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Clinical Biomedicine > W8: Toxicology > Flashcards

W8: Toxicology Flashcards

1
Q

toxicology

A

qualitative & quantitative study of adverse reaction of toxins & Toxicants on living organisms.

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2
Q

toxin

A

poison of natural origin

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3
Q

toxicant

A

hazardous substance of chemical origin

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4
Q

4 classifications of toxicology

A

occupational, env, forensic, clinical

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5
Q

pharmacokinetics

A

absorption, distribution, biotransformation & excretion of drugs & chemicals.

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6
Q

pharmacodynamics

A

biochemical & physiological effects of chemicals to the body & mechanisms of their actions.

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7
Q

sample types

A

urine
blood
hair
saliva

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8
Q

sample adulteration

A

Biological
Dilute sample by drinking large amounts H2O prior to test

Chemical
Acid, bleach, oxidants

Addition of drugs
eg spiking with methadone to demonstrate compliance

Urine substitution
Synthetic urine
Someone else’s
Pet’s
Other liquid

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9
Q

sample integrity checks

A

Supervised sample collection

Measure urine creatinine/electrolytes
Creatinine <2.0 mmol/L ‘dilute’
pH
Normal urine pH ~4.5-9.0

Specific gravity

Appearance
Temperature on collection
Green - ?methadone spike
Odour - ?bleach

Measure metabolites

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10
Q

why does toxicology matter?

A

Occupational: workplaces SAFE
Env: environmental contaminants are SAFELY disposed of
Forensic : responsible culprits identified correctly & made accountable for their actions.
Clinical : SAFETY & well being of every person

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11
Q

analytical techniques

A

Thin Layer Chromatography
Immunoassay
Gas Chromatography
Tandem Mass Spectrometry
Detection of unknown drugs by mass spectrometry
POCT

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12
Q

thin layer chromatography

A

Can detect parent drugs and their metabolites in most cases

Specialist manual assay requires considerable experience for interpretation of results

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13
Q

TLC precision/accuracy

A

Qualitative assay
Semi-quantitative assays possible with use of standards and densitometry

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14
Q

TLC sensitivity

A

relatively poor

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15
Q

TLC specificity

A

Poor; overlapping spots e.g methadone/EDDP
User variability in interpretation

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16
Q

TLC sample types

A

Primarily urine
Little/no sample preparation required

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17
Q

TLC speed

A

Long assays – at least 3-4 hr/plate, up to 20 samples/plate
Difficult to automate

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18
Q

TLC cost

A

TLC plates & solvents relatively cheap
Standards more expensive

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19
Q

TLC instrumentation

A

Requires fume cupboard for toxic solvents / developing

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20
Q

TLC staffing/ease of use

A

Experienced staff required for interpretation
Health and safety aspects of solvents and staining

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21
Q

TLC POCT

A

not suitable

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22
Q

immunoassays: precision/accuracy

A

Good precision on most automated analysers
Lack of specificity impacts on accuracy due to cross reactivity to structurally related drugs

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23
Q

immunoassays: sensitivity

A

depends on Ab

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24
Q

immunoassays: specificity

A

Limited – drug group specific rather than single drug specific, can also get cross reactivity between drug groups

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25
Q

immunoassays: sample types

A

Primarily urine
No sample preparation required.
Low sample volume

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26
Q

immunoassays: speed

A

Quick <1 hr
Amenable to large batches

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27
Q

immunoassays: cost

A

Immunoassay kits relatively expensive due to cost of Abs

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28
Q

immunoassays: instrumentation

A

Existing automated immunoassay analysers

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29
Q

immunoassays: staffing/ease of use

A

Can be added to existing IA repertoire with little or no change in staffing/training
Minimal additional H&S concerns other than handling liquid reagents

30
Q

immunoassays: POCT

A

Most POCT devices IA based

31
Q

gas chromatography: precision/accuracy

32
Q

gas chromatography: sensitivity

A

Flame ionisation / MS detectors very high sensitivity

33
Q

gas chromatography: specificity

A

Detectors used in GC very high specificity

34
Q

gas chromatography: sample types

A

Most sample types amenable to GC i.e. urine, blood, serum, plasma, hair
Forensics - Fluids, Tissue extracts

35
Q

gas chromatography: speed

A

Long sample preparation due to hydrolysis/derivitisation/extraction
Chromatography run times at least 10 min/sample

36
Q

gas chromatography: cost

A

Expensive - Hardware, Gases, Columns, Software (libraries)

37
Q

gas chromatography: instrumentation

A

GC, columns, detector, gases, sample prep/derivitisation materials

38
Q

gas chromatography: staffing/ease of use

A

Extensive experience required for method development, troubleshooting and interpretation
H&S aspects of gases and solvents

39
Q

gas chromatography: POCT

A

not suitable

40
Q

Liquid Chromatography (Tandem) Mass Spectrometry

A

Has become the standard clinical laboratory tool for confirmatory drugs of abuse screening

Advantages over GC:
Allows simultaneous detection of multiple compounds
Can analyse polar, non-volatile, heat labile compounds
No need to derivatise
Quicker run times

41
Q

LC-MS/MS: precision/accuracy

42
Q

LC-MS/MSL sensitivity

A

Good
Most urine DOA guideline cut-off concs well above functional sensitivity of MS

43
Q

LC-MS/MS: specificity

A

Excellent if using MRM, optimisation of chromatography required to ensure max resolution & separation of multiple drug peaks

44
Q

LC-MS/MS: sample types

A

Urine & oral fluid
May require extensive sample prep (hydrolysis & extraction)
Does not require derivatisation
Potential for matrix effects (ion suppression)

45
Q

LC-MS/MS: speed

A

5-6 min sample injection time, 100 samples ~10 hr (overnight run)

46
Q

LC-MS/MS: cost

A

V expensive hardware, columns, analytical grade purity solvents
Internal standards expensive

47
Q

LC-MS/MC: instrumentation

A

Specialist LC-MS equipment required, fume cupboard for solvent waste

48
Q

LC-MS/MS: staffing/ease of use

A

Considerable expertise required for method development, troubleshooting & interpretation
H&S aspects of solvents/gases

49
Q

LC-MS/MS: POCT

A

not suitable

50
Q

Time of Flight MS

A

Useful for detection of unknown compounds
Can be used to identify compounds based on their parent/fragment composition

51
Q

toxbase

A

A national database and learning tool for all toxins/toxicants
Regularly updated, includes treatment plans, etc.
Used by all medical professionals as the “go to” advice/info

52
Q

National Poisons Information Service (NPIS)

A

As well as all the above, also collates reports and issues national statistics

53
Q

POCT

A

Majority based on immunochemical ‘lateral flow device’ technology

Hence still have inherent disadvantages of immunochemical assays i.e poor specificity and cross reactivity

Mostly qualitative or semi-quantitative competitive IAs

Useful for emergency toxicology where treatment can be initiated or to explain signs / symptoms

Results of IA always require confirmation!!

54
Q

POCT: precision/accuracy

A

Antibody dependent
Lot-to-lot variability
Lack of QC use/availability

55
Q

POCT: sensitivity

A

Ab dependent

56
Q

POCT: specificity

A

Poor, largely IA based hence subject to poor specificity and cross reactivity

57
Q

POCT: sample types

A

Urine/oral fluid, no sample prep required
Can be performed by non-technical/non-lab staff

58
Q

POCT: speed

A

Rapid, typical result <1 min

59
Q

POCT: cost

A

high cost/test

60
Q

POCT: instrumentation

A

automated readers and IT interface to enable results are transmitted into patient record
CPA accreditation standards for POCT

61
Q

POCT: staffing/ease of use

A

Able to be performed by non-lab staff
No H&S concerns other than handling urine sample
Subjective results

62
Q

chromatography vs immunoassay: applicability

A

wide
limited

63
Q

chromatography vs immunoassay: specificity

A

yes
sometimes

64
Q

chromatography vs immunoassay: speed

65
Q

chromatography vs immunoassay: capital cost

A

high
low-medium

66
Q

chromatography vs immunoassay: consumable cost

A

low
medium-high

67
Q

chromatography vs immunoassay: skill required

A

medium-high
low-medium

68
Q

chromatography vs immunoassay: suitability for stat analysis

69
Q

medical laboratory service consists of… (4)

A

routine testing
ID of materials responsible for acute or chronic poisoning
detection of drugs of abuse
therapeutic drug monitoring

70
Q

therapeutic drugs

A

Monitoring drugs with narrow therapeutic range at designated intervals to maintain constant concentration in the blood and optimize the dosage regime.
Immunoassay methods-Automated platforms mainly used in routine medical laboratory settings.

Clinical Biomedicine (23 decks)

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