Pyridostigmine respiratory effects

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. 

Severely exposed casualties lose consciousness shortly after the onset of effects, usually before any signs of respiratory compromise. They have generalized muscular twitching or convulsive jerks and may initially have spontaneous but impaired respiration. Breathing ceases completely within several minutes after the onset of exposure in a severely poisoned person who has not been pretreated with pyridostigmine. 

The effectiveness of pyridostigmine pretreatment may not be conclusive evidence against the importance of central mechanisms in respiratory arrest it appears that there is at least partial permeability of the blood-brain barrier to polar compounds such as pyridostigmine, specifically in the regions of the fourth ventricle and brainstem, where respiratory centers are located. In addition, an increase in blood-brain barrier permeability occurs rapidly after soman administration.1314 The key observation... 

The nerve agent soman causes loss of muscle control and death from respiratory failure. Evidence of the effectiveness of pyridostigmine bromide as a pretreatment for exposure to soman was obtained primarily from studies in monkeys and guinea pigs. This evidence shows that administration of the drug before exposure to soman, together with atropine and pralidoxime administered after exposme, increases survival. The FDA believes... 

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