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xenobiotics

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1

xenobiotics

  • exogenous agents that have adverse effects on living organism

  • describes environmental chemicals or drug exposures

  • ex: antibiotics/antidepressants

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2

poisons

  • exogenous agents with adverse effect on biological system

  • describes animals, plants, minerals, gas poisons

  • ex: snake venom, poison hemlock, arsenic

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3

toxins

  • endogenous; substances biologically synthesized in living cells/microorganisms

  • botulinum, fungal toxins

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4

how do exposures happen?

  • 50% suicide attempts

  • 30% accidental (children)

  • remainder: homicide, industrial, agricultural

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5

what are common routes of exposure?

  • ingestion, inhalation, transdermal absorption

  • absorbed via processes meant for nutrients or passive diffusion

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6

factors affecting absorption

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

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7

TD(50)

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

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8

ED(50)

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

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9

LD (50)

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

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10

forensic permit

requires a chain of custody and drug confirmation

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11

chain of custody

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

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12

5 panel drug test (NIDA-5)

THC, PCP, cocaine, amphetamine, opiates

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13

12 panel drug test

  • 5 panel plus

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

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14

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)

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15

specimen requirements for blood

  • whole blood, plasma, serum depending on drug

  • used to correlate the conc of the drug with effect

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16

decomp tissue for drug testing

  • used when blood or urine is not possible

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

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17

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)

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18

urine specimen requirements

  • temp 90-100F

  • pH 4.5-8

  • SpG 1.003-1.019

  • creatinine >20

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19

two step procedure

  • screening (IA)

  • confirmatory

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20

screening test

  • IA, TLC

  • rapid, simple, qualitative

  • intended to detect specific substances

  • good analyte sensitivity but lacks specificity

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21

confirmatory test

  • used to confirm pos result from screening test

  • needed in forensic testing

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

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22

spot tests

  • used to ID unknown powder in sample

  • qualitative/non-instrumental

  • presumptive answer but less precise

  • colorimetric change

  • need confirmatory test

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23

acetaminophen spot test

  • p aminophenol reacts with ocresol and ammonium hydroxide

  • blue/indigo

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24

salicylate spot test

  • trinder reagent (iron)

  • blue/purple

  • brown = phenothiazines

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25

phenothiazine spot test

  • ferric, perchloric, nitric

  • red = violet

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26

tricyclic spot test

  • oxidation with forrests reagent

  • green

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27

ethchlorvynol spot test

pink

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28

TLC

  • Rf = distance solute moved/distance solvent moved

  • compare Rf to standards

  • use sprays/stains to compare

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29

IAs

  • enzyme IAs

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

  • ELISA, EMIT, CLIA, FPIA, CEDIA

  • disadvantage: cross reactivity with similar subs

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30

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

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31

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

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32

GC-MS

  • most common confirmatory test

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

  • distinct fingerprint of drug

  • uses EM

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33

extraction

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

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34

filtration

to remove non dissolved solids prior to HPLC

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35

reconstitution

after extraction, sample is dried and needs to be reconstituted

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36

amphetamines

  • CNS stimulant

  • white, odorless, crystalline

  • smoked, IV, orally

  • detect 2-3 days

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37

what are amphetamines used to treat?

narcolepsy, obesity, ADD hyperactivity disorders

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38

symptoms of amphetamine use

  • euphoria

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

  • dilated pupils = EMS

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39

how does pH affect amphetamine excretion rate?

  • low pH = inc

  • high pH = dec

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40

designer amphetamines

  • structurally similar to meth/mescaline

  • synthesized to mimic effects

  • MDMA

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41

symptoms of designer amphetamine use

euphoria, enhanced pleasure, sociability, sexual arousal

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42

toxicity of designer amphetamines

  • hypertension, diaphoresis, seizures, cerebral hemorrhage, hyperthermia

  • raves = inc mvt = hyperthermia = untreated = rhabdomyolysis

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43

barbiturates

  • depressant or sedative/hypnotic

  • detect 2-15 days

  • short acting more potent than long acting

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44

short to intermediate acting barbiturates

  • amobarbital, butobarbital, butalbital, pentobarbital, secobarbital

  • become tolerant so need higher dosage

  • sedative effects

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45

long acting barbiturates

  • help with seizures and sleep induction

  • not usually abused

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46

symptoms of barbiturate use (toxicity)

  • mild euphoria

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

  • tight, constricted pupils = EMS

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47

how to treat barbiturate overdose

alkalinize urine to increase excretion

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48

benzodiazepines

  • depressant = anxiety disorders

  • sedative, hypnotics

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

  • detect 2-10 days

  • oral ingestion, fast absorption

  • tolerance develops

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49

uses of benzodiazepines

insomnia, anxiety, seizures

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50

symptoms of benzodiazepine use

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

  • inc GABA in CNS to diminish electric transmissions in neurons

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51

cannabinoids

  • stimulant, sedative, tranquilizer, hallucinogen

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

  • detect 3-30 days

  • very lipophilic drug

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52

what is the major active ingredient in marijuana?

THC (delta 9 THC)

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53

uses of cannabinoids

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

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54

symptoms of cannabinoid use

  • euphoria, sense of well being, relaxation

  • short term memory loss, mild physical dependence

  • paranoia

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55

legalized marijuana

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

  • police use oral fluid testing

  • 5 = fatal crashes

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56

cocaine

  • stimulant

  • detect 2-10 days

  • inhaled, smoked, injected

  • parent metabolized very fast

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57

cocaine metabolites

benzoylecgonine, ecgonine, methyl ester, cocaethylene

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58

uses of cocaine

topical anesthetic in nasal surgery

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59

cocaine HCl

white to light brown crystalline powder, shiny

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60

cocaine base

white to beige, waxy/soapy to flaky solid chunks

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61

symptoms of cocaine use

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

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62

opiates

  • narcotic, analgesic

  • detect 1-3 days

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63

natural opiates

  • opium, morphine, codeine

  • from c pod of opium poppy

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64

semisynthetic opiates

  • heroin

  • oxycodone (percodan)

  • hydrocodone

  • oxymorphone (dilaudid)

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65

synthetic opiates

  • propoxyphene (darvon)

  • methadone

  • meperidine (demerol)

  • fentanyl

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66

uses of opiates

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

  • sedate pts pre-op

  • facilitate induction of anesthesia

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67

symptoms of opiate use

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

  • coma, pinpoint pupils, resp depression = overdose symptoms

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68

treatment for opiate overdose

naloxone (comp antagonist reverse overdose)

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69

metabolites seen after heroin use

6MAM, morphine > codeine

  • oxymorphone, norcodeine

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70

metabolites seen after morphine use

morphine

  • hydromorphone

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71

metabolites seen after codeine use

codeine>>morphine

  • norcodeine

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72

metabolites seen after hydrocodone use

hydrocodone, hydromorphone

  • norhydrocodone

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73

metabolites seen after hydromorphone use

hydromorphone

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74

metabolites seen after oxycodone use

oxycodone, oxymorphone

  • noroxycodone

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75

metabolites seen after poppy seed ingestion

codeine, morphine

  • norcodeine

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76

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

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77

uses of PCP

  • formerly surgical anesthetic

  • vet anesthetic or tranquilizer

  • recreational as psychedelic, hallucinogen

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78

symptoms of PCP use

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

  • overdose: superhuman strength = death

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79

test for PCP in urine

see parent drug (unchanged)

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80

lysergic acid diethylamide (LSD)

  • hallucinogen

  • white powder/colorless liquid

  • detect <1 day

  • blotter paper (under tongue to absorb)

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81

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

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82

dextromethorphan

  • anti-tussive, cough suppressant, CNS depressant

  • white powder

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83

use of dextromethorphan

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

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84

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

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85

alcohol metabolism

  • ADH converts it to aldehyde

  • ALDH converts it to acid

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86

alcohol testing sample

  • tightly capped

  • alcohol free disinfectant

  • sodium fluoride additive

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87

how to test for alcohol

  • osmolal gap inc

  • GC preferred; volatize sample and measure headspace

  • n-propanol used to quantitate

  • retention time

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88

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)

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89

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

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90

ethylene glycol

  • metabolized to oxalic acid and glycolic acid

  • crystals form in renal tubules (needles)

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91

ethylene glycol symptoms

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

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92

how to treat ethylene glycol overdose

  • ethanol, 4 methylprazole (comp to prevent metabolites)

  • sodium bicarb for acidosis

  • hemodialysis

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93

isopropanol

  • metabolized by ADH to acetone

  • fruity odor

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

  • treat with hemodialysis

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94

specimen collection for alcohol testing

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

  • keep sample sealed (will evaporate out)

  • preserve with sodium fluoride

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95

acetaminophen

  • analgesic and antipyretic

  • tylenol, datril, tempra

  • rumack-matthew nomogram to determine toxicity

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96

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

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97

how to treat acetaminophen overdose

  • gastric lavage and activated charcoal

  • extreme: mucomyst over several days

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98

how to test for acetaminophen

  • clinically: IA

  • forensically: HPLC, GC-MS

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99

salicylate

  • analgesic, antipyretic, anti inflammatory, anticoag

  • aspirin, acetylsalicylic acid

  • test via GC or spec (trinder)

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100

how does salicylate work

inhibits cyclooxygenase = dec thromboxane and prostaglandin synthesis

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