Pyridostigmine pretreatment with

A third approach to protection against excessive acetylcholinesterase inhibition is pretreatment with reversible enzyme inhibitors to prevent binding of the irreversible organophosphate inhibitor. This prophylaxis can be achieved with pyridostigmine but is reserved for situations in which possibly lethal poisoning is anticipated, eg, chemical warfare (see Chapter 7). Simultaneous use of atropine is required to control muscarinic excess. 

Dirnhuber, P., M.C. French, D.M. Green, L. Leadbeater, and J.A. Stratton. 1979. The protection of primates against soman poisoning by pretreatment with pyridostigmine. J. Pharm. Pharmacol. 31 295-299. 

Miosis, pain, dim vision, and nausea can be relieved by topical atropine in the eye. Pretreatment with carbamates may protect the cholinesterase enzymes before nerve agent exposure. Pyridostigmine bromide is available as a pretreatment for nerve agent exposure. It is available in 30 mg tablets tablets should be administered every 8h. When used prior to exposure, it should be followed by atropine and pralidoxime chloride after exposure. 

Animal studies that have employed prophylactic protocols, for antidotes that would not be used as prophylaxes should be extrapolated to post-poisoning treatment cautiously. Likewise, those studies involving antidotes used on pyridostigmine-pretreated animals should be extrapolated to non-pretreated human populations with caution. 

The concept of using carbamates as pretreatment which protects against OP intoxication was first mooted in 1956 by Koster who demonstrated that cats pretreated with a small dose of eserine (physostigmine) survived poisoning by supralethal doses of diisopropylphosphorofluori-date (DFP) (Koster, 1956). Subsequently, Berry and Davies (1970) demonstrated the effectiveness of a combination of atropine and carbamate pretreatment against soman poisoning. At that time, it was not considered that pretreatments with substances such as atropine, with marked actions on the central nervous system, would be acceptable for human use. For this reason, effort was concentrated upon pretreatment with pyridostigmine, a quaternary carbamate, which would not be expected to cross the blood-brain barrier and affect the central nervous system. 

The relative strengths and weaknesses of pretreatment with pyridostigmine and physostig-mine/hyoscine are exemplified by the results of... 

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