Class lA Antiarrhythmic Agents

Procainamide Hydrochloride

Procainamide hydrochloride; p-Amino-N-[2-(diethylamino)ethyl]benzamide monohydrochloride. It was developed in the course of research for compounds structurally similar to procaine, which had limited effect as an antiarrhythmic agent because of its central nervous system side effects and short-lived action resulting from the rapid hydrolysis of its ester linkage by plasma esterases. Procainamide hydrochloride is also more stable in water than procaine because of its amide structure.

Metabolism of procainamide hydrochloride occurs through the action of N-acetyltransferase. The product of enzymatic metabolism of procaina-mide hydrochloride is NAPA, which possesses only 25% of the activity of the parent compound (40). A study of the disposition of procainamide hydrochloride showed 50% of the drug was excreted unchanged in the urine, with 7% to 24% recovered as NAPA (41,42).

Disopyramide Phosphate

Disopyramide phosphate. a-[2-(Diisopropylamino)ethyl]-a-phenyl-2-pyridineacetamide phosphate (Fig. 2) is an oral and intravenous class lA antiarrhythmic agent. Oral administration of the drug produces peak plasma levels within 2 h. the drug is approximately 50% bound to plasma protein and has a half-life of 6.7 h in humans. More than 50% is excreted unchanged in the urine. Disopyramide phosphate commonly exhibits side effects of dry mouth, constipation, urinary retention, and other cholinergic-blocking actions because of its structural similarity to anticholinergic drugs.

Figure 2 Disopyramide phosphate.

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