Major side effects of class I antiarrhythmic drugs

Topic Outline

GRAPHICS

DISOPYRAMIDE

The side effect profile of disopyramide has been well established. Anticholinergic symptoms are most common, but cardiac toxicity is of greatest concern. In particular, the negative inotropic activity and proarrhythmic potential of disopyramide limits its use in settings in which it might otherwise be effective.

Anticholinergic side effects — The administration of disopyramide is associated with a number of anticholinergic symptoms including dry mouth (32 percent), urinary hesitancy (14 percent), and constipation (11 percent). As a result, disopyramide should not be used in patients with underlying conditions that may be exacerbated by decreased cholinergic activity including glaucoma, myasthenia gravis, and urinary retention.

The anticholinergic effects can be diminished by the coadministration of drugs that increase cholinergic activity such as physostigmine, pyridostigmine, or bethanechol [1]. These agents selectively reduce anticholinergic symptoms without affecting the electrophysiologic or antiarrhythmic properties of disopyramide [1,2].

Disopyramide concentration and its metabolite, mono-N-dealkyldisopyramide, concentration should be monitored in patients whose renal function is decreased to prevent anticholinergic side effects associated with disopyramide. When serum mono-N-dealkyldisopyramide concentration is over approximately 1 microg/mL, the dose should be decreased or discontinued [3].

Cardiac toxicity — Disopyramide has substantial negative inotropic activity in humans, resulting in reductions in cardiac contractility and cardiac output, and a reflex increase in systemic vascular resistance [4]. The degree to which this can occur has been clearly documented in studies in dogs [5,6]. When given intravenously, disopyramide causes a significant decline in cardiac contractility at doses as low as 1 mg/kg body weight (similar to that administered intravenously in humans). At higher doses (5 to 10 mg/kg), the decrease in contractile force is 50 to 100 percent greater than that induced by quinidine [5].

                                                                            

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Literature review current through: Aug 2014. | This topic last updated: Mar 20, 2014.
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