anticholinergic in nature and include dry mouth, blurred vision, constipation, and urinary retention. 

Not fully established. An in vitro study using human liver microsomes indicated that erythromycin inhibits the metabolism (mono-A-dealkylation) of disopyramide which, in vivo, would be expected to reduce its loss from the body and increase its serum levels. Clarithromycin and azithromycin probably do the same. The increased serum levels of disopyramide can result in adverse effects such as QT prolongation and torsade de pointes, and may result in enhanced insulin secretion and hypoglycaemia. - Both intravenous erythromycin and clarithromycin" alone have been associated with prolongation of the QT interval and torsade de pointes. Therefore, disopyramide and macrolides may have additive effects on the QT interval in addition to the pharmacokinetic interaction. 

A group of clinicians who had used single 400-mg oral doses of disopyramide successfully and with few adverse effects for reverting acute supraventricular arrhythmias, reported 5 cases of profound hypotension and collapse. Three of the patients developed severe epigastric pain. All 5 had previous myocardial disease and/or were taking myocardial depressants, either beta blockers or verapamil in small quantities [not specified]. ... 

The risk of adverse cardiac effects of disopyramide during intravenous administration relates to the speed of its administration rather than to the total dose given (SEDA-10,149). 

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