engleski

Therapeutic effect induced by atropine, pyridostigmine and oximes in tabun exposed mice

A misuse of some highly toxic organophosphorus compounds (OPc), called nerve agents, presents a continuos threat worldwide. The current standard treatment for poisoning by OPc includes the combined administration of cholinesterase reactivators (oximes), a muscarinic cholinergic receptor antagonist (atropine sulphate) and pretreatment with reversible carbamate AChE-inhibitor, such as pyridostigmine bromide. Unfortunately, an universale antidote which is efficient for poisoning by all known nerve agents does not exist. In this study an attempt was made to establish whether combination of pyridostigmine and atropine in pretreatment and oximes K048 and K074 with atropine in therapy have potency to increase the resistance of mice against multiple LD50 doses of tabun. TMB-4, which is the best-known antidote in tabun poisoning, was used for comparison. Pyridostigmine and oximes were used at doses of 5 % or 25 % of their LD50 while atropine was used at dose of 10 mg/kg. Prophylaxis with pyridostigmine showed minor dose dependent differences, but when pyridostigmine was applied with atropine better efficacy was observed especially with higher dose. However, the pretreatment of pyridostigmine with atropine 15 minutes before tabun-poisoning and therapy of oximes with atropine one minute after tabun administration to mice showed an improvement in the antidotal therapy and drastically decreased tabun toxicity. The best therapeutic effect was obtained when pyridostigmine (25 % of its LD50) in combination with atropine was used in pretreatment and oxime K048 (25 % of its LD50) in combination with atropine in therapy. This regimen insured survival of all tested animals after the application of 25.0 LD50 doses of tabun. We can conclude that simple prophylaxis (without postexposure therapy) against tabun was not sufficient enough ; yet by protection of experimental animals poisoned with tabun it enhanced the efficacy of antidotal treatment.

antidote; atropine sulphate; nerve agents; oximes; prophylaxis; pyridostigmine bromide; therapy

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