Sarin diazepam

Diazepam and pralidoxime iodide are prescribed for victims affected by sarin. 

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). 

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. 

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

Clinical experience with the use of PAM-2 iodide, given with atropine and diazepam, in the treatment of the victims of the Tokyo sarin attack in 1995 was extremely favourable (Stojdjkovic and Jokanovic, 2005). Still, 2-PAM should not be recommended as the drug of choice due to its lack of efficacy against tabun and soman (Kassa, 2005). 

Taysse, L., Calvet, J.H., Buee, J., Christin, D., Delamanche, S. and Breton, P. 2003. Comparative efficacy of diazepam and avizafone against sarin-induced neuropathology and respiratory failure in guinea pigs influence of atropine dose. Toxicology, 188 197-209. 

Efficacy of the anticonvulsant usage in antidotic formulas depends considerably on OPC type. Thus, index of protection (IP) for the composition of ChR (HI-6 inclusive), cholinolytics and diazepam is much higher for the treatment of intoxication with soman and tabun, than in poisonings with sarin and VX [93],... 

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. 

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. 

Pure sarin is a colorless, odorless, volatile and highly lethal compound. It inhibits the enzyme action of cholinesterase, causing the production of excessive amounts of acetylcholine, which in turn affects the central nervous system. Diazepam and pralidoxime iodide are prescribed for victims affected by sarin. 

As stated, a number of PBPK/PD models have been developed for individual nerve agents (sarin, VX, soman, and cyclosarin) in multiple species. Chapter 58 in the current volume discusses tiie development of such models. Standalone PBPK or compartmental models have also been developed that describe the pharmacokinetics of certain countermeasures, such as diazepam (Igari et al., 1983 Gueorguieva et al., 2004) and oximes (Stemler et al., 1990 Sterner et al., 2013). However, to date, few models for specific countermeasures have been harmonized and linked to NA PBPK/PD models to be able to quantitatively describe their pharmacokinetic and pharmacodynamic interactions. This is partly due to the fact that most PBPK/ PD models developed for NAs and other OPs focus on the inhibition of ChEs as the critical endpoint. The lack of a mathematical description of the disruption of other complex biochemical pathways presents a problem for linking these NA models to those of many countermeasures. For example, the conventional NA countermeasures, atropine and diazepam, as well as many novel countermeasures, do not directly impact ChE kinetics because they act at sites distinct from the active site of the esterases, such as muscarinic, GABA, or NMDARs (Figure 69.2). 

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