Reference Ranges for Drug Concentrations

In pathology, it is incorrect to use a drug concentration without any corroborating ancillary evidence including without regard to the clinical scenario. This is because the reference ranges are assigned based on very limited controlled studies of people taking normal low doses of medications. Meanwhile, toxic levels are a point at which some people may start to have symptoms, of any type, as an adverse effect of the drug. Truly fatal drug levels documented are the point at which some, but certainly not all, or even many, people may die from adverse effects of the drug. These numbers cannot be used without an understanding of the pharmacology of a drug and the variations in tolerance levels among people using widely different amounts of the drug. The toxic level of drug for a naïve user is not the same as a toxic level for a chronic/routine user. To suggest that a chronic user of a drug may experience “toxicity” from a drug level barely above the level that naïve users could experience some symptoms is irresponsible and scientifically unsupported.

The most important thing for a forensic pathologist to do when evaluating a potential drug- or medication-related death is to consider all available factors. This usually includes collecting the bottles of prescribed medications to perform a pill count that could indicate overuse. Pharmacy records are easily obtainable and can show indicators of overuse such as a history of attempts (successful or not) to fill prescriptions early. A good pathologist then needs to assess this information along with the prescribed dose, longevity of use, timing of doses, body habitus, and myriad other factors to reliably analyze claims of drug toxicity.

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