Sarin atropine

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. 

Nerve Agent Antidote Kit (NAAK or MARK I) consists of an atropine auto-injector (2 mg), a pralidoxime chloride auto-injector (2-Pam-Cl, 600 mg), the plastic clip joining the two injectors, and a foam case. The kit serve as a countermeasure to nerve agents, including tabun (GA), sarin (GB), soman (GD), GF, and VX. Military personnel can receive three MARK I for self/buddy aid. Possible side effects of atropine and/or 2-PAM-C1 are deemed insignificant in a nerve agent casualty. Intravenous atropine and 2-PAM-C1 can also be made available. The MARK I kit is manufactured by Survival Technology, Inc., Rockville, Maryland. 

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. 

The global standard for the treatment of sarin toxicity is the administration of (1) atropine, (2) an oxime agent like PAM, and (3) diazepam (Medical Letter, 2002). 

After the Tokyo subway sarin attack, St Luke s Hospital, which treated 640 victims, used about 700 ampules of PAM and 2,800 ampules of atropine (Okumura et al, 1998). This calculates out to 550 mg of PAM and 2.2 mg of atropine for each victim. The route of administration was intravenous in all cases with a total dose of atropine in severe cases 1.5 mg to 9 mg (Okumura et al, 1996) doses which reflect the low concentration and passive means of sarin dispersal used in the Tokyo attack. 

Based on the experience of Iranian physicians who treated sarin toxicity during the Iran-Iraq war (Newmark, 2004), PAM was not available on the front lines and atropine alone was used for treatment. The doses of atropine used were considerably higher than those used in the Tokyo subway sarin attack, or that are generally recommended in the USA (Medical Letter, 2002). The Iranian protocol called for initial administration of 4 mg intravenously. If no atropine effects (improvement in dyspnea or decrease in airway secretions) were seen after 1 to 2 min, 5 mg was then administered intravenously over 5 min while heart rate was monitored. A rise in heart rate of 20 to 30 beats per min was regarded as an atropine effect. In severe cases, 20 mg to 200 mg was given. Regardless of dose, the key to saving lives, in their opinion, was how soon the atropine was administered. 

Thus, treatment without the use of an oxime agent is possible. Of course, ideally, in countries where this is economically possible, treatment should use the three recommended drugs (I) atropine, (2) an oxime agent like PAM, and (3) diazepam, and the use of autoinjectors for administration is also helpfiil. Unfortunately, terrorist attacks using sarin are also carried out in less economically developed countries and even if the drugs are available, considerations related to cost performance need to be considered. In this sense, preference should be given to the availability of atropine and diazepam. In other words, unless it is economically feasible, funds should be used to obtain atropine and diazepam, rather than oxime agents, whose cost-benefit ratio is still inconclusive. 

Gupta, R.C., Dettbam, W-D. (1992). Potential of memantine, d-tubocurarine and atropine in preventing acute toxic myopathy induced by organophosphate nerve agents soman, sarin, tabun and VX. NeuroToxicology 13 500-14. 

Autoinjectors (AtroPen , Mark I , Combopen MC ) are atropine or atropine and pralidoxime combinations available for human use. They are not used in veterinary medicine as they are not adjustable for different sized patients. Experimental vaccines against nerve agent VX, and monoclonal antibodies which protect against soman, sarin, and tabun toxicity have been produced and are being tested (Dunn and Sidell, 1989 Somani et al, 1992). 

Tabun, sarin, Mild/moderate symptoms Neonates and Atropine 0.05 mg/kg IM/ Neonates Diazepam 0.1-0.3 mg/kg/dose... 

FIGURE 62.4. RBC AChE inhibition in rhesus monkey following administration of sarin [0.75 LD50 (15 pg/kg) i.v.] and with 2-PAM (25.8mg/kg) administered IM at 9 min postsarin i.v. administration. Atropine was administered (0.4 mg/kg) IM 15 min prior to sarin administration. The filled circles indicate experimental data (Woodard et al, 1994) the curves show our PBPK model simulations of AChE activity after sarin, both with (upper curve) and without (lower curve) 2-PAM administration. 

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. 

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