Atropine lethality estimates

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. 

Goodman noted that the usual textbook estimates of the lethal dose of atropine (and scopolamine) are undoubtedly too low. With respect to scopolamine, for example, he found 9 cases that survived scopolamine doses of 225-267 mg, 3 cases that survived 324-384 mg and 2 who survived 500 mg.. (Abood also reported personal observation of two recoveries from large oral doses of scopolamine 350 mg and 500 mg, respectively.) These doses are close to the highest reported lethal range for atropine. Since scopolamine has about 7x the potency of atropine centrally, but roughly equal potency peripherally, one can infer that death from belladonnoid drugs is probably due to a peripheral effect - most likely cardiotoxicity. 

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). 

Lethal Dose Estimates for Atropine in an adult population... 

Table 12 Lethality dose estimates for atropine derived from probit analysis...

We used an additional analysis to support the estimated LD50/ID50 ratio for BZ. Upon reviewing the LD50 of several glycolates in the mouse, it appeared that the lethality of each closely paralleled its peripheral (as reflected in heart rate changes) rather than central effects (as reflected in performance decrements). This calls into doubt the opinion, voiced in previous textbooks of pharmacology, that death from belladonnoids such as atropine results from respiratory paralysis -primarily a central nervous system effect. 

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