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Toxicology Final > Toxicology Final > Flashcards

Toxicology Final Flashcards

1
Q

Toxicology

A

The study of toxins

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2
Q

Toxin

A

Poison or substance that causes harm to organisms when sufficient quantities are absorbed, inhaled or injected.

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3
Q

Forensic Toxicology

A

Application of toxicology to law cases.

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4
Q

Three Major Categories of Forensic Toxicology

A

Postmortem FSC Toxicology, Human Performance Toxicology, Forensic Drug Testing

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5
Q

Postmortem Forensic Toxicology

A

Death investigation. The study of the analysis of drugs or poisons present in the specimens collected during autopsy to determine whether ingestion of those toxins may have caused or contributed to the death of the person. There is no limitation when choosing the specimens since the person is deceased. The other two categories have limited choices of specimens.

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6
Q

Human Performance Toxicology

A

Behavioral Toxicology. Quantifies the dose and affect relationship to manifest if this person’s behavior is under the influence of drugs like alcohol, marijuana etc. The study of the human response to environmental conditions and stimuli. The toxicologists can quantify how much of the toxin is present in the body and it will affect the person’s behavior. Dose and Affect. Increase in concentration means a change in behavior. Blood is the best choice.

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7
Q

Forensic Drug Testing

A

Chemical testing of biological specimens from athletes and individuals to determine their drug use. Also can be used prior to employment. Urine is the most popular choice.

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8
Q

Drug Facilitated Crime

A

Any criminal action in which an incapacitating agent is used to assist the perpetrator in the commission of the crime. • A separate subdiscipline of forensic toxicology, Popular means- drink spiking. Victims: some level of amnesia and suspicion, no direct memory but have suspicion, neither memory nor suspicion. History: Mickey Finn (1896-1903) He may have used chloral hydrate (one of the oldest CNS depressants). Drug-facilitated sexual assault (1901). A rise in the number of reported drug-facilitated crimes.

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9
Q

Early Activity in Toxicology

A

Ancient times, Egyptians and Greeks recorded some poisonings. Socrates was executed using poison. Paracelsus says “ What is there that is not poison. Solely the dose determines that a thing is not poison.”

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10
Q

Xi Yuan Ji Lu

A

Collected Cases of Injustice Rectified. From China which can be used to help coroner determine the cause of death.

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11
Q

Paracelsus

A

Father of Toxicology, he came up with the concept of poison for the first time.

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12
Q

Mathieu J.B Orfila. First attempt to study and categorize poisons. Father of FORENSIC toxicology. He came up with control testing for analysis. He also came up with the concept of the toxin take affects needs to be first absorbed into the system. Worked to make chemical analysis a routine part of forensic medicine. Indicated how intoxication begins.

A
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13
Q

Jean Stas

A

Developed the first effective method to extract alkaloids from plants and animal bodies.

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14
Q

F.J. Otto

A

Modified the Stas method into the Stas Otto Method. This is the base and still used for LLE.

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15
Q

First Forensic Toxicology Lab (Alexander Gettler)

A

New York City in 1918.

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16
Q

Maurice Nicloux and Erik Widmark.

A

Studied alcohol and made a formula to help determine the BAC which tells the relation between body weight, volume of distribution, blood alcohol content and amount consumed.

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17
Q

Rolla Harger

A

Invented the drunk-o-meter (like a breathalyzer). It helps determine is alcohol is present in breath. KMnO4 can be reduced by breath and turns into Mn2+ and it is colorless instead of purple. If its purple, it contains alcohol.

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18
Q

Robert Borkstein

A

Invented the first generation of a breathalzer.

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19
Q

Three Basic Functions of a Forensic Toxicologist

A

Analysis, Interpretation and Reporting.

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20
Q

Post Mortem Forensic Toxicology

A

AKA Death Investigation. The analysis of drugs or poisons present in the body collected during autopsy to determine if the presence of those toxins were the cause or contribution of death.

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21
Q

Coroner Vs. Medical Examiner

A

Similarities: Types of Cases (Natural but sudden deaths, suspicious, violent). Authority to conduct an investigation.
Differences: How the director is chosen. Coroners are elected by the people or appointed by an agency, Medical Examiners are never elected, always appointed by the department. Required Credentials to be the director. The coroner does not need specific training in forensic analysis, but for medical examiners they must be a physician, usually a forensic pathologist who received training about forensic medicine and autopsies.

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22
Q

Collection of Proper Specimen

A

Blood, Vitreous Humor, Urine, Bile and Liver. Blood is the most important post mortem specimen. Vitreous Humor is the least likely to be contaminated because it is in an isolated location. Vitreous Humor is helpful to detect alcohol. Urine can help because our kidneys. Its easier to find the presence of drug metabolites in the urine instead of the blood. Narcotics and Benzodiazepines can be concentrated in the Bile. Liver is the major organ responsible for metabolism.

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23
Q

Other Specimens

A

Lung Tissue, Spleen, Stomach Contents, Hair. Lung Tissue is good for inhalation of volatile substances. Spleen is useful for CO intoxication and if all of the blood is gone. Spleen contains large amounts of red blood cells and it can detect the presence of carboxy-hemoglobin. Stomach Contents is good for overdose cases like undigested pills or tablets, which is a strong indicator of the drugs ingested. Hair can provide information on long-term drug use.

24
Q

Preliminary Tests

A

Spectrophotometry (Color tests), Chromatography, Immunoassay (usually for urine samples)

25
Q

Gas Chromatography (GC)

A

Major Aspect of Post-Mortem Forensic Tox. Identify and quantify drugs, can be modified for sensitivity, resolution and specificity. detector selection.

26
Q

High Performance Liquid Chromatography (HPLC)

A

Is used for polar and thermolabile compounds. If it is very polar and sensitive to heat you must use HPLC but GC is cheaper and better.

27
Q

Immunoassay

A

Based on the competition between a labelled drug and the drug in the specimen for binding to the antibody. Advantages: Directly on urine samples (no pretreatment necessary) on blood and tissue samples after treatment. Good sensitivity to certain drugs/drug classes, commercially available.

28
Q

Confirmatory Testing

A

To be reported as positive, At least TWO different analytical techniques must be used. Mass Spectrometry combined with a separation technique (GC or HPLC) is the benchmark confirmatory test. GC-MS, GC-MS/MS or LC-MS, LC-MS/MS.

29
Q

Quantification

A

Requirements. Calibrators with known concentration to make a calibration curve that makes a linear relationship between instrument response (Signal) and then the concentration for individual calibrators, Need to use an internal standard which helps improve the analysis precision. When blood is unavailable, liver specimens are used

30
Q

Analytes: Ethanol.

A

Ethanol (MOST COMMON). Analyzed in all postmortem cases. Cutoff is a specific concentration, above is positive and below is negative. Peripheral Blood/Vitreous Humor/Urine (Important because production of ethanol can be antemortem. Vitreous humor and urine are less putrefaction). “+” blood and “+” vitreous humor/urine: Yes, consumption of ethanol before death. “+” blood and “-“ vitreous humor/urine: No, due to postmortem formation of alcohol.

31
Q

Methods of Ethanol Analysis

A

GC Method is Preferred. Headspace GC analysis, no need for sample prep.

32
Q

Henry’s Law

A

The amount of the volatile substance dissolved in the liquid phase is proportional to the partial pressure of the volatile substance in the vapor phase.

33
Q

Analytes: Carbon Monoxide

A

Causative agent in fire death. Great Affinity to Hemoglobin. Forming CoHb (measured by %). Less than 10% is not considered severe but above 50% considered the cause of death. Can be detected even in decomposed bodies.

34
Q

Methods for CO Analysis.

A

Direct methods: microdiffusion- Conway Cell. Outer walls will hold the sample like the blood containing CO and in the center the palladium chloride solution will go in the middle. Add chemical specimens to sample and once released it is diffused into the center and there will be a reaction. Palladium chloride will be reduced and then you will know its CO. • GC: Directly-TCD; reduced to CH4-FID. A reducing reagent must be used to release the CO from the hemoglobin. Potassium ferricyanide.
• Spectrophotometric method: measure COHb
• Absorbance of COHb in specimen is divided by the absorbance of saturated specimen.
• Specimens need to be pre-treated with Na2S2O4.

35
Q

Analytes: Drugs

A
  • Screening both therapeutic and abused drugs. Quantification of drugs in blood – available history. Synergistic effects. Therapeutic amount of drug may play a role in death. Complications: redistribution/decreased concentration in vitro. Methods = Screening Test and Confirmatory Tests. • Reporting: After testing all findings should be submitted to the laboratory director for review. The review should include: Administrative and analytical processes.
  • After review, a final report is drafted and signed by the analyst as well as the lab director
36
Q

Performance Enhancing Drug Testing (PE)

A

Traditionally associated with athletes. Typically marijuana, stimulants, opioids, anabolic-androgenic steroids and diuretics. Testing Approach: World Anti-doping agency (WADA). Drugs tested may vary by reason for testing. Specimens: blood (limited), urine (predominant), witnessed, “split specimen”, common forensics procedure. Quality control.

37
Q

ADME

A

Absorption, Distribution, Metabolism, Excretion. A: Routes of admin and bioavail, D: Apparent volume of distribution (Vd) and factors influencing D. M: Phase 1/Phase II/ First-pass effect. E: Hepatic and Renal. Distribution comes from lipophilicity, PH, and more. Metabolism. Was there a drug or toxin, When, How, Did it affect and was it cause of death

38
Q

Sample Prep

A

Direct sampling, gas phase sampling for gases and volatile liquid, protein precipitation, specimen digestion for metal determination, LLE (Key Principle)
• Immunoassay: Definition, working principle, 4 diff types of labels. Homo and Hetero, six commonly seen immunoassay types.
• Application of Mass Spec: How MS Works, Qualitative analysis: QTOF, Quant: internal and standard addition methods. Application examples: derivatization, library search. DEUTERATED INTERNAL STANDARD, DEUTERIUM TO REPLACE SOME HYDROGENS

39
Q

• Alcohols: Production/ Classification.

A

Ethanol, methanol, and ethylene glycol. Widmark equation, pharmacokinetics, tolerance, analysis. Mellanby.

40
Q

Cannabis

A

Most commonly abused illicit drug, various forms of products, has its own category. Major active ingredient (THC), Pharmacokinetics (Major metabolic Route), Toxic effects, Analysis, Different Specimens.

41
Q

• CNS Stimulants

A

cocaine and meth. What are they? Limited medical uses, different forms, ADME, Symptoms, Production methods of meth, analysis. Septum and tooth decay.

42
Q

Depressants

A

Benzos and GHB, barbs. Agonist vs. Antagonist, Benzos and Barbs

43
Q

Opioids

A

Morphine, Heroin and Fentanyl. Synthetic opioids. Pharmacokinetics. Why heroin is more potent than morphine. Heroin can pass through blood brain barrier easier. (Less Polar) Heroin also does not bind to receptor directly, goes through hydrolysis to produce 6AM which is more potent than morphine. Analysis.

44
Q

CO/Cyanide/Inhalants

A

What are they? Most abused? Leading cause of fire related death. Volatile. Headspace GC.

45
Q

Metals

A

What are Metals?

46
Q

Current Legal limit for max conc. of Ethanol in drivers

A

80 MG/100 mL

47
Q

Which is an Analgesic?

A

Fentanyl

48
Q

Specimen used in over 90% workplace drug testing

A

Urine

49
Q

Specimen for chronic drug abuse and metals such as arsenic

A

Hair

50
Q

Preferred Analytical Method for quantifying alcohol in blood is

A

Headspace GC

51
Q

Directly Analyzes Urine

A

Immunoassay

52
Q

Biggest advantage of using headspace GC for BAC

A

No need for sample preparation

53
Q

Key principle in adjusting pH for extraction is

A

Create non-salt forms of the drugs

54
Q

Phase 1

A

Metabolic Oxidations are catalyzed by enzymes

55
Q

Currently the benchmark confirmatory technique used in forensic tox

A

MS combined with GC or HPLC

Toxicology Final (1 decks)

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