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clinical chem 1 > therapeutic drug monitoring > Flashcards

therapeutic drug monitoring Flashcards

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1
Q

define therapeutic drug monitoring

A

the measurement of drugs and/or their metabolites in the body fluids - usually blood - to maintain therapeutic benefits

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2
Q

list important considerations of TDM

A
  • timing of collections
  • accurate measurement of drug concentrations
  • timely reporting of results
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3
Q

describe when TDM is used

A
  • drug has a barrow TR
  • marked pharmacokinetic variabilities
  • critical adverse effects
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4
Q

describe the main purpose of TDM

A
  • ensure correct dosages
  • ID drug-drug interactions
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5
Q

define pharmacokinetics

A

study of movement of drugs in the body

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6
Q

what does pharmacokinetics relate concentration of drug to

A
  • absorption
  • dist
  • metabolism
  • excretion
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7
Q

list routes of administration and the most common/most direct

A
  • oral - most common
  • intravenous - most direct
  • intramuscular
  • subcutaneous
  • aerosol
  • transdermal patch
  • rectal
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8
Q

what does oral absorption depend on

A

efficiency of GI absorption which depends on:
- dissociation
- solubility of GI
- diffusion

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9
Q

what form does a drug need to be in to be passively diffused

A
  • hydrophobic and non ionized
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10
Q

define drug distribution

A

the movement of a drug between blood circulation, tissues, organs and the relative proportion of the drug in the tissues

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11
Q

what does a drugs ability to leave circulation depend on

A

lipid solubility of the drug
- highly hydrophobic can easily cross
- polar and don’t ionize can cross cell membrane but don’t enter lipid compartments
- ionized diffuse out of vasculature but slowly

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12
Q

what is the volume of drug distribution equation

A

Vd = dose/concentration

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13
Q

true or false
- hydrophobic drugs have a large Vd
- ionizes or primarily bound to proteins has small Vd

A

true and true

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14
Q

what form do drugs need to be in to interact with site of action

A

free/unbound to result in biological response (active fraction)

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15
Q

how does albumin relate to free fraction of drugs

A

changes in [albumin] affect free vs bound since it is a major transporter

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16
Q

describe drug metabolism

A
  • all drugs enter hepatic portal system and get metabolized
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17
Q

define first pass effect in regards to drug metabolism

A

phenomenon in which a drug is metabolized, results in a reduced concentration of the drug before reaching the circulatory system

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18
Q

describe how impaired liver function effects drug metabolism

A

efficacy of a drug depends on a therapeutically active metabolite that occurs in the liver = biotransformation

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19
Q

true or false
most drugs are xenobiotics

A

true
- exogenous substances capable of entering biochemical pathways that are meant for endogenous substances

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20
Q

what system is responsible for a large part of drug metabolism

A
  • hepatic mixed-function oxidase (MFO)
  • turns hydrophobic to water sol to be transported
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21
Q

describe phases of drug metabolism

A
  • phase 1: produce reactive intermediates
  • phase 2: conjugate functional groups to reactive sites in water sol products
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22
Q

describe how the MFO system can be induced

A

seen as increase in synthesis and activity of the rate-limiting enzymes w/in pathway
- results in accelerated clearance of drug

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23
Q

how are free fractions eliminated

A
  • subject to glomerular filtration and/pr renal secretion
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24
Q

how does elimination rate relate to GFR

A

direct relation
- decrease GFR results in increased half life

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25
Q

independent of clearance mechanism, decreases in the plasma drug concentration most often occur as a ______

A

first-order process
- change in drug/change in time

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26
Q

how many doses are typically needed to enter steady-state oscillation

A

5-7

27
Q

define pharmacodynamics

A

the study of the biochemical and physiological effects of drugs and their mechanisms of action
- concentration at site and response

28
Q

what is the single most important factor in regards to therapeutic drug monitoring specimen collection

A

accurate timing

29
Q

when is peak oral dose drawn

A

1 hr after dose

30
Q

when is peak IV dose drawn from EDTA whole blood

A

90 minutes after dose

31
Q

true or false
drug peaks only after steady state is achieved

A

true

32
Q

define pharmacogenomics

A

the study of variations and development of drug therapies to compensate for the genetic differences impacting therapy regimes
-effectiveness depends on pt response

33
Q

define the prominent gene affecting drug metabolism and what it can be used for

A

CYP450
- encodes cytochrome P450
- to personalize drug dosages

34
Q

what is the most common cardioactive drugs

A

digoxin

35
Q

describe digoxin

A
  • treats arrythmias and CHF
  • inhibits Na/K ATPase to increase intracellular calcium to improve cardiac contractability
  • plasma protein binding rate of 25%
  • free form sequestered in muscle
  • measure bound and free with immunoassays
36
Q

describe quinidine

A
  • cardioactive drug to treat arrythmias
  • absorption rapid through oral-GI
  • eliminated through hepatic metabolism
  • monitor trough, peak if toxic
37
Q

describe disopyramide

A
  • cardioactive drug
  • sub for quinidine
  • renal elimination
  • binds several plasma proteins
38
Q

describe procainamide and relation to N-acetylprocainamide

A
  • oral and rapid absorption
  • 20% bound to plasma proteins
  • eliminated renal and hepatic
  • N-acetylprocainamide (NAPA) is the hepatic metabolite of procainamide => skips liver
39
Q

describe aminoglycosides

A
  • broad category antibiotic
  • treats GN and some GP infections
  • inhibits bacterial protein synthesis
  • nephrotoxicity and ototoxicity
  • needs IV or IM
40
Q

describe gentamicin

A
  • aminoglycoside antibiotic
  • treats GNR if life threatening
  • can do higher dosing if good renal function
41
Q

describe tobramycin

A
  • aminoglycoside antibiotic
  • treats GNR
  • ototoxic and nephrotoxic
  • baseline audiology testing
42
Q

describe amikacin

A
  • aminoglycoside antibiotic
  • treats severe blood infections
  • orally administered to lower intestinal flora
  • excreted by kidneys
43
Q

describe kanamycin

A

aminoglycoside antibiotic

44
Q

describe vancomycin

A
  • glycopeptide antibiotic
  • against GPC and GPR
  • poor GI abs = IV
  • redman syndrome
  • nephrotoxic and ototoxic
  • only trough is measured
45
Q

describe (general) antiepileptic drugs

A
  • used to treat and suppress seizures
  • only effective while drug metabolites are in the body
  • measured w/ immunoassays or chromatography
46
Q

describe primidone

A
  • AED
  • used for grand mal seizures if resistant to other AEDs
  • converted to metabolites (phenobarbital and phenylethylmalonamide)
  • reaches steady state quicker than phenobarbitol
47
Q

describe phenobarbital

A
  • slow acting oral AED
  • eliminated hepatic w/ renal
  • only troughs measured
48
Q

describe phenytoin and free phenytoin

A
  • AED
  • common seizure and short term prophylactic in brain injury
  • high protein bound portion 87-97%
  • free fraction is biologically active form
  • measure both free and bound for dosage adjustment
49
Q

describe valproic acid (depakote)

A
  • oral AED
  • high protein bound
  • hepatic elimination
  • toxic at upper end TR
  • hepatic dysfunction in some pt w/in TR
50
Q

describe carbamazepine (tegretol)

A
  • severe adverse events, only used if no other AEDs work
  • oral
  • toxicity diverse and variable but close to TR
51
Q

describe Gabapentin (neurontin)

A
  • common AED
  • oral max bioavailability of 60%
  • for for seizures and pain management
  • does not bind proteins
  • not metabolized in liver
  • eliminated unchanged in liver
  • used in pt w/ liver disease
52
Q

describe lithium

A
  • oral psychoactive mood altering drug
  • doesn’t bind protein
  • toxic at 1.5-2 ug/dL
53
Q

describe tricyclic antidepressants (TCAs)

A
  • treat depression, insomnia, extreme apathy, loss of libido
  • oral
  • high protein bound (85-95%)
  • hepatic metabolism
  • immunoassay screening NOT TDM due to cross reactivity
  • chromatographic TDM
54
Q

describe clozapine

A
  • psychoactive drug for refractory schizophrenia
  • 97% protein bound
  • TDM used for adherence checks and toxicity
  • metabolized in liver
55
Q

describe olanzapine

A
  • psychoactive drug for: schizophrenia, acute manic episodes, recurrence of bipolar disorders
  • IM or oral (usually oral)
  • 40% inactivated after first pass
  • 93% bound to plasma proteins
  • metabolized in liver
56
Q

describe (general) immunosuppressive drugs

A
  • TDM used to prevent organ rejection
  • individual dosage regimens to minimize toxic
  • chromatographic, liquid chromatography-tandem mass spec
57
Q

describe cyclosporine

A
  • immunosuppressive drug
  • cyclic polypeptide
  • suppress graft vs host rejection
  • oral w/ low abs
  • whole blood specimen
58
Q

describe tacrolimus FK-506

A
  • oral
  • 100x more potent that cyclosporine
  • 98% bound to plasma proteins
  • whole blood sample
59
Q

describe sirolimus

A
  • immunosuppressive
  • antifungal to prevent graft rejection in kidney transplants
  • rapid oral abs
  • co administered w/ cyclosporine or tacrolimus
  • 92% bound to lipoproteins
60
Q

describe everolimus

A
  • derived from sirolimus
  • more rapid steady state achievement
  • whole blood specimen
61
Q

describe mycophenolic acid (MPA)

A
  • immunosuppressive
  • prodrug converted in liver to active MPA
  • oral but abs in neutral pH
  • 95% protein bound
  • renal elimination
62
Q

describe antineoplastics

A
  • immunosuppressant
  • not aided by TDM
  • rapidly metabolized or incorporated into cellular macromolecular structures
  • delivered dose more important than circulating concentrations
63
Q

describe methotrexate

A
  • antineoplastic
  • oral administration
  • 50% bound to plasma protein
  • extretated renal
  • trough specimens preferred
64
Q

describe bronchodilators

A

theophylline
- used to treat respiratory disorders
- for pt who can’t use inhaler
- 50-65% bound to plasma proteins

clinical chem 1 (23 decks)

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