Chempath - Forensic Toxicology

Question 1

Types of death reported to coroner

Answer 1

Violent
Unnatural or sudden
Cause of death is unknown

Question 2

Types of samples

Answer 2

Ante-mortem serum / blood
Post-mortem blood
- Heart blood, cavity blood (screening)
- Femoral vein blood (screening & quantitation)
Urine
Stomach contents (what hasn’t been digested e.g. tablets)
Vitreous humor (if you can’t get blood, thought to have similar levels). Measure glucose in vitreous in diabetic deaths.
Hair  good for chronic drug history (only tissue that can do this), drugs get laid down at growing point so get a picture of drug use over time with hair growth
Liver- can screen but can’t quantify
Others – bile (opiates concentrate here, used to be useful but not used these days), muscle, powders, syringes

Post mortem blood most important
Get different concs of drugs at different sites
Femoral vein away from central sites (less vulnerable to changing levels of drugs being released from tissues when they break down) –> reference ranges build around this

Question 3

Analysis

Answer 3

GC-MS = Gas chromatography mass spectrometry
EIA- immunoassay (will always have false positives and negatives)

• Alcohol (+ acetone, important for ketoacidosis deaths then beta hydroxybutarate to measure degree of ketoacidosis) Head-space GC
• General Drug Screen GC-MS
• Urine drugs of abuse screen GC-MS
• Specific screens: morphine EIA, cannabis GC-MS, amphetamines GC-MS
• Quantitation GC-MS, HPLC DAD, LC-MS
• Hair simultaneous screen & quantitation GC-MS
• Others - COHb, glucose, Mast Cell Tryptase (for anaphylactic shock deaths), specific requests

Question 4

Ethanol

Answer 4

OD
Accidents including RTCs
Additive effects other respiratory depressant drugs

Question 5

Heroin (measured as morphine)

Answer 5

IV injection, volatilised (inhaled vapour)
Fatal OD with both routes of ingestion
Additive effects other respiratory depressant drugs
Few rapid deaths (usually 1-2 hours until resp depression causes CO2 to build up and cause death, or aspiration pneumonitis, or airways just get blocked)
Most respiratory depression or aspiration pneumonitis
Tolerance

Question 6

Methadone

Answer 6

Tolerance
After ingestion fatal amount takes 4-6 hours to die
Additive effects other respiratory depressant drugs
5 mL can kill a child, 60 mL can kill healthy adult male
Maintenance dose can vary from 5 to 200 mL (big range, usually about 20-40) - taken once every 24 hrs

Question 7

Benzodiazepines (diazepam, temazepam)

Answer 7

Additive effects other respiratory depressant drugs

Extremely rare to cause death alone

Question 8

Cannabis

Answer 8

Never fatal alone
Find in RTAs
Driving after alcohol + cannabis, lethal combination

Question 9

Cocaine

Answer 9

Injected with heroin, “speedball”
Tolerance
Acute dangers : cardiac dysrhythmias, acute heart failure, myocardial infarction –> if they are presenting with one of these, you won’t see cocaine in the urine drug screen
Slowly developing damage to the myocardium - ventricular arrhythmias, sudden death
Body packers
Effects prolonged if used with ethanol, get cocaethylene formed (longer half life)

Question 10

Amphetamines / stimulants

Answer 10

MDMA (ecstasy), Crystal meth (methylamphetamine), Amphetamine
Large OD causes direct toxic effect on heart
Can cause hyperthermia, leads to rhabdomyolysis –> leads to muscle necrosis and renal failure

Question 11

Pregabalin/Gabapentin

Answer 11

Coroners’ cases - 3% Gabapentin, 6% Pregabalin (cf 10% morphine from heroin)

Prescribed for epilepsy, neuropathic pain
Used by drug users for euphoria similar to that from heroin
Going to become Class C controlled drugs

Question 12

“Legal Highs”“Designer Drugs”

New Psychoactive Substances (NPSs)

Answer 12

Stimulants (cathinones) (“bath salts”)
Synthetic Cannabinoids or “Spice”
Synthetic Opioids (eg acetylfentanyl)
Hallucinogenic Compounds (eg 1P-LSD)

Question 13

Synthetic Cannabonioids - “Spice”

Answer 13

Modify one of the groups –> similar activity, done to get round the misuse of drugs act
Can modify it in many ways –> around 180 synthetic cannabinoids, many are v potent in v low concentrations

Synthesised in clandestine labs
Impregnated herbal material, smoked
Very cheap
Don’t have characteristic smell of cannabis –> useful in prison
Higher prevalence severe adverse effects - Hypertension, tachycardia, hallucinations, agitation, paranoia, seizures, panic attacks

Question 14

Synthetic fentanyls

Answer 14

Fentanyl = 100x more potent than morphine
USA opioid problem “no body should suffer pain”
2013 synthetic fentanyls, clandestine labs started to appear
Problem numerous available, huge variation in potency
Carfentanil is 10,000 times more potent than morphine- (carfentanil used as tranquiliser for large animals e.g. elephants)

Question 15

Other drugs found in coroners toxicology

Answer 15

Difficult cases –> can’t tell if they have just tried to ease their pain or deliberately overdosed

Antidepressants - Amitriptyline, Citalopram, Fluoxetine, Sertraline
Antipsychotics - Risperidone, Quetiapine, Olanzapine, Clozapine
Analgesics- Tramadol, Codeine/dihydrocodeine preparations, Oxycodone, Morphine, Fentanyl

Antiemetic			   Antihypertensives
Anticonvulsants		   Antihistamine
Solvents			           β-Blocker
Hypnotics			   Anaesthetic
Anxiolytics			   Antimalarial
Ca+-channel blockers  Oral hypoglycaemic

Question 16

Drug Sources

Answer 16

Over-the-counter preparations
Prescription medication
Illegal street drugs
Migrant population
Bought over internet - key now

Question 17

Interpretation of investigations

Answer 17

Tolerance
Site dependence
PM redistribution of drugs (PM blood conc cannot be used to calculate the dose) --> tissues break down --> Drugs released from tissue stores --> cannot apply pharm equations to post mortem work 
Individual variation in response
Stability of drugs

CANNOT interpret without a complete history –> need context for the individual case

Question 18

CASE - postmortem redistribution of drugs:

Pt has been on amitriptyline for 7 years (under psych) - had suicidal thoughts and the following was found in femoral blood sample

Amitriptyline blood : 1.27 ug/mL
Nortriptyline blood : 2.33 ug/mL
Combined blood : 3.60 ug/mL

No alcohol/other drugs detected on blood screen

Answer 18

She didn’t think it is significant –> had been on it for a long time so likely there was a lot in tissues which was released after death . High nortrip implies chronic use

Question 19

CASE - postmortem redistribution of drugs:
45 male, history of depression
Previously attempted to take own life
Found with paracetamol, brown tablets (COX), ¼ full bottle port
Problems at work

Specimens: femoral vein blood, urine

Amitriptyline blood : 1.63 ug/mL

Nortriptyline blood : 0.23 ug/mL

Combined blood : 1.86 ug/mL

Combined therapeutic plasma conc: 0.12 to 0.25
Combined potentially fatal conc: >2.0

No other drugs detected in general screen blood
No drugs of abuse detected in urine

Answer 19

Amitrip here is significant as tablets belonged to wife, no history of using and ratio of amytrip to nortrip

Question 20

CASE - individual variation:

32yrs, male, in residential home
Treatment for depression & schizophrenia

Believed sudden death in epilepsy

Specimens: stomach contents, femoral vein blood, urine

CLOMIPRAMINE blood : 1.35 ug/mLDESMETHYLCLOMIPRAMINE blood : 11.62 ug/mL

Therapeutic : 0.10 to 0.48 Toxic : > 0.40 Potentially fatal : 1.0 ug/mL9 fatalities due to clomipramine: clomipramine 1.6 - 2.4 ug/mL desmethylclomipramine 0.8 - 2.0 ug/mL

CLOZAPINE blood : 2.01 ug/mLDESMETHYLCLOZAPINE blood : 2.33 ug/mL

Therapeutic : 0.10 to 0.80 Toxic : > 0.80 Potentially fatal : 3.0 ug/mLRatio clozapine to desmethylclozapine indicates chronic dosingSub-therapeutic lithium, neg chlorpromazine, neg zopiclone

Answer 20

Desmethylclomipramine is the active metabolite. In this case is a huge dose. Something wrong with their metabolism to cause this to build up.

Question 21

Stability of drug - cocaine

Answer 21

Degrades in PM blood (fluoride oxalate only slows the process)

• pseudocholinesterases –> EME
• Chemical hydrolysis –> BE

PM blood conc & blood conc at time of death not same

To interpret cocaine- witness behaviour, cardiovascular pathology, medicinal/drug use history

Addict can tolerate high levels
Causes heart problems, death with low levels

Question 22

What blood to use if you can

Answer 22

Ante-mortem, also ask detailed drug Hx

Question 23

Hair Analysis - Uses

Answer 23

• Blood/serum, drugs typically can be detected for no more than 12 hours
• Urine, drugs typically detected for 2-3 days
• Hair is the only specimen can give information about long term drug use
• Drugs are incorporated into hair from the blood stream during the growth phase
• Hair growth approx 1cm/month – “tape-recording of drug use”
• Can provide valuable evidence which cannot be provided by any other means
• Segmental analysis provides pattern of past use
• Established technique
• Increasingly used in crime investigation
• Seldom used in routine Coroner’s Toxicology

Used quite a lot in child custody cases –> to see if parent is abstinent and to see if child is coming into contact with drugs

Question 24

Hair Analysis - Issues

Answer 24

Environmental Contamination –> if you’re in a room with someone smoking crack, your hair might pick it up
Absorbed from sweat or sebum coating hair
Passive inhalation
Cosmetic treatment –> will affect conc but won’t remove the drug
- Shampoo washing
- Perming, dyeing, bleaching
Hair colour –> drugs associated with melanin in hair (racial bias)

Question 25

Chemsex

Answer 25

Sex under the influence of drugs (commonly men who have sex with men)

Specifically:

1) γ-hydroxybutyrate (GHB) / γ-butyrolactone (GBL)
2) Methylamphetamine (crystal meth)
3) Mephedrone

Harms:
GHB/GBL have steep dose response curve
Mix other drugs e.g. alcohol
Increased risk HIV