Atropine sarin poisoning

Some very interesting results on the prophylaxis of sarin poisoning with DAM in normal and TOCP-pretreated rats are reported by Myers (1959). The author observed that with DAM prophylaxis the LD50 of sarin in the atropinized TOCP-pretreated rats was only one-seventeenth of LD50 in the atropinized normal rats. This may be regarded as a consequence of sarin binding to plasma CarbE in the normal rats, since any direct reaction between sarin and the prophylactic administered DAM should be similar in the normal and TOCP-pretreated animals. 

In the experiments in rats with acute sarin poisoning (DL50), antidotes were administered intraperitoneally as follows dipiroxym 15 mg/kg, atropine 20 mg/ kg (2 times a day, every 12 hours, for 2 days). The first dose of antidote was administered to the animals 10 minutes after exposure to the poison. It was established that, in acute intoxication with sarin, the usage of atropine amplified its immunotoxic effect. Dipiroxymc, on the contrary, reduced manifestations of the postintoxication immunodeficiency state. 

Fleisher, J.H., Harris, L.W., Miller, G.R., Thomas, N.C., and Cliff, W.J., Antagonism of sarin poisoning in rats and guinea pigs by atropine, oximes, and mecamylamine. Toxicol. Appl. Pharmacol., 16, 40-47,1970. 

At the St. Luke s International Hospital, after 9 00 am but before sarin poisoning was clearly suspected, atropine sulfate was administered pal-liatively to treat muscarinic symptoms such as miosis and increased secretion. A total of 515 mg was administered to 640 victims, and while this dose was sufficient, it was considerably lower than the recommended dose in war zones (Okumura et al, 1996,1998b,2005) and may have been related to the fact that the concentration of sarin used in the attack was 35%. The administration of 2-PAM by the St. Luke s hospital at approximately 11 00, appeared to control fasciculation, but the effects associated with sarin poisoning could have been alleviated by time and it is difficult to say whether 2-PAM was therapeutically effective. None of the patients were saved by the use of 2-PAM. In addition to atropine sulfate and 2-PAM, diazepam was used in patients with convulsions. 

TABI.E 4. Relationship between Plasma Oxime Concentrations and Mortality in Sarin-Poisoned Rats Also Given Atropine 17.4 mg/kg ... 

Loomis, T. A. (1963). Distribution and excretion of pyridine-2-aldoxime methiodide (PAM) Atropine and PAM in sarin poisoning. To.xicot. Appl. Pharmacol. 5,489—499. 

Different doses of 2-PAM Cl were administered (with atropine) in several studies. In sarin-poisoned rabbits, the protective ratio (PR the ratio of the LD50 with treatment to the LD50 without treatment) increased from 25 to 90 when the intravenous dose of 2-PAM Cl increased from 5 mg/kg to 10 mg/kg144 the PR increased from 1.6 to 4.2 when the intramuscular dose of 2-PAM Cl increased from 30 mg/kg to 120 mg/kg in sarin-poisoned rats122 and the PR increased from 1.9 to 3.1 when the intramuscular dose of 2-PAM Cl increased from 11.2 mg/kg to 22.5... 

High therapeutic effect was received with the usage of atropine (10 mg/kg, i.m.) and carboxime (30 mg/kg, i.m.) in animals poisoned with sarin, soman and VX. 

Davies, D.R., and P. Holland. 1972. Effect of oximes and atropine upon the development of delayed neurotoxic signs in chickens following poisoning by DFP and sarin. Biochem. Pharmacol. 21 3145-3151. 

Koplovitz, I., Harris, L.W., Anderson, D.R., Lennox, W.J., Stewart, J.R. (1992). Reduction by pyridostigmine pretreatment of the efficacy of atropine and 2-PAM treatment of sarin and VX poisoning in rodents. Fundam. Appl. Toxicol. 18 192-6. 

Worek, F., Kirchner, T., Szinicz, L. (1995). Effect of atropine and bispyridinium oximes on respiratory and circulatory function in guinea-pigs poisoned by sarin. Toxicology 95 123-33. 

A special issue from this Japanese experience are ocular effects of poisoning with sarin and their treatment. Some authors unsuccessfully treated strong miosis and consequential visual darkness with systemic atropine [15, 29], Others used 0.25% or 1.0% atropine sulphate eye drops, but these patients complained of atropine-induced photophobia and poor focusing [25], Our suggestion for optimal treatment of ocular manifestations of intoxication with organophosphorus cholinesterase inhibitors is topical use of pralidoxime chloride eye drops instead of atropine [42], Ocular pain should be treated with tropicamide 0.5% [28],... 

However, there are publications demonstrating that some oximes are not considered to reach a plasma concentration of > 4 pg/ml to counteract the toxic effects of OPC. Shiloff and Clement reported that a plasma concentration of HI-6 of only 0.72 pg/ml and plasma concentration of pralidoxime of only 2.56 pg/ml were required to protect 50% of rats against a subsequent dose of three times the LD50 of sarin when followed immediately by atropine. On the other hand, obidoxime has to reach the plasma concentration of 9.05 pg/ml to protect 50% of rats poisoned with sarin at a dose of 3xLD50 (18). 

Urbanski, R., Evaluation of the therapeutic effectiveness of optimal doses of atropine sulphate, obidoxime and diazepam in acute poisoning with soman, sarin and VX, Lek. Wojsk., 64,486-490, 1988. 

Weger, N., and Szinicz, L., Therapeutic effects of new oximes, benactyzine and atropine in soman poisoning. Part I. Effects of various oximes in soman, sarine and Vx poisoning in dogs, Fundam. Appl. Toxicol. 1(3-4), 161-163,1981. 

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