Disopyramide-pyridostigmine interaction: Selective reversal of anticholinergic symptoms with preservation of antiarrhythmic effect

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 less than 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 less than 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 less than 0.005). Baseline tear and saliva production was significantly reduced during disopyramide therapy, but was restored toward normal by the addition of pyridostigmine.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of Obstructive Hypertrophic Cardiomyopathy Symptoms and Gradient Resistant to First-Line Therapy With β-Blockade or Verapamil

“…This allows continuation of adequate disopyramide dosing. 15 Patients who had no symptom improvement, or who experienced drug side effects were referred for surgical septal myectomy, unless they had significant medical comorbidity or refused surgery. 3 Selected patients were referred for surgical septal myectomy without an intervening disopyramide trial.…”

“…15 Half of our patients received pyridostigmine timespan at least temporarily. The safety of the combination in obstructive HCM is shown in the present study.…”

Xerostomia: aetiology and management in cancer patients

“…Other drugs, such as the anticholinesterases distigimine [96] and pyridostigmine [84], have also been used in managing xerostomia, although to a much lesser extent.…”

Acute electrophysiologic consequences of pyridostigmine inhibition of cholinesterase in humans

“…Pyridostigmine has been traditionally used for the treatment of myasthenia gravis due to its action on the motor plate in skeletal muscle (11). In addition, it has been shown to counteract the adverse anti-cholinergic effects of disopyramide, such as decreased baseline saliva and tear production (12). We have previously shown that short-term administration of pyridostigmine may be also potentially useful for cardiovascular protection since in healthy individuals and patients with cardiovascular diseases it results in beneficial effects on markers of cardiovascular risk and dysfunction (8,(13)(14)(15)(16)(17)(18)(19).…”