Pyridostigmine prophylaxis

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. 

It appears from these results that simple prophylaxis (without post-exposure treatment) against OP is not sufficient. Therefore, pyridostigmine has importance as a prophylactic drug especially when it is combined with post-exposure antidotal treatment. For further development, it is necessary to search for novel prophylactic drugs and new routes of administration. In this context, preparations of cholinesterases are of special importance for the development of more effective prophylactics. 

The fact that rodent plasma CarbE has a scavenger function against the highly toxic OP compounds is the basis for the CarbE concept, which is an outline of how the toxicity of soman may be influenced by the different content of plasma CarbE in different species in both the absence and presence of therapeutic interventions such as pyridostigmine prophylaxis or any artificially supplied scavenger in the plasma (Sterri and Fonnum, 1989 Sterri, 1989). This is further described below (see Toxicity of nerve gases and Therapeutic interventions). 

The effect on soman toxicity by pyridostigmine prophylaxis in different species could in principle also be explained by the CarbE concept of Sterri and Fonnum (1989). This means that the protection factors of carbamate prophylaxis as calculated for the different species were similar to the experimental protection factors of pyridostigmine prophylaxis against soman as observed for rat and guinea pig (Gordon et al, 1978) as well as marmoset and rhesus monkey (Dimhuber et al, 1979). Thus, due to the CarbE concept, we were fairly convinced that the hiunan species would achieve a similar protection by pyridostigmine prophylaxis as rhesus monkey, since both species lack the... 

Reversible ChE inhibitors of the pyridostigmine type are used for prophylaxis of OPC poisonings. Good effect was gained in the combined use of pyridostigmine and diazepam [107],... 

In the case of soman, therefore, once ageing has occurred, recovery of enzyme function depends on re-synthesis of AChE. As a result, it is important that an oxime is administered as soon after soman exposure as possible so that some reactivation of AChE occurs before all of the enzyme becomes aged. The phenomenon of soman-induced ageing led to the development of carbamate (pyridostigmine) prophylaxis for nerve agent poisoning. 

K.C., Population pharmacokinetics and pharmacodynamics of pyridostigmine hro-mide for prophylaxis against nerve agents in humans, J. Clin. Pharmacol., 38, 227, 1998. 

Marino, M. T., Schuster, B, G, Brueckoer, R. R, Lin, E., Kaminskis, A and Lasseter, K, C. (1998). Ftopulation pharmacokinetics and pharmacodynamics of pyridostigmine bromide for prophylaxis against nerve agents in humans. J. Clin. Pharmacol. 38,227-235. 

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