Pyridostigmine Bromide, PB

Sabot
Pyridostigmine Bromide (PB) pills.

Planning for the Gulf War included numerous countermeasures to the threat that Iraq might use chemical warfare agents. One of those countermeasures was the distribution of pyridostigmine bromide (PB) tablets to service members in the field. These tablets were a "pre-treatment", intended to be taken in advance of a threatened chemical warfare attack in order to increase the likelihood that the usual antidotes atropine and pralidoxime would better reverse the effects of the nerve agent soman.

Organophosphate nerve agents (such as sarin, cyclosarin, and soman) combine with and inactivate the enzyme acetylcholinesterase (AchE). As a result, acetylcholine (Ach) builds up in the nervous system, causing excessive muscle stimulation that ends in muscle fatigue, paralysis, and death. The antidotes, atropine and pralidoxime, are designed to reverse this poisoning. Soman, or GD, is a particularly dangerous nerve agent because its combination with AchE becomes permanent in minutes, after which it cannot be reversed by the antidotes. PB taken before exposure to soman combines with some normal AchE, protecting that fraction of the enzyme from soman, and allowing it to resume normal activity later.

During the 1990-1991 Gulf War, PB was classified by the Food and Drug Administration (FDA) as an Investigational New Drug (IND) for use as a pretreatment for soman poisoning. Although the protective action of PB against soman had been demonstrated in animal experiments, its ability to protect humans could not be tested for ethical reasons. Ample data on the safety of PB in normal people was demonstrated before the FDA approved PB in 1955 for the treatment for a medical condition called myasthenia gravis. In February 2003, the FDA approved the military combat use of PB to prevent death from exposure to soman.

PB tablets were issued to service members in blister packs of 21 tablets, and were to be taken by service members upon receipt of an order at the time of a perceived threat of chemical warfare agent attack. Service members were to take one 30-milligram tablet every eight hours until the order was given to stop. Records documenting individualsí use of PB during the Gulf War were not kept. Based upon supply system records, it has been estimated that perhaps 250,000 American service members ingested at least one PB tablet. Individual accounts by veterans indicate a wide variation in PB use. Some service members reported taking none, others a small number of tablets. Some reported taking double doses in the hope of enhancing the protective effect, and still others reported taking PB continuously for months. Many veterans reported stopping PB use because they found the side effects unpleasant (e.g., nausea, abdominal cramps, urinary urgency, headache).

Following the Gulf War, the onset of illnesses in many Gulf War veterans prompted concerns that pyridostigmine bromide might have contributed to some of these illnesses. In response, the government funded research projects to evaluate the possible health effects of pyridostigmine bromide. Research in animals has focused on toxicological effects of PB and on the possible interactions of PB with other chemicals, sand, and stress. Research in humans has focused on the short-term effects of the low doses used for pretreatment against soman and on individuals who took PB during the Gulf War.

Major reports on pyridostigmine bromide have been published by RANDís National Defense Research Institute and by the National Academy of Sciencesí Institute of Medicine.

REFERENCES

Institute of Medicine, National Academy of Science. Committee on Health Effects Associated with Exposures During the Gulf War, Gulf War and Health, Volume 1. Depleted Uranium, Sarin, Pyridostigmine Bromide, Vaccines, 2000.

Golomb BA. A Review of the Scientific Literature As It Pertains to Gulf War Illnesses, Volume 2: Pyridostigmine Bromide, RAND Corporation, National Defense Research Institute, Santa Monica, CA 1999.

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