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therapeutic drug monitoring Flashcards

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
independent of clearance mechanism, decreases in the plasma drug concentration most often occur as a ______
first-order process - change in drug/change in time
26
how many doses are typically needed to enter steady-state oscillation
5-7
27
define pharmacodynamics
the study of the biochemical and physiological effects of drugs and their mechanisms of action - concentration at site and response
28
what is the single most important factor in regards to therapeutic drug monitoring specimen collection
accurate timing
29
when is peak oral dose drawn
1 hr after dose
30
when is peak IV dose drawn from EDTA whole blood
90 minutes after dose
31
true or false drug peaks only after steady state is achieved
true
32
define pharmacogenomics
the study of variations and development of drug therapies to compensate for the genetic differences impacting therapy regimes -effectiveness depends on pt response
33
define the prominent gene affecting drug metabolism and what it can be used for
CYP450 - encodes cytochrome P450 - to personalize drug dosages
34
what is the most common cardioactive drugs
digoxin
35
describe digoxin
- 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
describe quinidine
- cardioactive drug to treat arrythmias - absorption rapid through oral-GI - eliminated through hepatic metabolism - monitor trough, peak if toxic
37
describe disopyramide
- cardioactive drug - sub for quinidine - renal elimination - binds several plasma proteins
38
describe procainamide and relation to N-acetylprocainamide
- 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
describe aminoglycosides
- broad category antibiotic - treats GN and some GP infections - inhibits bacterial protein synthesis - nephrotoxicity and ototoxicity - needs IV or IM
40
describe gentamicin
- aminoglycoside antibiotic - treats GNR if life threatening - can do higher dosing if good renal function
41
describe tobramycin
- aminoglycoside antibiotic - treats GNR - ototoxic and nephrotoxic - baseline audiology testing
42
describe amikacin
- aminoglycoside antibiotic - treats severe blood infections - orally administered to lower intestinal flora - excreted by kidneys
43
describe kanamycin
aminoglycoside antibiotic
44
describe vancomycin
- glycopeptide antibiotic - against GPC and GPR - poor GI abs = IV - redman syndrome - nephrotoxic and ototoxic - only trough is measured
45
describe (general) antiepileptic drugs
- used to treat and suppress seizures - only effective while drug metabolites are in the body - measured w/ immunoassays or chromatography
46
describe primidone
- AED - used for grand mal seizures if resistant to other AEDs - converted to metabolites (phenobarbital and phenylethylmalonamide) - reaches steady state quicker than phenobarbitol
47
describe phenobarbital
- slow acting oral AED - eliminated hepatic w/ renal - only troughs measured
48
describe phenytoin and free phenytoin
- 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
describe valproic acid (depakote)
- oral AED - high protein bound - hepatic elimination - toxic at upper end TR - hepatic dysfunction in some pt w/in TR
50
describe carbamazepine (tegretol)
- severe adverse events, only used if no other AEDs work - oral - toxicity diverse and variable but close to TR
51
describe Gabapentin (neurontin)
- 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
describe lithium
- oral psychoactive mood altering drug - doesn't bind protein - toxic at 1.5-2 ug/dL
53
describe tricyclic antidepressants (TCAs)
- 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
describe clozapine
- psychoactive drug for refractory schizophrenia - 97% protein bound - TDM used for adherence checks and toxicity - metabolized in liver
55
describe olanzapine
- 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
describe (general) immunosuppressive drugs
- TDM used to prevent organ rejection - individual dosage regimens to minimize toxic - chromatographic, liquid chromatography-tandem mass spec
57
describe cyclosporine
- immunosuppressive drug - cyclic polypeptide - suppress graft vs host rejection - oral w/ low abs - whole blood specimen
58
describe tacrolimus FK-506
- oral - 100x more potent that cyclosporine - 98% bound to plasma proteins - whole blood sample
59
describe sirolimus
- immunosuppressive - antifungal to prevent graft rejection in kidney transplants - rapid oral abs - co administered w/ cyclosporine or tacrolimus - 92% bound to lipoproteins
60
describe everolimus
- derived from sirolimus - more rapid steady state achievement - whole blood specimen
61
describe mycophenolic acid (MPA)
- immunosuppressive - prodrug converted in liver to active MPA - oral but abs in neutral pH - 95% protein bound - renal elimination
62
describe antineoplastics
- immunosuppressant - not aided by TDM - rapidly metabolized or incorporated into cellular macromolecular structures - delivered dose more important than circulating concentrations
63
describe methotrexate
- antineoplastic - oral administration - 50% bound to plasma protein - extretated renal - trough specimens preferred
64
describe bronchodilators
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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