Chapter 6

• A toxicologist can detect metabolism of the drug.
• General areas of Forensic Toxicology

  • Postmortem drug testing
  • Workplace drug testing
  • Contraband materials
• Postmortem Toxicologist

  • Focuses on why the deceased died
  • Samples collected by the ME are sent to the toxicology to check for drugs and poisons
  • The toxicology lab analyses the samples and report the findings
  • The ME takes those results, the findings during autopsy, and any other evidence and decides on the manner and cause of death
• A xenobiotic is a substance foreign to the body.
• A drug is a compound that causes a physiological effect.
• Poison is a substance that when ingested results in a toxic or damaging physiological effect or effects.
• Toxins are substances that are poisonous to humans, including some that are helpful in small doses.
• An example of a drug is Aspirin because it reduces fever and inflammation.
• Sugar is not a drug because it does not cause a physiological effect that we want.
• An example of a toxin is botox.
• Mathieu Orfila (1787-1853)

  • Born in Spain but moved to France
  • Professor of Forensic Chemistry and Dean of Medicine
  • Founder of Forensic Toxicology
  • Published his first paper on poisons when he was 26 in 1814
  • Specialized in the detection of arsenic
  • Gave testimony in the Marie La Farge (arsenic case in 1840)
• Marie LaFarge

  • Accused of poisoning her husband with arsenic
  • The first reports showed the presence of arsenic
  • The defense lawyer contacted Orfila, who read the report and deemed the experiment wrong
  • The court requested a different pair of scientists to perform the experiment again using the Marsh test and they did not detect any arsenic
  • Orfila had to come himself to carry out the test and analyzed the soil around the coffin
  • He concluded that only the body had arsenic
  • She was sentenced to death but her sentence was commuted to life in prison
• The dose in a toxin makes it poison.
• LD50 is the dose that kills 50% of people taking it.
• Water Poisoning

  • excessive water intake could kill a person (intentional intake)
  • too much water can dilute the blood so much that the concentration of sodium drops below safe levels (hypnoatremia)
  • sodium regulates the amount of water around the cells
  • cells will swell and the condition could lead to a coma and subsequent death
  • LD50 is 6L or 1.5 gal
  • seen in athletes participating in endurance events (marathons, triathlons, ultradistance)
• 75% of the nearly 92,000 drug overdose deaths in 2020 involved an opioid.
• Over 82% of all opioid overdose deaths in 2020 involved synthetic opioids. (excluding methadone)
• Stimulants (Ritalin, Concerta, Adderall) are used to treat narcolepsy, ADHD, and other conditions.
• Stimulants speed up brain activity causing increased alterness, attention, and energy that come with elevated blood pressure, increased heart rate and breathing.
• Misuse or abuse of stimulants can lead to dangerous increased blood pressure, which places added strain on the heart. Dangerous increase in heart rate and respiration are also possible
• Sedatives/tranquilizers (Valium, Xanax, Ativan, Klonopin, Ambien) are used to treat anxiety, tension, panic attacks, and sleep disorders.
• Sedatives/tranquilizers slow down or "depress" the functions of the brain and central nervous system.
• Misuse or abuse of sedatives/tranquilizers can cause withdrawal seizures.
• Opioid analgesics (Vicodin, OxyContin, Percocet, Methadone) are used to treat moderate to severe pain and may be prescribed after surgery.
• Opioid analgesics block pain messages from reaching the brain.
• Misuse or abuse of opoid analgesics can cause respiratory depression, slow and shallow breathing.
• Opiates derive directly from the opium poppy plant
• Opium, morphine, heroin, codeine are examples of opiates.
• Opiods are a compound that attaches to the opioid receptor.
• Vicodin, Percocet, Oxycodone, and Fentanyl are examples of opioids.
• Opiates and Opioids

  • depressants
  • euphoria and analgesic
  • death by paralysis or the respiratory center
• The Marsh Test

  • developed in the 19th century by Marsh
  • can detect arsenic, antimony, and germanium
  • zinc metal in Flask A along with the forensic sample obtained
  • add sulfuric acid to the flask
  • if there is arsenic present in the sample, arsine gas (AsH3) and hydrogen gas (H2) will be formed
  • heat it up and arsenic metal will be deposited on any cold surface touched with the fire
• For a drug to go to market, it needs discovery and development (bench research-organic synthesis), translation research (animal testing), FDA approval, and clinical research. The process can take x>10 years
• Phase 1 Trials

  • 20-100 healthy volunteers and/or volunteers with the condition
  • several months
  • establish safety and dosage
• Phase 2 Trials

  • several hundred volunteers that suffer from the condition
  • efficacy and side effects
  • up to 2 years
• Phase 3 Trials

  • 300 to 3000 volunteers that suffer from the disease
  • efficacy and monitoring adverse reactions over time
  • 1-4 years
• Phase 4 Trials

  • several thousand volunteers
  • efficacy and safety
• FDA Investigational New Drug (IND) Review

  In the IND application, developers must include:

  • animal study data and toxicity (side effects that cause great harm) data
  • manufacturing info
  • clinical protocols (study plans) for studies to be conducted
  • data from any prior humnan research
  • info about the investigator
• Absorption is the ability of a compound to go through a membrane or barrier (intestinal lining, lungs, skin, blood brain barrier)
• Distribution is the distrubution of the drug around the body. Some compounds tend to accumulate in specific organs or tissues.