All substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy. (Paraclesus, )

Transcription

1 All substances are poisons: there is none which is not a poison. The right dose differentiates a poison and a remedy (Paraclesus, )

2 Discussion Questions About Paraclesus Quote 1. Do you agree or disagree with this statement? Why or why not? 2. Why does the dose determine if a substances is a poison or a remedy? 3. What is a toxic substance? 4. What does it mean for something to be toxic? 5. What is the effect of a toxic substance? 6. Do all substances have the potential of being toxic? 7. Are toxic substances natural or man-made? 8. Who or what are affected by toxic substances? 9. How would you define toxicology?

3 Rat Poison? Alcohol? Vitamins? Are these toxic or not? Water?

4 Outline Definitions and purpose of postmortem toxicology Samples of forensic interest Pitfalls in postmortem toxicology Interpretation of results

5 Postmortem Forensic Toxicology The analysis of drugs or poisons in specimens collected during an autopsy

6 What Can Be Determined? The presence or absence of a drug or poison in a submitted sample The amount of drug or poison that is present in the submitted sample

7 Types of cases Suspected drug intoxication cases Fire deaths Homicides Driver and pilot fatalities Therapeutic drug monitoring Sudden infant death (SIDS)

8 Samples of Forensic Interest

9 Issues in Specimen Collection Selection sites: Multiple, varied sites of collection Collection Appropriate method of collection Adequate volumes for analysis Storage and handling Important to ensure results are accurate and interpretations are sound

10 Typical autopsy specimens Blood Urine Stomach contents Bile Liver Hair Vitreous humor The transparent jellylike tissue filling the eyeball behind the lens.

11 Blood Antemortem (before death) blood ideal blood sample Postmortem (after death) blood is not truly blood Anatomical site of collection at autopsy should be noted

12 Subclavian Central sites Heart Iliac Heart Peripheral sites Femoral Iliac Subclavian Femoral Other sites Head blood Hematoma blood

13 Hematoma Hematoma: a solid swelling of clotted blood in the tissues Protected from metabolism Analysis will indicate what drugs were present in the blood at the time of the hematoma was formed

14 Hematoma case example A 26 year old man was found dead at the bottom of a staircase. Death was due to physical injuries. Question as to alcohol use prior to fall down stairs No urine available at autopsy Alcohol not detected in femoral blood Alcohol in hematoma blood 150 mg/100 ml The deceased had been drinking prior to receiving the head trauma. The deceased had survived for several hours after the injury.

15 Hematoma Caution: There may be a delay between the incident which resulted in hematoma and the actual formation of the hematoma Therefore, this alcohol concentration does not necessarily indicate the BAC (blood alcohol calculation) at the time of the fall down the stairs.

16 Blood Alcohol Calculation Activity

17 Urine Produced by the kidneys Blood filtered by the kidneys Stored in the bladder until voided The presence of a drug in the urine of an individual indicates that some time prior to death the drug or poison was present in the blood of the individual

18 Stomach contents Visual examination may reveal tablets Drugs that have been orally ingested may be detected in stomach contents Caution: Drugs administered by other routes may also diffuse into stomach contents from the blood Useful for directing further analysis

19 Case Example A 26 year old woman is found dead in bed Numerous medications in her home: Amitriptyline, Oxycodone, Morphine, Paroxetine, Diphenhydramine, Pseudoephedrine, Phenobarbital, Codeine, Temazepam, Diazepam Only 3 ml of blood collected at autopsy Analysis of stomach contents: Amitriptyline: detected Nortriptyline: detected

20 Liver Drug metabolism occurs in the liver Both parent compounds (main drug) and metabolites (what the drug breaks down to) may be present in higher concentrations in the liver than in the blood ease of detection Limitation is that drugs are not uniformly distributed throughout the liver confounds interpretation

21 Bile Digestive secretion Continuously produced by the liver Stored in the gallbladder Qualitative - the presence of a drug in the bile of an individual indicates that sometime prior to death, the individual was exposed to the drug

22 Vitreous humor Fluid that occupies the space between the lens and the retina of the eye. Useful in cases where decomposition is advanced, body is exhumed or in fire deaths Limitation is blood : vitreous ratio may not be known

23 Hair Recent specimen of interest Metabolism does not occur in hair Can provide a historical record of drug or poison exposure Pros and cons of hair analysis still being uncovered racial variability?

24 Case Example Poklis, A Abstract SOFT, Dearborn, Michigan. 30 year old woman, previously in good health Nausea, vomiting, diarrhea, rash, fever Weakness in hands and feet Guillian Barre? Hospitalized with hypotension, seizures Misplaced laboratory result Arsenic! Sequential hair analysis for arsenic showed chronic arsenic poisoning over 8 month period

25 Non-biological submissions Used to direct analysis of biologicals (toxins or drug obtained) May indicate the nature of substances that may have been ingested, inhaled or injected Examples: Containers found at the scene Syringes Unidentified tablets or liquids

26 Samples taken after embalming Methanol is a typical component of embalming fluid Most drugs are soluble in methanol Embalming process will essentially wash the vasculature and tissues

27 Case Example A 72 year old woman, given meperidine to control pain following surgery, later died in hospital. The woman was in poor health and it is possible that death was due to natural causes. However, coroner requests toxicology to rule out inappropriate meperidine levels. BUT: Body had been embalmed Liver and spleen submitted

28 Storage and Handling

29 Storage and Handling Not feasible to analyze specimens immediately Sample should be in well-sealed container (NOT GLASS) Sample containers must be sterile Use of preservatives and anti-coagulants

30 Storage of Samples Preservative Sodium fluoride Anti-coagulants Sodium citrate Potassium oxalate EDTA Heparin Not imperative for postmortem blood samples

31 Pitfalls in Postmortem Forensic Toxicology

32 Decomposition Fewer samples available for collection Quality of samples is diminished Putrefaction produces alcohols Ethanol Isopropanol Acetaldehyde n-propanol

33 Volume of Distribution Volume of distribution is the amount of drug in the whole body (compared to the amount of drug in the blood) If a drug has a large volume of distribution, it is stored in other fluids and tissues in the body

34 Example: Digoxin p. 60, Principles of Forensic Toxicology A 33 year old white female is admitted to hospital after taking 60 digoxin tablets An antemortem blood sample collected 1 hour prior to her death indicates a blood digoxin level of 18 ng/ml Heart blood digoxin concentration obtained at autopsy is 36 ng/ml Postmortem increase in blood digoxin concentrations is suspected to be due to the release of the drug from the myocardium (heart)

35 Postmortem Redistribution Coping with the problem of postmortem redistribution: Analysis of both central blood and peripheral blood in cases where postmortem redistribution may be a factor Compilation of tables to determine average and range of postmortem redistribution factors for drugs

36 Incomplete Distribution Site dependent differences in drug levels due to differential distribution of drugs at death Has been noted in rapid iv drug deaths Example: Intravenous injection of morphine between the toes Fatal amount of drug reaches the brain Full distribution of the morphine throughout the body has not occurred Femoral concentration > Heart concentration

37 The end

38 Toxic Cause You will be given 1 of 5 case studies. You will divide questions 2-5 among your team. You will need to determine the following: 1. What is the toxic substance that was the cause of death? 2. What is this toxic substance used for? 3. What is the lethal/non-lethal dose (or is any amount lethal)? 4. How is it detected in the body? What test is used? 5. How long after death can this substance be detected?