CLINICAL EFFICACY OF PROPANTHELINE BROMIDE IN NEUROCARDIOGENIC SYNCOPE - PHARMACODYNAMIC IMPLICATIONS

The pharmacological response with tilt-table testing predicts long-ter m efficacy in neurocardiogenic syncope. However, beta-blockers for neu rocardiogenic syncope are often not tolerated or are ineffective, Sinc e cholinergic tone is important in the efferent part of the neurocardi ogenic reflex, we investigated the pharmacodynamics and efficacy of pr opantheline bromide in preventing neurocardiogenic syncope. We studied 16 patients (11 males) with a mean age of 48.8 (+/- 15.1) years with presyncope or syncope and who had positive baseline tilt-table studies at a mean of 15.8 (+/- 10.3) minutes into the upright 60 degrees tilt . They were given propantheline bromide orally, an anticholinergic age nt, at a dose of 64.3 (+/- 21.8) mg/day for 7 days, and tilt-table tes ting was repeated 1 hour after readministration of propantheline bromi de, 30 mg orally. After propantheline bromide treatment, 13 of 16 pati ents (81%) had no inducible presyncope or syncope on repeat tilt-table testing. In this group of responders, the mean minimum heart rate dur ing upright tilt-table testing increased from 43.2 (+/- 77.3) beats/mi n to 77.3 (+/- 17.2) beats/min after propantheline bromide (p < 0.005) . More significantly, the minimum mean arterial blood pressure increas ed from 42.2 (+/- 25) mmHg to 81.3 (+/- 16.7) mmHg (p < 0.0005) during upright tilt. At a follow-up of 15.2 (+/- 7.4) months, in the respond er group (12 patients with long-term follow-up), the average dose of p ropantheline bromide was 32.5 (+/- 23.8) mg/day, which was significant ly reduced from the initial dose (p < 0.05). A clinical recurrence of symptoms occurred in only 4 out of 12 patients on propantheline bromid e (33%), none of which were directly attributable to drug failure. It was concluded from this study that propantheline bromide is highly eff ective in preventing neurocardiogenic syncope. In addition, propanthel ine bromide's effectiveness is more than would be expected by preventi on of cardioinhibition in neurocardiogenic syncope and would support a role for direct cholinergic control of vascular tone.