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Kinetics - year 4 > TDM and Drug Assays > Flashcards

TDM and Drug Assays Flashcards

1
Q

What is TDM impacted by?

A
  1. Demograhics factors
  2. He;ath rwltaed factors
  3. extracorporeal Treamentets
    4.. Personalf factors - ADME
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2
Q

Specimane types - Most common

A
  1. venous blood
  2. serum
  3. Plasma
  4. urine - not as commonly used
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3
Q

What is phlebpotmy

A

the drawing of blood from the body

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4
Q

what is the common site for blood draws?

A

mediam cubital vein or any vein in arm

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5
Q

Tube types -

What do plasma tubes need?

A

anticogulants

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6
Q

Tube types -

What do serum tubes need?

A

blood clotting - fibrinogen

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7
Q

tube types - what are the top 4?

A
  1. plan tube - serum (red)
  2. Plain tube with SST gel - serum (orange)
  3. EDTA - anticoagulants - plasma (Pink)
  4. Lithium heparin anticoagulant - plasma (green)
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8
Q

what is centrifugtaion?

A

part of specimen processing so specimen separtes based on desnity

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9
Q

adtanvage of centirfugation?

A

these specimens then have np cells and are much cleaner allowing fro photometric analysis

  • separator gel
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10
Q

what are the four pre analytic factors

A
  1. Drug dpsing accurancy
  2. appropreite sampling time
  3. handlcing and collection of sample
  4. physiological changes in patient
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11
Q

what are some specimen clean up or purification mean?

A
  1. centrifugation
  2. proetin precipitaion
  3. liquid-liquid extraction
  4. solid phase extraction
  5. chromatogrpahy
  6. ultrafiltration
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12
Q

measuring free drug level via what tecnique?

A

immunoassay

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13
Q

Free drug or bound drug, active?

A

free drug

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14
Q

what drugs are specically important to monitor free drug levels?

A

Phenytoin
Valproic acid
Carbamazapine

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15
Q

Specimen processing: free drug measurement when and why?
-4 points

A
  1. meausremnt of serum drug concetration may be misleading fro highly;y protein bound drugs
  2. under conditions of uremie, liver disease and hypoalbuminemia, free drug levels may be high however the drug levels are in therapeutic range
  3. drug -drug interaction may lead to increased free drug levels
  4. in elderly they have hypoalbunemic so increased free drug concentration
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16
Q

how to measure a freed drug if we have bound drig?

A

must separte so can use ultrfiltration

must have assay with good analytical sensitivity

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17
Q

cons of free-drug measuring (3)

A
  1. more costly and lower accuracy
  2. more time and resources (highly sensitive to temp, ph)
  3. thought to be similar to Total drug levels as long as free drug levels don’t vary much between people
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18
Q

Immunoassay methods vs chromatography method

A

Immunoassay
- less labor entensive and faster turn around
- limited by lack of spcificay between parent drug and metabolite (potential false positive) and cross-reactivity with similar drugs
- susceptible to interfere by bilirubin and lipedemmia, hemoglobin, paraproetins and heterophiloc antibodies

Chromatogprhy
- liquid chromotpgarhy - tandem mass chemtogaprhy can simultaneously analyse multiple drugs in a single assay
- typically higher specificity for the drug

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19
Q

TDM - immunassays, gas chromatogrpahy, and liquid chromatogrphay

A

Immunoassays
- for over 25 commercial assays

gas chromatography
- flame ionization detection/mass spectrometry

liquid chromatography
- UV/flurescence/mass spec

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20
Q

Immunoassays pros and cons

A

pros
- rapid
- sensitive
- loe cost
- small sample size
- mainly vis plasma or serum

cons
- major concern is antibody specificity

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21
Q

Propeties of an antibody- antigen bond

A
  • non-cavalent
  • reversible
  • intermolecualr focres (hydrongen bonding, ionic bonding, hydrophobic interactions, van der wall forces)
  • clonal varaition
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22
Q

antigen antibody bonding causes what?

A

structual changes consistent with indiced fit mec

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23
Q

whats provides specificalty to antibody and antigens interactions?

A

amino acid residues

24
Q

Antobody affinity in equilibrium. process

A

Ag + Ab reverisble AB X AG

Ka = (ABxAG)/(Ab=Ag)

25
Q

Immunassays use monclonal or polyclonanle antobodies?

A

both

26
Q

What is a monclonald antibody

A

population os antibodies that recognize antigen at several epitopes

27
Q

what is a polyclonal antibody

A

population of antibodies that recognize target antigen at a single epitope

28
Q

where do the labels used in ummunoassay go?

A

on the analogue of the target or the antibody

29
Q

what kind of labels are there?

A

Enzymatic or non-enzymatic

30
Q

what kind of immunoassay do we have?

A
  1. competitive
    - measures small molecules
    - uses single antibody but competes with labeled analogue of the target compound
  2. immunometric
    - measure larger molecules
    - uses two antibodies and formed a sandwich with the target ( labeled antibody and captured antibody)
31
Q

what are drug assay commenly?

A

competive immunoassay

32
Q

describe how a PETINA works

A
  • uses light sacttering to measure drug levls
  • if bound more tubity
  • of unbound less turbity
33
Q

features of chromatogrpahy

A
  • less common
  • used when immunoassay not availble
  • less rapid
  • sample requirement variable
  • serum, plasma and blood
34
Q

why do we sue chromatogrphy?

A

for separtaion of compounds for MS meaudrmenst

35
Q

different type of chromatogrohay

A
  1. gass chormatogprhy
    - votalaity of gases
  2. liquid chromatography
    - polarity of substances
36
Q

sensitivity of glass chromatography depends on what?

A

the detector

37
Q

Big advantage of chromatography

A

multiplexing

38
Q

Where do therapeutic drug ranges come from?

A

usually RCTS

39
Q

what are the analytical factors impacting TDM results?

A
  1. method selctivity for target drug vs metabolites
  2. method reproducibility
  3. avaialibily of pure satdnard reference materials
  4. interfering substances in the sample
40
Q

what are common types of error

A

Systematic error and random error

41
Q

what can systemcatis and random error lead to?

A

issues in accuracuy

42
Q

trueness refers to

A

systematic error

43
Q

imprescision referes to

A

random erro

44
Q

inaccuracy refers to

A

systematic and random error

45
Q

acidic drugs bind to

A

albumin

46
Q

basic drugs bind to

A

alpha 1 - acid glycoproetin

47
Q

when are free drugs levels very imporatn?

A

when we have altered binding
1. disease
2. drug interaction
3. non-linear binding

48
Q

what to know about blood collection from young children

A

uses micro-containers and capillary sampling

many preanalytics issues
- hemolysis
- onadequant volume
- improper ratio bw blood and anticoagulant

49
Q

collection tube red

A

no anticoagulant or gel
- all drugs including free drugs

50
Q

collection tube green

A

Heparin (lithium, sodium, ammonium)
- lithium Heparin should not be used for a Li meausrment
- aminoglycosides not used on heparin plasma if EMIT method

51
Q

collection tube purple

A

EDTA
- preferred for immunoassay (whole blood)
- mycophenolic acid (plasma)

52
Q

collection tube yellow/orange

A

Serum (sst)
- unsuitable for certain drugs

53
Q

hemolyisis affect on acetminophen

A

hemolyis can cause high acteaminophen

54
Q

concers with cross reactivity

A

especially with competive immunoassay

55
Q

different method yield differnt results

A
  • problem for immunoasssay
  • less for chromatogrpahy

Kinetics - year 4 (4 decks)

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