Disopyramide-pyridostigmine interaction

Selective reversal of anticholinergic symptoms with preservation of antiarrhythmic effect

S. L. Teichman, A. Ferrick, Soo G. Kim, J. A. Matos, L. E. Waspe, John Devens Fisher

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

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 pyridostigmine: 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 period; 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.

Original languageEnglish (US)
Pages (from-to)633-641
Number of pages9
JournalJournal of the American College of Cardiology
Volume10
Issue number3
StatePublished - 1987

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Pyridostigmine Bromide
Disopyramide
Cholinergic Antagonists
Ventricular Tachycardia
Placebos
Tears
Saliva
Electrocardiography
Ventricular Premature Complexes
Cholinesterase Inhibitors
Exercise Test
Cross-Over Studies
Exercise

ASJC Scopus subject areas

  • Nursing(all)

Cite this

Disopyramide-pyridostigmine interaction : Selective reversal of anticholinergic symptoms with preservation of antiarrhythmic effect. / Teichman, S. L.; Ferrick, A.; Kim, Soo G.; Matos, J. A.; Waspe, L. E.; Fisher, John Devens.

In: Journal of the American College of Cardiology, Vol. 10, No. 3, 1987, p. 633-641.

Research output: Contribution to journalArticle

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