Pyridostigmine side effects

Why choose pyridostigmine as the anticholinesterase (consider the duration of action, side-effects and the formulations available) ... 

Pyridostigmine bromide studies have been performed in dogs, guinea pigs, monkeys, rabbits, rats, and mice. Diarrhea, salivation, tremors, and respiratory failure were seen prior to death. Side effects of the drug are related to muscarinic and nicotinic effects. Toxicity is also related to cholinergic stimulation. Effectiveness of pretreatment to reduce lethality after exposure to nerve agents (in particular, soman) is dependent on the administration of atropine and pralidoxime, postexposure. 

Acute side effects occur from therapeutic doses in 1 % of patients. However, an excessive dose of an anticholinesterase drug results in a cholinergic crisis. The condition results from stimulation of muscarinic receptors and depolarization of the motor end plate. Symptoms of salivation, lacrimation, diaphoresis, weakness, and respiratory failure may result. Therapeutic use of pyridostigmine should be discontinued in the presence of nerve agent poisoning, as it may exacerbate symptoms in certain exposures. 

Cook, J. E., Kolka, M. A., Wenger, C. B. (1992). Chronic pyridostigmine bromide administration Side effects among soldiers working in a desert environment. Military Medicine, 157, 250-254. 

It has also been suggested that side effects from the pyridostigmine bromide (PB) prophylactic (see above) were responsible for Gulf War syndrome. 

Pharmacodynamic actions of PB were studied as early as 1946 by Koster and Koelle. Anticholinesterase activity of PB was about one-fifth of the activity of neostigmine " whereas, the comparative activity reported by Blaschko et al." was about one-tenth. One of the most noticeable differences between neostigmine and pyridostigmine is the inability of the latter compound to produce a direct stimulant action on smooth muscle either in vitro,or in vivof It has been suggested that this may account for the occurrence of fewer unpleasant side effects when pyridostigmine is used clinically." " Foldes and Smith reported maximum inhibition of butyl-cholinesterase with 7 X 10 " M PB at 1 h. 

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