PB (Mestinon) is a prostigmine analogue that has been used since the 1950s to control the myasthenic phenomenon without any major side effects reported (Schwarz, 1956). The usual oral daily dose prescribed to control muscle weakness in myasthenic patients ranges from 120 to 600 mg (Aquilonius et al., 1983), although oral doses may vary from 60 to 1,500 mg per day (Breyer-Pfaff et al., 1990). Despite a short half-life, the pre-dose plasma concentration is relatively stable (Aquilonius et al., 1983). Blood levels of PB do not correlate with the degree of clinical toxicity observed, although they are somewhat predictive of cholinergic crisis in myasthenia gravis patients (Breyer-Pfaff et al., 1990).

In a large series of myasthenic patients followed for 5 years, 34 percent of those receiving PB had one or more, mostly mild, side effects (Beekman et al., 1997). The most common effects were gastrointestinal (30 percent); infrequent effects were hypersalivation (6 percent), increased perspiration (4 percent), urinary urgency (3 percent), increased bronchial secretion (2 percent), rash (1 percent), and blurred vision (1 percent). Only 1 percent of the patients had to stop the drug because of stomach complaints.

A number of studies dating back to the 1950s consistently have shown PB to be safe and effective in the treatment of myasthenia gravis (Schwab and Timberlake, 1954; Schwab et al., 1957; Osserman et al., 1958). PB provides short-term benefit and is still used in the treatment of myasthenia gravis, despite the introduction of surgery, immunotherapy, and intravenous gamma globulin as therapeutic modalities.

Oral doses of 180 mg per day of PB are also used to treat the generalized fatigue and pain of patients with postpolio syndrome. Even though the drug is ineffective in improving the symptoms associated with postpolio syndrome, patients tolerate the medication well with minimal side effects (Trojan and Cashman, 1995; Trojan et al., 1999, described later in chapter).

In conclusion, the majority of studies in the clinical literature focus on the efficacy of PB in the treatment of myasthenia gravis; however, most of the studies reviewed were not designed to determine adverse health effects. The widespread use of this compound has not typically been associated with short-or long-term adverse effects in myasthenia gravis patients.

Clinical Studies of PB in Veterans and General Health Outcomes

Information on symptoms and health status of 41,650 soldiers (6.5 percent of whom were women) who received PB at the onset of combat during Operation Desert Storm has been described (Keeler et al., 1991). Thirty medical officers in close daily contact with the combat units they served were queried retrospectively about the general physiological response of soldiers to PB and potential adverse effects. The reported effects represent impressions of the unit officers and were based on the number of clinic visits, discontinuations of PB, hospitalizations, and evacuations attributed to PB that came to their attention. Based on these anecdotal reports, the authors concluded that soldiers taking PB under combat conditions performed at full effectiveness, but experienced more



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