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MLSCI 466 > Forensics Toxicology > Flashcards

Forensics Toxicology Flashcards

1
Q

What does forensic toxicology deal with?

A
  • postmortem cases = cause and manner of death
  • impaired driving and sexual assault
  • workplace drug testing
  • sports (Olympics for example)
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2
Q

civil issues or cases that could include forensic tox?

A

non-criminal accidents like falling or drowning

workplace drug testing - usually urine
> condition of employment or site access

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3
Q

T or F. MLTs can testify as a witness in court

A

T

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4
Q

expert witness in court

A

must be qualified by the judge to give “opinion” evidence (based on education, training or experience)

doesn’t have to have done any lab work on the case

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5
Q

what do witnesses in court do?

A
  • testifies to facts and observations
  • medical techs usually in this category
  • what they did or nor mally would have done
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6
Q

during a death investigation which provinces use a medical examiner system?

A

Alberta
Manitoba
Nova Scotia
Newfoundland
= headed by a forensic pathologist, whereas a coroner system may or may not be headed by a physician

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7
Q

cause of death definition

A

immediate medical cause of death
NOT circumstances
ex: blunt force trauma rather than motor vehicle accident

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8
Q

manner of death specific categories

A

homicide
suicide
accident
natural
undetermined
unclassified (MAID deaths)

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9
Q

postmortem BAC

A
  • we dont like to rely on blood alone for alcohol bc of postmortem fermentation (alc formed in blood after death)
  • if blood is not accompanied with fluoride = alc formation
  • we use vitreous fluid too (eye remains sterile for about 3 days after death; so if alc found here that means person drank before death)
  • can get postmortem AC up to legal limit due to fermentation; in rare circumstances >300 mg%
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10
Q

historical belief before postmortem redistribution

A

drug conctn in blood after somebody died = reflects conctn at time of death

but no found that there can be changed after death

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11
Q

define postmortem redistribution

A
  • time and conctn dependent
  • releade and diffusion of drugs from the major organs
  • occurs as cells die = pH changes and protein binding weakens
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12
Q

candiddates for postmortem redistribution

A
  • drugs w a high vol of distribution (>5L/kg)
  • drugs with basic character like forming HCl salts
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13
Q

impaired metabolism can be due to:

A
  • genetic impairment due to enzyme def (ex: cytochrome P4502D6; 7-10% in Caucasians)
  • drug-drug impairment of enzyme system (ex: impairment by SSRIs of CYP4502D6)
  • impairment due to high single drug conctn
  • impairment due to reduced liver function (age, alc)
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14
Q

difficulties of interpreting postmortem data

A
  • don’t know when drug last taken, rate of metabolism, rate of excretion
  • don’t know if postmortem blood level of drug represents blood level at time of death (some conctns increase postmortem, and some decrease)=
    cannot reliably calculate dose
  • don’t know tolerance if person to toxic effects of drug
  • must consider autopsy findings, medical history, circumstances of death
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15
Q

how should one interpret tox results in postmortem cases?

A

interpret with full consideration of:
- circumstances of death
- post-death investigation = medical history, medication history, autopsy findings, toxicology on alternate specimens

if not enough information, don’t offer interpretation or give clear caveats!

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16
Q

describe medication counts

A

for each important medication determine:
- number prescribed
- date dispensed
- dosage (tablets per day for ex)
- number remaining at death
- calculate meds “unaccounted for”

why? = suicide vs. ‘build-up’

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17
Q

assumptions made in the past about THC

A
  • THC always drops near to zero a few hours after the last smoke
  • blood THC >2-3 ng/mL consistent with recent use within 6h = could be used to indicate impairment
  • THC:THC-COOH ratio can be used to estimate time of last use – now know it is not reliable
  • little postmortem change w THC conctn (but actually can be very significant change)
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18
Q

what we now know about THC

A
  • baseling blood THC several hrs after smoking:
    > <2 ng/mL in light smokers (<1 after 24h)
    > can be >5 in heavy (could be >10)
    > 1.2-5.5 7d after last use
    > very high body burden of THC slowly release into blood ( esp. from fatty tissue)
  • only refers to living ppl
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19
Q

postmortem THC conctn

A
  • undergoes postmortem redistribution (can increase after death)
  • PM femoral blood THC = MUCH higher in postmortem blood than pre-mortem clinical blood
  • THC concentrates in muscle tissue and may be redistributing postmortem
  • much larger effect may be presence of fat in postmortem blood drawn
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20
Q

T or F. THC is very fat soluble

A

T

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21
Q

how is postmortem blood taken?

A

external exmaination = no dissectoon, blood taken before dissection => techs take blood do not visualize vein bc can’t see = poking around aggressively to find femoral vein = pulling syringe back = disrupts fatty tissue = therefore blood and fat sucked up

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22
Q

spice and K2

A

synthetic cannabinoids or cannabimimetics = can mimic effects of cannabis

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23
Q

where is CB1 located?

A

nervous system

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24
Q

where is CB2 located?

A

immune system

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25
Q

cannabinoid receptors

A

CB1 and CB2

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26
Q

T or F. Many cannabimimetics are quite toxic and do not have true THC effects

A

T

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27
Q

adverse effetcs of synthetitic cannabinoids

A
  • psychiatric: psychosis, agitation, irritability confusion, aggression, etc.
  • CV: hypertension, tachycardia, MI, etc.
  • neurologic: generalized seizures, somnolence, brisk reflexes
  • GI: nausea, vomiting, anorexia, increased appetite
  • other: hypokalemia, blood shot eyes, hyperglycemia, AKI, xerostomia, diaphoresis
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28
Q

analysis of synthetic cannabinoids

A

difficult!!
- low blood conctns; lower than THC bc much more potent
- extensively and rapidly metabolized
- over 200 known structures
- keep changing as regulations change
- screening methods do not detect all
- need high-end methods for confirmation such as LC/MS/MS = difficult and time-consuming to develop

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29
Q

bath salts

A

cathinone
- found in Khat
- used by some African cultures
- some South Americans chew coca leafe
- Europeans use this as caffeine

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30
Q

earliest substances used for doping

A

cocaine, strychnine, caffeine

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31
Q

initial dope testing mainly focused on this..

A

stimulants

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32
Q

TUE

A

Therapeutic use exemption
- certain drugs allowed for athletes if recommended by physician AND approved by WADA
- must be approved before use (duyring or out-of-event)
- athlete’s physician must apply to WADA medical team ahead of tine

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33
Q

monitoring program for sports competititons

A

to monitor incidence and conctns of drugs not banned but subject to abuse
- stimulants
- narcotics
- glucocorticoids
- B-2-agonists

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34
Q

stimulants effect

A

sympathomimetic
- raised BP
- increased HR
- greater endurance
- combats fatigue
- improve endurance

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35
Q

T or F. Caffeine is a mild stimulant

A

T
- used to not be allowed; can be abused by non-coffee drinkers and abstinece followed by use
- main desired stimulant effect is increased aggression

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36
Q

what do masking agents do?

A

masks presence of banned substances

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37
Q

diiuretics

A

MASKING AGENT
CAUSE DILUTE URINE
indrirectly masks presence of varous drugs including anabolic steroid metabolites

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38
Q

plasma expanders

A

masking agent
impairs detection of EPO
- albumin
- Dextran infusion
- gelatin succinylaated
- hydroxylethyl strach

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39
Q

forensic analytical toxicology testing

A
  • not usually “limited”
    > drugs can be prescription, non-prescription, and illicit + other poisons such as pesticides and chemicals
    > high contcns; overdoses
    > low conctns; sexual assault
    > may use many methods for single “screen”
  • most testing on urine or whole blood (clinical lab = serum, plasma or urine)
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40
Q

T or F. Whole blood specimens are more difficult and give more interference than fresh serum or plasma

A

T

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41
Q

define specimen matrix

A

the fluid or tissue in which the analyte is contained, such as proteins (blood or solid tissue), lipids/phospholipids, electrolytes, water

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42
Q

when is specimen processing or extraction necessary?

A

most samples have to be processed/extracted prior to analysis

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43
Q

two main purposes of specimen processing/extraction

A

minimize or eliminate matrix interference (involves extracting out the analyte)

concentrate the analyte to improve sensitivity of assay

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44
Q

sample extraction for immunoassays

A

degree of sample extraction depends on assay design
- homogenous enzyme immunoassay vs ELISA
> most clinical immunoassays are designed for urine or serum/plasma

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45
Q

these immunoassays are best suted for forensic work as they are optimised to work with diluted whole blood

A

ELISA (96-well) plates
tissues must be homogenized and diluted

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46
Q

define tissue homogenization

A

tissues can rarely be analyzed directly; so need to make fluid sample
- use homogenizer
- eg: Polytron homogenizer
- 1+3 tissue:water

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47
Q

what is critical when differentiating between GC/MS vs. LC/MS/MS

A

column inlet

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48
Q

GC inlet

A

heated to vaporize the solvent and the analyte; many drugs will not “chromatograph”

will cause pyrolysis of some analytes, and the matrix = interference

more sample prep needed than for LC-based methods

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49
Q

T or F. GC requires more sample prep than LC-based methods

A

T

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50
Q

LC inlet

A

cool (on-column) = little or no destruction of analyte or matrix

sample introduced to MS spray chamber as liquid = then vaporized and ionized

less sample prep required

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51
Q

two basic approaches to sample preparation

A
  1. extract the analyte from the sample and leave matrix behind
    > liquid-liquid or SPE extractions
    > most common for GC-based assays
  2. remove interferences from sample and leave analytes behind
    > ex: protein “crash” extracts
    > increasingly common approach for LC-MS and LC-TOF
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52
Q

important consideration for sample preparation

A

considering the analytical instrumentation

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53
Q

simplest sample prep

A

dilution
- dilute out proteins in plasma or blood sample to allow direct analysis
- ex: Immunoassay

headspace analysis
- ex: alcohols by GC

protein “crash”
- ex: acetonitrile, methanol
> smoe highly selective LC-MS/MS and LC-QTOF assays

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54
Q

headspace GC analysis

A

used for volatile liquids such as alcohols and solvents

only volatiles from air above the sample get injected on to the GC

very clean with little interference

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55
Q

how to prepare non-volatile substances such as drugs for chromatography

A

simpler methods such as protein crash if analytical methods are specific enough

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56
Q

describe acetonitrile/methanol “crash”

A
  • add cold acetonitrile/methanol to blood (or serum/plasma)
  • proteins and peptides in whole blood denatured => centrifuge to form pellet
  • clear supernatant injected (sometimes after concentration like dilute and shoot)
  • increasingly used for LC/MSMS or LC-QCTOF
  • this does not remove salts, lipids of phospholipids
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57
Q

caution when using acetonitrile/methanol “crash”

A

analytes can be trapped in precipitation matrix
need good, validated methods with deuterated internal standards

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58
Q

why are traditional protein precipitation methods (“crash” not good for GC

A

it does not remove lipids

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59
Q

liquid-liquid extractions with solvents

A
  • simple
  • analyte more soluble in solvent than aq specimen
  • add solvent to liquid specimen
  • mix to temporarily blend phases
  • centrifuge to separate
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60
Q

principle of solvent-based extraction

A
  • un-ionized analyte more lipid-soluble
  • ionized analyte (like salt form such as HCl or sulfate) is more water soluble
  • need to get analyte to un-ionized form in order to extract into organic solvent
  • use buffers (adjust pH)
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61
Q

how to simple extract basic drugs

A

add pH12 buffer to specimen with the solvent

mix & centrifuge

will separate into organic (GC/LC) and aqueous (WASTE) substances

extract acid drugs by adding an acidic buffer

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62
Q

how to back-extract basic drugs

A

add pH 12 to solvent and specimen

mix & centrifuge = aqueous waste and organic substances

add pH2 to organic

mix & centrifuge = organic waste and aqueous

add pH 12 to aqueous and solvent

mix & centrifuge = ORGANIC to GC/LC and aqueous WASTE

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63
Q

what is back-extraction

A

extraction of basic drugs that leaves behind neutrals (like fats) and acidic drugs

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63
Q

these are considered problematic drugs for extraction

A

amphoteric drugs and zwitterions

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64
Q

examples of amphoteric functions

A

phenolics
amino (morphine)

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65
Q

examples of zwitterion functions

A

carboxylic
amino (ex: GABA)

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66
Q

extraction method considerations

A
  • specimen type
  • instrumentation used/available
  • robustness and precision of assay
  • purpose of test (quick screen vs quantitative)
  • processing time (urgency and speed of test)
  • type of analyte/drug being tested
  • cost of reagents (solid phase extraction uses less solvent than liquid/liquid, but solid phase extraction columns can be expensive)
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67
Q

pHs to ionize amphoteric drugs

A

pH 2 = initially + charge

then pH 8 = neutral

then pH 12 = - charge

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68
Q

another method to extract amphoteric and zwitterion analytes

A

SPE
solid phase extraction

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69
Q

which type of death investigation does Alberta particpate in?

A

Medical Examiner system
- along with NFL, Manitoba and Nova Scotia
- headed by a forensic pathologist

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70
Q

Coroner system

A

may or may not be headed by a physician

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71
Q

is time of death reliable in post mortem investigations?

A

no, not accurate

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72
Q

In Alberta, how many deaths does the OCME investigate annually? and what is the manner of death usually?

A

~6500 (cases have increased substantially over the past 6-10 yrs)

natural (34%) and accidental (49%)

undetermined and homicidal (both ~2%)

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73
Q

Where are RCMP labs located?

A

Vancouver, Edmonton, Ottawa
- only handle criminal cases

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74
Q

T or F. Most fatalities due to drugs or poisons will not show specific signs at autopsy

A

T!
- an autopsy can rule out natural disease or trauma as the cause of death

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75
Q

T or F. We can use serum or plasma for postmortem investigations

A

F!
Use: whole blood, vitreous, urine, liver, stomach contents, other tissues, hair, other exhibits like syringes and drinking glass

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76
Q

most consistently available abundant fluid

A

blood

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77
Q

T or F. Postmortem blood is usually partially to fully hemolyzed

A

T

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78
Q

T or F. Postmortem blood is usually homogenous throughout the body

A

F!

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79
Q

Why is blood not usually useful for biochemical tests?

A

drug concentrations can go up or down after death (dependent on drug)

drug concentrations should not be interpreted in isolation

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80
Q

vitreous humour

A
  • clear fluid inside eye
  • limited vol (~3mL per eye)
  • very useful for alcohol
  • can be useful for some drugs like cocaine, heroin, digoxin
  • cannot interpret as you would blood
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81
Q

T or F. Vitreous humour fluid concentrations often higher than in blood

A

F!
Often lower than in blood = especially highly lipid soluble and protein-bound drugs like benzos, tricyclic antidepressants

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82
Q

clear fluid, no protein, and very little lipid

A

urine
- exception = decomposed bodies

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83
Q

T or F. Urine is always available in postmortem cases

A

F! not always
- but if it is = some drug concentrations very high
- some drugs not excreted due to extensive metabolism, but metabolites can be detected

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84
Q

Urine has little to no relationship between _______ _______ ________ and pharmacological effect with some exceptions

A

urine drug concentration
exceptions = alcohol and some metals

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85
Q

T or F. We can relate urine drug concentration and degree of impairment

A

F!

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86
Q

liver as postmortem specimen

A
  • always present
  • large amount
  • need to make liquid prep (homogenize)
  • high protein and lipid content can interfere
  • drug conctns don’t change much after death
    > exceptions:drugs may diffuse from stomach into liver if concentration is high; some drugs are unstable
  • liver drugs concentrations are often much higher than in blood
  • often useful to have BOTH liver and blood conctns
  • widely used in past but less now
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87
Q

stomach contents for postmortem

A
  • variable from clear fluid to a “meal”
  • drug concentrations can be very high
  • need to relate drug concentration to total volume
  • total AMOUNT, not concentration
  • drug/metabolite can be in stomach after parenteral use due to secretion in gastric juice
  • presence in stomach does not prove oral use
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88
Q

is a phenytoin gastric concentration of 150 mg/L toxic? (therapeutic range is 10-20 mg/L in blood)

A

NO! 150 mg/L may be 15 mg/100mL if volume of gastric contents is 100 mL
- could man partially absorbed 100 mg dose

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89
Q

other specimens used for postmortem investigations

A

bile, CSF, virtually any fluid
lungs, kidney, muscle, or any solid tissue
bone, nails, hair
injection sites
- need “control” site away from suspected injection site
- can be difficult to prove injection sit if elapsed time, esp. if i/v injection

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90
Q

T or F. Most drugs are distributed to virtually all fluids and tissue in the body

A

T

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3
4
5
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91
Q

when are syringes helpful in a postmortem investigation

A

heroin

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92
Q

drinking glasses as exhibits

A

can be useful in drug-facilitated sexual assault cases

can indicate manner of death in suicide

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93
Q

bottles as postmortem exhibits

A

can indicate source of poison

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94
Q

defin chain of custody

A

a means of tracking exhibits o specimens from the pt and time of collection to analysis and ultimately disposal

95
Q

what does a chain of custody entail?

A

place, date, time and persons (analysts)

purpose is to demonstrate that analysis and reporting was performed on the stated exhibit/specimen

usually involves a reasonable degree of physical security (locked storage), secured facility, and restricted access

physical or electronic log of those entering and leaving the facility

authorized staff may have electronic key card

96
Q

carbon monoxide binds to Hb ____x stronger than oxygen

A

200x more

97
Q

order of increasing magnitude of postmortem redistribution

A

cardiac > subclavian > femoral > antemortem

increases 2-10 fold or greater

98
Q

these can cause hypoxic brain damage

A

depressants such as narcotics and sedatives (with or without alcohol)

99
Q

near-fatal ethanol can clear in ..

A

<24 hrs

100
Q

why are antemortem specimens important

A

so forensic toxicology can better assess postmortem cases (have something to compare to)

hospitals are encouraged to hold on to antemortem specimens at least until after it seems that pts will recover

101
Q

besides depressants and ethanol, delayed deaths are also a factor with these…

A

methanol
ethylene glycol
acetaminophen

102
Q

case study of young boy who died from his ADHD medication

A

he had no prior history of side effects

autopsy negative; toxicology = imipramine poisoning (ADHD med)

specimens showed that desipramine (metabolite of imipramine) was high

boy was deficient in CYP2D6 (hydroxylates and glucuronidates imipramine for rapid excretion) so CYP3A4 was breaking own drug to desipramine = accumulation = death

103
Q

interpretations of postmortem _______ blood levels are very tricky

A

narcotics
- if naive user = easier
- prescribed = acquire records
- need to know dos and duration as well as a medication count

104
Q

medical tolerance of fentanyl

A

starting dose = 25 ug/hr for chronic pain

potentially fatal for non-tolerant pts = 100 ug/hr

105
Q

what cannabis products do most forensic labs measure?

A

delta 9 THC
11-OH-THC
THC-COOH
most forensic labs do not measure CBD

106
Q

delta 9 tetrahydrocannabinol (delta9THC)

A

highly lipid soluble
usually measured in whole blood
majority of research was conducted in serum or plasma
THC blood:plasma ratio is 0.5 - 0.6

107
Q

11-hydroxytetrahydrocannabinol (11-OH-THC)

A

pharmacologically “active”
concentrations higher after oral ingestion (first pass effect)

108
Q

11-caboxytetrahydocannabinol (THC-COOH)

A

inactive metabolite
forms waer soluble glucuronide metabolite
majority present as glucuronide
most labs measure the UNconjugated THC-COOH in blood
most urine testing labs for workplace measure TOTAL THC-COOH

109
Q

Cannabidiol (CBD)

A

can be up to 40% of cannabis plant extract
has been studied to treat anxiety, cognition, movement disorders, pain and epilepsy
little (if any) psychoactivity
may modify the effect of THC if both are present
legal in USA (cannabis extracts are NOT)

110
Q

Cannabinol (CBN)

A

mildly psychoactive, but present in only small amounts in cannabis
delta-9-THC metabolite

111
Q

psychoactive effects of delta-9-THC

A
  • relaxation, euphoria
  • philosophical thinking, introspection
  • anxiety, paranoia
  • increased heart rate, hunger, reddening of eyes
  • reduces nausea and vomiting
  • impaired motor skills
  • impaired judgment of tie and distance
112
Q

T or F. THC interpretation is much easier than alcohol

A

F! for alcohol, there is a generally direct correlation between blood concentration and effect/impairment

ethanol: can estimate “dose” from a blood level and can estimate a blood level from a dose

THC: the correlation between blood level and “effect” is very poor except in very early stages of smoking

113
Q

T or F. In most people, duration of ‘high’ lasts 2-6 hours which is much longer than the blood THC concentration is elevated

A

T

114
Q

pharmacokinetics of delta-9-THC

A

short distribution half-life

long elimination of half-life resulting in baseline blood THC concentrations up to 7 ng/mL after heavy chronic use

115
Q

Bill in Canadian criminal code regarding cannabis

A

Bill C-46
- June 21, 2018

116
Q

low-level THC concentrations of __ ng/mL to <__ng/mL within 2 hours of driving is an offense

A

2 - <5 ng/mL

117
Q

higher-level THC concentrations of __ng/mL or more within __ hours of driving

A

> =5ng/mL
2 hrs

118
Q

this offence recognizes the effects of combined marijuana and alcohol consumption

A

50 mg of alcohol per 100 mL blood plus >/=2.5 ng/mL THC within 2 hours of driving

119
Q

THC has relatively short half-life here

A

in blood

120
Q

THC longer half-life here

A

BRAIN - where it has its main effect related to impairment
and much longer half-life in body

121
Q

T or F. THC concentration decreases after death due to postmortem redistribution

A

F, it increases

122
Q

baseline blood THC several hours after smoking:

A

typically <2 ng/mL in light smothers (<1 after 24 hr)
can be > 5ng/mL in heavy smokers (may be >10)
in one study - 1.2-5.5 ng/mL seven days after last use
very high body burden of THC slowly released into blood
- living ppl

123
Q

THC concentrates in ____________ tissue and may be redistributing postmortem but a much larger effect may be the presence of ____ in the postmortem blood drawn

A

muscle; fat

124
Q

T or F. THC is very fat soluble

A

T

125
Q

spice and K2

A

synthetic cannabinoids
aka cannabimimetics

126
Q

synthetic cannabinoids

A
  • chemicals impregnated into various dried plant materials
  • synthetic chemicals that may or may not be closely related to the structure of delta-9-THC
    > interacts with cannabinoid receptors
    > partial agonist activity at the cannabinoid receptor CB1 located mainly in the CNS
    > and the CB2 receptor, mainly in cells of the immune system
  • many do not have true THC effects
127
Q

cannabimimetic properties

A
  • similar to cannabis
  • some may have more intense effect in ability to produce psychosis
  • psychoactive effects include:
    > relaxation, perhaps euphoria
    > philosophical thinking, introspection
    > anxiety and paranoia, also increase in HR and hunger, reddening of eyes
    > reduces nausea and vomiting
    > impaired motor skills; judging time and distance
128
Q

psychiatric adverse effects of synthetic cannabinoids

A

psychiatric
- psychosis (new-onset, or exacerbation of pre-existing disease)
- agitation
- anxiety,
- irritability
- confusion
- suicidality
- memory changes
- aggression
- tolerance
- withdrawal
- dependence

129
Q

CV adverse effects of synthetic cannabinoids

A
  • hypertension
  • tachycardia
  • ST- segment changes
  • chest pain
  • myocardial infarction
  • tachyarrhythmia
130
Q

neurologic adverse effects of synthetic cannabinoids

A

generalized seizures, somnolence, brisk reflexes

131
Q

gastrointestinal adverse effects of synthetic cannabinoids

A

nausea, vomiting, anorexia, increased appetite

132
Q

other symptoms or side effects of synthetic cannabinoids

A

hypokalemia
conjunctival injection (bloodshot eyes)
hyperglycemia
acute kidney injury
xerostomia (dry mouth)
diaphoresis

133
Q

refers to any chemical that activates mu receptors mainly in spinal cord and brain

A

opioid
- endogenous neuropeptides (ex: endorphins/ endogenous morphine)
- opiates (opium-derived, found naturally in opium poppy)
- semi-synthetic opioids (derived thebaine/opium poppy); NOT naturally occurring
- synthetic opioids: not usually structurally related to morphine; fentanyl, methadone, tramadol, meperidine

134
Q

opioid tolerance

A

the ability to withstand increasing dosages with static or decreasing side effects

135
Q

this can enable a person to take doses doses of an opioid that would kill most non-tolerant persons

A

tolerance
- tolerance is relative
(dose-related; not absolute)

136
Q

T or F. Cross-tolerance from one opioid to another occurs

A

T!
eg. if a person develops tolerance to heroin, they will also have a degree of tolerance to fentanyl
- the degree of cross-tolerance can be difficult to predict

137
Q

naloxone

A

reversing agent of opioids
- competitive antagonist that binds mu receptor
- displaces opioids that are already bound there, without activating the receptors (no analgesia)

138
Q

naloxone half-life

A

30 to 80 minutes

139
Q

fentanyl half life

A

3-12 hours

140
Q

why is repeat naloxone injection often required?

A

naloxone half life 30-80 mins
and fentanyl half life is 3-12 hrs
- if minimal or no response within two to three minutes, dosing may be repeated every 2 mins to a max of 10 mg
(ex: 0.4 mg per injection -> 25 injections for 10 mg)

141
Q

what happens if no opioids and you give someone naloxone

A

minimal toxicity if opioids not present; very low risk for repeat administration!

142
Q

how to administer naloxone

A

medical administration intravenous or intramuscular
- intra-nasal formulation available for public
- orally = poor oral bioavailability, takes too long to act

143
Q

are some opioids tolerant to naloxone?

A
  • effectiveness depends on dose of naloxone administered vs potency and dose of opioid
  • highly tolerant abusers using high doses will require higher doses of nalocone to reverse a coma
  • some newer opioids may be more dangerous bc users not familiar to right dose/potency of specific batch being sold
144
Q

these will increase CNS depression caused by opioids

A

benzos (etizolam)
NOTE: benzos are not reverse by naloxone

145
Q

medical use for fentanyl

A
  • short-term anesthesia
  • induction of anesthesia
  • adjunct to anesthesia in more prolonged surgical procedures
  • transdermal patches for long-term chronic pain
  • sublingual lozenge for breakthrough pain (0.1 to 1.6 mg)
146
Q

fentanyl for shortterm anesthesia

A

acute surgial procedures such as intubation
50 -200 ug intravenous

147
Q

fentanyl for induction of anesthesia

A

often with midazolam

148
Q

fentanyl as adjunct to anesthesia in longer procedures

A

dose dependent on surgery type
airway must be supported for higher doses and longer surgeries

149
Q

fentanyl as transdermal patches for long-term chronic pain

A

12.5, 25, 50, 100 ug/hr
NOT for acute or post-surgery pain

150
Q

fentanyl analogues studied with animal testing

A

carfentanil and 3-methylfentanyl

151
Q

fentanyl abuse

A

highly addictive narcotic
- injectable fentanyl - abused by medical personnel with easy access
- 50 to 100x more potent than morphine and 25x> heroin
abuse also as ilicit tablets and powder

152
Q

Duragesic

A

transdermal patch (fentanyl) for chronic pain

153
Q

how is fentanyl abused?

A

snorting
smoking
injecting
TD patch: inject, chew

154
Q

less convention modes of abuse of fentanyl

A

nasal spray
e-cig

155
Q

T or F. Most fentanyl fatalities include a stimulant

A

T!
fentanyl rarely acts alone, usually methamphetamine or cocaine; some have both
- many fentanyl-related deaths include ethanol and/or prescription or illicit benzos and/or prescription drugs

156
Q

xylazine

A

vet sedative
stimulant used with fentanyl

157
Q

unintentional fentanyl poisoning deaths in Alberta - most common additional substances

A

methamphetamine
carfentanil
cocaine

158
Q

estimated fatal dose of fentanyl (non-medical)

A

0.5 to 1.0 mg
presuming low tolerance and IV administration

  • lower with alcohol or depressant drugs
  • higher with tolerance, >2-3 mg
159
Q

fake Oxys: amount of fentanyl

A

1-4 mg
but not always fentanyl; may be carfentanil or another drug

160
Q

this is estimated to be 100x more potent than fentanyl (based on animal studies)

A

carfentanil
- restrivted for vet use for large animals
- fatal doses could be as low as 10-20 ug!!!

161
Q

nitazenes

A

isotonitazene
- same potency as fentanyl
- some estimated to be 20x more potent than fentanyl
- classed as benzimidazol opioid analgesics

162
Q

pharmaceutical benzos as fentanyl adulterants

A

alprazolam
bromazepam
clonazepam
diazepam
nitrazepam

163
Q

illicit benzos

A

adinazolam
bromazolam
clonazolam
etizolam, etc.

164
Q

how to increase the success of finding the more potent fentanyl and other opioid analogues

A
  • seizing and analyzing drug paraphernalia
  • optimizing and/or developing new analytical methods (screening urine samples bc likely more concentrated!)
  • information gathering
165
Q

drugs: stimulants, psychedelics and hallucinogens

A

cocaine
amphetamines
phenethylamines
> 2C-X series and N-BOMe drugs
cathinones (aka bath salts)
tryptamines
others = LSD, PCP, mescaline, psilocin

166
Q

powerful stimulant, local anesthetic, highly addictive and routinely used in lower doses (South America)

A

cocainm

167
Q

cocaine adulteration: cardiac drug

A

Diltiazem

168
Q

cocaine adulteration: antihistamine/sedative

A

hydroxyzine

169
Q

cocaine adulteration: anticancer/vet de-worming agent

A

Levamisole
- life-threatening blood dyscrasias = agranulocytosis/neutropenia

170
Q

phenacetin

A

obsolete OTC analgesic (“Superbuff”)
- causes kidney damage and potentially carcinogenic?
- cocaine cutting agent

171
Q

amphetamine vs methamphetamine

A

methamph = crystal meth
amph = metabolite used for ADHD, narcolepsy, weight loss

172
Q

ecstasy group

A

MDMA
MDA
MDEA
PMMA
PMA
etc.

173
Q

this has become a MAJOR contributing factor in the opioid crisis

A

methamphetamines

174
Q

psychopharmacology of cocaine and methamphetamine

A
  • both stimulate release and block reuptake to varying degrees of dopamine, serotonin, norepi = increased CNS stimulation, CV, and other systems
  • abuse = tolerance, sleep disturbances, psychosis, violent/aggressive behaviour (esp. meth)
175
Q

meth vs cocaine halflife

A

meth = 10-15h
cocaine = 0.5-1.5h

176
Q

meth binge can last…

A

2-3 days
- involves doses of up to 1000 mg or more a day
- may be in 100-250 mg doses
- “therapeutic” = 5-20 mg
- neurotransmitter levels in brain may be depleted and sensitivity of neurons to meth decreased

177
Q

psychosis

A

a severe mental disorder
- thought and emotions so impaired that contact is lost with external reality
- can be a form of medical illness unrelated to drugs or can be caused by alc or drug use
> delusional behaviour
> hallucinations
> delirium

178
Q

these can cause psychosis

A

stimulants like cocaine and meth

179
Q

where a person has strong beliefs that are not shard by others

A

delusional behaviour
- common = someone believing there is conspiracy to harm them (paranoia)

180
Q

when a person hears, sees, and, in some cases, feels, smells, or tastes things that do not exist outside their mind but can feel very real to the person affected by them

A

hallucination
- common = hearing voices

181
Q

temporary mental state characterized by confusion, anxiety, incoherent speech, hallucinations

A

delirium

182
Q

excited delirium

A

potentially fatal state
- extreme agitation and delirium
- potentially violent behaviour
= agitated delirium
- often bc of acute abuse of cocaine, meth or other powerful stimulants but not always

183
Q

these death causes frequently involve heavy police restraint

A

excited delirium deaths
- could be the cause of death and not drugs themselves

184
Q

initial effects of meth, MDMA, and PMMA

A

stimulant
wakefulness
hyperactivity
risk-taking
mydriasis

185
Q

toxic effects of meth, MDMA, PMMA

A

jerky movements, muscle rigidity, hyperthermia, reduced consciousness, rhabdomyolysis, coma, death

186
Q

love drug

A

MDMA due to serotonin effects

187
Q

PMMA effects

A

similar to MDMA but slower to act, less potent initially, users may take additional doses, increased lethality compared to MDMA

188
Q

phenethylamine

A

structurally related to amphetamine
has been used as a “weight loss” ingredient
putrefactive amine seen in decomposing samples

189
Q

T or F. substituted phenethylamines have stimulant and psychedelic properties

A

T! - most common are 2C-X series = 2C-B, 2C-C, 2C-I, etc.

190
Q

what distinguishes toxic phenethylamines?

A

degree of psychedelic properties and overt toxicity
- detection not as easy as meth but good lab should be able to detect

191
Q

N-Bombs

A
  • very potent derivatives of 2C-X family of phenethylamines with effects similar to LSD
  • strongly hallucinogenic, toxic, low-dose drugs
    = sub mg doses = 0.05 to 0.8 mg)
  • difficult for labs to detect in bodily fluids
192
Q

most common N-Bomb

A

25I-NBOMe
- also 25B-NBOMe, 25C-NBMe, 25H-NBOMe, 25N-NBOMe

193
Q

bath salt designer drugs

A

substituted and modified cathinone
- stimulants with some psychedelic activity
- MDPVm, mephedrone pyrovalerone, etc.

194
Q

monitoring program: to monitor incidence and concentrations of drugs not banned outright, but subject to abuse -

A
  • stimulants: in-comp only = Bupropion, caffeine, nicotine, phenylephrine, etc.
  • narcotics: in-comp only = hydrocodone, mitragynine, morphine/codeine ratio, tapentadol, tramadol
  • glucocorticoids: in-competition only = by routes of administration other than oral, IV, IM, or rectal; out of competition too (all routes of admin)
  • beta-2-agonists/bronchodilators: any combination of two
195
Q

stimulants allowed in sports

A

now ephedrine and pseudoephedrine and other mild stimulants allowed
- in monitoring program
- ephedrine allowed if <10 mg/L in urine
- pseudoephedrine allowed if <150 mg/L in urine

196
Q

main desired stimulant effect of caffeine

A

increased aggression

197
Q

how can caffeine be abused?

A

by non-coffee drinkers
abstinence followed

198
Q

B2 agonists

A

bronchodilators
- most banned, except salbutamol, salmeterol, terbutaline, and formoterol allowed in inhaled form if athlete is granted TUE for asthma or similar condition

199
Q

asthma, similar conditions allowed drug

A

B2 agonists/bronchodilators
- must be <1000 ng/mL in urine unless athlete can above abnormal metabolism

200
Q

main reason for narcotic ban

A

protects the athlete
= prevents aggravation of an injury through competition
- morphine and most other narcotics
like buprenorphine, dextromoramide, heroin, etc.

201
Q

T or F. NSAIDs, acetaminophen, salicylate, and recently codeine permitted

A

T, but codeine:morphine ratio monitored
hydrocodone and tramadol also allowed

202
Q

beta blockers

A

beta-adrenergic blockers
- reduce BP and are antiarrhythmic
- by reducing BP and HR, produces a “steadying effect” = archery, shooting, etc.

203
Q

beta blockers sport

A

archery
shooting
Darts

204
Q

examples of beta blockers

A

Propranolol
metaprolol
oxprenolol
atenolol
timolol
acebutolol

205
Q

these actively promote excretion of water via the kidneys, including:

A

diuretics
- furosemide
- hydrochlorothiazide
- chlorothiazide

206
Q

two main uses for diuretics:

A

reduce body weight in “weight class” sports (eg. boxing)
produce dilute urine in a bid to avoid detection of banned drugs

207
Q

These are rarely used medically, mainly in diseases involving severe muscle wasting

A

anabolic steroids

208
Q

bolasterone
nandrolone
stanozolol
methandionin
methyltestosterone

A

anabolic steroids

209
Q

serious side effects from anabolic steroid use

A

massive doses
- stunted growth
- defeminizing of females (androgenic effects)
- demasculinizing of men (suppression of testosterone synthesis?)
-impaired liver function
- heart disease
- cancer

210
Q

primarily an androgenic steroid with minor anabolic effects

A

testosterone

211
Q

testosterone tests

A
  • T:epi-T ratio normally 1:1; >4:1 is suspicious
  • > 150 ug/L in urine is suspicious
  • now labs may look at C12:C13 ratio
212
Q

aromatase inhibitors

A

prevents excess testosterone from being converted to estrogen
- aminoglutethimide, anastrozole, etc.

213
Q

anti-estrogenic substances

A

clomiphene, cyclofenil, fulvestrant

214
Q

SERMs

A

selective estrogen receptor modulators
- inhibits action of estrogen on estrogen receptor
- raloxifene, tamoxifen, toremifene

215
Q

SARMs

A

selective androgen receptor modulators (SARMs)
- have anabolic effects with minimal androgenic effects
- some in clinical or -preclinical trial; available illicitly

216
Q

myostatin

A

muscle loss
so myostatin inhibitors leads to increased muscle mass

217
Q

metabolic modulators

A
  • increases exercise endurance
  • activators of AMP-activated protein kinase (AMPK); peroxisome proliferator-activated receptor agonists
  • insulins, trimetazidine
218
Q

define SERMs

A
  • class of compounds that act on estrogen receptor
  • not a pure agonist/antagonist
  • prevents estrogen from binding to receptors by binding itself to the receptor in its place which can be advantageous
219
Q

effects of SERMs

A

stimulates release of LH & FSH = produce and release testosterone
- also helps block paradoxical feminizing effects of testosterone caused by excess estrogen = hypogonadism (lack of testosterone)

220
Q

a selective androgen receptor

A

Ligandrol
- VK5211, LGD-4033
- osteoporosis and muscle wasting treatment

221
Q

this can stimulate muscle growth and has shown superior side effect profiles compared to anabolic steroids

A

SARM

222
Q

ostarine

A

SARM

223
Q

S-23

A

SARM

224
Q

soda loading

A

consuming large amounts of alkali like sodium bicarb to increase body’s base rserve = delay lactic acid onset /buildup and cramps

225
Q

blood doping

A

injecting one with own blood
increases O2 carrying capacity of body
- side effect = erythrocythemia (+ clotting), even if cross-matching not an issue (i.e. athlete’s own packed cells)

226
Q

how can recombinant EPO be detected?

A

isoelectric points

227
Q

ESAs & Mimetics

A

erythropoeisis stimulating agents
- EPO receptor agonist, non-EPO receptor agonist

228
Q

ESAs

A

darbepoetin
EPO
EPO-Fc
EPO-mimetic peptides (EMP)
CNT-530
peginesatide
- methoxy polyethylene glycol-epoetin beta

229
Q

Non-erythropoitic EPO receptor agonists

A

ARA-290
asialo EPO
carbamylated EPO

230
Q

hypoxia-inducible factor stabilizers

A

HIF stabilizers
cobalt
FG-4592
activators such as argon, xenon, krypton

231
Q

a protein that in humans is encoded by the HIF1A gene

A

hypoxia inducible factor 1-alpha

232
Q

this is used to treat chronic kidney disease

A

HIF stabilizer

233
Q

this activates the activity of EPO due to anemia induced hypoxia, metabolic stress, and vasculogenesis = creation of new blood vessels

A

HIF stabilizer

234
Q

cyclists use this

A

HIF stabilizers in combo with cobalt chloride/desferrioxamine
- stimulate and de-regulate natural production of EPO

MLSCI 466 (19 decks)

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