LECTURE 19 AND 21: FORENSIC TOXICOLOGY // ILLICIT DRUG CHAPTER // FORENSIC TOXICOLOGY CHAPTER Flashcards
toxicology
- The study of the adverse effects of chemicals on living organism
- This involves the study of mechanisms, symptoms treatments and detection
Ideal poisons
- Colourless
- Odourless
- Tasteless
- Cheap
- Easily obtained
- Soluble
- Undetectable
- Delayed action
- Lethal at low dose
- Mimics a natural disease
necrosis
non-programmed cell death
3 primary causes of necrosis
- ATP depletion
- Excitotoxicity
- Oxidative stress
Plant secondary metabolites
- There are many chemical classes of plant-derived toxin
- The most important class are the alkaloids
alkaloids
- organic compounds containing nitrogeen
- 90% found in plants
- divided into two classes heterocyclic and non heterocyclic
first alkaloid discovered was
morphine
Non-heterocyclic alkaloids
Examples of non-heterocyclic alkaloids
- Dopamine - Neurotransmitter found in many species
- Ephedrine - Affects sympathetic nervous system via adrenergic receptors
- Morphine - Psychoactive analgesic drug, mimics action of endorphins
- Mescaline - Hallucinogenic alkaloid found in peyote cacti
Heterocyclic alkaloids
Examples of heterocyclic alkaloids
- Caffeine - Insecticide in plants, stimulant in humans
- Capsaicin - Irritant found in chilli peppers, does not affect birds
- Cocaine - central nervous system stimulant
- Lysergic acid - Psychedelic metabolite found in fungi and plants
- Quinine - Antimalarial drug with many other pharmacological actions
- Samandrin - Highly toxic compound from the fire salamander
- Serotonin - Neurotransmitter in many species
- Solanine - Pesticide in plants, produced in potatoes (green spots)
Caffeine toxicology
- Caffeine is an antagonist at the A1 and A2A receptors
o It is lipid soluble, so can readily cross the blood-brain barrier and affect these receptors - This will lead to increased heart rate and decreased inhibition of the central nervous system
o Decreasing inhibition of the CNS will increase levels of neurotransmitters such as dopamine
o Hence caffeine is a stimulant - Adenosine receptors are also involved in regulating the sleep-wake cycle
- Caffeine is also a phosphodiesterase inhibitor, prolonging the activity of cAMP in cells
Arsenic
- Chemical symbol As; atomic number 33
• Complex chemistry – multiple forms - Trivalent arsenicals are the most toxic
• Interfere with energy generation in cells
• Trivalent form resembles phosphate - Energy depletion is one of the key causes of necrosis (cell death)
- Acute exposure: causes heart failure; ~100 mg fatal
- Chronic exposure: causes neurotoxicity
Lead
- Chemical symbol Pb; atomic number 82
- Widespread in environment
- Chronic exposure has serious consequences for children
o It interferes with cell communication in the brain, causing both physical and chemical changes - In adults, lead will primarily affect the brain
o Also impairs formation of haem, causing anaemia
Mercury
- Chemical symbol Hg, atomic number 80
- Exists in multiple chemical forms
- Exposure primarily from environment and food
- Elemental and inorganic mercury exposure less toxic
- Organic, e.g. methylmercury more toxic
o Primarily affects the CNS
Drug =
a natural or synthetic substance that is designed to produce a specific set of psychological or physiological effects on the human body.
Drug abuse =
occurs when people take drugs for purposes other than for which they are intended; usually for their psychoactive effects.
Classification of illicit drugs by ‘derivation’
naturally occuring
plant extracts
semisynthetic
synthetic
Naturally occurring = found in nature. Eg:
a) Marijuana – leaves are dried & smoked
b) Psilocybin mushrooms – eaten, cause hallucinations
c) Peyote cactus – buttons are eaten, contain a hallucinogen
Plant extracts = naturally occurring extracted from plants & ingested. Include:
a) Cocaine – extracted from coca plant
b) Morphine & codeine – extracted from opium poppy
Semisynthetic = derived chemically from naturally occurring substance. Eg:
a) Heroine – manufactured from morphine
b) LSD – manufactured from lysergic acid
Synthetic = manmade. Eg:
a) Amphetamines
b) Barbiturates
c) Phencyclidine (PCP)
d) Oxycodone
classification of drugs based on their psychoactive effects
stimulants
depressants
narcotics
hallucinogens
Stimulants
Amphetamines:
- A derivative is called methamphetamine.
- Smokable – ice
Cocaine:
- Crack = form of crystalline cocaine.
Depressants e.g. alcohol
The Barbiturates
- decrease brain activity
- small dose = reduce anxiety
- sedative
- barbituric acid and thiobarbituric acid
- Meprobamate (Miltom), Methaqualone (college kids abused this) Benzodiazepines
lethal injection
1) Sodium pentothal or pentobarbital to render the prisoner unconscious
2) Pancuronium bromide to cause muscle paralysis
3) Potassium chloride to stop the heart & cause death by cardiac arrest.
Narcotics
Opium poppy - medicinal plant used for pain and suffering
Narcotics derived from opium
1) Morphine is extracted from opium.
2) Heroin = drug that is easily made from morphine, is approximately 10 times more potent.
3) Codeine is the other popular derivative from opium. Popular cough suppressant.
Synthetic Narcotics
- Synthetic Narcotics:
1) Include demerol (meperidine), oxycodone, hydrocodone, fentanyl.
2) Methadone is a synthetic narcotic that is used in the US as a heroin substitute to get addicts off heroin
3) Fentanyl (China White) is the backbone of the a series of designer drugs = illegal substances that are synthesized with particular pharmacological characteristics designed for abuse purposes.
Hallucinogens
D-Lysergic Acid Diethyl Amide
- LSD
- not naturally occurring but comes from grain fungus (mold)
Psilocybin
- found in mushrooms
- similar to LSD
Marijuana
- belongs to genus Cannabis
- contains THC
Mescaline
3,4-methylenedioxy-methamphetamine
- MDMA
- Ecstasy
Phencyclidine
- first used in surgical procedues
what is the active ingedint that gives plant its hallucinogenic properties
THC - tetrahydrocannabinol
plant material of marijuana is boiled, filtered and evaporated to a gooey liquid known as
hashish oil
seedless marijuana
sinsemilla
Excipients =
substances that may mimic the activity of the main illicit drug present in order to make it more difficult for the user to know just how much of the drug there really is in the exhibit.
Diluents =
chemicals that are used to dilute an illicit drug & to give it more bulk. “Cut the purity of the drug.”
presumptive test Ruybal (Scott) test
cocaine
turquoise colour
Marijuana has some distinct features that can be used to help in identification,
these include the presence of cystolith hairs on one side of the leaf surface & numerous, small white hairs on the other side.
presumptive test for marijuana
the Duquenois-Levine test, followed by some form of chromatography, usually TLC.
presumptive test for LSD
Ehrlich’s test
- light purple
Alcohols
general term that refers to organic compounds with hydroxyl functional groups
- ethanol or ethanol based drinks
surrogate alcohols
- not meant for consumption ‘
- over 95%
- H2O2, anticeptics, methanol
most common form of denatured alcohol is
- methylated spirits which contain methanol (10%)
ethanol
- CNS depressant
- primarily metabolised in liver
methanol
- simplest alcohol
- CNS depressant
how can prescription drugs be toxic
- Overdose
- Hypersensitivity
- Lack of selectivity
- Allergy
- Cutaneous reactions
- Pregnancy and lactation
paracetamol
- acetaminophen
- non-narcotic analgesic
NSAIDs
- Non-steroidal anti-inflammatory drugs (NSAIDs)
o e.g. aspirin, ibuprofen - Block cyclooxygenase-2 (COX-2) enzymes that produce inflammatory mediators
- Also block COX-1, which regulates gastrointestinal secretions
- Risk of GI bleeding and ulceration
Illicit drugs
- Recreational use of prohibited drugs
- Includes illegal drugs, misuse of prescription drugs and use of other substances
- Illegal drugs include both natural and synthetic substances
- The first drug to be widely abused was opium
Heroin
- CNS depressant opiate that is widely abused
- Converted to morphine and 6-MAM in the body
- Bind to opioid receptors and provide euphoria, analgesia, and anxiolytic effects
- Also causes respiratory depression
Cocaine
- Alkaloid used as a local anaesthetic
o Crack cocaine is the freebase form (most addictive drug known) - Blocks sodium channels to act as anaesthetic
- Also inhibits reuptake of neurotransmitters
o This is what has the stimulant effect
Cannabis
- Used for medicinal purposes for over 5000 years
- 76% of illicit drug users use cannabis
- Active ingredients are cannabinoids
- e.g. delta-9-tetrahydrocannabinol
- Primarily act through CB1 receptors
- When activated, they decrease sensitivity of the nervous system
LSD
- Lysergic acid diethylamide
o Developed from the ergot fungus - Acts on serotonin receptors to produce vivid hallucinations
- Substantial influence on popular culture
o Lucy in the Sky with Diamonds
MDMA (ecstasy)
- Methylenedioxymethamphetamine
o Emerged as a party drug in the 1980s - Triggers release of serotonin and blocks reuptake
o CNS stimulant - Reduces ability of brain to regulate temperature
o This can lead to death by overheating
o Excessive consumption of water can also be fatal
Methamphetamine (ice)
- Crystal meth
o Synthesised from ephedrine - CNS stimulant via multiple neurotransmitters
o Dopamine, noradrenaline, serotonin - Will have neurotoxic effects, so long term users at high risk of psychosis
2 of the most important jobs of forensic toxicologist
the identification of the drugs & the determination of their quantities.
Tolerance =
a phenomenon whereby the body’s organ systems adapt to the drug. More pronounced in morphine and heroin, as well as cocaine & barbiturate.
synergism =
Drugs work together to magnify their effects or create effects that would not have occurred otherwise
field sobriety testing
1) Horizontal gaze nystagmus = subject is asked to follow with their eyes only, a pencil or other object as the officer moves it slowly back & forth across the subject’s field of vision. If a person is sober, they will be able to follow the pencil easily & their eyes will move smoothly. If they are under the influence, eyeballs will jerk as they get moved.
2) Other 2 tests measure dexterity which deteriorate as BAC increases. Common ones are the walk & turn.
3) Other test is to close one’s eyes and touch one’s nose with the tip of a finger.
