PVR, this effect might be a beneficial one. No adverse reactions were observed. The investigators concluded that these results indicate the relative safety of the combination of PB and beta-blockers. However they acknowledged that such a small sample and brief period of treatment with PB do not rule out possible rare side effects, especially among people with significant cardiac conduction defects or congestive heart failure.

Teichman and colleagues (1985) described a beneficial interaction between PB and the ventricular antiarrhythmic agent disopyramide. Use of disopyramide is limited by its anticholinergic side effects (xerostomia, dryness of nose and eyes, urinary retention, constipation, abdominal pain, and blurred vision). To prevent or relieve these side effects, a sustained-release form of PB was administered to 27 of 106 disopyramide-treated patients referred for arrhythmia therapy. Doses varied from 90 mg every 12 hours (the usual dose) to as high as 180 mg every 8 hours. When PB was administered prophylactically, none of the patients receiving disopyramide developed anticholinergic side effects compared with 29 percent of those not treated with PB. Of the 10 patients treated at the onset of anticholinergic symptoms, 7 had complete resolution of their symptoms and 3 improved. There were no cardiac side effects attributable to PB, nor was there any evidence of decreased efficacy of disopyramide among PB-treated patients. The authors concluded that since PB caused no measurable decrease in disopyramide blood levels, the prevention or amelioration of anticholinergic side effects was related to its cholinomimetic activities and PB might be a useful agent for the treatment of disopyramide-related anticholinergic side effects.

In conclusion, studies of PB in patients with underlying medical problems are difficult to generalize to the normal healthy population because the disease state may affect the outcome of the response. The greatest experience with the cardiovascular side effects of PB is drawn from the clinical histories of patients with myasthenia gravis, usually at doses higher than those likely to have been used in the Gulf War. The incidence of drug-related cardiac arrhythmias appears to be approximately 1 percent and reversible with a decrease in dosage of PB. It is unlikely that the arrhythmias were due primarily to the underlying illness since myocardial involvement in myasthenia gravis is relatively uncommon. Older patients and those with pre-existing conduction abnormalities are at highest risk. It is of interest that studies of other patient groups also support the relationship between greater age and the risk of untoward cardiac events. This concordance among patient groups supports the association observed between age and cardiovascular side effects in PB-exposed individuals in the general population.

Other drug interactions have been described (see Box 6.1). In the literature reviewed above, no clinically significant side effects were noted when patients on beta-adrenergic blocking agents were treated with PB; although the study was brief and the number of subjects relatively small, no cardiac side effects of PB were observed.

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