For postmortem toxicology, the two most important concepts for any death investigator are:
1.Ā Ā Drug concentrations should never be interpreted in a vacuum.
2.Ā Ā There is no such thing as a ālethal drug concentration.ā
The purpose of this book is to assist forensic pathologists in the interpretation of common toxicology results. This book is in no way meant as a substitute for a thorough death investigation and complete autopsy.
Important points to consider are listed in the following:
ā¢Ā Ā The concentrations given in this book are a compilation of the data from the literature.
ā¢Ā Ā The therapeutic/nontoxic concentrations given were determined either in serum during pharmacokinetic studies or were from whole blood samples taken from postmortem data from individuals dying of unrelated causes ā who died with the drug present but without it contributing to death;
ā¢Ā Ā The toxic concentrations are serum concentrations obtained from individuals who suffered toxicities due to the drug listed but survived;
ā¢Ā Ā The lethal concentrations listed are for whole blood unless otherwise noted;
ā¢Ā Ā The lethal and toxic cases listed represent pure, single-drug intoxications unless otherwise noted.
ā¢Ā Ā Consider the source.
ā¢Ā Ā Peripheral blood is preferable
āĀ Ā Understand postmortem redistribution and the variables involved;
āĀ Ā Some drugs are not as affected as others.
āĀ Ā Not all peripheral blood is created equally ā femoral is preferred.
ā¢Ā Ā Antemortem specimens may be serum and could affect interpretation.
ā¢Ā Ā Liver, urine, bile, and stomach contents do not necessarily indicate acute toxicity, only exposure.
ā¢Ā Ā Consider the test.
ā¢Ā Ā Immunoassays may have cross reactivity giving false positive or false negative results.
ā¢Ā Ā Make certain to direct the testing for the drugs of interest.
āĀ Ā Know which drugs are on the testing panels ordered and which drugs are found on which panels.
āĀ Ā Some drugs may require specialized testing or sample collection.
ā¢Ā Ā Consider the time.
ā¢Ā Ā Time elapsed since death may affect concentrations.
āĀ Ā Some drugs may be metabolized after death or during the agonal period.
āĀ Ā Postmortem redistribution may occur.
ā¢Ā Ā Consider the circumstances.
ā¢Ā Ā When was the decedent last seen? What was the decedent doing? How was the deceased acting?
ā¢Ā Ā Are the terminal events consistent with a drug toxicity?
ā¢Ā Ā Consider the decedent.
ā¢Ā Ā Are there other disease processes present?
ā¢Ā Ā How do the drugs and the diseases interact?
ā¢Ā Ā Consider tolerance.
ā¢Ā Ā How long has the deceased been on the drug? At what dose? On what regimen?
āĀ Ā Specifically consider in deaths with opiates/opioids, benzodiazepines, barbiturates, and ethanol.
ā¢Ā Ā Could withdrawal be possible?
āĀ Ā Specifically consider with ethanol and benzodiazepines.
ā¢Ā Ā Consider the presence of other drugs.
ā¢Ā Ā The presence of multiple drugs with similar effects can result in death or other adverse effects, such as serotonin syndrome.
ā¢Ā Ā Consider intrinsic drug properties.
ā¢Ā Ā QT interval
āĀ Ā Certain prescription and illicit drugs can prolong the QT interval.
āĀ Ā Can be associated with sudden death, especially in the presence of underlying rhythm disturbances.
ā¢Ā Ā Metabolism
āĀ Ā Approximately 30% of all drugs are affected by a drug metabolizing enzyme, the majority are part of the CYP450 system
āĀ Ā Drug concentrations can vary by a factor of 600 between two individuals given the same dosage.
āĀ Ā Genetic factors may play a role in how an individual absorbs, distributes, and metabolizes a drug.
āĀ Ā A mutation in a drug metabolizing enzyme can lead to accumulation of a drug and toxicity.
Acetylcholinesterase Inhibitors
While acetylcholinesterase inhibitors were historically used as pesticides and herbicides, in recent years they have been used to develop medications to treat Alzheimerās disease and myasthenia gravis. Commonly, their toxicity is measured by the percentage of acetylcholinesterase (ACh) activity with toxicity beginning 20% below the level of normal activity (or 80% activity level) and becoming pronounced by 50% activity level. Severe toxicity and death occur at 90% suppression (measured activity level = 10%). Postmortem testing should utilize the red blood cell (RBC), ACh as it better reflects neural ACh activity.
Table 2.1 is a non-comprehensive list of common drugs, nerve agents, and insecticide/pesticides that are acetylcholinesterase inhibitors.
Table 2.1 Acetylcholinesterase Inhibitors
DrugsāAlzheimerās disease Donepezil (Aricept) Galantamine (Razadyne, Reminyl, Nivalin) Huperzine A Ladostigil Metrifonate Rivastigmine (Exelon) Tacrine (Cognex) | Drugsāmyasthenia gravis Ambenonium (Mytelase) Edrophonium (Tensilon, Enlon, Reversol) Neostigmine (Prostigmin) Physostigmine (Antilirium) Pyridostigmine (Mestinon, Regonol) | Drugsāglaucoma Demecarium (Humorsol) Echothiophate (Phospholine iodide) | Poisonsānerve agents Cyclosarin Sarin Soman Tabun VX VE VG VM |
Insecticides or pesticides | | | |
Acephate (Orthene) Aldicarb (Temik) Azinphos-methyl (Guthion) Bendiocarb (Ficam) Bufencarb Carbaryl (Sevin) Carbofuran (Furadan) Carbophenothion (Trithion) Chlorfenvinphos (Birlane) Chlorpyrifos (Dursban, Lorsban) Coumaphos (Co-Ral) Crotoxyphos (Ciodrin, Ciovap) Crufomate (Ruelene) Demeton (Systox) Diazinon (Spectracide) | Dichlorvos (DDVP, Vapona) Dicrotophos (Bidrin) Diisopropyl fluorophosphate (Dyflos) Dimethoate (Cygon, De-Fend) Dioxathion (Delnav) Disulfoton (Di-Sys... |