Lecture 14: Forensic toxicology Flashcards

1
Q

What is toxicology?

A

Study of the adverse effects of chemicals (including drugs) on living systems and the means to prevent or ameliorate such effects.

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2
Q

What is forensic toxicology?

A

The application of the scientific study of poisons/intoxicants to questions raised in judicial proceedings

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3
Q

Workplace for forensic toxicologists

A

> Police units
Medical facilities
Regulatory bodies
Research institution
Educational institution
Private laboratories

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4
Q

Forensic toxicology: subdisciplines

A

> Postmortem toxicology (investigation of death)
Behavioural / Human Performance
- Driving under the influence alcohol / drugs
- Drug-facilitated sexual assaults
- Doping Control
Workplace drug testing
Environmental, industrial and public health legislation.
Work for the Police and criminal courts.

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5
Q

Key responsibilities

A

> Conduct toxicology analysis
Report and document
Consulting and testifying in court
R&D

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6
Q

What are poisons?

A

Any substance, chemical, physical or biological that is harmful to a biological (living) system.

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7
Q

Most frequent occurrences of poisonings

A

> Most cases result from social and economic stress or mental disorders.
A minority results from illicit substance abuse.
Substances administered against will e.g. facilitate robbery /sexual abuse (e.g. Rohypnol)
Unintentional / accidental.

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8
Q

Toxicological investigations

A

> Establish poisoning as cause of death.
Investigate unlawful poisoning by a third party.
Establish the presence of substances that may affect a person’s behaviour/ judgement.
Detect performance enhancing drugs.
Detect non-compliance with for work-place policies etc.
Provide evidence for allowing parental access, if history of drug abuse
Analytical checking of statements

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9
Q

Role of the pathologist

A

> Perform medico-legal autopsies to establish the cause of death; Issue Death Certificate
Suspicious deaths: attend locus
Estimate time of death
Removal of specimens to assist in the investigation.
Prepare report; precognition; court testimony.

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10
Q

Importance of case notes

A

> Recent history of patient / deceased
Signs and symptoms on admission / death which may suggest poisoning
Medicaments and other materials found near the patient/body (scene)
- Empty tablet containers etc.
Laboratory investigation result (biomedical and toxicological test)
Post-mortem examinations

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11
Q

Chain of custody

A

A process that tracks the movement of evidence through its collection, safeguarding, and analysis lifecycle by documenting each person who handled the evidence, the date/time it was collected or transferred, and the purpose for the transfer.

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12
Q

Maintaining chain of custody

A

> Demonstrate validity of test specimens
Chronological disposition and condition of specimens from the time of collection to time of disposal.
Collection: What specimen is, time and date, by whom, tamper evident tape.
Ensure integrity and security of specimens.

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13
Q

UK Government Legislation: Misuse of Drugs Act (1971)

A

States that it is an offence to:
> Possess a controlled substance unlawfully.
> Possess a controlled substance with intent to supply.
> Supply or offer to supply a controlled drug (even if it is given away for free).
> Allow a house, flat or office to be used by people taking drugs.
> Serious punishment
- Possession with intent to supply = life imprisonment
> Many also controlled by:
- Medicines Act 1968
- Psychoactive Substance Act 2016

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14
Q

Spectrum of drug use, mis-use and abuse

A

The 6 main classes of mis-used drugs are :
1. Opiates (morphine, heroin, methadone, dihydrocodeine)
2. Depressants (alcohol, barbiturates)
3. Minor tranquilisers (benzodiazepines, e.g. Diazepam (Valium), Temazepam)
4. Stimulants (cocaine, amphetamines, Ecstasy, ADAM, EVE, ICE)
5. Hallucinogens (LSD, magic mushrooms, mescaline)
6. Others (cannabis, nicotine, volatile solvents)

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15
Q

Types of poisons and poisonings

A

> Anions: cyanide, fluoride, nitrate, oxolate.
Corrosives: sulphuric acid, sodium hydroxide.
Gases and volatiles: ethanol, products of combustion, solvents.
Metals and metalloids: Iron, lead, arsenic.
Toxins: plant, animal, bacterial, fungi.
Pesticides: organophosphates, herbicides.
Prescription & illicit drugs.
Household chemicals: cleaning products, toiletries, hair products etc.

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16
Q

Exposure to toxicants: acute exposure

A

Contact with a substance that occurs once for only a short time (up to 14 days)

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17
Q

Exposure to toxicants: Chronic exposure

A

Contact with a substance that occurs over a long time (more than 1 year)

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18
Q

General symptoms of poisonings

A

> Neurological: CNS depression, CNS stimulation
- Glasgow coma score.
Respiratory.
Cardiovascular: Dysrythmia, hypotension / hypertension.
Ocular: miosis (constriction), mydriasis (dilation), Nystagmus (“jerky”)
Mouth: Damage, salivation, odour, dysphagia.
GIT : vomiting, diarrhoea

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19
Q

Drugs of abuse

A

> ‘Any substance used for an alternative purpose than that intended’.
‘Any substance the possession and supply of which is restricted by law’.
Most fall within a few pharmacological groups:
- CNS stimulants, narcotic analgesics, hallucinogens and hypnotics
Most prevalent = plant derived/ semisynthetic
Future - fully synthetic? Fentanyl opioid

20
Q

Illicit drugs

A

> Illicit drugs are highly addictive substances
They are illegal to sell, make, and use.
Variable sources: pharmaceutical drugs, plant-based drugs, and synthetic drugs.
Illicit drugs are not used for medical purposes and are illegal to use in these settings.

21
Q

Most drug misuse deaths are accidental poisonings

A

> Drug misuse deaths from mental and behavioural disorders (only 5 to 6% ).
- Deaths are due to drug dependence or abuse, but they may involve an acute overdose of drugs similar to an accidental poisoning.
Drug-misuse deaths which are suicides = intentional self-poisoning or poisoning of undetermined intent.
- Rate higher in females (28%, 175 deaths) than males (11%).
- 80% of female drug misuse suicides involve an overdose of an opiate drug (heroin, morphine, tramadol and codeine); some involve drugs such as zopiclone, benzodiazepines and barbiturates.

22
Q

Toxicological screening techniques

A

> Aim = confirm and quantify chemical.
Choice depends upon:
- Analytical sensitivity
- Analytical specificity
- Need to know amount present (Qualitative vs. Quantitative)
Various Techniques:
- Immunoassays.
- Spot colour tests – limited specificity, depends upon functional group.
- Thin-layer Chromatography (TLC).
- Gas chromatography (GC) – separates chemicals based on volatility.
- High Performance Liquid Chromatography (HPLC).
- Mass Spectrometry (MS) - identify chemicals based upon their mass – to –charge (m/z) ratio.
Appropriate sample.

23
Q

Steps to analysis

A

> Separation of poison and metabolites from biological material
Identification
Confirmation of identity
Quantification/ Concentration
Interpretation

24
Q

General Schematic of a Toxicological screen

A

> Choice of sample
Sample preparation
Analysis
Processing data and workflows
Data re-use

25
Presumptive tests- screening
> Qualitative > Cheap > Quickly ID analytes > Rely upon characteristic colour changes - Hindered by impurities > Requires blank & positive control > 1mg analyte
26
Qualitative analysis: observations
> Naked eye / microscope > Colour > Morphology: shape, dimensions > Manufacturers marks > Packaging > Unusual odours
27
Immunoassays steps
> Step 1 - Drug is labelled with an enzyme, fluorescent molecule. > Step 2 - Drug competes with the ‘label’ > Step 3 - Interaction of a drug with an antibody.
28
3 commonly used TDM homogeneous immunoassays
> Enzyme-multiplied immunoassay technique (EMIT) > Fluorescence polarization immunoassay (FPIA) > Cloned enzyme donor immunoassay (CEDIA)
29
High performance liquid chromatography (HPLC)
> Sampling- Sample preparation and injection > Phase separation- Separate compounds based on partitioning between a stationary phase and a mobile phase > Detection- Detection of the signal and visualization
30
Mass spectrometry (mass analyser)
> The analytes are separated on an LC column and passed to the MS where they are ionized and fragmented and detected. > Separated by their mass to charge ratios (m/z). > Highly selective and sensitive.
31
Drug deposition
> Absorption > Distribution > Metabolism > Excretion
32
Routes of administration/exposure
> Ocular > Oral > Intrathecal > Sublingual > Rectal > Inhalation > Dermal > Intravenous > Intramuscular
33
Absorption
The movement of a drug/ chemical from the site of administration into the blood stream
34
Oral administration
> Easy for patient / > High patient compliance > Drugs must cross through or between cell membranes to reach target > Absorbed from GUT via blood stream - Main site for most drugs - Large Surface area: microvilli ~ 200 m2
35
Intravenous Administration
> Directly into blood stream > Bypass first pass metabolism
36
Drugs distribute into bodily fluids
Distribution: The movement of a drug / chemical around the body, into and out of tissues and fluids.
37
Elimination
> Elimination = Irreversible loss of drug from the body by any mechanism. > 2 Processes: Metabolism and Excretion Unchanged drug and metabolites
38
Excretion
> Kidneys --> Urine > Hepatobiliary system è Faeces > Lungs --> Breath > Others e.g. sweat, semen, sebum, breast milk > Half-life = rate of drug removal Clearance = extent of drug removal
39
The liver
> BIOTRANSFORMATION: Major site of xenobiotic metabolism. > First pass metabolism: GI à Liver [metabolism reduces bioavailability] > Eliminated via bile > ENTHEROHEPATIC CISRCULATION: Reabsorption of eliminated molecules
40
Factors affecting passage of drugs through cell membrane
> Plasma protein binding > Free drug (unbound) concentration gradient > Active transport > Molecular weight > Degree of ionisation > Lipid solubility > Water solubility
41
Drug metabolism
The enzyme-catalysed conversion of a drug into a chemically-distinct product (a metabolite)
42
Half life
Time taken for drug concentration to decline by half
43
Fractional bioavailability
Bioavailability = amount absorbed relative to the dose administered
44
Dose response curve
> Plot % response (e.g % viability) against log of dosage - Typically, sigmoid curve. > Determine the lethal dose (LD50)- dose which kills 50 %
45
Postmortem redistribution (PMR)
> Artificially elevated [drug] in >heart after death. As time interval between death and blood collection increases, [drug] in heart blood increases. > Order of collection: femoral > iliac > subclavian vessels > heart. > Drug are sequestered by central compartment organs.
46
Specimen collection from decomposed bodies for toxicology
> Blood/ vitreous – gone ~ 48h > Liver used to determine [drug] in absence of blood. > After a few days decomposition, [drug] rise in liver due to fluid loss and anatomical location (GIT). > [drug] muscle – more reliable matrix
47
Interpretation of toxicology results: other considerations
> Post-mortem redistribution > Post-mortem production and loss of substances > Analyte stability > Post-mortem findings (e.g. histopathology) > Route of administration/ingestion > Alternative source of positive findings (paraphernalia) > Use appropriate reference samples