Toxicology Flashcards
what is toxicology
the study of the adverse effects of chemicals (including drugs) on living systems and the means to prevent or ameliorate such effects
what are the 5 different kinds of toxicologist
descriptive
mechanistic
regulatory
clinical
forensic
define forensic toxicology
the application of the scientific study of poisons/ intoxicants to questions raised in judicial proceedings
name a few subdisciplines of toxicology
post mortem toxicology
behavioural/ human performance
workplace drug testing
public health legislation
what are the 4 main responsibilities of a toxicologist
- Conduct toxicological analysis
- Report and document
- Consulting and testifying (court)
- Research and development
define poison
a substance that can cause illness or death of a living organism when introduced or absorbed
who is the father of poison and what is his main quote - what does it mean
Paracelsus - ‘All substances can be poisons; there is none which is not a poison’ - that the dose determines toxicity
what are the most frequent occurrences of poisoning
most cases result from social and economic stress or mental disorders but some are from substance abuse or even accidental
name a few things a toxicologist can do during an investigation
- 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
what are the 4 main roles of a pathologist
- Perform medico-legal autopsies to establish the cause of death; issue death certificate
- Estimate time of death
- Removal of specimens to assist in the investigation
- Prepare report, precognition and court testimony
why are case notes important in toxicology
they contain the recent history of the patient, their signs and symptoms on admission/ death, what medications they are on and any lab results, which may help suggest poisoning and of which kind
define chain of custody
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 of the transfer
why do we ensure chain of custody
to demonstrate validity, ensure integrity and, security of specimens so that they are accepted in court
what are the two common legal drugs of abuse
alcohol and prescribed meds
what are the 4 common illegal drugs of abuse
amphetamine, cocaine, ecstasy and opioids
what year was the misuse of drugs act passed in the UK
1971
what 3 things does the misuse of drugs act (1971) state
that it is an offense to:
- possess a controlled substance unlawfully
- possess a controlled substance with intent to supply
- supply or offer to supply a controlled drug
allow a house, flat or office to be used by people taking drugs
what are the 6 main classes of mis-used drugs
- Opiates
- Depressants
- Minor tranquilisers
- Stimulants
- Hallucinogens
- Other - cannabis, nicotine, volatile substances
how do we classify drugs into three categories
A, B, C - based on how much a drug will affect your brain function/ activity
what are the main roles of a forensic toxicologist
- Maintain chain of custody
- Identify drugs and poisons
- Screen through entire body
- Search for parent chemicals and metabolites
- Help to suggest possible side effects on the victim
what are the 8 types of poison
- Anions
- Corrosives
- Gases and volatiles
- Metals and metalloids
- Toxins
- Pesticides
- Prescription and illicit drugs
- Household chemicals
give 3 examples of anion poisons
cyanide, fluoride, nitrate - things that are charged
give 2 examples of corrosive poisons
sulphuric acid and sodium hydroxide
give 3 examples of gaseous/ volatile poisons
ethanol, products of combustion and solvents
give 3 examples of metal/metalloid poisons
iron, lead and arsenic
give 4 examples of toxin poisons
plant, animal, bacterial and fungi
which type of poison is a good example of indirect poisoning
pesticides
what is the difference between acute and chronic exposure to toxicants
acute = contact with a substance that occurs once for only a short period of time (up to 14 days)
chronic = contact with a substance that occurs over a long period of time (more than one year)
what are the typical symptoms of poisoning
nausea, vomiting, seizure, coma and death
define drugs of abuse
any substance used for an alternative purpose than that intended
why are more and more synthetic drugs being produced
easy to produce and transport, ae cheaper and take less time to make
what are illicit drugs
highly addictive substances that are illegal to sell, make and use - not used medically
what is the limbic system
a region in the core of the brain where everything happens regarding highs/ addictions
what 5 regions of the brain are included in the limbic system
- Cingulate gyrus
- Ventral striatum
- Hypothalamus
- Amygdala
- Hippocampus
what do all the regions of the limbic system communicate through
the nucleus accumbens
what are the two aims of toxicological screening techniques
to confirm and quantify chemicals
what are the three types of reward systems
mesocortical
mesolimbic
nigro-striatal
name 6 techniques of toxicological screening
- Immunoassays
- Spot colour tests
- Thin layer chromatography and column chromatography
- Gas chromatography
- HPLC
- Mass spectrometry
what are the 5 main general steps to analysis of a chemical
- Separation of poison and metabolites from biological material
- Identification
- Confirmation of identity
- Quantification/ concentration
- Interpretation
name 4 advantages of presumptive testing
- Qualitative
- Cheap
- Quickly ID’s analytes
- Only requires a small sample
name a few qualitative analysis observations
colour
morphology - shape, dimensions, etc
manufacture marks
packaging
unusual odours
what are the three main spot tests used in toxicological analysis
Marquis
Mandelin’s
Cobalt isothiocyanate
what are the two main steps in an immunoassay
- Drug is labelled with an enzyme - fluorescent molecule
- Interaction of a drug with an antibody
name the 3 most commonly used TDM homogenous immunoassays
- enzyme-multiplied
- fluorescence polarisation
- cloned enzyme donor
what does ADMET stand for
A = absorption
D = distribution
M = metabolism
E = excretion
T = toxicity
what does metabolism + excretion =
elimination
what is absorption mean in ADMET
the movement of a drug/ chemical from the site of administration into the blood stream
name the 9 ways drugs can enter the blood stream
- Intramuscular
- ocular
- Oral
- Intrathecal
- Sublingual
- Rectal
- Inhalation
- Dermal
- Intravenous
what does distribution mean in AMDET
the movement of a drug/ chemical around the body, into and out of tissues and fluids
what is the NPIS and what does it do
National Poisons information service - advises NHS healthcare professionals on the diagnosis, treatment and care of poisoned patients
what causes the largest proportion of drug misuse deaths
accidental poisonings
what is elimination mean in ADMET (metabolism + excretion)
irreversible loss of drugs - unchanged and metabolites - from the body by any mechanism
what is excretion in ADMET
removal of intact drug from the body e.g. urine, faeces, breath
define half-life and clearance in regards to excretion
half-life = rate of drug removal
clearance = extent of drug removal
what is biotransformation
major site of xenobiotic metabolism
what is first pass metabolism and what does it do
GI to liver - reduces bioavailability
name a few factors affecting the passage of drugs through cell membranes
- plasma protein binding
- free drug concentration gradient
- active transport
- molecular weight
- degree of isolation
- lipid solubility
- water solubility
define drug metabolism
the enzyme-catalysed conversion of a drug into a chemically-distinct product (a metabolite)
what’s key to remember about kinetics
it it refers to time its usually about kinetics
what’s the difference in a kinetic graph of drug metabolism when comparing oral vs intravenous administration
the half-lives remain the same but the absorption phase is extremely different
define bioavailability
the amount absorbed relative to the dose administered
what is the typical shape of a dose response curve and what do they show us
sigmoidal - tells us the lethal dose (what dose kills 50%)
what is the order of collection in standard postmortem specimen procedure in regards to drugs in the blood and why
femoral, iliac, subclavian vessels, heart - due to accumulation
why does the heart contain an artificially elevated concentration of drugs after death
as blood collection increases in the heart, so does the drug concentration
where is a more reliable matrix for drug testing after death
in muscles
what are some other considerations to consider when interpreting toxicology results
- post-mortem redistribution
- post-mortem production and loss of substances
- analyte stability
- post-mortem findings
- route of administration
- alternative source of positive findings
- use of appropriate reference samples
