Forensic Toxicology - Exam 1

pharmacology

the study of drugs

toxicology

the study of poisons

forensic toxicology

applying toxicology to aspects of the law

“poison” hemlock

neurotoxin, blocks neuromuscular transmission, 6-8 leaves is a toxic dose

tetrodotoxin

found in puffer fish and blue-ringed octopus

botulinum toxin

most lethal toxin known to man, produced by bacteria

arsenic

king of poisons, silent, deadly, virtually undetectable

paracelsus

everything is a poison at the right dose

hyponatremia

over-hydration (water toxicity), skull pressure squeezes brain and spinal cord, swollen brain cells

marijuana, cocaine, amphetamines, opiates, pcp

NIDA-5 tests for

receipt of evidence, conduct analyses, review data, prepare a report, review a report

forensic lab workflow

pharmacokinetics

what the body does to the drug

pharmacodynamics

what the drug does to the body

dose-response effect

dose determines blood concentration determines effect

absorption, distribution, metabolism, elimination

movement of a drug over time through the body

bioavailability

the fraction of drug that reaches the systemic circulation after oral ingestion

intravenous, intramuscular, subcutaneous, oral, rectal, inhalation, transdermal

routes of administration in order of bioavailability

dosage form, additives, delayed response preparations

rate of dissolution and release of drug from pharmaceutical preparation are determined by _____________

uncharged

permeability favors small _____ solutes

low pH

acidic drugs are better absorbed at _______

high pH

basic drugs are better absorbed at __________

one compartment model of distribution

instantaneous distribution after administration, even distribution throughout body (blood)

two compartment model of distribution

different distribution rates, more rapid distribution into high perfused tissues, followed by a slower distribution into less well-perfused tissues (blood and fat)

blood brain barrier

lipid membrane located between the plasma and extracellular space in the brain, limited to small and highly lipophilic drugs

volume of distribution

theoretical volume of fluid into which the total drug administered would have to be diluted to produce the concentration in plasma

dose (mg)/ plasma concentration (mg/L)

volume of distribution equation

agonist

drug binds to and activates a target, maximal response when used at high enough concentrations

partial agonist

drug produces less than maximal response even at high enough concentrations to cause maximal response

antagonist

inhibit the ability of targets to be activated by physiologic or pharmacologic agonists

competitive antagonist

key that fits in lock, does not open door, usually reversible

non-competitive antagonist

dead-bolt lock, door will never open, even if key is put into lock

unbound receptor

agonist binding

competitive antagonist binding

noncompetitive antagonist binding

metabolism

biotransformation of chemicals into water soluble compounds to be eliminated in urine/bile

first pass metabolism

phenomenon of drug metabolism whereby the concentration of a drug is greatly reduced before it reaches the bloodstream

cytochrome P450 enzymes

75% of metabolism of drugs

inducers

speed up CYP, lower drug blood concentrations

inhibitors

slow down the CYP, increase drug blood concentrations

elimination

elimination of unchanged drug or metabolite from the body

glomerular filtration, tubular reabsorption, tubular secretion

mechanisms of the kidney

glomerular filtration

small molecules/drugs filtered through the glomerulus, drugs bound to plasma proteins are too large

tubular reabsorption

lipid soluble drugs are reabsorbed from the lumen of the nephron back into the systemic circulation

tubular secretion

carrier-mediated active transport system that requires energy, shows competition effects

acidify the urine

to increase the renal clearance of a drug that is a weak base you should ____________

first-order

a constant fraction of drug is eliminated with time (exponentially)

zero-order

a constant amount of drug is eliminated with time (linear)

cyanide

________ inhibits Cyt C (electron transport chain)

LC/MS

gold standard for instruments

albumin

most common protein that binds to drugs

glucuronidation

a metabolic process that attaches glucuronic acid to a drug, increasing its solubility, making it easier for the body to eliminate

sulfation

a metabolic process were a sulfate group is added to a molecule to facilitate its excretion

intravenously

drugs administered ____________ do not go through first pass metabolism

cmax

maximum concentration

tmax

time at cmax

cocaine, sympathomimetic amines, methylxanthines, nicotine

types of CNS stimulants

pupils dilated, HGN and VGN absent, pulse and blood pressure elevated, hot, rigid muscles, injection sites

DRE assessment for stimulants

paranoia, psychosis, impaired task performance, euphoria, violence

characteristics of stimulant symptoms

schedule II, ENT surgeries

cocaine schedule

cocaine hydrochloride

powder form, cut with things like caffeine or benzocaine

inhaled, smoking, intravenous, orally

routes of administration of cocaine

mechanism of action of cocaine

blocks Na channel conductance (anesthetic), blocks reuptake of neurotransmitters like dopamine, norepinephrine, and serotonin

metabolism of cocaine

metabolizes to benzoylecgonine and methylecgonine, becomes cocaethylene in presence of EtOH, long term storage of samples convert to BZE

0.5-1 hour

half-life of cocaine

3-5 hours after formed

half-life of BZE

2 hours after formed

half-life of cocaethylene

analysis of cocaine

GC/MS, filtration/extraction then LC/MS

methamphetamine, amphetamine, MDMA, ephedrine

types of sympathomimetic amines

schedule II, narcolepsy or ADD

sympathomimetic amine schedule

meth/amphetamine mechanism of action

stimulates neurotransmitter release and then inhibits metabolism

10-12 hours

methamphetamine half-life

11-12 hours

amphetamine half-life

elimination of sympathomimetic amines

eliminated via kidney, unchanged

teeth grinding, desire to move

MDMA symptoms

theophylline, theobromine, caffeine

types of methylxanthines

cardiac arrhythmia

symptom of cocaine

vasoconstriction

decreasing surface area of a blood vessel

D

__-methamphetamine is deadly

schedule IV

phentermine schedule

schedule I

MDMA schedule

opiate

used to describe drugs that are derived from opium

opioid

synthetic and semi-synthetic entities that have morphine-like actions

narcotic

applied to any drug that induces sleep

analgesic

a drug used to relieve pain without loss of consciousness

brainstem

mediate respiration, cough, maintenance of BP, pupillary diameter, and control of stomach contents, nausea, vomiting

medial thalamus

mediate deep pain that is poorly localized and emotionally influenced

spinal cord

involved with the receipt and integration of incoming sensory information, leading to the attenuation of painful stimuli

hypothalamus

affect neuroendocrine secretion

limbic system

may influence emotional behavior

periphery

bind to peripheral sensory nerve fibers and their terminals and inhibit release of pro inflammatory substances

immune cells

receptors have been found on immune cells, but the role in response to painful stimuli has not been determined

mu, kappa, delta, sigma

receptor subtypes

morphine, fentanyl, heroin, meperidine, methadone

full agonist opioids

naloxone, naltrexone

antagonist opioids, do not activate the receptor-mediated response

opioid uses

chronic pain, trauma, burns, cough suppression, diarrhea, detoxification of opioid use

opioid disadvantages

respiratory depression, addiction potential, tolerance, sedation

opioid mechanism of action

at spinal site they inhibit neurons that transmit pain transmission, at brainstem they activate neurons that send impulses to the spinal cord to inhibit pain transmission

pupils constricted, HGN and VGN absent, pulse and blood pressure lowered, cold, droopy eyelids, on the nod, raspy speech

DRE assessment for opioids

insufflation, smoked, injected, oral

opioid ingestion methods