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Combined effect of disopyramide and bethanechol: use of bethanechol to prevent anticholinergic side effects of disopyramide without reduction of antiarrhythmic efficacy.

Authors
  • Konishi, T
  • Kadoya, M
  • Ikeguchi, S
  • Sakai, K
  • Tamamura, T
  • Kawai, C
Type
Published Article
Journal
Journal of Cardiovascular Pharmacology
Publisher
Ovid Technologies (Wolters Kluwer) - Lippincott Williams & Wilkins
Publication Date
Aug 01, 1989
Volume
14
Issue
2
Pages
341–350
Identifiers
PMID: 2476611
Source
Medline
License
Unknown

Abstract

Because bethanechol chloride (B) relieves the anticholinergic side effects of disopyramide (D), we examined the combined effects of D and B on the heart and urinary bladder. B was confirmed to counteract dose dependently the effect of D on the dog bladder. In the ventricular muscle, the combined electrophysiological effects (D + B) were additive, with no reduction in the effect of D. With the control value set as 100%, the decrease in the maximum rate of depolarization with 5 X 10(-6) g/ml D (90 +/- 6%) was not affected by the same dose of B (D + B: 84 +/- 14%). Moreover, the effective refractory period (ERP) was larger with D + B (128 +/- 12%) than with either B (109 +/- 9%, p less than 0.01) or D (115 +/- 11%, p less than 0.05). In contrast, in the atrial muscle and AV and SA nodes, B had marked acetylcholine-like effects. These were completely suppressed by the addition of D except for the atrial ERP with the highest tested concentration of B (5 X 10(-6) g/ml). In the latter case, the prolongation of ERP was minimal (B + D: 105 +/- 14%) as compared with D alone (130 +/- 15%). Since the plasma concentration of B after oral administration of a clinical dose is expected to be on the order of 10(-7) g/ml, no practical effect is anticipated. We conclude that B can be expected to counteract urination disorders caused by D without reducing D's antiarrhythmic efficacy.

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