Chempath - Forensic Toxicology Flashcards
Types of death reported to coroner
Violent
Unnatural or sudden
Cause of death is unknown
Types of samples
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
Analysis
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
Ethanol
OD
Accidents including RTCs
Additive effects other respiratory depressant drugs
Heroin (measured as morphine)
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
Methadone
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
Benzodiazepines (diazepam, temazepam)
Additive effects other respiratory depressant drugs
Extremely rare to cause death alone
Cannabis
Never fatal alone
Find in RTAs
Driving after alcohol + cannabis, lethal combination
Cocaine
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)
Amphetamines / stimulants
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
Pregabalin/Gabapentin
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
“Legal Highs”“Designer Drugs”
New Psychoactive Substances (NPSs)
Stimulants (cathinones) (“bath salts”) Synthetic Cannabinoids or “Spice” Synthetic Opioids (eg acetylfentanyl) Hallucinogenic Compounds (eg 1P-LSD)
Synthetic Cannabonioids - “Spice”
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
Synthetic fentanyls
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)
Other drugs found in coroners toxicology
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
Drug Sources
Over-the-counter preparations Prescription medication Illegal street drugs Migrant population Bought over internet - key now
Interpretation of investigations
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
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
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
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
Amitrip here is significant as tablets belonged to wife, no history of using and ratio of amytrip to nortrip
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
Desmethylclomipramine is the active metabolite. In this case is a huge dose. Something wrong with their metabolism to cause this to build up.
Stability of drug - cocaine
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
What blood to use if you can
Ante-mortem, also ask detailed drug Hx
Hair Analysis - Uses
- 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
Hair Analysis - Issues
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)
Chemsex
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
