A large number of clinical studies have reported that PB causes acute transient cholinergic effects in normal volunteers, patients given PB as a diagnostic test of hypothalamic pituitary function, and myasthenia gravis patients treated with the drug for extended periods. When used as a diagnostic test, PB is generally administered as a single oral 30- to 180-mg dose, which produces acute transient cholinergic symptoms in a minority of patients and normal volunteers. Within several hours of ingesting PB, 25 percent of subjects experience abdominal symptoms (cramps, increased digestive sounds, pain, diarrhea, and nausea), and 10 percent have muscular symptoms (skeletal muscle and tongue fasciculations sometimes accompanied by dysarthria) that typically last 1–2 hours (see, for example, Ross et al., 1987; Ghigo et al., 1990a,b,c, 1996a,b; Giustina et al., 1990, 1991; Murialdo et al., 1991, 1993; Bellone et al., 1992; O’Keane et al., 1992, 1994; Cordido et al., 1995; Yang et al., 1995; Coiro et al., 1998). The symptoms are usually mild, transient, and tolerable; seldom require medical intervention; and are not accompanied by central nervous system symptoms. Although the studies summarized in this report did not show a relationship between increasing dose and more severe side effects, none was designed specifically to demonstrate a dose–response relationship. There is, however, a trend toward a greater rate of symptoms at higher PB doses among subjects given several different doses in the same study.
The main therapeutic use of PB is to control muscle weakness in myasthenic patients; the daily doses of PB usually range from 120 to 600 mg. About one-third of those who take PB have one or more side effects, which are usually mild. The most common symptoms are gastrointestinal in origin. A few patients experience other cholinergic symptoms such as hypersalivation, increased perspiration, urinary urgency, increased bronchial secretion, and blurred vision. Patients seldom stop taking the drug because of side effects.
During the Gulf War, acute accidental poisoning with PB in doses ranging from 390 to 900 mg resulted in mild-to-moderate cholinergic symptoms occurring within several minutes of ingestion and lasting up to 24 hours. Patients typically developed muscarinic effects (e.g., abdominal cramps, diarrhea, nausea, hypersalivation, vomiting), urinary incontinence, and transient muscle fasciculation and weakness. The effects were self-limited and were well tolerated.
The most extensive information available on the acute effects of PB comes from studies of its use for diagnosis of growth hormone deficiency and its therapeutic use for myasthenia gravis. The doses of PB in these applications are higher than those used for prophylaxis during the Gulf War, yet these studies consistently indicate that PB is safe and effective in clinical applications. Side effects are predominantly gastrointestinal and muscular, do not last long, and have no long-term residual effects.
Results from other human studies, in both clinical and healthy volunteer populations, report the same gastrointestinal and muscular side effects, which