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Clinical Chemistry 2 (Lecture) > Therapeutic Drug Monitoring (Bishop | F) > Flashcards

Therapeutic Drug Monitoring (Bishop | F) Flashcards

1
Q

What is TDM?

A

It is the analysis, assessment, and evaluation of circulating concs. of drugs in serum, plasma, / whole blood (WB)

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2
Q

What is the purpose of TDM?

A

To ensure that a given drug dosage produces maximal therapeutic benefit and min. toxic adverse effects

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3
Q

When is TDM used?

A

It is used when safe dosage regimens have not been established and a trial and error approach is not appropriate

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4
Q

In TDM, where is std dosage derived?

A

It is derived from observations in healthy population

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5
Q

TDM involves what?

A

It involves quantitative evaluation of circulating drug conc.

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6
Q

What are the key factors of TDM?

A

1) Route of administration
2) Rate of absorption
3) Distribution of drug within body
4) Rate of elimination

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7
Q

What are the different routes of administration?

A

1) Intravenous (IV)
2) Intramuscular (IM)
3) Subcutaneous (SC)
4) Transcutaneous
5) Suppository
6) Oral administration

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8
Q

What is the principle of IV (w/c is 1 of the routes of administration)?

A

Injected directly into circulation

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9
Q

What is the principle of IM (w/c is 1 of the routes of administration)?

A

Injected into muscle

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10
Q

What is the principle of SC (w/c is 1 of the routes of administration)?

A

Injected just under skin

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11
Q

What is the principle of transcutaneous (w/c is 1 of the routes of administration)?

A

Inhaled or absorbed through skin

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12
Q

What is the principle of suppository (w/c is 1 of the routes of administration)?

A

Rectal delivery

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13
Q

What is the principle of oral administration (w/c is 1 of the routes of administration)?

A

By mouth

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14
Q

For orally administered drugs, efficiency of absorption from GIT depends on what factors?

A

1) Formulation of drug
a. Tablets
b. Capsules
c. Liquid solutions
2) Uptake by transport mechanisms intended for dietary constituents vs. passive diffusion
3) Changes in :
a. Intestinal motility
b. pH
c. inflammation
d. food
e. other drugs
4) Variation among population
5) Age
6) Pregnancy
7) Pathologic conditions

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15
Q

What are the types of drugs?

A

1) Free (unbound)

2) Bound

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16
Q

What is the characteristic of free fraction of drug?

A

It can interact w/ site of action and cause biologic response

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17
Q

The percentage of free fraction of drug depends on what?

A

1) Physiologic parameters

2) Biochemical parameters

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18
Q

The physiologic and biochemical parameters where the percentage of free fraction of the drug depends on are what?

A

1) Inflammation
2) Malignancies
3) Pregnancy
4) Hepatic disease
5) Nephrotic syndrome
6) Malnutrition
7) Acid-base disturbances

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19
Q

The percentage of free fraction of drug also depends on what?

A

Conc. of other substances competing for binding sites

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20
Q

What is the principle of drug distribution?

A

1) Ability of drug to diffuse out of circulation

2) Depends on lipid solubility of drug

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21
Q

What is the principle of drug elimination?

A

Rate of change of drug conc. over time varies continuously in relation to conc. of drug

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22
Q

What is the elimination equation?

A

ΔC/ΔT = -kC

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23
Q

What are the cmpts related to drug elimination?

A

1) Metabolic clearance

2) Renal clearance

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24
Q

What is the system of metabolic clearance?

A

Hepatic mixed function oxidase (MFO) system

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25
Q

What are the events that occur in hepatic MFO system?

A

1) Converts hydrophobic substances into H2O-soluble ones

2) Transports them into bile or circulation, eliminates them by filtration

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26
Q

What is pharmacokinetics?

A

It is the mathematic modeling of drug conc. in circulation

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27
Q

Pharmacokinetics assists in what?

A

It assists in establishing or modifying a dosage regimen

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28
Q

Pharmacokinetics takes into account what?

A

It takes into account all factors that determine conc. of a serum drug and its rate of change (absorption, distribution, and elimination)

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29
Q

What is the timing for sx collection?

A

It is critical

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30
Q

When does trough concs. occur (in sx collection)?

A

Right before next dose

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31
Q

When does peak concs. occur (in sx collection)?

A

1 hr after oral dose

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32
Q

What is the sx of choice for TDM?

A

1) Serum

2) Or plasma

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33
Q

What are the cmpts of pharmacogenomics?

A

1) Responders

2) Non-responders

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34
Q

Who are responders (in pharmacogenomics)?

A

Pts benefitting from therapeutic and desired effects of drug

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35
Q

Who are non-responders (in pharmacogenomics)?

A

Pts not benefitting from therapeutic and desired effects of drug

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36
Q

What is pharmacogenomics?

A

Therapeutic effectiveness of drugs has been attributed to inter-individual variation in genetic polymorphisms of drug metabolism pathways

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37
Q

What is cytochrome P450?

A

It is the gene grp family that affects drug metabolism

38
Q

What are the cardioactive drugs requiring TDM?

A

1) Cardiac glycosides
a. Digoxin
2) Antiarrhythmics
a. Quinidine
b. Procainamide
c. Disopyramide

39
Q

What is the purpose of digoxin?

A

It is used in treatment of congestive heart failure (CHF)

40
Q

What is the fxn of digoxin?

A

It inhibits membrane Na-K-ATPase

41
Q

What are the characteristics of absorption (in digoxin)?

A

1) It is variable
2) It is influenced by dietary factors
3) It is influenced by GI motility
4) It is influenced by formulation of drug

42
Q

How is digoxin eliminated?

A

Via renal filtration of plasma free form

43
Q

What is the half-life (plasma; in connection to digoxin)?

A

38 hrs in ave adult

44
Q

What is the method (and what is its purpose) done for measurement of digoxin?

A

Immunoassay (to determine total conc. in serum)

45
Q

What are the most common formulations of quinidine?

A

1) Quinidine sulfate

2) Quinidine gluconate

46
Q

What is the action of disopyramide?

A

It is used as a quinidine substitute when quinidine’s adverse effects are excessive

47
Q

What are the exs of antibiotics?

A 
1) Aminoglycosides
     Most common:
         a. Gentamicin
         b. Tobramycin
         c. Amikacin 
         d. Kanamycin
2) Vancomycin
48
Q

What are aminoglycosides?

A

A grp of chemically related antibiotics used for treatment of infections w/ gram-(-) bacteria that are resistant to less toxic antibiotics

49
Q

What is vancomycin and what is its action?

A

It is a glycopeptide antibiotic that is effective against gram-(+) cocci and bacilli

50
Q

What are the different antiepileptic drugs?

A

1) First generation
a. Phenobarbital
b. Phenytoin
c. Valproic acid
d. Carbamazepine
e. Ethosuximide
2) Second generation
a. Felbamate
b. Gabapentin
c. Lamotrigine
d. Levetiracetam
e. Oxcarbazepine
f. Tiagabine
g. Topiramate
h. Zonisamide

51
Q

What is phenobarbital and what is its action?

A

It is a slow-acting barbiturate that effectively controls several types of seizures

52
Q

What are the uses of phenytoin?

A

1) A commonly used treatment for seizure disorders

2) It is used as a short-term prophylactic agent in brain injury to prevent loss of fxnal tissue

53
Q

What is the use of valproic acid?

A

It is used as a monotherapy for treatment of petit mal and absence seizures

54
Q

What are the characteristics of carbamazepine?

A

1) It is an effective treatment in various seizure disorders

2) It has serious toxic adverse effects

55
Q

What is the result of the characteristic of carbamazepine due to its serious toxic adverse effects?

A

It is less frequently used

56
Q

What is the use of ethosuximide?

A

It is used for control of petit mal seizure

57
Q

How is felbamate administered?

58
Q

What is the characteristic of felbamate (in connection for it as being orally administered)?

A

It is nearly completely absorbed by the GIT

59
Q

What is the characteristic of felbamate?

A

It is toxic (/ it is known for its toxicity)

60
Q

What is the primary indication of felbamate?

A

It is primarily indicated in severe epilepsies (such as Lennox-Gastaut syndrome [children]) and refractory epilepsy (adults)

61
Q

What may be the indication of gabapentin?

A

It may be indicated as monotherapy or in conjunction w/ other antiepileptic drugs in pts suffering from complex partial seizures w/ or w/out generalized seizures

62
Q

What is the indication of levetiracetam?

A

It is indicated in partial and generalized seizures

63
Q

What is oxcarbazepine and what is its characteristic?

A

It is a pro-drug that is almost immediately metabolized to licarbazepine

64
Q

What is the indication of oxcarbazepine?

A

1) It is indicated for monotherapy of partial seizures

2) In generalized tonic-clonic seizures

65
Q

What is the indication of tiagabine?

A

It is indicated in partial seizures

66
Q

What are the indications of topiramate?

A

It is indicated in partial and generalized seizures

67
Q

What are the indications of zonisamide?

A

It is indicated in partial and generalized seizures

68
Q

What are the exs of psychoactive drugs?

A

1) Lithium
2) Tricyclic antidepressants
3) Clozapine
4) Olanzapine

69
Q

How is lithium administered?

70
Q

What is the use of lithium?

A

It is used to treat manic depression

71
Q

What are the uses of tricyclic antidepressants?

A

It is a class of drugs used to treat:

1) Depression
2) Insomnia
3) Extreme apathy
4) Loss of libido

72
Q

What is clozapine?

A

It is an atypical antipsychotic

73
Q

What is the use of clozapine?

A

It is used to treat otherwise treatment-refractory schizophrenia

74
Q

What is olanzapine?

A

It is a thienobenzodiazepine derivative

75
Q

Olanzapine effectively treats what conditions?

A

1) Schizophrenia
2) Acute manic episodes
3) Recurrence of bipolar disorders

76
Q

What are the exs of immunosuppressive drugs?

A

1) Cyclosporine
2) Tacrolimus
3) Sirolimus
4) Mycophenolic acid

77
Q

What is the primary clinical use of cyclosporine?

A

Its primary clinical use is suppression of host-versus-graft rejection of heterotropic transplanted organs

78
Q

What is the characteristic of tacrolimus?

A

It is 100 times more potent > cyclosporine

79
Q

What is sirolimus?

A

It is an antifungal agent

80
Q

What is the activity present / capable of doing of sirolimus?

A

Immunosuppressive activity

81
Q

FDA approved sirolimus can be administered to whom?

A

To / for pts receiving kidney transplants

82
Q

What is mycophenolic acid?

A

It is a lymphocyte proliferation inhibitor

83
Q

Mycophenolic acid is most commonly used as what?

A

As supplemental therapy (w/ cyclosporine and tacrolimus) in renal transplant pts

84
Q

Provide an ex of antineoplastics

A

Methotrexate

85
Q

What is 1 of the few antineoplastic drugs in w/c TDM offers benefits to a therapeutic regimen?

A

Methotrexate

86
Q

High-dose methotrexate followed by leucovorin rescue has been shown to be what?

A

To be an effective therapy for various neoplastic conditions

87
Q

Basis of the therapy (for various neoplastic conditions w/c is shown by high-dose methotrexate followed by leucovorin rescue) involves what?

A

Involves relative rate of mitosis of normal vs. neoplastic cells

88
Q

What are the characteristics of neoplastic cells (in connection w/ the effective therapy w/c is shown by high-dose methotrexate followed by leucovorin rescue)?

A

1) These divide more rapidly > normal cells
2) These have higher requirement for DNA
3) These are susceptible to deprivation of this essential constituent before normal cells

89
Q

The efficacy of methotrexate depends on what?

A

Controlled period of inhibition

90
Q

How is the efficacy of methotrexate accomplished?

A

It is accomplished by leucovorin

Clinical Chemistry 2 (Lecture) (17 decks)

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