This double-blind, randomized, placebo crossover study was used to evaluate the effects of a Cholinesterase inhibitor—slow-release pyridostigmine (180 mg orally every 12 hours)—on the anticholinergic and antiarrhythmic properties of disopyramide. Quantitative side effects questionnaire scores were used to guide disopyramide administration in 20 men with ventricular tachycardia. Disopyramide was given to each patient both with placebo and with active pyridostigmine. The maximal administered dose for each regimen was used in conjunction with corresponding questionnaire scores to calculate an index or estimate of the maximal tolerable dose of disopyramide. Additional evaluations performed at baseline and at each maximal administered dose regimen included tear and saliva quantitation, 24 hour electrocardiogram (ECG), exercise testing and programmed ventricular stimulation. Results showed that the maximal administered dose of disopyramide was greater with active pyridostigmine than with placebo: 295 ± 75 versus 245 ± 100 mg every 6 hours (p < 0.05). The calculated maximal tolerable dose was substantially greater in the presence of pyri-dostigmine: 355 ± 90 versus 260 ± 115 mg every 6 hours (p < 0.001). Maximal side effects questionnaire scores also reflected decreased anticholinergic activity in the presence of pyridostigmine compared with placebo: 101.9 ± 2.2 versus 104.6 ± 2.8, respectively (p < 0.005). Baseline tear and saliva production was significantly reduced during disopyramide therapy, but was restored toward normal by the addition of pyridostigmine. Analysis of 24 hour ECGs, exercise tests and programmed stimulation showed that pyridostigmine had no effect on the following properties of disopyramide: 1) reduction of ventricular tachycardia, couplets and premature ventricular complexes; 2) induced ventricular tachycardia cycle length; 3) refractory periods; and 4) QT intervals. At similar doses of disopyramide, peak and trough blood levels were unaffected by pyridostigmine. It is concluded that pyridostigmine selectively reverses the troublesome anticholinergic side effects of disopyramide without affecting its electrophysiologic or antiarrhythmic properties.
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine