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Gulf War and Health: Volume 1. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines
Pyridostigmine bromide was used during the Gulf War as a pretreatment for exposure to nerve agents. It has been used for more than 40 years in the routine treatment of myasthenia gravis and may be used following surgery in the reversal of neuromuscular blockade (Williams, 1984).
PB, a reversible cholinesterase inhibitor, was synthesized in 1945 by Hoffman-La Roche Laboratories in Switzerland and is sold under the trade name Mestinon bromide (Williams, 1984). PB is one of the quaternary ammonium anticholinesterase compounds, which generally do not penetrate cell membranes. Compounds in this category are poorly absorbed from the gastrointestinal tract and are excluded by the blood–brain barrier (Williams, 1984; Goodman et al., 1996).
Mestinon was approved by the Food and Drug Administration (FDA) in 1955 as safe for the treatment of myasthenia gravis. The FDA also approved an injectable form known as Regenol for reversing the effects of some anesthetic formulations (Rettig, 1999). In the treatment of myasthenia gravis, the average oral dose is 120–600 mg per day (in divided doses); however, the size and frequency of the dose must be adjusted to the needs of the individual patient (Physicians’ Desk Reference, 2000). The drug is poorly absorbed after oral administration, and peak plasma levels occur 2 to 3 hours after oral dosing. The drug is eliminated almost exclusively via the kidneys in the urine (Williams, 1984).
Side effects of PB are generally related to the large doses given to myasthenics; in surgical patients, adverse reactions are controlled by simultaneous administration of atropine (Williams, 1984). The acute cholinergic side effects of PB are due to stimulation of muscarinic or nicotinic receptors by increased acetylcholine (ACh). Muscarinic reactions include nausea, vomiting, diarrhea, abdominal cramps, increased peristalsis, increased salivation, increased bronchial secretions, miosis, and heavy perspiration. Nicotinic effects are chiefly muscle cramps, fasciculations, and weakness (Williams, 1984).
PB binds reversibly to AChE and prevents the enzyme from binding irreversibly with nerve agents. PB pretreatment is used by the military to obtain 10–20 percent inhibition of whole-blood AChE (Hubert and Lison, 1995). PB is not an antidote and has no value when administered after nerve agent exposure. It is not a substitute for atropine or 2-pralidoxime chloride; rather, it enhances their efficacy (Madsen, 1998).
The DoD reported that 5,328,710 doses of PB were fielded and estimated that approximately 250,000 personnel took PB during the Gulf War. It was supplied as a 21-tablet blister pack; the dosage prescribed was one 30-mg tablet every 8 hours. Variation in use occurred, however, because it was self-administered and was to be taken only when ordered by the unit commander (PAC, 1996). Thus, veterans’ actual exposure to PB is not known, and there are few examples of documentation in either individual health records or unit records (PAC, 1996).