asthenia gravis treated with the drug for extended periods. As a diagnostic test, PB is generally administered as a single oral 30–180-mg dose, which produces acute transient cholinergic symptoms in a minority of patients and normal volunteers. Within 1 or 2 hours after ingesting PB, about 25 percent of subjects experience abdominal symptoms, and about 10 percent have muscular symptoms that typically last 1–2 hours. The abdominal symptoms are cramps, increased digestive sounds, pain, diarrhea, and nausea, and the principal nicotinic cholinergic symptoms are skeletal muscle and tongue fasciculations sometimes accompanied by dysarthria. The symptoms are characteristically mild, transient, and tolerable, without requiring medical intervention, and are not accompanied by central nervous system symptoms. Although a clear dose–response effect on symptoms was not apparent from a review of the studies summarized in this report, none were designed to demonstrate this effect. There is, however, a trend toward a greater rate of symptoms at higher PB dose ranges among subjects given several different doses in the same study.

PB is used to control muscle weakness in myasthenic patients, and the daily dose of PB usually ranges from 120 to 600 mg. Studies indicate that about 34 percent of those receiving PB have one or more, mostly mild, side effects, usually gastrointestinal, although a few patients experience other cholinergic symptoms such as hypersalivation, increased perspiration, urinary urgency, increased bronchial secretion, and blurred vision. Patients rarely have to stop the drug because of abdominal complaints.

During the Gulf War, acute accidental poisoning with PB in doses ranging from 390 to 900 mg resulted in mild to moderate cholinergic symptoms within several minutes of ingestion, which lasted up to 24 hours. Patients typically developed muscarinic effects such as abdominal cramps, diarrhea, nausea, hypersalivation, vomiting, and urinary incontinence. The effects are self-limited and well tolerated by young adults.

As noted above, the most extensive information available on the acute effects of PB comes from studies of its use for diagnosis of growth hormone deficiency in adults and children and its therapeutic use in the treatment of myasthenia gravis. These studies, of doses higher than those used for prophylaxis during the Gulf War, consistently indicate that PB is safe and effective in clinical applications. Side effects noted are predominantly gastrointestinal and muscular, and are of a short duration with no long-term residual effects.

Results from other human studies of both clinical and healthy volunteer populations, report the same gastrointestinal and muscular side effects, which are transient and characteristically mild. A small number of idiosyncratic reactions are noted.

The committee concludes that there is sufficient evidence of an association between PB and transient acute cholinergic effects in doses normally used in treatment and for diagnostic purposes.

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