Atropine therapeutic ratio

These statistics tends to belie the notion that children and the elderly, although somewhat more vulnerable, are extremely more likely to succumb to overdose. None of these data clearly establish the LD50 however, which is required to estimate the therapeutic ratio (LD50/ID50) for atropine. This ratio is an important key to making reasonable estimates of lethality for the other belladonnoids, since there are no BZ deaths (for example) from known dosage on which to base such estimates. 

Of course, none of these data precisely establish the LD50, which is needed to estimate the therapeutic ratio (LD50/ID50). Nevertheless, extrapolation of the approximate therapeutic ratio for atropine (while also taking into account that lethality among the glycolates is proportional to their peripheral potency) provides the most feasible way to estimate the LD50 for the other belladonnoids (none of which have been known to have caused death in humans). 

Standard therapy of OP poisoning consists of the administration of a combination of atropine, oxime, and diazepam with other supportive measures when necessary. However, the possibility of addition of purified enzymes such as AChE, ChE, CarbE, and A-esterases to this therapeutic scheme has been considered and preliminary experiments in animals have shown much better protective effect after addition of exogenous enzymes. In this respect, protective effects of AChE, ChE, and CarbE are based on formation of covalent conjugates or phosphory-lated enzymes in the stoichiometric ratio 1 1. Capacity for binding of these enzymes is limited by the number of active sites on the enzyme to which OP molecules can be bound. This means that more enzymes have to be administered in order to achieve better detoxification of OPs which may not always be possible due to adverse effects. This can also be infiuenced by differences in the extent of spontaneous reactivation of these enzymes inhibited by OP. 

The therapeutic efficacy of oximes is usually focused on the evaluation of the protective ratio (PR), which is the ratio of the LD50 value of nerve agents for therapeutically protected animals to the LD50 value of nerve agents for unprotected animals. The authors usually publish data obtained from experiments where a combination of atropine and an oxime is used as an antidotal treatment because this possibility is much more relevant to anticipated military use than atropine or oxime alone. The results of published experiments are listed in Table 4(10, 32-47). 

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