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Clinical Biomedicine > W8: Toxicology > Flashcards

W8: Toxicology Flashcards

(70 cards)

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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
immunoassays: sample types
Primarily urine No sample preparation required. Low sample volume
26
immunoassays: speed
Quick <1 hr Amenable to large batches
27
immunoassays: cost
Immunoassay kits relatively expensive due to cost of Abs
28
immunoassays: instrumentation
Existing automated immunoassay analysers
29
immunoassays: staffing/ease of use
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
immunoassays: POCT
Most POCT devices IA based
31
gas chromatography: precision/accuracy
good
32
gas chromatography: sensitivity
Flame ionisation / MS detectors very high sensitivity
33
gas chromatography: specificity
Detectors used in GC very high specificity
34
gas chromatography: sample types
Most sample types amenable to GC i.e. urine, blood, serum, plasma, hair Forensics - Fluids, Tissue extracts
35
gas chromatography: speed
Long sample preparation due to hydrolysis/derivitisation/extraction Chromatography run times at least 10 min/sample
36
gas chromatography: cost
Expensive - Hardware, Gases, Columns, Software (libraries)
37
gas chromatography: instrumentation
GC, columns, detector, gases, sample prep/derivitisation materials
38
gas chromatography: staffing/ease of use
Extensive experience required for method development, troubleshooting and interpretation H&S aspects of gases and solvents
39
gas chromatography: POCT
not suitable
40
Liquid Chromatography (Tandem) Mass Spectrometry
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
LC-MS/MS: precision/accuracy
v good
42
LC-MS/MSL sensitivity
Good Most urine DOA guideline cut-off concs well above functional sensitivity of MS
43
LC-MS/MS: specificity
Excellent if using MRM, optimisation of chromatography required to ensure max resolution & separation of multiple drug peaks
44
LC-MS/MS: sample types
Urine & oral fluid May require extensive sample prep (hydrolysis & extraction) Does not require derivatisation Potential for matrix effects (ion suppression)
45
LC-MS/MS: speed
5-6 min sample injection time, 100 samples ~10 hr (overnight run)
46
LC-MS/MS: cost
V expensive hardware, columns, analytical grade purity solvents Internal standards expensive
47
LC-MS/MC: instrumentation
Specialist LC-MS equipment required, fume cupboard for solvent waste
48
LC-MS/MS: staffing/ease of use
Considerable expertise required for method development, troubleshooting & interpretation H&S aspects of solvents/gases
49
LC-MS/MS: POCT
not suitable
50
Time of Flight MS
Useful for detection of unknown compounds Can be used to identify compounds based on their parent/fragment composition
51
toxbase
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
National Poisons Information Service (NPIS)
As well as all the above, also collates reports and issues national statistics
53
POCT
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
POCT: precision/accuracy
Antibody dependent Lot-to-lot variability Lack of QC use/availability
55
POCT: sensitivity
Ab dependent
56
POCT: specificity
Poor, largely IA based hence subject to poor specificity and cross reactivity
57
POCT: sample types
Urine/oral fluid, no sample prep required Can be performed by non-technical/non-lab staff
58
POCT: speed
Rapid, typical result <1 min
59
POCT: cost
high cost/test
60
POCT: instrumentation
automated readers and IT interface to enable results are transmitted into patient record CPA accreditation standards for POCT
61
POCT: staffing/ease of use
Able to be performed by non-lab staff No H&S concerns other than handling urine sample Subjective results
62
chromatography vs immunoassay: applicability
wide limited
63
chromatography vs immunoassay: specificity
yes sometimes
64
chromatography vs immunoassay: speed
slow fast
65
chromatography vs immunoassay: capital cost
high low-medium
66
chromatography vs immunoassay: consumable cost
low medium-high
67
chromatography vs immunoassay: skill required
medium-high low-medium
68
chromatography vs immunoassay: suitability for stat analysis
poor good
69
medical laboratory service consists of... (4)
routine testing ID of materials responsible for acute or chronic poisoning detection of drugs of abuse therapeutic drug monitoring
70
therapeutic drugs
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.

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