tox flashcards

xenobiotics

xenobiotics

• exogenous agents that have adverse effects on living organism

• describes environmental chemicals or drug exposures

• ex: antibiotics/antidepressants

poisons

• exogenous agents with adverse effect on biological system

• describes animals, plants, minerals, gas poisons

• ex: snake venom, poison hemlock, arsenic

toxins

• endogenous; substances biologically synthesized in living cells/microorganisms

• botulinum, fungal toxins

how do exposures happen?

• 50% suicide attempts

• 30% accidental (children)

• remainder: homicide, industrial, agricultural

what are common routes of exposure?

• ingestion, inhalation, transdermal absorption

• absorbed via processes meant for nutrients or passive diffusion

factors affecting absorption

pH, rate of dissolution, gastric motility, resistance to GI tract degradation

TD(50)

the dose that produces a toxic response in 50% of the population

ED(50)

the dose that produces an effective response in 50% of the population

LD (50)

the dose the produces a lethal response in 50% of the population

forensic permit

requires a chain of custody and drug confirmation

chain of custody

document sample from time it is drawn to the time the results are released to the clinician

5 panel drug test (NIDA-5)

THC, PCP, cocaine, amphetamine, opiates

12 panel drug test

• 5 panel plus

• methamphetamines, benzos, barbiturates, methadone, propoxyphene, methaqualone, expanded opiates

why is urine the most common sample?

• large sample

• easy to obtain

• contains some of the parent and a lot of the metabolites

• random urine

• good for low levels of drug in any other fluid (highest in urine)

specimen requirements for blood

• whole blood, plasma, serum depending on drug

• used to correlate the conc of the drug with effect

decomp tissue for drug testing

• used when blood or urine is not possible

• blend tissue than extract drug out of it (homogenize)

list some other less common specimens for drug testing

• vitreous humor

• meconium (for last half of gestational period)

• hair (long term exposure) (harder to adulterate)

• sweat

• saliva (harder to adulterate) (ideal for alcohol)

urine specimen requirements

• temp 90-100F

• pH 4.5-8

• SpG 1.003-1.019

• creatinine >20

two step procedure

• screening (IA)

• confirmatory

screening test

• IA, TLC

• rapid, simple, qualitative

• intended to detect specific substances

• good analyte sensitivity but lacks specificity

confirmatory test

• used to confirm pos result from screening test

• needed in forensic testing

• GC, ICP-MS, AA, LC-MS, HPLC, GC-MS**

spot tests

• used to ID unknown powder in sample

• qualitative/non-instrumental

• presumptive answer but less precise

• colorimetric change

• need confirmatory test

acetaminophen spot test

• p aminophenol reacts with ocresol and ammonium hydroxide

• blue/indigo

salicylate spot test

• trinder reagent (iron)

• blue/purple

• brown = phenothiazines

phenothiazine spot test

• ferric, perchloric, nitric

• red = violet

tricyclic spot test

• oxidation with forrests reagent

• green

ethchlorvynol spot test

pink

TLC

• Rf = distance solute moved/distance solvent moved

• compare Rf to standards

• use sprays/stains to compare

IAs

• enzyme IAs

• most common, easy to perform, no pretreatment, sensitive, fast TAT

• ELISA, EMIT, CLIA, FPIA, CEDIA

• disadvantage: cross reactivity with similar subs

HPLC

• liquid mobile phase

• high pressure to move through column so the time it takes to elute out is retention time = drug ID

• non polar drugs

• HMW substances

GC

• broad spectrum of drugs can be tested

• drug interacts with column so time taken to elute out = ID

• mobile phase = gas

• solid phase = column

• can also be screening

GC-MS

• most common confirmatory test

• quadrupole creates ions that are separated on mass to charge ratio

• distinct fingerprint of drug

• uses EM

extraction

to remove the drug/metabolite of interest from other interfering subs in urine/blood/tissue

filtration

to remove non dissolved solids prior to HPLC

reconstitution

after extraction, sample is dried and needs to be reconstituted

amphetamines

• CNS stimulant

• white, odorless, crystalline

• smoked, IV, orally

• detect 2-3 days

what are amphetamines used to treat?

narcolepsy, obesity, ADD hyperactivity disorders

symptoms of amphetamine use

• euphoria

• inc heart rate/BP (lead to AMI/stroke), insomnia, irritability, restlessness, personality changes

• dilated pupils = EMS

how does pH affect amphetamine excretion rate?

• low pH = inc

• high pH = dec

designer amphetamines

• structurally similar to meth/mescaline

• synthesized to mimic effects

• MDMA

symptoms of designer amphetamine use

euphoria, enhanced pleasure, sociability, sexual arousal

toxicity of designer amphetamines

• hypertension, diaphoresis, seizures, cerebral hemorrhage, hyperthermia

• raves = inc mvt = hyperthermia = untreated = rhabdomyolysis

barbiturates

• depressant or sedative/hypnotic

• detect 2-15 days

• short acting more potent than long acting

short to intermediate acting barbiturates

• amobarbital, butobarbital, butalbital, pentobarbital, secobarbital

• become tolerant so need higher dosage

• sedative effects

long acting barbiturates

• help with seizures and sleep induction

• not usually abused

symptoms of barbiturate use (toxicity)

• mild euphoria

• slurred speech, slow mental function, resp depression, cardiac insuff

• tight, constricted pupils = EMS

how to treat barbiturate overdose

alkalinize urine to increase excretion

benzodiazepines

• depressant = anxiety disorders

• sedative, hypnotics

• diazepam (valium), alprazolam (xanax), triazolam (halcion)

• detect 2-10 days

• oral ingestion, fast absorption

• tolerance develops

uses of benzodiazepines

insomnia, anxiety, seizures

symptoms of benzodiazepine use

• resp depression**, sedation, hypnosis, muscle relaxation, anticonvulsive

• inc GABA in CNS to diminish electric transmissions in neurons

cannabinoids

• stimulant, sedative, tranquilizer, hallucinogen

• green/gray mixture of dried shredded flowers/leaves from cannabis sativa plant

• detect 3-30 days

• very lipophilic drug

what is the major active ingredient in marijuana?

THC (delta 9 THC)

uses of cannabinoids

treats anorexia, nausea (cancer pts), asthma, glaucoma

symptoms of cannabinoid use

• euphoria, sense of well being, relaxation

• short term memory loss, mild physical dependence

• paranoia

legalized marijuana

• 20 states (medicinal), 20 (rec/med), 10 (illegal)

• police use oral fluid testing

• 5 = fatal crashes

cocaine

• stimulant

• detect 2-10 days

• inhaled, smoked, injected

• parent metabolized very fast

cocaine metabolites

benzoylecgonine, ecgonine, methyl ester, cocaethylene

uses of cocaine

topical anesthetic in nasal surgery

cocaine HCl

white to light brown crystalline powder, shiny

cocaine base

white to beige, waxy/soapy to flaky solid chunks

symptoms of cocaine use

euphoria, inc heart rate, seizures, coma, sudden death

opiates

• narcotic, analgesic

• detect 1-3 days

natural opiates

• opium, morphine, codeine

• from c pod of opium poppy

semisynthetic opiates

• heroin

• oxycodone (percodan)

• hydrocodone

• oxymorphone (dilaudid)

synthetic opiates

• propoxyphene (darvon)

• methadone

• meperidine (demerol)

• fentanyl

uses of opiates

• relieve moderate/severe pain (acute/chronic management)

• sedate pts pre-op

• facilitate induction of anesthesia

symptoms of opiate use

• euphoria, sedation, resp depression, hypotension, nausea, vomiting

• coma, pinpoint pupils, resp depression = overdose symptoms

treatment for opiate overdose

naloxone (comp antagonist reverse overdose)

metabolites seen after heroin use

6MAM, morphine > codeine

• oxymorphone, norcodeine

metabolites seen after morphine use

morphine

• hydromorphone

metabolites seen after codeine use

codeine>>morphine

• norcodeine

metabolites seen after hydrocodone use

hydrocodone, hydromorphone

• norhydrocodone

metabolites seen after hydromorphone use

hydromorphone

metabolites seen after oxycodone use

oxycodone, oxymorphone

• noroxycodone

metabolites seen after poppy seed ingestion

codeine, morphine

• norcodeine

phencyclidine PCP

• hallucinogen

• white crystalline powder (contam = tan/brown); clear yellowish liquid

• detect 10 days

• lipophilic

• smoked, IV, snorted, eye drops, oral, transdermal absorption

• can be mixed with other drugs

uses of PCP

• formerly surgical anesthetic

• vet anesthetic or tranquilizer

• recreational as psychedelic, hallucinogen

symptoms of PCP use

• hallucination, euphoria, tachy, delusions of grandeur, paranoia, stupor, resp depression, death

• overdose: superhuman strength = death

test for PCP in urine

see parent drug (unchanged)

lysergic acid diethylamide (LSD)

• hallucinogen

• white powder/colorless liquid

• detect <1 day

• blotter paper (under tongue to absorb)

symptoms of LSD use

• hallucinations, inc color perceptions, altered mental state, thought disorders, temporary psychosis, delusions, dysmorphia, impaired depth, time, space perceptions

• tachy, hypertension, dilated pupils, sweating, loss of appetite, sleeplessness, dry mouth, tremors, speech difficulties, piloerection, rhabdomyolysis

dextromethorphan

• anti-tussive, cough suppressant, CNS depressant

• white powder

use of dextromethorphan

anti-tussive for temp relief of coughs caused by minor throat and bronchial irritation

symptoms of dextromethorphan

• acute euphoria, elevated mood, dissociation of mind from body, creative dream like experiences

• toxicity: disorientation, confusion, pupillary dilation, altered time perception, visual and auditory hallucinations, dec sexual functioning

alcohol metabolism

• ADH converts it to aldehyde

• ALDH converts it to acid

alcohol testing sample

• tightly capped

• alcohol free disinfectant

• sodium fluoride additive

how to test for alcohol

• osmolal gap inc

• GC preferred; volatize sample and measure headspace

• n-propanol used to quantitate

• retention time

ethanol

• CNS depressant

• metabolized by ADH to acetaldehyde then to acetic acid

• depends on individual tolerances

• stages: euphoria, disorientation, coma/death

• DWI = 0.08 (80)

methanol

• wood alcohol, solvent

• metabolized by ADH to formaldehyde then formic acid = formate (highly toxic)

• symptoms: acidosis, optic neuropathy = blindness

• treat: ethanol and 4-methylprazole; hemodialysis

ethylene glycol

• metabolized to oxalic acid and glycolic acid

• crystals form in renal tubules (needles)

ethylene glycol symptoms

CNS depression, coma, convulsions, acute renal failure, met acidosis, cardiac toxicity

how to treat ethylene glycol overdose

• ethanol, 4 methylprazole (comp to prevent metabolites)

• sodium bicarb for acidosis

• hemodialysis

isopropanol

• metabolized by ADH to acetone

• fruity odor

• induces dizziness, mitotic pupils, stupor, coma, death, GI bleed

• treat with hemodialysis

specimen collection for alcohol testing

• clean venipuncture site with alcohol free disinfectant (use iodine)

• keep sample sealed (will evaporate out)

• preserve with sodium fluoride

acetaminophen

• analgesic and antipyretic

• tylenol, datril, tempra

• rumack-matthew nomogram to determine toxicity

hepatic toxicity from acetaminophen

• nausea, vomiting, abdominal pain

• from toxic metabolism in overdoses (glutathione depleted = free radicals)

• liver transplant is the only option after extensive overdose

how to treat acetaminophen overdose

• gastric lavage and activated charcoal

• extreme: mucomyst over several days

how to test for acetaminophen

• clinically: IA

• forensically: HPLC, GC-MS

salicylate

• analgesic, antipyretic, anti inflammatory, anticoag

• aspirin, acetylsalicylic acid

• test via GC or spec (trinder)

how does salicylate work

inhibits cyclooxygenase = dec thromboxane and prostaglandin synthesis